irii jiiijiilillii iiiiililillliNJjJiJJiJjJiiiiiliiliiiiiiiirii iiiiiiiiMiii IIII1IIII1J|(I^ ••P LIBRARY NEW YORK STATE VETERINARY COLLEGE ITHACA, N. Y. iiiiiinjiiiiiiMiiiiiiiiiiii ui piiiiiiiiirrtiiriiiiriiiiiiiiiiiiilliiiiiiitiiitiiMiiiiHiiiii ii|ijiiiiiiii(iii|||ilJilittiiiii|iiiiiiiiiiiiiiii.- Cornell University Library RB 43.R86 1 Lessons In pathological histology 3 1924 000 885 503 Cornell University Library The original of tiiis book is in tine Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/cletails/cu31924000885503 LESSONS IN PATHOLOGICAL HISTOLOGY BY GUSTAVE ROUSSY and IVAN BERTRAND PROFESSEUR AGREGE, CHEF DES TRA- VAUX PRATIQUES D'ANATOMIE PATHOLOGIQUE A LA FACULTE DE PARIS CHEF DE LABORATOIRE DELEGUE A LA CLINIQUE DES MALADIES NER- VEUSES DE LA FACULTE DE PARIS TRANSLATED FROM THE SECOND FRENCH EDITION BY JOSEPH McFARLAND, M.D., Sc.D. PROFESSOR OF PATHOLOGY AND BACTERIOLOGY IN THE MEDICAL DEPARTMENT OF THE UNIVERSITY OF PENNSYLVANIA ILLUSTRATED WITH 124 ENGRAVINGS LEA & FEBIGER PHILADELPHIA AND NEW YORK Copyright LEA & FEBIGER 1922 |PJiINTED IN U. S. A. PREFACE. This interesting and intensely practical little book is novel in almost every particular and has no parallel among the books offered to students of medicine. It bears the same relation to pathologic histology that a "dissector" does to anatomy; it is a self-instructor, teaching the salient features of the tissues studied. It is not a text- book of pathology, nor can the student possibly suppose that it can take the place of one; it is not a hand-book of technic. It is a guide, and a very inteUigible one, to the microscopic study of morbid tissues. It may not contain all of the sections that the student is called upon to study — they differ in different institutions — ^but it contains enough to teach him the correct method, and gives the most important facts, after which new material may be approached without hesitation and with full confidence that the same methods applied will yield the same satisfactory results. The approach to the diagnosis is always systematically made : The student is first told what should be seen with the naked eye, then what is to be seen with the low-power lens, and finally, if necessary, what with the high-power lens. Particular fields for examination with the higher powers are frequently indicated upon the drawing by lines inclosing small squares. When the book is opened, the right-hand pages are found to show the beautiful drawings of M. Bessin, to which in this American edition have been added additional ones by Mr. Erwin Faber, so drawn as to correspond with the originals, from which it is impossible for one not in possession of the French copy to differentiate them. On the left-hand page is a text cor- related with the illustration, and telling how one should proceed in studying it. Although brief, this text is descriptive, critical and diagnostic, and transforms the book from an atlas to a guide by being of a value equal to the illustrations. J. McF. LESSONS IN PATHOLOGICAL HISTOLOGY. INTRODUCTION At the beginning of this little book, intended to direct the student in his first steps in the study of pathological histology, are brought together a few elementary facts about practical microscopy. It is done as briefly as possible, in the hope that it will be appreciated by these for whom it is intended. Certain details of histological technic are important in the successful interpretation of microscopic preparations. Only the most important of them will be mentioned, espe- cially as nearly all of the sections have been fixed and stained in the same manner. It is indispensable to follow certain rules in the interpretation of histological slides, and it is through lack of knowing and observing them that beginners, too soon employing high-power lenses, lose themselves in the reading of the sections and commit the grossest errors of interpretation. A histological diagnosis ought to be conducted much as a clinical diagnosis at the bedside. It is only after having exposed the patient and examined him in his entirety, that the clinician goes on to the successive methods of inspection, palpation, auscultation, etc. Methods of Using the Microscope and Interpreting the Sec- tion. — A microscope consists of a stand, an optical system (objectives and oculars), and an illuminating apparatus com- prising an Abbe parabolic condenser, a mirror and an iris diaphragm. The Abbs condenser should not be employed with very low- power lenses whose magnification does not exceed that of a hand lens. Besides the diminution of the light that results 18 LESSONS IN PATHOLOGICAL HISTOLOGY from its employment in such cases, images of the window, the wall and other objects are apt to appear in the field of vision. The condenser is, therefore, to be removed from the optical axis with such powers. It is, however, necessary with middle- and high-power lenses, but it ought to be placed at some distance from the object in order that the best illumina- tion be obtained and distinctness of vision secured. The higher the magnification, the nearer the condenser must be brought to the stage; with an oil-immersion lens it should be in immediate contact with the slide. The mirror has plane and concave sides, each of which sub- serves a special purpose. The concave side should be used when the source of light is small, as in artificial light; the plane side for natural light. The iris diaphragm serves to cut out the excessively oblique rays of light when high-power lenses are used. How widely it should be open or how tightly closed is a matter that can only be learned by experience. As a matter of fact, the student should open and close it more or less with each change of mag- nification and with each different object examined, as with different degrees of light different structural details are brought out. The Objectives and Oculars. — The microscopes used by students vary in different laboratories, some being provided with two, some with three objectives, according to the different character of the work to be done. When this is histological only, two objectives— a low power and a high power— are all that are required; if bacteriological or cytological work is to be included it may be necessary to add another— higher power— or even an oil-imersion lens. It will be supposed that the student using this manual finds his equipment to consist of two objectives— a low power and a high power. He usually also receives two oculars by which to reach the extremes of high and low powers within the range of his objectives. In general, however, it is best to work only with the low-power ocular as it affords the best definition. The Low-power Objective.— It is with this magnification that the study of every microscopic section ought to be begun. It gives a general, that is, a topographical view of the whole section, and enables the different component tissues and their INTRODUCTION 19 relations to be determined, and the parts requiring further examination to be recognized. For example, in a section of a uniform structure, such as the pulmonary tissue, the low power enables sections of the bronchi and bloodvessels quickly to be found, and if there be any deeply-colored masses, such as bronchopneumonic areas or tubercles present, they quickly catch the eye. Again, in sections of any part of the wall of the alimentary tract it easily discovers any breach of surface continuity such as constitutes an ulceration. The examination with the low-power lens ought, therefore, be continued for some time as it enables the trained eye not only to discover the organ concerned, but also to make a pre- sumptive diagnosis of its principal lesions. The Medium-power Objective. — Should there be a medium- power lens, its use will in most cases sufl5.ce to complete the diagnosis. The High-power Objective. — This should only be employed to complete the observation. It shows but a very circumscribed field of the section, and its chief uses are for defining the cyto- logical and nuclear structural details — protoplasmic granules, vibratory cilia, mitotic figures, etc. THE ELEMENTARY PRINCIPLES OF HISTOLOGICAL TECHNIC. Only the methods of fixing and staining indispensable to the interpretation of the sections described in this manual will be mentioned. I. Fixation.— Pieces of tissue selected for histological exami- nation should be immersed in a preserving fluid for the purpose of fixing their structure by coagulating the albumins with the least possible modification of their cells. According to the size and fixation of the blocks of tissue will their cellular char- acteristics be well preserved. (a) Pieces of tissue obtained from surgical operations and fixed upon the spot may be regarded as in a state of perfect preservation. (b) Pieces of tissue taken from autopsies made twenty-four hours after death will be found in a very unequal state of preservation. They have not only been subjected to the 20 LESSONS IN PATHOLOGICAL HISTOLOGY disadvantages of putrefaction, but also to the action of auto- lytic enzymes, whose effects are especially marked upon the alimentary mucosa. The adrenal body and the cerebellum also rapidly show the effects of postmortem change. In all such cases care must be taken not to confuse the results of the postmortem changes with the pathological lesions. In general, the cadaveric or postmortem changes are uniformly dis- tributed throughout the entire section, all of the elements of the same kind being similarly affected and about to the same degree. Among the fixatives most commonly used the following may be mentioned. (a) Formaldehyde.— It is employed in a dilution of i part of the commercial 40 per cent solution with 9 parts of water.'^ It also forms the base of such other fixatives as Bouin's solution which is made up of 75 parts of a saturated solution of picric acid, 20 parts of formaldehyde and 5 parts of acetic acid. This solution, however, frequently imparts an undesirable yellowish color to the tissue. (b) Corrosive Sublimate.— This may be employed in the form of a solution composed of corrosive sublimate 3 parts, acetic acid I part and distilled water 100 parts. It also enters into the composition of numerous other fixatives such as Domi- mici's solution which is made of a saturated aqueous solution of corrosive sublimate 100 cc, formaldehyde 15 cc and enough tincture of iodine to give the fluid a port-wine color. Whenever solutions of corrosive subHmate are used as fixa- tives it is necessary to wash the tissue, after twelve to twenty- four hours' immersion, in running water for twenty-four hours. The chemical has the disadvantage of forming a combination with the albumins of the tissue which subsequently appears in the form of a black acicular crystalline deposit. This some- times causes confusion with blood and other pigments naturally present, though its acicular form ought to enable it to be easily recognized. It is, however, best to remove it by adding tincture of iodine to the alcohols subsequently used for dehydration. 2. Imbedding and Cutting.— After fixation the blocks of tissue are subjected to washing, progressive dehydration by passage through alcohols of increasing strength, and are finally imbedded 1 Better results result from the use of physiological salt solution instead of water as the diluent. INTRODUCTION 21 in some substance such as paraffine or celloidin that subsequently solidifies sufiiciently to permit them to be cut into sections from 5 to lo microns in thickness, with a microtome. If the edge of the microtome knife is uneven the sections may present a striated appearance which deforms their struct- ural elements. The parallel direction of these striae enables them to be recognized as artefacts. The colloid substance of the thyroid body commonly presents a "picket fence," or palisade appearance, but that is an arte- fact that depends rather upon the peculiar fragility of the substance itself than upon defects in the edge of the knife. 3. Staining. — The sections, fastened to the slides, are stained in various ways, of which only these most commonly used will be mentioned, as it is most important to simplify the technic as much as possible for beginners, and employ as nearly as as possible the same methods for all of the different tissues described. Hematoxylon.— This is a basic dye extracted from logwood. It stains the nuclei of the cells a deep blue color. Eosin.— This is an acid anilin dye. It stains connective- tissue fibers a pale rose color and striated and unstriated mus- cular fibers a bright red. Van Giesen's Stain. — This consists of a solution made up as follows: I per cent aqueous solution of acid tuchsin 5 cc Saturated aqueous solution of picric acid 100 cc It is used as a counter-stain with iron hematoxylon. With the combination vascular connective tissue is stained intense red by the acid f uchsin, the protoplasm of the cells is colored yellow by the picric acid and the nuclei are black from the iron hema- toxylon. The method is especially appropriate for the demonstration of the vascular connective tissue in the study of the various scleroses — chronic nephritis, cirrhosis, pancreatitis, etc. Acid Orcein. — This stain is composed of: Orcein ... .... . i gr. Hydrochloric acid . i cc 96 per cent alcohol ... 100 cc The orcein has an elective affinity for the elastic tissue which it colors brown-black. THE NORMAL LUNG. 1. Low-power Lens. — The pulmonary tissue presents an alveolar appearance that is recognizable even to the naked eye, and depends upon the presence of numerous spaces, the pulmonary alveoli, of very similar size and shape in the normal lung. These air spaces, irregularly lozenge shaped, are bounded by sinuous walls, the inter alveolar septce. Here and there, as in the center of the drawing, bloodvessels and air tubes are seen cut transversely or longitudinally, and for the most part grouped together in the connective-tissue. trabeculcB or broncho-vascular axes of the pulmonary structure. Black patches, anthracotic accumulations, especially distinct in the neighborhood of the bronchial tubes, are almost con- stantly present in the lungs of the adult and the aged, and in the reading of the microscopic sections form a precious element in making the differential diagnosis of the organ. The lungs with their associated lymph nodes are the organs most frequently pigmented with carbon particles. The alveoli, broncho- vascular axes and anthracotic collections form a triad that should always be looked for with care in recognizing the pulmonary parenchyma. If the section reaches to the external surface of the lung it may include the pleura which is composed of a layer of vascular connective tissue covered by endothelium. 2. High-power Lens.— The structural details now become more distinct. The interalveolar septse seem to be composed of cells of a shape varying in different cases. In lungs obtained at autopsy some of them are often found to have detached and to lie free in the air spaces. In certain areas the cells seem to be gathered together in masses— an appearance that results from the tangential sectioning of the wall of one or several alveoli. In the interalveolar septse there are capillary bloodvessels which in the normal state contain only one or two red blood corpuscles. If the section be stained with orcein (as in Fig. 2) elastic fibers can be seen in the interalveolar septEe in the form of fine filaments of dark brown or black color, insinuating them- selves between the cells and the capillaries and passing from one alveolus to another. 22 Cartilage in the bronchial wall. s^ lJ:(fS^ >^i lir Pulmon- ary artery Pulmon- ary alveoli Pulmon- ary vessel. Pulmon- ary vein containing laked blood. Pulmon- ary vessel. Fig. 1. — Normal lung. Lung of a suicide. Stained with hematoxylon and eosin. Magnified 25 diameters. This shows the characteristic triad upon the finding of which the diagnosis of the pulmonary tissue depends — the pulmonary alveoli, the vessels, which in this case contain some laked blood, and the bronchial tube with its supporting cartilage. The anthra- cotic accumulations cannot be easily recognized with this magni- fication. 23 In the neighborhood of the broncho-vascular apparatus the high-power lens enables one to recognize : 1. The bronchioles, or air tubes, with a cylindrical epithelial lining supported upon a connective-tissue wall, at the periphery of which, in those of middle and large size, there may be carti- laginous plates. These appear blue violet in sections stained with hematoxylon and eosin. 2. The bloodvessels which are easily recognized by their smooth endothelial lining, which contrasts strongly with the columnar epithelium so distinctly seen in the bronchial tubes. The branches of the pulmonary artery can be distinguished from those of the pulmonary veins by the thickness of their walls, and by the fact that they are usually empty while the veins usually contain blood. Note.— The anatomical unit of pulmonary structure is the lobule; but for its demonstration special methods of prepara- tion— insufHation, injection of coagulable substances, serial sections, etc.— must be resorted to, so that it does not clearly appear in microscopic sections. It is of interest in enabling the morphological structure of the lung to be understood, but has very little importance in pathological histology. In any section of a diseased lung the lesions of the alveoli, the bronchioles, the interalveolar septae and the vessels are the important features for study, their lesions, through synthe- sis of the findings, enabling a diagnosis of the condition to be reached. The pulmonary alveolus ought to be regarded as the unit of structure in pathological histology. It may be compressed or collapsed as in the fetus {atelectasis), distended to bursting {emphysema), or filled with morbid products (edematous fluid blood, fibrin, pus, etc.), in edema, infarction, pneumonia, or bronchopneumonia {alveolitis serosa, hemorrhagica, fibrinosa, purulenta, respectively). The same is true of the bronchial tubes. It is only after study of the various elementary lesions and their distribution in the section that the whole can be inter- preted, purely contingent lesions cast aside and proper evalua- tion given the most important. The condition of the pleura should also be considered if the surface of the lung be included in the section. 24 Elastic fiber. Tangen- tial sec- tion of an alveolus. Tangen- — tial sec- tion of an alveolus. Alveolar space. Alveolar wall. Respira- . tory epi- thelium. Capillary Fig. 2. — Normal lung. Lung of a suicide. Stained with acid orcein. Magnified 250 diameters. The reticulum of elastic fibers is shown colored black by the orcein. At two points, above and to the right, and below and to the left, the alveolar epithelium, seen in full face instead of in pro- file, seems to occur in plates. This is the result of tangential cutting of the section. 25 PULMONARY EMPHYSEMA AND CONGESTION. The Diagnosis of the Organ.— This is easy to make: One recognizes the pulmonary alveoli and sees in the center of the drawing a section of a broncho- vascular axis containing a bron- chial tube with its lining of cylindrical epithelial cells. A pulmonary artery and vein and patches of carbon particles are also shown. The Diagnosis of the Lesion. — That which at once strikes the observer is the great size of certain of the air cells. There are all intermediate stages between normal alveoli and enor- mous cavities. Many of the alveolar walls have ruptured (emphysema), though they appear distinctly thicker than in the normal lung because of distention of the capillaries (congestion) . The air cells are almost entirely empty (contain air), but in some a few red blood corpuscles may be seen. A higher power lens permits the alveolar walls to be studied. In sections stained with hematoxylon and eosin, they are almost entirely composed of extremely dilated capillaries con- taining numerous red blood corpuscles. Sometimes they make hernial protrusions into the alveolar cavity, and even rupture here and there, permitting the escape of the corpuscles into the air cells {hemorrhagic alveolitis). The nuclei visible in the section belong, for the most part to the endothelial cells of the capillaries. It is scarcely possible to find any of the alveolar epithelial cells, either because of pathological alteration (desquamation or degeneration), or because of cadaveric alteration (defective fixation of very fragile elements). In sections especially stained with orcein (Fig. 5, B), which brings out the elastic-tissue network of the pulmonary structure, it is possible to study its alterations — fragmentation and extension— which are very important in emphysema. The elastic tissue of the alveolar wall is found to be composed of delicate fibrillae, colored black, mostly cut longitudinally and following a course that spreads out according to the obliquity of the section. To the right in the drawing a black stippling results from transverse section of the fibers. To the left a capillary in the alveolar wall distinctly shows its elastica. The interalveolar walls are stretched and thinned. There are no changes in the microscopic appearance of the bronchial tubes. 26 ' V- ^ - Pulmon- " ary artery Bron- chiole without cartilagin- ous sup- port. Blood in an alveo- lus. Emphy- sematous' bladder Fig. 3. — Pulmonary emphysema and congestion. Staining with hematoxylon and eosin. Magnified 20 diameters. // is the lung of an old man with chronic emphysema and con- gestion. The unequal size of the pulmonary alveoli, the rupture of the interalveolar septce and the thickness of the alveolar walls from distention of the capillaries are to be particularly noted. 27 All of the bloodvessels, large and small, are dilated and distended with blood and show as bright red dots in the section. About the larger vessels there is a slight increase in the con- nective tissue (beginning sclerosis). The condition corresponds with what is called essential emphysema, by which is meant that neither in the gross morbid specimen nor in the microscopic section can any explanation of the distention of the air cells be found. In subsequent descriptions, and especially in that of bron- chopneumonia, it will become evident that though emphysema sometimes occurs as a primary lesion, it also occurs in associa- tion with other important conditions such as fibrinous alveolitis, purulent alveolitis, hemorrhagic alveolitis and edema, which take precedence over it in importance in the interpretation of what is seen in the section and to which it is secondary. Resume. — Pulmonary emphysema with beginning sclerosis and intense congestion. The latter may be referred in part, if not altogether, to the agonal condition of the circulation. It is common in lungs removed at autopsy, and no importance should be attributed to it unless it is found in association with other conditions evincing its priority. 28 Small hemor- rhage. Dilated capillary. Septum with a capillary. Longi- ftudinal elastic fibers. ] Trans- ( versly cut I elastic J fibers. Fig. 4. — Pulmonary emphysema and congestion. A. — Stained with hematoxylon and eosin. Magnified 200 diameters. With this power the congestive changes of the inter- alveolar wall can he better appreciated. B.— Stained with orcein. Magnified 250 diameters. With this stain the elastic fibers are brought out with distinctness on account of their black color. 29 PULMONARY INFARCTION. The section consists of a hemorrhagic focus and its immediate surroundings. To the naked eye it seems to be homogeneous. Diagnosis of the Organ.— At the lower edge of the section one can make out the alveolar network, and by moving it about (under a low-power lens) can find sections of vessels and a bronchial tube (the last is not shown in the drawing). I. Low-power Lens.— "By passing from the center to the periphery of the hemorrhagic focus three zones may be dis- tinguished : (a) A central zone which is the seat of a hemorrhage that has effaced all the details of pulmonary structure, and appears to be composed of nothing but densely packed red blood cor- puscles whose contours are still quite distinct. Occasional leukocytes appear, the nuclei of both lymphocytes and poly- morphonuclears being stained blue, by the hematoxylon. Dis- seminated throughout the area occasional blackish crystals of hematoidin, derived from the hemoglobin, may be seen. {h) A median zone in which the alveolar contours can be distinguished though the air spaces are all filled with blood. The alveolar walls seem to have disappeared, their places being taken by blood pigment and cellular debris. (c) An outer zone in which the pulmonary tissue has reacted — inflammatory zone. Here the alveoli are filled with a finely meshed fibrinous exudate (stained red), mononuclear leuko- cytes, desquamated endothelial cells and a great number of crystals of hematoidin either free or in the interior of mono- nuclear cells {macrophages). In the upper right-hand fourth of the drawing the cause of the pulmonary hemorrhage appears as a branch of the pul- monary artery completely obUterated by a large clot adhering to the inner wall about its entire circumference, the result of thrombosis or embolism. The upper part of the thrombus is formed of red corpuscles densely packed together as in the hemorrhagic focus in the neighboring lung, but in the lower part its structure is less homogeneous and pigment crystals appear. Lastly, at the periphery of the thrombus there are minute vessels of new formation whose office it is to transform it into viable organized tissue {organization of a thrombus). Resume.— Pulmonary infarction from embohsm. It is not recent as is shown by the transformation of the blood pigment and the penetration of new vessels into the thrombus, 30 Throm- bosed pulmon- ary artery containing • a partly organized clot. New vessels. ^■^a^L^zi'*^*'- ih^ .K. / Fibrinous alveolitis. Small [ii hemor- 4'' M^ ^ rhagic Vlff-'^^''' '",. "^■^ayga^.g' ••'.-3>m--J area. I Central zone of massive hemor- rhage. Small throm- bosed vessel. II Median zone apoplectic Hemor- rhagic alveolitis. Fig. 5. — Pulmonary infarction. Stained with hematoxylon and eosin. Magnified 25 diameters. Embolic pulmonary apoplexy or infarction complicating acute endocarditis. The thrombus which closes the pulmonary artery is penetrated by newly-formed bloodvessels and is undergoing organization. Passing outward from the thrombosed artery as a center, the infarction shows three zones: I, a zone of massive hemorrhage; II, a zone of hemorrhage in which some of the alveolar walls can still be seen; and III, a zone of fibrinous alveolitis. 31 FIBRINOUS PNEUMONIA. Croupous Pneumonia. Diagnosis of the Organ.— This is difficult in consequence of the uniformity of. the inflammatory reaction. The character- istic triad— alveolar- network, vessels and bronchi and anthro- cotic accumulations can be found only in the less atypical areas. The lesion is very uniform and consists of a fibrinous exudate filling all of the alveoli, giving the pulmonary tissue a gross quality comparable to the liver, Hence the term hepatization. From the red color resulting from the presence of large numbers of red corpuscles in the alveoli it is called red hepatization. I. Low-power Lens.— The exudate consists of a network of fine meshes of eosin staining material, whose organized form contrasts with the red amorphous character of the serous fluid found in edema. Sometimes the fibrinous meshwork is separated from the alveolar wall by a narrow interval, this appearance being caused by the contraction effected by the reagents used in fixing and preparing the tissue. Some of the bundles of filaments pass through ruptures in the alveolar walls and connect with exudate in neighboring air cells. In the meshes of the network are numerous formed ele- ments—large endothelial cells with abundant cytoplasm, poly- morphonuclear and mononuclear leukocytes and red blood corpuscles. The fibrin and red blood corpuscles characterize the stage of pneumonia called red hepatization {fibrinous alveolitis). In the subsequent stage the fibrin disappears, and polymorpho- nuclear leukocytes fill the- alveoli — gra,y hepa.tiza.tion (purulent alveolitis) . In sections stained with methylene blue or by Gram's method numerous lanceolate diplococci — pneumococci — can be seen in the exudate. The proportion of elements in the alveoli varies very slightly; the lesion is uniform and diffuse, and quite different from that found in bronchopneumonia (see Fig. 7) in which it occurs in scattered foci. The respiratory epithelium is desquamated; the capillaries are much dilated, often ruptured, thus permitting the red corpuscles to escape into the exudate. The smaller bronchi sometimes contain a serofibrinous exudate mixed with polymorphonuclear leukocytes. Lastly, the pleura, not shown in the drawing, but often 32 affected in pneumonia, may be covered with a thick layer of norm [false membrane). Resume.— Fibrinous alveoHtis, corresponding to the second stage of frank acute pneumonia. The uniformity of the lesion shows It to be diffuse and lobar, at least if the fragment was not taken from a nodule of bronchopneumonia, which histo- logical examination alone does not enable one to determine. Alveolar wall Inter- alveolar fibrinous filaments V. Intact bronchus " Poly- jj^. '. 4 »^ I nuclears Desqua- ■^ mated epithelial cells * r _ i _^ __ - Fibnn Inter- ,.— alveolar fibrinous filaments. Ruptured alveolar wall. U Red blood corpuscles. Vessel. Fig. 6. — Fibrinous pneumonia. (Fibrinous alveolitis.) Stained with hematoxylon and eosin. Magnified 200 diameters. Section made from a solid block of frank acute pneumonia in an adult whose other lung showed, at autopsy, the lesion of gray hepatization. The disturbance is precisely the same throughout the entire section and consists in fibrinous alveolitis, characterized by the presence of fibrinous reticula, red blood corpuscles, poly- morphonuclear leukocytes and desquamated epithelium in the alveoli. It is the stage of red hepatization, the second stage of pneumonia. 3 33 BRONCHOPNEUMONIA. Diagnosis of the Organ.— With a low-power lens one can recognize the alveolar network and sections of bronchi and vessels in the less affected pale parts of the section. Diagnosing the Lesion. — That which at once attracts atten- tion is the occurrence of the lesion in foci, indicated by scattered dark areas; nodules of peribronchial disturbance separated by healthy tissue. Low-power Lens. — In the upper part of the drawing the debris of bronchial epithelium is recognizable by the columnar epithelium, arranged in palisade form, mixed with numerous abnormal polymorphonuclear leukocytes. Near the bronchial tube there is an arteriole. Both of these are in a broncho- vascular axis about which, according to the classical concep- tion, the peribronchial nodule has developed. Passing from the center to the periphery, which is not always easy to recognize when the diseased areas are numerous and close together; the alveoli present extremely diverse appearances. But that which characterizes bronchopneumonia is the extreme variety of the alveolar lesions. These consist of: 1. Fibrinous alveolitis, much like that of fibrinous pneumonia, with network of fibrin enmeshing epithelial cells, leukocytes and red blood corpuscles. 2. Purulent alveolitis, where the fibrinous network has dis- appeared, giving place to an enormous number of partly degen- erated polymorphonuclear leukocytes, with deeply staining nuclei from which the nuclear network has disappeared (pycnosis). Sometimes the alveoli are filled with polymorphonuclear leukocytes mixed with desquamated epithelial cells and red blood corpuscles; sometimes they are bathed in serous fluid {edematous alveolitis); sometimes the alveolar walls have ruptured and large purulent cavities formed. The large, middle-sized and small bronchial tubes are filled with pus— a condition constant in bronchopneumonia, but not a reliable character upon which to base a differential histological diagnosis between fibrinous and lobular or bron- chopneumonia. It is the lobular distribution and the dissem- ination of the lesions that characterize bronchopneumonia. In the zones of the pulmonary parenchyma that appear healthy (not shown in the drawing) contingent alveolar lesions may be observed— alveolar edema, emphysema, etc. Resume.— The extreme variety of the alveolar lesions, their 34 occurrence in disseminated foci and their frequent arrangement about the broncho-vascular axes are characters that permit the diagnosis of acute bronchopneumonia.. Branch of the pul monary artery Poly morpho nuclear cells bathed in edema tous fluid Fibrinous alveolitis Desqua- mated bronchial epithe- lium. Alveolus filled with poly- morpho- nuclear cells. Purulent alveolitis. Endothe- lial cell. Edema- tous fluid with poly- morpho- nuclear cells (ede- matous alveolitis. Fig. 7. — Acute bronchopneumonia. Stained with hematoxylon and eosin. Magnified 150 diameters. Bilateral nodular bronchopneumonia. The specimen was secured from the lung of a child that died of measles. With this magnification the peribronchial distribution of the areas does not appear. The diversity of the alveolar changes, which vary from edematous to purulent infiltration is to be noted. There are also marked changes in the bronchial epithelium. 35 MILIARY TUBERCULOSIS OF THE LUNG. With the naked eye the rose-colored centers of small dark patches the size-of millet seeds can easily be distinguished. Diagnosis of the Organ.— With a low magnification the diagnosis of the organ can easily be made through the presence of the pulmonary alveoli, vessels and bronchial tubes, Diagnosis oif the Lesion.— The dark patches are formed of dense rose-violet masses, the topography of which is quite irregular and without the peribronchial arrangement seen in bronchopneumonia. Examination of the nodules shows them to be miliary tubercles in different stages of development. In some the center is occupied by one or more giant cells and is surrounded by a zone of epithelioid cells, large and trans- parent, with elongated and frequently bilobed nuclei; while the periphery is composed of lymphoid cells whose nuclei, colored a deep blue, are surrounded by a very small amount of protoplasm. In others the center is caseous, with occasional fissures brought about through the action of the fixing reagents. The giant cells are then crowded to the periphery or absent. Sometimes the tubercles tend to fuse into conglomerate masses of much greater size. In the upper left-hand portion of the drawing (Fig. 8) there is a structure that can easily be confounded with a tubercle. It is rounded and has a central lumen limited by a very indis- tinct undulating line. It is a small artery with a thickened diseased wall. Such arteritis is frequent in tuberculosis. Between the tubercles the pulmonary parenchyma shows a variety of lesions : (a) Catarrhal alveolitis with desquamated epithelial cells and some red blood corpuscles escaped through rupture of the alveolar capillaries, which are everywhere dilated and filled with blood. (b) Purulent alveolitis, characterized by accumulations of polymorphonuclear leukocytes in alveoli with normal or ruptured walls. (c) Edematous alveolitis, characterized by the presence of serous fluid in the air cells. There are no lesions of the bronchial tubes, the epithelium of whose walls is .intact. Resume.— Pulmonary tuberculosis in which the tubercles are fairly discrete and in various stages of development, some already having undergone caseation in the center: Miliary Tuberculosis. 36 Artery with peri- arteritis. Miliary tubercle with giant cells. Edema- tous alveolitis. Giant cell. Fig. 8. — Miliary tuberculosis of the lung. Stained with hematoxylon and eosin. Magnified loo diameters. It is a case of bilateral miliary tuberculosis of the lungs in an adult. The tubercles visible to the naked eye are a little larger than the fine gray granules of the granulia} Further they are distributed in loose clusters about the bronchi, and not at hazard as are the granulia. The dissemination of the tuberculous areas is to be noted. All are about the same size, but not all contain giant cells. Between the tubercles the alveoli show contingent lesions such as edematous and catarrhal alveolitis. ' Granulia is a name given by Empis for an inflammatory condition that like tuberculosis is characterized by the presence of small granulations upon the serous surfaces and in the organs. It is not recognized in America, and the term is almost never heard. 37 THE MILIARY TUBERCLE. The tubercle selected as the type was taken from a section of pulmonary tuberculosis. Diagnosis of the Organ.— This is easily made through the presence of an alveolus which shows in the upper left-hand part of the drawing, and a part of a bronchial wall seen in the upper right-hand corner. Diagnosis of the Lesion.— With the low-power lens the . tubercle can be divided schematically into three zones. 1. A central part of a more or less bright rose color. 2. A median part composed of a crown of pale cells and of giant cells. 3. A peripheral part, dense and formed of blue cells. This is the miliary tubercle in the stage of its full develop- ment, i. e., with central caseation. In the same section some can be found in less advanced stages with or without central giant cells, and almost entirely composed of lymphocytes. With the high-power lens the same tubercle shows: 1. The central zone formed of caseous material and structure- less or finely granular, taking the eosine strongly, with occa- sional cracks caused by retraction during fixation. 2. The middle zone composed of epithelioid and giant cells. The giant cells are of very irregular shape, and frequently of indefinite outline because their prolongations insinuate them- selves between the neighboring cellular elements. The proto- plasm is granular, homogeneous and acidophil; the nuclei are numerous, sometimes 20 or 30, in general arranged near the periphery of the cell in the form of a coronet when complete, or a horse-shoe when incomplete. The giant cells of tumors (giant-cell sarcoma) do not have the peripheral arrangement of the nuclei and their cytoplasm is basophihc, i. e., colored by the hematoxylon. The foreign- body giant cells may have the nuclei pushed out toward the periphery, but the cytoplasm is always basophilic in reaction. The epithelioid cells surround the central caseous mass as a bluish ring. They are polyhedral cells with abundant dis- tinct protoplasm, and an elongated, often bilobed, nucleus. The lymphocytes insinuate themselves in greater or smaller numbers between them. Through pressure the epithelioid cells become fused into masses that eventuate in giant cells. In sections stained by Ziehl's method, tubercle bacilli may be seen in the centers of the giant cells and between the epithe- lioid cells. 3. The peripheral zone of lymphocytes contrasts with the 38 preceding both by its density and by its color. The nuclei are small, dark and are surrounded by very scanty cytoplasm. If the central area of caseation be large the softened and liquified material may be evacuated through a neighboring bronchial tube in the form of a sudden profuse expectoration (vomica) and a cavity thus be formed. Catarrhal and hem- orrhagic alveolitis. "U-^-'^*'^ ,,.f if/p^,'. , -^ II. Zone of epithe- lioid and giant cells. I. Zone of casea- tion. Fig. 9. — Miliary tubercle Stained with hematoxylon and eosin. Magnified 300 diameters. The figure shows under a high magnification a part of a tubercle taken from a case of ulcerative tuberculosis of the pulmonary apex. It shows the different zones of the miliary tubercle very distinctly. I. Zone of central caseation. II. Zone of epithelioid and giant cells. III. Zone of lymphoid cells. About the tubercle, desquama- tion of the alveolar epithelium {catarrhal alveolitis), and dilated capillaries with blood in the alveoli {hemorrhagic alveolitis), both of which are contingent lesions. 39 TUBERCULOUS BRONCHOPNEUMONIA. Naked-eye Examination.— This shows a series of dark patches scattered over a clear field. Diagnosis of the Organ.— This is made by the recognition of the alveolar network, the bronchial tubes (almost normal), and of the bloodvessels. Diagnosis of the Lesions. — Low-power Lens. — The patches riddling the pulmonary parenchyma resemble those of the ordinary bronchopneumonia, but differ from them in that their staining reaction varies from the center to the periphery. They are most frequently grouped about the bronchial tubes. High-power Lens. — Here are found for study: 1. The inflamLmatory areas. 2. The bronchi and alveoli in the intermediate zones, with their principal and contingent lesions. 1. The Inflammatory Areas: These consist of rounded formations having the structure of miliary tubercles, with caseous centers, giant cells, epithelioid cells and lymphocytes. Besides these, above and to the left, above the bronchial tube, in the drawing, there are conglomerate tubercles, closely pressed together. Such an assembly of small rounded grapsh tubercles in the lung is visible to the naked eye. It is composed of young tubercles without central caseation. In the middle of the drawing there are two dark patches consisting of structureless caseous granular masses, colored bright red by the eosin. About them are giant cells, epitheli- oid cells and lymphocytes. When the process of caseation becomes more advanced the caseous material is eliminated by the bronchi and gives rise to the tuberculous cavities. 2. The Pulmonary Parenchyma: At the periphery of less confluent tuberculous masses the pulmonary alveoli are found distended, with the walls ruptured (emphysema), either empty, or filled with serous fluid (edema). Elsewhere, but not shown in the drawing, there may be alveolar ca.tarrh, with desquamation of the epithelial cells, hemorrhagic alveolitis, fibrinous alveolitis with dehcate net- work of fibrin fibriUae containing desquamated epithehal cells and leukocytes— purulent alveolitis in which the alveoh are filled with degenerated polymorphonuclear leukocytes. The bronchioles are normal. Resume.— The distribution of the lesion in foci about the bronchi permits the diagnosis of bronchopneumonia; the presence of the caseation and giant cells, that of tuberculosis: Tuberculous bronchopneumonia. 40 3 conglom- erated miliary tubercles with giant cells. Bronchus. Distended (emphyse- matous) alveolus. Nearly normal bronchial tube. Fig. 10. — Tuberculous catarrhal pneumonia. Stained with hematoxylon and eosin. Magnified 50 diameters. It is a case of chronic tuberculous bronchopneumonia in an old man. Note the peribronchial arrangement of the bronchopneu- monic nodule, the zones of caseation (of which there are two), and the numerous young miliary tubercles with giant cells. The bronchi are normal. 41 MASSIVE CASEOUS PNEUMONIA. Diagnosis of the Organ.— This is difficult to make as the whole section is formed of a compact and uniform mass. An experienced eye, however, is able to recognize the alveolar reticulum at several points. It is ill-defined and badly colored but recognizable. The most striking feature of the lesion is the presence of a finely granular substance colored red by eosin, a character by which the caseous tuberculous substance can be recognized. But here one has to do with a diffused caseation not localized in the central part of a tubercle. This caseous mass occupies the median zone of the section. Below, a fine bluish reticulum shows against a reddish back- ground. It is formed of elastic fibers, the skeletons of the alveolar walls that have resisted the process of caseation, strongly stained by the hematoxylon. They are grouped in parallel fasciculi, free, without branchings, distinctly limited to the periphery of alveoli in which all the other elements — epithelial cells, capillaries, etc. — are subject to the necrotic change. The alveolar spaces contain filaments of fibrin and some scarcely recognizable elements, such as desquamated epithelial cells and leukocytes. In the upper part of the drawing the reaction zone of the pulmonary parenchyma can be seen, following the usual com- monplace type of catarrhal, fibrinous and purulent alveolitis with dilatation of the interalveolar capillaries. Between this zone of commonplace pneumonia and the massive caseation there is a transition zone which explains the histogenesis of the principal lesion. The fibrinous exudate disappears; polymorphonuclear leukocytes and desquamated epithelial cells fill the alveoli. All of these elements, as well as the interalveolar walls lose their staining properties, and little by little take on the uniform rose tint of the complete caseation. Resume. — The nature of the lesion with necrosis terminating in complete caseation shows that we have to do with a massive caseous pneumonia. The extent of the caseous foci proved to be such by histological study confirmed by anatomo-clinical knowledge, permits us to speak of a caseous pneumonia. The absence of giant cells should throw no doubt upon its nature, as the caseation is evidence of its tuberculous origin; but in proof it is easy to demonstrate the presence of tubercle bacilli by staining other sections by Ziehl's method. 42 §>^*{^» W(+ V ^*^ '^ ■ Caseous matter. Alveoli containing caseous matter. ,,; ?.^ -' r -^^^i'^' - ^^ Fibrinous alveolitis. I. Zone of common place pneu- monia. Dilated vessel. II. Zone of necrosis. III. Zone of caseous alveolitis, with preserva- " tion of the partitions and elas- tic fibers. Fig. 11. — Massive caseous pneumonia. Stained with hematoxylon and eosin. Magnified 30 diameters. A section taken from the periphery of a mass of caseous pneu- monia in a case of tabes dying with large pulmonary cavities. 43 TUBERCULOUS SEROFIBRINOUS PLEURISY. Diagnosis of the Organ.— This is diflScult as the pulmonary parenchyma is greatly modified. It is arrived at, however, by finding the pulmonary reticulum (in a part of the section not shown in the drawing), some debris of bronchial epithelium and numerous anthracotic granules. Diagnosis of the Lesion.— The red edge at the upper border of the drawing corresponds to the visceral layer of the pleura, much thickened, transformed and covered with false membrane. Below this the pulmonary tissue is greatly modified. Let us study the section from above downward. 1. A frayed-out surface, granular and somewhat homogen- eous, represents the false membrane consisting of fibrin, a frequent form of reaction on the part of the pleural endothehum against noxious agents. 2. Below this, a very thick zone of granular tissue: little blue cells— lymphocytes— distributed throughout a loose reticu- lum; epithelioid cells mixed up with lymphocytes and lastly a caseous mass with numerous tuberculous giant cells with nuclei in horse-shoe arrangement. These giant cells must not be confused with the numerous dilated capillaries dis- tributed throughout the section, and are usually readily recog- nized by the presence of red blood corpuscles in their interiors. In many areas lymphocytes, epithelioid cells and giant cells are arranged in such manner as to form typical miliary tubercles. 3. Beneath the zone of the inflamed pleura the pulmonary tissue is greatly changed. There are numerous newly formed capillary vessels, with or without carbon particles around them. Between them the pulmonary tissue is formed of indifferent connective-tissue cells lost in the meshes of a fine reticulum of coUogen and elastic-tissue fibers. All of the elements of the pulmonary tissue have disappeared or been transformed. Resume.— Tuberculous serofibrinous pleurisy with pulmo- nary sclerosis and atelectasis. This is a classic form of pleurisy and is frequently spoken of as "afebrile "{a frigore) pleurisy, and is in reality always of tuberculous origin. To make the diagnosis certain sections may be stained by Ziehl's method for demonstrating the tubercle bacillus. 44 Fibrinous false mem- branes. Miliary tubercle. I . r^ Caseated tissue. 2 miliary tubercles with giant cells. Anthra- cotic granules. Dilated Capil- laries. Fig. 12. — Tuberculous pleurisy. Stained with hematoxylon and eosin. Magnified 25 diameters. It is from a case of tuberculous pleurisy with large serofibrinous effusion, dying of asystole. 45 EPITHELIOMA OF THE TONGUE. Carcinoma Spinocellulare with Epithelial Pearls. Diagnosis of the Organ.— The section includes two portions: That in the upper part of the drawing, uniform in appearance, represents the normal organ; the other, below, the lesion.^ In the normal portion it is possible to recognize a stratified squamous epithelium with its papillary layer, whose basal cells are separated from the underlying muscular tissue by a thin corium. The muscle tissue is easily recognized by the dense cytoplasm, the cross striations and the excentric position of the nuclei. The muscle fibers are cut transversely, longitu- dinally and obliquely. This last point, together with the nature of the covering epithelium and the absence of fat cells enables one to recognize the buccal mucosa and to make a tentative diagnosis of the tongue. Diagnosis of the Lesion.— In that portion considered as nor- mal, there is keratinization of the superficial layers of the epithelium: Fine lamina of the cornified substance exfoliate as from the surface of the skin. This marks the position of a plaque of lingual leukoplakia, such as is common among smokers, and in syphilis. At the edge of this plaque, which some regard as the precancerous stage, the cancer has developed. If the epithelium be followed from above downward it is seen to thicken and change its staining affinities, becoming a deeper red, and descending deeply into the tissue. These processes and extensions of the epithelium thrust their multiple ramifications along the interstitial spaces and into the muscles— a characteristic of malignant tumors. In the centers of many of the epithelial masses there are epithelial pearls— cornified cells formed layer upon layer like the skins of an onion. This may be regarded as a perversion of the normal transformation of the epiderm, whose outer cells normally cornify and are shed. In the cancer masses desquama- tion is impossible and the cornified cells are retained. Between and about the epithelial masses there is connective tissue forming a stroma in which mononuclear and polymorpho- nuclear leukocytes occur in considerable numheis— inflamma- tory infiltration— whose presence is to be referred to the ulcera- tion of the cancer and its subsequent infection. Resume. — (i) The presence of the epithelial processes pene- trating in every direction into the depths and breaking through the limits of the basal membrane (the separation between epiderm and corium), (2) the presence of the epithelial pearls, and (3) the presence of atypical cells with monstrous nuclei are sufiicient to permit the diagnosis of squamous-cell carcinoma of the tongue. 46 Corium Rete Malpighii Leucoplakia Transition zone. Cancer. -J^ T / .«' m S Epithelioma . processes. Longitu- dinally cut striated muscle fibers. Trans- versely cut mus- cle fibers. Vessel. Inflamma- tory infil- tration. Pearly body. Fig. 13. — Epithelioma of the tongue. Stained with hematoxylon and eosin. Magnified 75 diameters. A fragment of a non-ulcerated cancer on the point of the tongue, removed at operation. The upper part of the drawing shows the normal tongue; the lower part, the tumor invading the submucous and muscular layers. 47 TUBERCULOSIS OF THE TONGUE. Diagnosis of the Organ.— When the section is examined with the naked eye or with a low-power lens it is found to be formed of a homogeneous tissue, one edge of which is covered by a deeply stained border. A stronger magnification shows the border to be composed of a stratified squamous epithelium, separated by a thin connective-tissue layer from a thick mass of interlacing striated muscle fibers. The epitheUum shows a cornified surface layer throughout the greater part of its extent. As in the preceding illustration, we have to do with a lesion in an epithelial covered tissue without adipose tissue and with a structure composed of striated muscle fibers passing in every direction. These are sufficient evidence that we have to do with the mucous membrane of the cheek or tongue— at any rate, of the mouth. Diagnosis of the Lesion.— Let us consider the different layers passing from the surface downward. The superficial horny layer of the epithelium is seen to take the stain badly, though with a uniform color, and without showing indi- vidual cellular elements. It is composed of thin layers, some of which are in process of desquamation, and keratinization of the epithelium-t4eukoplakia lingualis. The epithelium sends descending processes between the papillae, which penetrate more deeply than normal — acanthosis — in consequence of an inflammatory reaction. Infiltrating the corium, and even penetrating into the muscular layer, are a great number of small round cells — lymphocytes. In the depths of the corium, and even occurring as deeply as the muscular layer, are a number of rounded formations — miliary tubercles — recognizable through the presence of numer- ous giant cells, epithelioid cells and lymphocytes. These do not show any central caseation. This histological lesion corresponds clinically to the indu- rated leukoplacic patches of the tongue so often superimposed upon an indurated base, and makes one hesitate to make a differential diagnosis between tuberculosis and cancer. This reminds us that the clinical diagnosis can be very difficult and is often subject to serious error. Also that it is often necessary to remove a fragment of tissue from the living subject in order to make a diagnosis and institute the appro- priate treatment. Resume. — Lingual tuberculosis without ulceration, as the covering epithelium, is complete everywhere, and shows only leukoplakia. 48 Corium. Giant cells. Giant cells. Peripheral zone of lymphoid cells. Miliary ^ tubercle. v& 1 « Leuco- plakia. Rete Mal- pighii. Miliary tubercle. Striated - muscle fibers. Miliary tubercles without giant cells Fig. 14. — Tuberculosis of tine tongue. Stained with hematoxylon and eosin. Magnified 20 diameters. A fragment taken from the edge of a large patch of induration which simulated cancer. The microscopic examination showed the tuberculous nature of the lesion. Above is the surface of the tongue with some leukoplakia, below are seen the miliary tubercles, with numerous giant cells. 49 SIMPLE ULCER OF THE PYLORUS. The section is sufficiently broad to include a part of the wall of the stomach on each side of the ulcer. In the center of the drawing there is an excavation with vertical border. This corresponds to the seat of ulceration. Diagnosis of the Organ.— One notes the following: 1. The epithelial cells of the gastric mucosa. These are cyhn- -drical, with elongated nuclei, and are arranged in a single layer upon a connective-tissue stroma, into which bifurcating glandular tubules penetrate deeply. 2. Below the gastric glands there are occasional lymphoid follicles —less numerous than in the intestine. 3. The submucosa, formed of dense connective- tissue fibers, sep- arating the mucosa from the muscularis, which is here thick and forms a true sphincter and is not separated into distinct layers. 4. The serosa, which does not concern us except as a part of the thickness of the section. The epithelium and muscularis make one think of the struct- ure of the digestive apparatus; the absence of villi cause us to exclude the duodenum and small intestines; the complexity of the glandular structure is not compatible with the structure of the large intestine, so we are probably concerned with a portion of the stomach. The absence o^ parietal cells in the tubular glands show us that the tissue does not come from the fundus, and the mucosa being formed exclusively of clear undifferentiated cells, we see that we have to do with the pylorus. The thickness of the muscular layer finally gives us the diagnosis of the precise topography, the pyloric sphincter. Diagnosis of the Lesion. — The borders of the ulceration are covered with epithelial cells that tend to disappear in propor- tion as one approaches the bottom of the ulcer. The glands also become less distinct and are stuffed with an enormous number of round cells— leukocytes. At the bottom of the ulcer the mucosa is completely absent. The smooth fibers of the muscular coat, covered by a thin serous exudate containing a few pus cells, are scarcely recognizable; they are trans- formed into a granulation tissue. On each side the muscular tissue resumes its normal appearance. The serous coat consists of dense and compressed connective- tissue fibers formed through a defensive inflammatory reac- tion, resulting in sclerosis by which the gastric wall is locally thickened and its perforation prevented. Resume. — Simple ulcer of the pylorus: a common, non-specific subacute inflammatory lesion. 50 Mucous exudate. Pyloric glands cut longi- tudinally. Pyloric glands cut trans- versely. Lymph follicle. Sub- Ulcera- tion. Vessel in the scler- osed tissue. Pyloric mucosa. Sub- mucosa. Muscu- laris. Sub- serosa. Fig. 15. — Simple ulcer of the pylorus. Stained with hematoxylon and eosin. Magnified 20 diameters. A small ulcer oj the pyloric region of the lesser curvature found at autopsy. The base of the ulcer is shown in the center of the figure. To the right and left the borders seem to be cut out of the mucosa as with a punch. Numerous glands of Brunner can be seen in the mucosa. Beneath the ulceration there is reactive inflam- mation of a defensive character. 51 CANCER OF THE PYLORUS. Beginning Epithelioma. Diagnosis of the Organ.— The section divides itself into two distinct layers, one blue, the mucosa; the other bright red and thicker, the muscularis. To the right in the drawing— the normal part— there is a simple layer of epithelial cells, contiguous to, and descending into the mucosa to form tubular glands. In the mucous layer, which is of the gastro-intestinal type, the absence of villi shows that the section does not come from the duodenum or small intestine; the absence of the cells differentiated into chief cells and parietal cells, the fundus of the stomach. The presence of glands of the serous type and the thickness of the muscular coat — sphincter— show that the section comes from the pylorus. Diagnosis of the Lesion.— If we begin the study of the section under a low-power lens and follow the mucosa from right to left we find that at a certain point the arrangement of the cells into glands disappears, the tubular glands themselves become unrecognizable and are replaced by irregular masses of cells with transparent nuclei that sometimes bud and extend into the muscular coat. This is not a simple inflammatory infiltration of cells in which one scarcely sees anything but nuclei, but is composed of cells that more or less closely resemble the glandular cells themselves. In certain foci they may be seen originating at the expense of the gland cells. It is not, therefore, an inflammation but a neoplasm. At one point the neoplasmic cells pass through the muscularis and infiltrate the subjacent tissue, hence the cancer— a malig- nant tumor that progressively invades and destroys the neighboring tissues— is formed. In the submucosa there are lymph vessels with very thin walls filled with cells identical with the primitive neoplasmic cells— lymphatic neoplasmic emboli— cells of the cancer trans- ported by the vessels to colonize at a distance. Resume.— A tumor developed from the pyloric glands in which one can find all the stages of transformation, that is to say, beginning glandular epithelioma, of which the malignant nature of the growth is already shown by the invasion of the wall of the stomach, and by the probable formation of metas- tases as indicated by the cancer cell emboli in the lymph vessels. 52 Cancer nodule in a lymph- atic. Sub- mucosa. Mucosa. Cancer node. Lymph vessel filled with neoplas- mic cells. Muscu- laris. Fig. 16. — Beginning cancer of the pylorus. Stained with hematoxylon and eosin. Magnified 45 diameters. The fragment of tissue was surgically removed during pylo- rectomy. From above downward the drawing shows the mucosa with its glands, the suhmucosa and the muscularis. Above and to the left of the mucosa is seen the beginning of the glandular epithelioma. The submucosa shows cancer emboli in the lym- phatics. 53 TYPHOID ULCERATION OF THE INTESTINE. Diagnosis of the Organ.— At one extremity of the section, that shown at the bottom of the drawing, one can distinguish a mucous membrane of the intestinal type whose epithehal cells and nuclei are scarcely visible on account of postmortem change. The glands of Lieberkiihn, together with the villi, enable the small intestine to be recognized. The epithelium rests upon a delicate corium which separates it from the muscularis mucosa. Beneath it is a vascular layer, the submucosa. In it there are no glands of Brunner, hence the tissue cannot come from the duodenum. Below the submucosa are two definite muscular layers which form the muscularis. The internal of these runs transversely, the outer longitudinally. The organ is, therefore, the small intestine. Diagnosis of the Lesion.— Following the mucosa from above downward it is found to flatten little by little, its villosities disappearing. Further down the glands and villi reappear. A careful study of the flattened part of the section shows that the change does not depend upon postmortem maceration, but upon a true pathological lesion of inflammatory nature— ulcera- tion. As the etige of the ulceration is approached the villi crumble away, the cells show a dull staining and their pycnotic nuclei dissolve in the cytoplasm. Most of the capillaries are con- siderably dilated and their eosin-stained red corpuscles stand out distinctly against the dark blue of the mucosa. All of the tissue of the mucosa is infiltrated with an enormous quantity of small round cells. In the normal intestinal wall such small round cells are collected in aggregations of varying size in the mucosa, where they form the soUtary follicles and Peyer's patches. Their abundance and diffused infiltration in this case indicate ulceration of one of Peyer's patches. The bottom of the ulceration is formed of a granulation tissue in which are seen occasional scarcely-recognizable vestiges of the epithelial cells of the glands of Lieberkuhn. The tissue is very vascular and has many capillaries, some of which project above the sur- face of the ulceration. Resume.— The microscopic examination permits the diag- nosis of inflammatory ulceration of the small intestine, but does not enable us to go further through histological study alone. But the frequence of typhoid fever and the ulcerations that characterize it justify the opinion that the lesion is typhoid ulceration. The final and definite diagnosis can be made only through the information gained from the clinical notes of the case and the bacteriological examination. 54 Layer of longitu- dinal mus- cle fibers. Perito- neum and ^. serosa. |g,|^if Peyer's patch. Dilated capillaries. Fig. 17. — Typhoid ulcer of the intestine. Stained with hematoxylon and eosin. Magnified IS diameters. The right-hand side of the drawing shows the mucosa, sub- normal above and below, and ulcerated in the middle. To the left are the deeper layers and the peritoneal covering. 55 TUBERCULOUS ULCERATION OF THE SMALL INTESTINE. Diagnosis of the Organ.— Two parts are distinguishable: The one thin, dark-colored and upon which intestinal villa can be seen, the mucosa; the other, thicker and distinct, the muscu- laris. The concave lower surface of the figure corresponds to the peritoneal surface covered by the serosa; the convex upper surface to the mucosa. This curvature, easily seen with the naked eye, is the result of the unequal retraction of the tissue in the fixing reagents, and in seeking to make the diagnosis of the organ no attention should be paid to it. The normal mucosa, well-preserved at the left hand of the illustration, is covered by a single layer of columnar epithelium with elongated nuclei. Here and there a goblet cell shows as a clear vesicle between the regular columnar cells. The epi- theium dips down to form crypts— glands of Lieberktihn. Scattered in large numbers through the corium, and occasion- ally gathered together in masses, are large numbers of small round cells. These are the normal lymphoid cells and their aggregations are the solitary glands of the small intestine. Beneath the mucosa is the muscularis mucosa and the sub- mucosa in which the absence of Brunner's glands indicates that the tissue does not come from the duodenum. The pres- ence of villi on the other hand shows that we have to do with the jujenum or ileum. Beneath all these are the muscularis and finally the serosa. Diagnosis of the Lesion. — Following the mucosa from left to right of the illustration it is found to entirely disappear at the extreme right. This is because of ulceration, of which only a part is represented. All of the bottom of the ulcer and a great part of the submucosa consists of an infiltration of miliary tubercles with caseous centers and more or less num- erous giant cells. Resume.— The grouping and distinctly follicular arrange- ment of the infiltration, and the large number of giant cells, permit one to affirm the tuberculous nature of the ulceration. The final proof— the demonstration of the tubercle bacilli in the lesion— should present no difficulties when the appropriate staining is performed. The lesion is, therefore, tuberculous ulceration of the small intestine. 56 Villi.. Glands of Lieber- kiihn. Muscu- laris mucosa. Miliary tubercles with 2 giant cells. Miliary tubercle. Vessel. Circular muscle fibers. Longi- tudinal muscle fibers. Perito- neum and sub- serosa. Ulcera- tion. Giant cells. Infiltra- tion of lymphoid cells. Sub- mucosa. Trans- versely cut mus- cle fibers of the cir- cular layer. Longi- tudinally cut fiber* of the outer muscular layer. Fig. 18. — Tuberculous ulcer of the small intestine. Stained with hematoxylon and eosin. Magnified 20 diameters. li is a fragment of a tuberculous ulceration of the terminal portion of the small intestine, the cecum and vermiform appendix {with invasion of the peritoneum) removed at operation. Above, and to the left, is the surface of the mucosa with normal villi, above and to the right, the ulcer. Below the mucosa are numerous miliary tubercles with giant cells. 57 NORMAL VERMIFORM APPENDIX. Naked-eye Examination.— The section shows a circular organ with a small central lumen and thick walls. If we examine the various layers from within outward we find the following: 1. The Mucosa.— This is formed of an epithelium composed of tall cells placed side by side, with occasional goblet cells between them, and resembling those of the intestinal mucosa. From it, prolongations descend into the deeper layers between collections of lymphoid tissue to form glands, some of which are cut transversely, some longitudinally. The former appear as small rounded cell collections isolated from the surface. The cavity of the organ is small and empty. 2. The Submucosa.—Belo-w the mucosa the corium or sub- mucosa shows an enormous infiltration of lymphoid cells. Many of these are collected into definite groups, of rounded shape, with pale centers— germinal centers— and comprise the solitary lymphoid follicles. These, similar to those of the other lymphoid organs— tonsils, lymph nodes, etc.— serve as precious elements in the diagnosis of the appendix vermiformis. 3. The Mtiscularis.— This coat is much less in evidence but it and the submucosa are arranged as in the sections of the wall of the small intestine. 4. The Serosa.— At the periphery is the peritoneum with its subserosa, from one point upon which the attachment of the meso-appendix can be seen to arise. The small size of the lumen, the regularly circular shape of jthe section, the abundance of the lymphoid deposits, and finally the structure of the walls enable the diagnosis of the vermiform appendix to be made. The absence of mucopus in the interior, the perfect preserva- tion of the epithelial layer, the regular arrangement of the follicles which show no trace of hemorrhage and the absence of polymorphonuclear leukocytes among the lymphocytes in the mucous corium show that there are no inflammatory lesions, either acute or chronic. Differential Diagnosis. — i. An artery or vein — aorta or vena cava— can at once be differentiated by the absence of an epithe- lial and the presence of the endothelium lining, as well as by the absence of lymphoid collections from the walls. 2. A section of the esophagus is easily differentiated by its interior lining of stratified squamous epithelium. 3. A section of a large bronchial tube is easily recognized by the cartilaginous support that its wall contains, tiiough the lining epithelium is of the same columnar type as that in the vermiform appendix. 58 W-^ Mesoappendix .^yf-^' Lymph j^ foUicle. -^^'^ ■ ' Epithe- lium. ^f*— Cellular tissue. A. — Transverse sectii of the entire append seen under a low-poii magnification — lo diai eters. B. — The inner surf a showing the mucosa wi the glands of Lieherkiii and a solitary follit with its germinative ce ter. Magnified 80 diai eters. Fig. 19. — Normal vermiform appendix. Stained with hematoxylon and eosin. Organ removed at operation. 59 ACUTE PERFORATIVE APPENDICITIS. Diagnosis of the Organ.— This is easily made if attention has been paid to the differential points given in the discussion of the preceding section. Diagnosis of the Lesion.— That which at once attracts attention is the communication between the interior and the exterior shown in the upper left-hand portion of the drawing. It is a perforation. The epithelium is slightly altered but at certain points, notably in the neighborhood of the perforation, it has dis- appeared. In the lumen of the appendix there is a serous exudate con- taining pus ceils— polymorphonuclear leukocytes and some mononuclear leukocytes with altered nuclei. There is no foreign body in the interior, nor is there any accumulation of agglomerated or inspissated fecal matter, nor a calculus, nor any parasite — oxyurissuch as are frequently encountered in the appendix when the seat of pathological change. If the epithelial layer does not show any pathological altera- tion it is not the same with respect to the lymphoid deposits. One cannot help being struck by the small number of pale germinal centers that are present; there are not more than two or three such to be found. There seems to be complete dis- arrangement of the lymphoid cells which are mixed up with a considerable number of polymorphonuclear leukocytes. The lesions of these follicles are very important and are the point of departure of the disturbance of neighboring tissues — notably of the peritoneum. The inflammatory cells, polymorphonuclears, mononuclear leukocytes and lymphocytes infiltrate the entire thickness of the wall, even to the meso-appendix itself. The capillaries are very much dilated and often ruptured, but not much attention is to be paid to that, as it is commonly present in operative cases (false hemorrhagic appendicitis), and is caused by traumatic injury done to the tissues by the forceps or the fingers at the time of the operation. The peritoneal coat is roughened and is more or less covered with false membranous deposits— fibrin— infiltrated with leuko- cytes. The edges of the perforation have a necrotic appearance and scarcely show any normal structure on account of the enormous collection of leukocytes by which they are infiltrated. Resume.— The presence of mucopus in the interior of the appendix, the excellent preservation of the epithelial lining 60 (except at the point of perforation) and the striking changes in the lymphoid structures of the walls indicate the lesion to be acute perforative appendicitis. It would be difficult if not impossible to say from the examination of the section whether or not this lesion had occurred in an appendix already the seat of chronic appendicitis. Perfora- "^>/V tion. i i * i Muco- ^ pus. \-^^-' Disap- 1 * pearing vl solitary 1 lymph follicle. V Glands of — 1 s:^'oi Lieber- ■ kiihn. 'Sm soappendix. infiltration. Solitary lymph follicles. '^'•, /r^^^ 1 I tissue. iltration. "i.^^*©" 1 J i„as exudate. Fig. 20. — Acute appendicitis with perforation. Removed at operation. Stained with hematoxylon and eosin. Magnified 1 diameters. The perforation is seen above and to the left. The contrast between the extensive vascular and connective-tissue lesions and the well-preserved epithelium is to be noted. The solitary glands have almost entirely disappeared. The interior contains pus, the exterior is covered with fibrinous false membranes. The^meso- appendix, especially at its attachment is greatly infiltrated with inflammatory cells. 61 CHRONIC OBLITERATIVE APPENDICITIS. Diagnosis of the Organs.— This is difi&cult to make. Examination with a low-power lens shows a section of a cylinder, or tube, whose interior is completely filled up. Its walls are formed of smooth muscular tissue arranged in two layers and about which there is a serous coat. The center of the tube is formed of connective tissue and of cells whose nature this magnification does not permit to be recognized. The arrangement of the muscular tissue and the absence of any elastic layer enables us to eliminate a bloodvessel from con- sideration and makes us suspect a section of some other oblit- erated tube such as as the vermiform appendix or a Fallopian tube. Knowledge of the clinical source of the material must be be depended upon for a correct final diagnosis. Diagnosis of the Lesion. — The general architecture of the organ being completely upset, a greater magnification must be employed to determine the lesion. Having learned that the tissue is vermiform appendix, the first thing that strikes us is the absence of a lumen, of a lining epithelium and of the glands belonging to the epithelium, as well as the goblet cells usually so numerous among them. Another element equally character- istic of the vermiform appendix has equally disappeared, that is, the lymphoid tissue with its follicles. In the place of all of these elements one finds only a dense connective tissue filled with cells of an embryonal appearance— lymphocytes. It is a granulation tissue and contains numerous young bloodvessels — arterioles with thick walls and capillaries — of new formation. Finally, at various points there are groups of fat cells of adult type which give somewhat the appearance of minute openings punched in the tissue. Their presence is referred to metaplasia of the connective tissue caused by the inflammation. Under the influence of chronic inflammation of the organ the mucous corium has proliferated, crowding out the epithelial and lym- phoid formations. The sclerosis even extends to the muscularis, in which the fibers can be seen to be more or less dissociated, so that the tunic has a striated appearance comparable to that seen in the mesarterium of atheromatous arteries. The peritoneal coat— serosa — is unchanged. Resume. — The absence of all epithelial and lymphoid ele- ments, the disappearance of the central lumen and its replace- ment by connective tissue of embryonal character lead to the diagnosis of chronic obliterative appendicitis. 62 ^ h >>- .% Longi- tudinal \i"J ,^ ' ^^' Tk muscle ' »^' ' '^ fibers. - •''' ,*!5f Circular Fatty sub- peritoneal tissue. muscle fibers. Capillary Fat cells. ■ Arteriole. Fig. 21. — Chronic obliterative appendicitis. Stained with hematoxylon and eosin. A. — Entire section of the appendix magnified 15 diameters. The portion included in the rectangle is shown in Fig. B. B. — A portion of the muscular wall showing the details of con- nective-tissue proliferation which end in the complete obliteration of the appendix. Magnified about 150 diameters. 63 CANCER OF THE CECUM. Cylindrical Cell Carcinoma. Diagnosis of the Organ.— At the upper part of the figure there is a mucous membrane of the intestinal type; in the lower part, numerous tubular formations recalling the structure of tubular glands. The entire thickness of the mucosa is formed of tubular glands side by side— glands of Lieberkiihn— resembling those of the small intestine. In the thickness of the corium there are numerous lymphoid deposits; follicles like those seen in the normal small intestine. The muscularis mucosa distinctly sepa- rates the mucosa from the subjacent formations. The other layers of the intestinal wall are not distinct. The size of the glands of Lieberkiihn and the absence of villi enable us to recognize the large intestine— cotow. Diagnosis of the Lesion. — So long as a neoplasm, even though it be large, respects the muscularis mucosa as a boundary and develops only upon one side of it, the tumor is benign. But if the boundary of the muscularis be passed and the tumor propagates itself by contiguity throughout the thickness of the intestinal wall the tumor is malignant — cancer. In this case the muscularis mucosa is passed and the whole thickness of the intestinal wall is invaded. The tumor is a typical glandular epithelioma, that is to say, a tumor that deviates but slightly from the original glandular type of the tissue from which it grows, in the arrangement or grouping of its cells. It is composed of cylindrical tubes, somewhat irregular, and giving the general effect of ramifying and branching glands. Sometimes the spaces lack distinct walls. The cells have atypical structure and functions, and show hypertrophy of the nuclei, nucleoli, karyokinetic figures, etc. These cancerous formations are to be found in the entire thickness of the intestinal wall as well as between the muscular fibers as in the submucosa. 'R^svan.h.— Typical glandular epithelioma of the colon, infiltrat- ing the wall but not ulcerating upon the surface; It is a form of infiltrating cancer of the intestine, different from the large cauliflower masses that ulcerate and bleed upon the slightest contact— the ulcero- vegetative form. 64 Mucus exudate. Mucosa. Muscu- laris mucosa. Cancer. Pseudo- glandular cancer forma- tions. Muscular tissue. j;,\ 'i- Stroma. Neoplas- mic gland- like tubules. Cancerous exudate. Fig. 22. — Cancer of the cecum. Stained with hematoxylon and eosin. Magnified is diameters. A large infiltrating tumor of the cecum without either vegetations or ulcerations. In the upper part of the drawing is shown the mucosa separated from the tumor by the muscularis mucosa, in the center of which there is a breach of continuity and an invasion of the cellular tissue by the neoplasmic tubules. Below and to the right, in the square the appearance of the neoplasmic tubules is shown in a magnification of 150 diameters. 65 CHRONIC PASSIVE CONGESTION OF THE LIVER. Liver of Chronic Heart Disease. Diagnosis of the Organ.— Under a low-power magnification the tissue appears to be formed of strands arranged like the spokes of a wheel about central points composed of various elements. Sometimes these are constituted by a single vessel- hepatic vein— sometimes, on the contrary, of a series of elements enclosed in connective tissue— portal space— in which are found the following: 1. A venule, a ramification of the portal vein, with flattened lumen and thin musculo-elastic tunic. In the interior a few red blood corpuscles may be seen. 2. One or more branches of the hepatic artery, circular, with thicker walls than the branches of the portal vein, and usually empty of blood. 3. Bile capillaries, single or multiple, having about the same diameter as the hepatic artery, but lined with a cuboidal epithe- lium (colored blue with hematoxylon). Lastly, in the periportal tissue, sections of the nerves and lymphatics. The columns of cells arranged like the spokes of a wheel, the central or subhepatic veins and the periportal spaces con- stitute characteristic elements forming a tripod upon which the diagnosis of the liver depends. The student, of course, knows that the hver is formed of a series of histological units, the hepatic lobules. The sub- hepatic vein represents the center of the lobule— the central zone. The periportal connective tissue is at the periphery of of the lobule— peripheral zone. Diagnosis of the Lesion.— With the aid of a low-power mag- nification considerable modifications can be detected in the hepatic parenchyma. Even with the naked eye or a hand lens the section can be seen to be made up of a series of zones alter- nately dark and pale. The dark zones comprise the hepatic trabeculae colored rose-violet by the eosin and hematoxylon and corresponding to the periportal or peripheral zones of the lobules. The pale areas, on the other hand, scarcely contain any of the columns of liver cells, but are formed by a consid- erable hemorrhagic exudation about the branches of the sub- hepatic veins— central area of the lobule. This arrangement, a little schematic, corresponds to the naked eye appearance of the liver of chronic passive congestion, in which the eye differ- 66 , Bile duct Portal space Portal vein i^.~ .»~t ** rhagic Sub- hepatic vein. Fig. 23. — Chronic passive congestion of tine liver — liver of heart disease. Stained with hematoxylon and eosin. Magnified lOO diameters. Section made from an enlarged liver showing the nutmeg appear- ance, removed at autopsy from a patient dead of asystole. The parenchyma is differentiated into a portal zone in which the hepatic cell columns are still recognizable and perihepatic zones in which the parenchyma is destroyed by hemorrhage. 67 entiates dark zones— blood— and pale yellowish zones— liver tissue— the alternation of colors giving the tissue the so-called nutmeg appearance. The topographical arrangement seen in the drawing (Fig. 23) is then as follows: a zone of hepatic parenchyma, relatively healthy, is surrounded on all sides by hemorrhagic areas from which all the parenchymatous tissue has disappeared. The result is an entirely changed appearance of the liver lobule which seems to center about a periportal space instead of about a subhepatic vein. This has been called an inverted lobule. If the examination be continued with a higher power lens (Fig. 24) the following becomes apparent: Leaving the portal space (near the center of the drawing), the columns of liver cells radiate like the spokes of a wheel from a central point. Close to the periportal tissue the liver cells appear healthy and separated from one another by scarcely dilated blood- vessels (capillaries). But in proportion as we pass from the portal space the columns of hepatic cells appear to become shorter, dissociated and separated from one another by closely packed red blood corpuscles. Still further toward the center of the lobule the blood capil- laries become larger and larger to the detriment of the liver cells, which eventually form only narrow cellular columns, flattened, stretched and composed of only two or three cells, and finally of single ctWs— monocellular dislocation. In the upper right-hand portion of the drawing there are considerable areas of recent hemorrhage in which the red corpuscles have escaped from some of the ruptured dilated capillaries. Examination with a still higher power lens enables an esti- mate of the nature and severity of the cellular changes to be made. The protoplasm is found to be homogeneous or to contain fatty or pigmentary granules; the nuclei are pycnotic, fragmented or have disappeared. These lesions are especially marked as the central vein is approached. Resume.— Intense congestion of the hepatic parenchyma, preponderating in the center of the lobules where the blood stasis tends to cause dilatation of the capillaries, separation and dissociation of the colunms of liver cells, and ends by causing hemorrhage. Such are the lesions of hepatic congestion in heart disease— Ae^a/ic asystole. 68 Portal space. Fig. 24. — Chronic passive congestion of the liver. Stained with hematoxylon and eosin. Magnified i oo diameters. The same section from which the preceding drawing was made, showing the edge of a hemorrhagic zone— to the right — and the still preserved parenchyma with cell columns separated by the dilated capillaries— to the left. 69 THE FATTY AND CONGESTED LIVER. Liver of Heart Disease and Tuberculosis. Diagnosis of the Organ.— With the low-power lens the col- umns of liver cells are recognized, radiating hke the spokes of a wheel from the central— subhepatic— veins. In the lighter colored areas the periportal connective tissue, with its usual inclosed sections of the portal vein, hepatic artery and bile ducts, are easily found — the artery with its thick wall by which it is recognized, the bile duct with its cuboidal epithelium. Diagnosis of the Lesion.— One is at once struck by the appearance of dark central zones separated by broad stretches of pale tissue in which the portal vessels occur. 1. In the central area — zone about the central vein — there are alterations in the columns of liver cells which are some- times separated widely by dilated capillaries, sometimes reduced to small groups of cells or to single cells (mononuclear disloca- tion). In the hepatic cells themselves there are small, non- confluent fatty granules. These cells frequently have badly colored or invisible nuclei. 2. In the peripheral zones — periportal zones — there are important fatty changes. In order to comprehend the histo- logical appearances it is necessary to recall that every part of the tissue from which the section was cut was immersed for a time in reagents— xylol, alcohol, chloroform, ether, etc.— which are fat solvents. It is on this accouiit that the fat does not occur in the form of drops; it is only the outlines of the spaces that formerly contained the fat that show (a negative image). The httle droplets seem to coalesce to form larger and larger drops until some of the cells contain large transparent vesicles that displace the nuclei to the periphery of the cell (seal-ring appearance), or may determine that they cannot be seen. The hepatic tissue is thus gradually replaced by adipose tissue not unhke that normally occurring beneath the skin. The areas of fatty change are arranged about the periportal tissue whose vessels and ducts are otherwise normal. Resume.— Liver showing two types of lesion, well systema- tized as regards topography. I. A pronounced congestion without hemorrhage situated about the central vein and affecting only the central area of the lobules. 2. Fatty disease localized in the periportal areas. These together make the diagnosis fatty and congested liver. 70 Sub- hepatic vein. Liver cell columns Trabecu- ^ lar disloca- tion. Fatty degen- eration. Portal space. Sub- hepatic Fig. 25. — Fatty and congested liver. Stained with hematoxylon and eosin. Magnified lOO diameters. A section of a large, flabby, reddish-yellow liver removed at autopsy from a case of pulmonary tuberculosis. In the center and a little to the right there is a portal space surrounded by an extensive zone of fatty degeneration. Above and below it are columns of hepatic cells separated by dilated capillaries centering about a subhepatic vein. 71 FATTY DEGENERATION OF THE LIVER. The liver was removed from the body of a patient dying of sarcoma, with profound anemia affecting all of the viscera. Diagnosis of the Organ.— This can at once be made, as in the preceding case, by observing the columns of liver cells and the arrangement of the bloodvessels and bile ducts in the peri- portal connective tissue. Diagnosis of the Lesion.— A little to the left and slightly below the middle of the drawing there is an opening which, being single, thin-walled and without surrounding connective tissue, can be recognized as a central vein. From it, in all directions, radiate columns of liver cells like the spokes of a wheel. But all of the cells for a considerable distance from the central vein are scarcely recognizable because of contained transparent, highly refracting vacuoles — fat droplets. It will be observed that the distribution of the fatty deposit in this case is exactly the reverse of that in the preceding illus- tration. There it was at the periphery of the lobule, here it is at its center. The meaning of visible fat in the cells is not sufficiently clear to enable positive inferences to be drawn, but it is supposed that in the preceding case the fat brought to the liver in the portal blood not being quickly oxidized collected in the adja- cent cells pending combustion. In the present case, however, it is supposed that the malnutrition arising from the impover- ished condition of the blood has been followed by retrogressive changes in the liver cells with partial chemical dissolution of the protoplasm and the setting free of its combined fat. Resume.— Centrally situated fatty change of the liver cells— fatty metamorphosis. 72 Normal liver tissue. Fatty degener- ated liver Central vein of lobule. Perfor- ated tis- sue with vessels. Fig. 26. — Fatty degeneration of the liver. Stained with hematoxylin and eosin. Magnified 200 diameters. From a man dying of sarcoma, with profound anemia of the viscera. 73 AMYLOID INFILTRATION OF THE LIVER. Section of a portion of a large firm dark-colored liver from a case of chronic pulmonary tuberculosis. Diagnosis of the Organ. — This is not easy on account of the advanced degree of the morbid process present. But careful examination of the right-hand margin of the drawing will show cells arranged in columns and of the appearance most commonly seen in the liver. Near the center of the drawing there is a section of a single, thin-walled vessel, probably a central vein. By moving the section about it may be possible to find peri- portal connective tissue with sections of the hepatic artery, subportal vein and bile ducts. Diagnosis of the Lesion.— That which at once strikes the observer is the fact that the greater part of the sketch represents a structureless, waxy, amorphous, pink-stained substance that seems to have taken the place of the liver cells. Upon careful examination one can scarcely escape the impression that this is a new substance that has infiltrated between the liver cells and crowded them out. In many places small (atrophic) liver cells may be seen caught between the masses of infiltrating substance. Thus separated from their fellows and from their nutrient supply such are doomed to extinction. This new homogeneous substance, because of a fancied resemblance to boiled starch and because it sometimes gives a blue color with iodine and sulphuric acid, is called amyloid. It has no relation to the starches, however, but is a conjugated protein. With Lugol's solution it gives a mahogany red-brown color, with gentian violet (i per cent aqueous solution) a pink color. It stains pink with eosin as in the case under observation. Supposing that the vessel near the center of the drawing is a central vein, one can make out that the amyloid deposit occu- pies a distribution intermediate between a central and a periph- eral zone. This is, however, rarely as clearly shown as in this drawing. Resume.— Infiltration of the intermediate zone of the liver lobule by a translucent waxy substance with affinity for iodine and gentian violet— amyloid infiltration. 74 Atrophic liver cells caught in ■ amyloid substance. . Amyloid substance. Fig. 27. — Amyloid infiltration of tfie liver. Stained with hematoxylin and eosin. Magnified i oo diameters. 75 LAENNEC'S ATROPHIC CIRRHOSIS OF THE LIVER. Diagnosis of the Organ.— In spite of the transformation of the architecture of the organ, the liver is easily recognized, thanks to the triad of diagnostic features already given : portal spaces, central veins and columns of liver cells. Diagnosis of the Lesion. — One is at once struck by the presence of bands of fibrillar tissue that divide the hepatic tissue into a series of islands. These are best demonstrated in sections stained by Van Giesen's method in which they appear bright red. The abnormal development of the connective tissue is sujfi- cient to lead to the opinion that in this case we have to do with a sclerosis, or, what comes to the same thing, an annular cirrhosis of the liver. With the higher magnification the more or less thick bands of connective tissue are found to be formed of fine and feebly undulating fibrillse, in the meshes of which there are small dots representing the nuclei of fixed connective-tissue cells. At certain points, as, for example, in the upper left-hand part of the drawing, these round cells occur in patches which often preponderate in the portal spaces or beneath the capsule of the liver (not visible here). Among the bile ducts some are large enough to show the cuboidal epithelium, but a great" many are serpentine strands of cells without appreciable lumen. It is a mistake to regard these latter as canaliculi or bile capillaries of new formation. More likely they are columns of atrophic liver cells that are compressed between the fibers of the connective tissne—pseudo- canaliculi. The columns of liver cells are confused in their relations and in their structure. They no longer seem to radiate from the central vein like the spokes of a wheel. Furthermore, many of the liver cells are in a state of fatty disease. Resume.— Annular cirrhosis of the liver also called the bivenous cirrhosis because the bands of connective tissue con- nect the central vein and the periportal veins and penetrate into the lobules. This type of annular cirrhosis corresponds, from the microscopic point of view, either with the atrophic cirrhosis of Laennec or with the hypertrophic cirrhosis of alcoholism. 76 Portal vein. Island of hepatic tissue. Stained by Van Giesen's method. Magnified lOO diameters. The liver from which this section was made was removed at autopsy. It was atrophied, irregular, nodular (hob-nail), and upon section showed hands of sclerotic tissue throughout its sub- stance. In the center of the drawing a large island of the hepatic parenchyma is shown surrounded by a thick ring of connective tissue {annular cirrhosis). Portions of other similar islands are seen at the periphery. 77 BILIARY PIGMENTATION OF THE LIVER. From a Case of Chronic Obstruction of the Bile Ducts. Diagnosis of the Organ.— Under the high power so hmited an area of the Hver tissue is shown as to make the diagnosis a matter of doubt. One should confirm his suspicion tJtiat the organ is the liver by using a low-power lens and finding central veins with radiating columns of liver cells and periportal con- nective tissue with hepatic artery, subportal vein and bile ducts. Diagnosis of the Lesion.— In the upper right-hand corner and elsewhere throughout the tissue represented in the drawing there are some normal liver cells. But the greater number of liver cells are modified through the presence of granules, single or in groups, of varying size and a color varying in intensity to opaque dark green. Here and there, between the columns of liver cells, in spaces supposed to be bile capillaries, there are larger and coarser masses of the same substance, sometimes rounded, sometimes clavate, sometimes dumb-bell in shape. These are composed of inspissated and more or less oxidized bile pigments and in the bile capillaries are surrounded by amorphous translucent matter which is probably a protein constituent of the bile condensed by the obstructive process and precipitated by the reagents. The seat of biliary obstruction is not shown in the section. It may have affected the duct system low down, even entirely outside of the liver proper, but its effect has been the retention of the bile in the ducts and capillaries, with resulting separation of the pigment and its disposition in the distribution figured. Resume.— Biliary pigmentation of the liver from obstruction of the ducts. 78- Pigment in a bile capillary. it^rfl^ 'yQ' ^i^rV^-Ms'''-^' -i- " ' '' ■ W^'i^s^p^E' ' VM^&5i#P'.;^W' ^_^l . Liver cells. Kupffer cell con- . taining granular bile pig- ment. Fig. 29. — Bile ducts containing inspissated bile, from a case of biliary obstruction. Stained with hematoxylin and eosin. Magnfied 500 diameters. 7.9 MALARIAL PIGMENTATION OF THE LIVER. From a Case of Chronic Paludism. Diagnosis of the Organ.— This cannot be certainly made from the limited extent of tissue shown in the drawing. In most cases the arrangement of polyhedral cells in columns such as shown here is suflScient to make the diagnosis, but the student should not be satisfied. What he first thought liver might turn out to be part of the adrenal or part of a corpus luteum of pregnancy. By moving the section about under a lower magnification, however, the central veins with radiating columns of liver cells and peripheral connective tissue with sections of the renal arteries, subportal veins and bile ducts ought to be found to complete the diagnosis. Diagnosis of the Lesion. — The liver cells in this case show no distinct abnormality. But between them and in the capillary plexuses— hepatic sinusoids— there are numbers of cells of irregular shape and unequal size whose protoplasm is filled with black granules of fairly uniform size to such an extent as to make it dififtcult to discover the rather darkly stained ovoid vesicular nuclei. These are the cells of Kupffer, and are phago- cytes. The black pigment they contain is hemozoin, or melanin, a metabolic product of the malarial Plasmodium which is set free in the circulation at the time of sporulation and is subse- quently taken up by phagocytic cells, among which are these cells of Kupffer in the liver. The cells react similarly to other minute particles in the circulation. 80 Normal liver cells. ■ ' ^ e, «. -L .,x ■ >V •., fti Cells of Kupffer? - filled with hemozoin granules. Fig. 30. — Malarial pigmentation of the liver in a case of chronic paladlsm. Stained with hematoxylin and eosin. Magnified 350 diameters. 81 CAVERNOUS ANGIOMA OF THE LIVER. In the substance of hepatic parenchyma without other defi- nite disturbance the naked eye discovers a large bright red patch (Fig. 31, A). Under the low power of the microscope this is found to be composed of large spaces whose inner walls are lined with a dehcate endothelium. These cavities are filled with blood. They are, in fact, blood spaces, whose walls are formed of a connective tissue that is mostly fibrous and contains very few cells. A few capillaries can be seen here and there in the connective-tissue partitions which form a vast network with coarse meshes, marking out the spaces which freely intercommunicate with one another, forming a veritable cavernous tissue similar to that of the corpus caverno- sum of the penis in the state of erection. The occurrence of such a tissue in the liver constitutes an angioma— cavernous angioma— a benign tumor, never giving metastasis. At the periphery of the angioma the cavernous tissue is separated from the hepatic parenchyma by a layer of connective tissue, as is the rule with benign tumors. There are no com- pressed columns of liver cells at the edge of the tumor such as one sees at the borders of cancer nodules. The absence of all signs of compression is explained by the very slow growth of the tumor which is of congenital origin. Differential Diagnosis. —It is important not to confound the tumor with a hemorrhage: If it were such the trabecule would be dissociated and the hemorrhagic foci would not be so nicely delimited by endothelium. In capillary angioma there are no large blood spaces, but, on the contrary, very small spaces corresponding in size with the capillaries themselves compacted in considerable numbers. Capillary angioma is almost never encountered in the liver, but occurs in the skin where it is known as nevus vasculosus. Resume. — Cavernous angioma of the liver, a small benign tumor, sometimes single, sometimes multiple, and constituting a not uncommon and rarely important autopsy finding. 82 ■'^9 I -■•,% Liver. ~> ■.«-/,'< ^-71^ Angioma. Fibrous septum cut trans- versely. Capillary. Hepatic trabeculse. Dilated capillary. Fig. 31. Cavernous angioma of the liver. Stained with hematoxylon and eosin. A. — A section of the entire tumor, surrounded on all sides by the liver tissue. It was unexpectedly found at autopsy. B. — Drawing showing the appearance of the margin of the tumor and the adjacent liver substance. Magnified 80 diameter's. 83 BILIARY ABSCESS OF THE LIVER WITH CIRRHOSIS. Diagnosis of the Organ.— It is quite easy to recognize the section as coming from the liver because of the visible columns of liver cells and the distinct periportal connective tissue with its usual accompaniment of vein, artery and bile ducts. Diagnosis of the Lesion.— Two things attract attention: 1. Dark colored oval patches, two of which show in the draw- ing and sharply contrast their dark blue color with the generally rose-red color of the section. These are the abscesses. 2. The excess of connective tissue in the form of islets that concentrate about the periportal tissue and send out narrow bands between the hepatic parenchyma, dissecting apart its columns of cells. This is the indication of the cirrhosis. Under a higher power the dark-colored, homogeneous patches show themselves to be composed of aggregated cellular elements with nuclei of variable form. Some of these are elongated and of large size and correspond to the mononuclears; others are smaller and many-lobed, and evidently polynuclears. The nuclei are in the condition of pycnosis, that is to say, in process of degeneration, and show only as blue masses of chromatin without any visible finer structural details. The protoplasm itself is not altered, but the cellular outlines are distinguished with difficulty. These cells are pus cells, formed of white blood corpuscles in a state of degeneration, whose aggregation forms microscopic abscesses. At the edge of the abscess are fine strands of young connective tissue. The connective tissue islets are particularly dense in the neighborhood of the bile ducts, in the periportal spaces. The bile canaliculi have a lining of cuboidal epithelium, well pre- served, though in the center of some of them there may be a few desquamated cells and polymorphonuclear leukocytes. About the bile ducts the lesions of periangiocholitis are shown by concentric sheaths composed of layers of connective tissue and inflammatory collections of cells of blue color. In this connective tissue are many pseudocanaliculi — false bile ducts — that call attention to themselves by a double layer of cells and potential but not distinct lumina. These are signs of endo- and pericholangitis. Occasional collections of bile pigment in the portal connective tissue indicate retention of bile. The 84 columns of liver cells are dissociated; the cells here and there in a state of fatty degeneration. Resume.— Multiple abscess of the liver, of which the biliary origin is shown by the lesions of the bile canaliculi (angiocholitis), by the retention of bile and the periductal sclerosis. V Hepatic . artery. Peri- portal sclerosis. m Lamin- ated appear- ance of the col- umns of liver cells. •^TJ^-e- Abscess. Fig. 32. — Biliary abscess of tlie liver with cirrhosis. Stained with hematoxylon and eosin. Magnified 30 diameters. Cirrhotic liver of an old woman with cholelithiasis. The organ was crowded with little abscesses most of which were visible to the naked eye, and had become a spongy mass filled with pus. The drawing shows two of the abscesses surrounded by reactive inflamma- tion (sclerosis), and columns of liver cells separate and compressed. 85 SECONDARY CANCER OF THE LIVER. Diagnosis of the Organ.— This is quite easy in the lower part of the drawing where the columns of liver cells show distinctly. Diagnosis of the Lesion. —An examination by the naked eye or with a low-power lens shows distinct masses of a dark color and varying size, sharply separated from the more pale and uniform part of the section. These masses are composed of epithelial cells often arranged in the form of glandular acini. Some narrow strands of connective tissue carry the nutrient bloodvessels of the tumor and at the same time its stroma. Under a higher magnification the nature of the tumor can be better made out. The cells are columnar and arranged in columns or acini. The nuclei are elongated and not infrequently show karyokinetic figures, indicating abnormal cellular activity. Amorphous matter frequently fills the spaces— products of secretion. The cells, both by grouping and structure suggest those of a glandular mucosa such as might occur in some part of the alimentary canal — stomach or intestin. At the periphery of the nodules are small cellular masses of the same type as those of the principal tumor which is thus shown to be infiltrating the organ. In the hepatic paren- chyma itself (far to the right and low down in the drawing) a mass of the tumor cells (cancer embolus) can be seen in a portal vein. It is by the vessels and notably by the portal vein that the distribution of the cancer cells takes place. From the examination of this section one quickly grasps the two principal and most important features of malignant tumors: the destructive invasion and the metastasis, char- acters that joined to the signs of cellular activity enable one to say at once that he has to do with a cancer. Is it a primary cancer developed on the spot through malig- nant transformation of the columns of liver cells, or bile ducts, or is it a secondary cancer? The type of cells found does not suggest hepatic cells. On the contrary, their arrangement in glandular acini and the absence of transition between the hepatic parenchyma and the cancer make us incline to the opinion that the tumor is secondary. At the periphery of the cancer nodule there is no connective- tissue separation as is found in the benign tumors. The trabe- cule are compressed and reduced to thin lamellje. 86 There is also a contingent lesion in the form of congestion that chiefly centers about the central veins. Resume. — Secondary cancer of the liver. Cylindrical epithe- lioma, or adenocarcinoma, the primary seat of which seems to be some part of the alimentary canal. Lamin- ated appear- ance of the col- umns of liver cells. Cancer embolus. Columns of liver cells. Fig. 33. — Secondary cancer of the liver. Stained with hematoxylon and eosin. Magnified 90 diameters. Secondary cancer of the liver characterized by the occurrence of numerous tumor nodules secondary to cancer of the pylorus. A. — Fragment of tissue showing numerous nodules, natural size. B. — Periphery of one of the nodules shown in A magnified 90 diameters, and showing the hepatic parenchyma with the columns of liver cells separated and compressed. 87 WALL OF AN ECHINOCOCCUS CYST OF THE LIVER. Diagnosis of the Organ.— This is absolutely impossible. There is no liver tissue in the section which is altogether made up of a pathological new formation. For the diagnosis, there- fore, we must depend upon information obtained from the pathological anatomical clinic where the specimen was obtained. This informs us that the specimen was a frd,gment of an echinococcus cyst of the liver. Diagnosis of the Lesion.— The upper figure, A, shown under a low magnification, gives the general topography of the wall of the cyst. In the interior of the concavity, turned toward the left, there is nothing more than debris of a fibrinopurulent character. Nothing remains either of the membrane or of the cyst contents. The wall of the cyst consists of a rather thick composed of adult fibrous connective tissue. This wall repre- sents a defensive reaction against the parasite (echinococcus) formed at the expense of the connective tissue of the organ in which the cyst developed, in this case the liver, which, as has been said, is not visible in the section. Under a higher magnification (see B.) the structure of the wall itself is shown. That which should at once strike the observer is the great number of eosinophilic cells it contains. These are polymorphonuclear leukocytes that contain great numbers of granules — acidophilic granules — that have aflSnity for acid aniline dyes such as eosine. Several of these cells seem to contain two nuclei, but this is only an appearance that results from the close approximation of cells whose limits cannot be accurately defined. Here and there eosinophilic granules may be seen free in the stroma. The stroma itself, as shown in the drawing, includes a capil- lary bloodvessel and connective-tissue cells, some of which are elongated, others irregular — fixed cells. The intensity of the local eosinophilia parallels that found when the blood is examined, for eosinophilia is almost con- stantly found in parasitic affections, especially in cases of infesta- tion by the echinococcus. In this very case the eosinophiles in the circulating blood were from 4 to 6 per cent, as contrasted with the I per cent which is supposed to be normal. Resume.— Subacute inflammatory reaction constituting the wall of an echinococcus or hydatid cyst, with eosinophilia both local and in the circulating blood. 88 A B Fixed connec- tive- tissue cells. Vessels. - Fibrous wall of the cyst. Eosino- - philic cells. _ Fibre blasts. Fig. 34. — Wall of a hyatid cyst. Stained with hematoxylon and eosin. A.— About one-half of the cyst magnified twice, and showing its wall and fibrinous contents. B.—Part of the wall magnified 200 diameters, and showing the great number of eosinophilic cells it contains. 89 SCLEROSIS OF THE PANCREAS. Diagnosis of the Organ.— Under a low-power magnification the parenchyma of the organ seems to be formed of small masses of glandular cells disposed about a potential rather than distinctly visible central cavity. The finely granular structure of the protoplasm, deeply colored by the hematoxylon, the circular arrangement of the cells, the excentric position of their nuclei and the very small size of the cavity of the acini make one think of a gland in full activity and of the salivary gland in particular— parotid, for example. But upon more careful inspection it is found that there are certain small pale areas distributed throughout the parenchyma— the islands of Langerhans. In these one finds pale or dark nuclei distributed throughout a protoplasmic mass not distinctly divided into cells — syncytial or plasmodial mass. The glandular acini plus the islands of Langerhans enable the diagnosis of the pancreas to be made. The acini represent the organ of external secretion, the islands of Langerhans, the organ of internal secretion. Between these two formations there are various intermediates which correspond to transition stages. The acini can transform themselves into islands of Langerhans and vice versa. In the interior of the gland, in the substance of the connective-tissue partitions, the presence of ducts is to be noted. These are branches of the ducts of Wirsung and Santorini and are composed of small cubical cells supported by a dense basement membrane. Diagnosis of the Lesion. — That which attracts attention is the thickness of the bands of connective tissue that pass through the tissue in all directions, dividing it into lobules. There are even points at which little islands of the acinous tissue are separated from the main mass and lost in the substance of the connective-tissue partitions. Here we see some correspondence with what was found in the liver in Laennec's cirrhosis; but the nature of the parenchyma differs. The sclerosis is at the same time peri- and intralobular. The large bands of connective tissue divide the gland into lobules; the finer bands of the same tissue penetrate into the lobules and dislocate the glandular &c\m—periacinous sclerosis, and even in some cases monocellular sclerosis. The ducts contain a number of desquamated cells which either betray the inflammatory nature of the process, or may be the result of errors in fixation and treatment. Resume.— Chronic inflammation of the pancreas: chronic sclerotic pancreatitis. 90 Ducts. Ducts sur- rounded by sclerotic tissue. Band of sclerotic tissue 3 islands of Langerhans. Duct of Wirsung. Vessel. Fig. 35. — Chronic pancreatis. Stained with hematoxylon and eosin. Magnified 8 diameters. Sclerosis of the pancreas in a case of chronic pancreatitis con- secutive upon cholelithiasis in an old man. 91 ADENOCARCINOMA OF THE PANCREAS. The section shows both the cancer and the healthy gland and is, therefore, composed of two distinct parts that differ in their staining quahties: the one dark colored and blue, the other a great deal paler and more rose colored. Diagnosis of the Organ.— In the upper drawing (Fig. 36, A), the dark part to the right can easily be recognized as pancreas because of the presence of the glandular acini and the island of Langerhans. Diagnosis of the Lesion.— To the left in the same drawing, in the pale-colored area, one may see some of the islands of Langerhans and pancreatic acini, but cannot fail to be struck by the disorderly arrangement. Instead of being composed of cells regularly arranged about a central cavity there are long tubes, more or less attenuated, with a lumen scarcely visible and often, indeed, entirely absent. At other points, on the contrary, the central cavity may be very obvious. In many of the dilated acini there are masses of finely granular material coagulated by the reagents. Finally, and this is most charac- teristic, the neoplasmic cells escape into the stroma, no longer adopting an acinous arrangement and resemble the fixed con- nective-tissue cells except for their larger size and more spherical shape. Under a low-power lens the tumor seems to be completely separated from the normal gland, but under a high power one is surprised to find at various points, in what appears to be otherwise normal parenchyma, some areas in which the cells become atypical, show the same appearance as in the tumor (zone of invasion) and reproduce the same atypical cellular arrangement as in the cancer properly so called. Diflferential Diagnosis.— Interstitial pancreatitis with mono- nuclear sclerosis can be mistaken for cancer; but in the case before us the difference in the staining properties, the almost perfect preservation of the normal parenchyma and finally the occurrence of occasional cellular monstrosities make us throw aside the idea of simple sclerosis in favor of cancer. The dislocation of the glandular acini, the arrangement of the cells in tubules, their peculiar staining affinities, which all differ from the normal, enable us to say that the lesion is cancer of the pancreas developed from the cells of the acini, and which has in some places reached the point of actual infiltration. 92 Arteriole. »fi'^. Normal ■"" glandular ' acini. ■' ! Island of >nj'] Langer- *. • ) M* , hans. Atypical _ acinus. Acinus. Connec- tive* tissue. :o * . '^ ■** 'i »^^7S^ t^ Acinus with monstrous nuclei. Atypical cell formation Duct. Fig. 36. — Cancer of the pancreas. Stained with hematoxylon and eosin. Fragment removed at operation. Death shortly ajter followed from obstruction of the common bile duct. A. — Magnification of loo diameters, showing the separation between the cancer and the normal pancreas. B. — Magnification of 300 diameters, showing the cancer zone. 93 CHRONIC PASSIVE CONGESTION OF THE SPLEEN. Diagnosis of the Organ.— To the naked eye the section is found to consist of a pale background, distributed over which there are a number of dark points. With a medium-power lens the background is found to be composed of a pale tissue in which nuclei and red blood corpuscles are mixed up. The dark points are found to be masses of lymphoid tissue, nearly always centered about a small bloodvessel — arteriole. These are the Malpighian bodies characteristic of the spleen. The pale substance of the background is the red pulp; the dark points and the Malpighian corpuscles the white pulp. A greater magnification shows a Malpighian corpuscle in which is a section of an arteriole near the periphery. The cells are nearly all of the type of lymphocytes. Elsewhere in the section other Malpighian corpuscles can be found. These do not always show the central arteriole and are sometimes entirely without the vessel, appearing as lymphatic ganglia in the paler background of splenic pulp. Between the Malpighian corpuscles the red pulp is formed of a pale tissue in which various elements are easily recognizable. Tht most numerous are the red blood corpuscles, next lympho- cytes, then occasional polymorphonuclear leukocytes and cells with budding nuclei. Finally, separating these elements there is a reticulum comparable to that seen in the lymph nodes. Diagnosis of the Lesion. — In the section itself, the red pulp is differentiated from the white pulp, with a distinctness that causes the Malpighian corpuscles to stand out prominently. This is because of the extreme congestion of the red pulp and the consequent predominance of the red corpuscles over the lymphocytes. The red corpuscles are numerous and so massed together that there are small areas of actual hemorrhage in which brownish masses of blood pigment — hematoidin — can be distinguished. Some of the pigment is contained in the interior of large cells — mononuclear phagocytes. Attention must be again called to the connective tissue partitions— trabeculse— which indicate a pronounced sclerosis. Resume.— The enormous number of red blood corpuscles in the pulp, the presence of the small hemorrhagic areas, the numerous collections of pigment and the intensity of the con- nective-tissue reaction enable the diagnosis of chronic passive congestion of the s/>/ee»— cardiac spleen— to be made, 94 A Entire section magnified twice. Malpig hian *Jf corpus- cles B Iron Malpighian corpuscle X 120. White pulp. Capillary- Red pulp. - C Red pulp X 450. Reticu- lum. Mesh of the retic- ulum. Connec- tive tissue reticulum Malpig- hian cor- puscle of the white pulp- Thickened connec- tive tissue trabecula Vessel. Lympho- cyte. Mononu- clear. Polymor- phonu- clear. Red blood corpuscle. Fig. 37.— Chronic passive congestion of the spleen, in an old man dying of asystole. 95 AMYLOID INFILTRATION OF THE SPLEEN. Sago Spleen. The spleen, slightly enlarged, was removed from a patient dead of chronic pulmonary tuberculosis. Diagnosis of the Organ. — This is diflScult to make without examining more of the section than is shown in the drawing. By so doing it is easily possible to recognize the red pulp and locate the white pulp, some of which is not changed and occurs as typical Malpighian bodies with the associated arterioles and the numerous fibromuscular trabecules. Diagnosis of the Lesion. — To the right of the drawing is a rounded formation, at the center of which a transverse section of an arteriole occurs. The presence of the vessel and the rounded shape of the body suggest a Malpighian body, but the small size and resemblance to the surrounding red pulp show that if it be such, it is distinctly pathological. Moreover, instead of being composed of lymphoid cells, it is largely made up of " masses of translucent waxy substance, taking a pinkish color with the eosin stain. These are amyloid, a conjugated proteid composed of protein and condroitin sulphuric acid, deposited between the cells with resulting atrophy and dis- appearance of many of them. The peculiar shapes of the amyloid deposits, some of which are rounded, some sigmoid and some serpentine, suggest that the amyloid substance, as is commonly the case, has first infiltrated about the walls of the capillaries of the Malpighian body. By the apphcation of Lugol's solution to amyloid substance a mahogany red-brown color is produced. Gentian violet (i per cent aqueous solution) colors amyloid pink. Resume.— Deposits of homogeneous waxy substance about capillary vessels, striking characteristic colors with iodine and gentian violet — amyloid infiltration. 96 Amyloid ■ substance. Artery of the Mal- pighian body. . Splenic pulp. Fig. 38. — Amyloid infiltration of a nnalpighian body in the spleen. From a patient dying of chronic pulmonary tuberculosis. Stained with hematoxylin and eosin. Magnified 200 diameters. 97 TUBERCULOSIS OF THE SPLEEN. Diagnosis of the Organ. — The spleen can be recognized by the dark dotting of the Malpighian corpuscles upon the back- ground of almost homogeneous paler pulp (Fig. 39, A). Diagnosis of the Lesion.— That which at once strikes the observer is the presence of four or five spots of the color of "dregs of wine," scattered about irregularly, having the size of millet seeds and of no particular shape. Let us take one of these and subject it to a higher power for more careful study (Fig. 39, B). 1. At the right-hand part of the drawing, at a part correspond- ing very nearly to the center of one of the spots designated above, we see an amorphous granular tissue in which minute nuclear fragments are disseminated. This is easily recognized to be caseous substance. At the periphery of this substance there is a considerable mass of a black pigment. This is an artefact and results from the action of bichloride of mercury, in which the tissue was fixed, upon its proteins. 2. To the left of this caseous zone there is a second zone of cells of the 'type known as epithelioid cells. They have pale protoplasm, are of variable shape and their nuclei are not infrequently elongated. Between them are occasional giant cells. 3. Finally there is a third zone, at the extreme left of the draw- ing, in which appear a considerable number of lymphocytes, grouped about a central point, usually corresponding to the position of an arteriole. In these one recognizes the Malpighian corpuscles. The rarity of the element often, but wrongly, considered to be characteristic of tubercle— the giant cell— might confuse a beginner as to the tuberculous nature of the lesion. But the epithelioid inflammatory reaction, added to the intense and precocious caseous transformation and the tendency to nodular formation, speak only in favor of the tuberculous nature of the lesion. Resume.— From the histological characteristics it may be concluded that we have to do with a caseous tuberculosis of the spleen, but, of course, it requires a bacteriological examina- tion and the demonstration of the bacillus to confirm the diagnosis. B Iron containing pigment (hemo- siderin) . Malpig- hian corpuscle. Central arteriole. Caseated center. Giant cell. Epitheli- oid cell. Crystals of bichlo- ride of mercury (artefact) Malpighian corpuscles. 'JSW ""T Masses of caseated tubercles. Fig. 39. — Tuberculosis of the spleen. Stained with heraatoxylon and eosin. Tuberculosis of the spleen in a woman, aged forty-jive years, dying of tuberculous meningitis following pulmonary tuberculosis with cavity formation. p^,— Fragment of the spleen twice natural size, showing the distribution of the lesions, and a square showing the area from which B was taken. B __2"^g caseous center and periphery of a tuberculous mass magnified 250 diameters. TUBERCULOUS LYMPH NODE. Diagnosis of the Organ. — To the naked eye or under a low- power lens the section appears oval and shows at one of its poles a greater amount of pale substance than at the other. The lower part of the section, seen in the drawing (Fig. 40), is a reticulated lymphoid tissue composed of a great number of small deeply staining cells, and under a low power can be divided into two different portions. One of these, below the capsule, sends prolongations into the depths of the organ. It is formed of a loose tissue composed of a reticulum poor in nuclei and is the lacunar substance. The other, composed of cells arranged in dense masses, with pale centers— germinative centers— is the follicular substance. The oval shape of the organ, the presence of the reticulated and follicular substance permits the diagnosis of lymph node. The differentiation into two kinds of substance— the one pale and lacunar, the other dense and follicular— ought to be easily recognized by the student, though beginners frequently mistake the pale germinal centers of the follicles for a pathological condition and suppose the node to be the seat of secondary cancer. Differential Diagnosis. — Certain lymphoid organs are to be distinguished from the lymph node: 1. The spleen is recognized by the presence of the Malpighian corpuscles which are lymphoid-cell aggregations in the center of which there is an arteriole. 2. The tonsils can be recognized by the squamous epithelium that covers them by their crypts with glands and by the absence of any connective-tissue capsule. 3. The thymus is recognized by the absence of closed foUicles and by the presence of the corpuscles of Hassal which are characteristic. 4. The appendix is easily recognized by the glandular crypts and the presence of columnar epithelium. Diagnosis of the Lesion — In the upper part of the figure the collection of pale-colored areas recalls the general appearance of the miliary tubercles already seen in other sections, especially the lung. The caseous centers are easily found and there are numerous giant cells surrounded by coronets of epithelioid cells with the usual abundant protoplasm, large pale nuclei and the peripheral zone of lymphocytes. Resume.— If &'ary tuberculosis of a lymph node in an early stage. Later this might terminate in suppuration in which one would find nothing but a central caseous mass without structural details and surrounded by a fibrous envelope. 100 'i'' / )nic connec- capsule. t cell in the ;r of miliary rcle. Lacunar substance. V, - *■ * - ■ Fibro- tissue. Kj/ijj.,. V.VJ ««'' 3 normal lymph nodules. Lacunar substance. w, Fig. 40. — Tuberculosis of a iympli node. Stained with hematoxylon and eosin. Magnified i6 diameters. An iliac lymph node removed at an operation upon a case oj ulcerative tuberculosis of the cecum. The lower part of the node is normal and shows the lymph nodules with germinative centers; the upper part contains numerous miliary tubercles with giant cells. 101 CANCER OF A LYMPH NODE. Metastatic Epithelioma, Secondary to a Cancer of the Stomach. Diagnosis of the Organ. — This is difficult if not impossible to make. One is forced to have recourse to information from the clinic or autopsy, from which we learn that the structure is a lymph node from the lesser curvature of the stomach. The only indications that permit us to suppose the structure to be a lymph node are the presence of lymphoid tissue and the sur- rounding connective-tissue capsule. Diagnosis of the Lesion. — The greater part of the section is formed of cellular aggregations, pale in color, with insignificant masses of lymphoid tissue between them. In this case it is not to be expected that one could separate the gland into its classical elements, lacunar and ganglionic. We have to do with a pathological condition of some special nature, as the pale areas do not present any reticular aspect, but, on the contrary, are formed of cells with abundant protoplasm, dis- posed in long branching processes of epithelial cells— the cancer nests. Under a higher power (Fig. 41, B) one sees all of the cyto- logical modifications of malignant tumors; budding nuclei, often multiple in the same cell; numerous and often atypical mitotic figures, etc. The arrangement of the cells is anarchical, and nothing, apart from the rough draughts of acini, suggests the organ from which the cells were derived — atypical epithe- lioma. Nothing but their epitheliomatous character is recog- nizable. However, in other cases it is sometimes possible to find in the secondary tumors in lymphatic nodes an arrangement of the cells that indicates the structure of the organ from which the cells are derived, through a preservation of the primitive arrangement of the cells as in the original organ. RSsume.— We have to do with an epithelial tumor developed in a lymph node, that is to say, a lymphatic metastasis. The cancer cells transported by the currents of fluid have arrived in the lymph node where they have grown and multiplied before going further. The arrangement and nature of the cancer cells here is very atypical and does not permit one to say from what organ they originally came, and in what organ the tumor originally started. The acinous outlines, however, suggest it to be from a glandular organ. To make sure, it is necessary to depend upon information derived from the autopsy or from the clinic. 102 A Connec- tive capsule. _ Follicular substance. Cancer metas- tasis. Fig. 41 . — Secondary cancer of a lymph node. Stained with hematoxylon and eosin. The node was removed from the lesser curvature of the stomach in a case of cancer of the pylorus. A. — Magnified 25 diameters, and showing the appearance oj the periphery of the node. ^■—Magnified 150 diameters, and showing the epithelial cell masses with their monstrous cells. 103 CHRONIC MYOCARDITIS. Fibrous Plaques on the Myocardium. Diagnosis of the Organ.— If a section of the wall of one of the ventricles of the heart be examined with the naked eye, it is found to be limited on the external surface by an almost straight line and on the internal by a very sinuous one with large promontories and occasional islets which are sections of the muscular bundles. If the section be examined with low-power lens the central portion is found to be composed of the muscular tissue of the myocardium, the cells of which are easily recognizable by their centrally situated nuclei and their Y-like branchings. If we now turn to the part of the section shown in the draw- ing (Fig. 42) we see that at its superior part (A), which cor- responds to its external surface, the myocardial fibers are cov- ered with a thin layer of adipose tissue, above which there is a thin band of fibrillar connective tissue which is the visceral layer of the pericardium— the epicardium, of great importance in orienting one's self in studying sections of the heart. If the entire thickness of the section was shown the festooned line with its promontories and islets, which corresponds to the endocardium, would be at the bottom of the drawing. Diagnosis of the Lesion. — Here and there strands and bands of connective tissue penetrate into the muscular tissue and separate its fibers. They appear pale rose colored, the muscle being distinctly red. The connective tissue forms considerable masses — the fibrous patches of the myocardium — that can be distinctly seen with the naked eye. When the fibrous tissue is viewed with a higher magnification it is found to be com- posed of collagenous fibrillae, with some cells of which the nuclei are visible. These are fixed cells of the connective tissue and betray an inflammatory reaction. Starting from the large plaques, the fibrous tissue infiltrates fasciculi in bundles of varying thickness — interfascicular sclerosis — and sometimes even between the cardiac cells — interfibrillar sclero- sis. Under the high-power lens the myocardial fibers may show degeneration; they become pale, the protoplasm becomes finely granular and here and there there may be transverse fragmentation — segmentary dislocation of the fibers, long con- sidered to be characteristic of cardiac degeneration, but now looked upon as an artefact of cadaverization. Attention must be called to accumulations of pigment granules surrounding the nuclei of the cardiac cells— pigmentary degeneration. Resume. — Chronic myocarditis: sclerosis or formation of fibrous patches in the myocardium, very common in the aged. 104 A Epicardiam. Myocardial fibers cut transversely. Myocar dial fibers §^ cut trans- versely. Myocar- diac fibers cut longi- tudinally. Fig. 42. — Chronic myocarditis. Stained with hematoxylon and eosin. A fibrous plaque in the right ventricle of the heart oj a case of Brighfs disease. A. — Magnified 25 diameters. B. — Magnified 120 diameters. 105 COR ADIPOSUM. Obese Heart. Diagnosis of the Organ.— Under the low magnification repre- sented in the drawing this is scarcely possible. At the extreme lower margin the section passes perpendicularly through a fibrous and vascular membrane which is the epicardium. Ascending from this we reach a thick layer of adipose tissue containing a vessel, and above this, beginning at about the middle of the drawing there appear irregularly-shaped aggre- gations of red dots, while in the upper third of the section there are groups of horizontal wavy red lines. Employing a higher magnification these latter can be resolved into bundles of transversely striated muscle fibers, made up of quadrilateral segments with centrally situated nuclei and lateral anastomoses by which the cardiac muscle can at once be recog- nized, and the tissue diagnosed as the heart. Diagnosis of the Lesion. — Three things should at once impress the student as peculiar: (i) The large quantity of adipose tissue; (2) its distribution among the muscle bundles and fibers; (3) the small size of the muscle fibers. The heart was removed from an obese individual who suffered from shortness of breath upon exertion. The microscopic findings explain, at least in part, the symptoms mentioned. The increase in the subepicardial adipose tissue and its descent between the muscle bundles and fibers has separated them so as to interfere with conjoint action and diminish their power, as well as compressing them so that many of them atrophy— i. e., become smaller in size. 106 Separated and atro- phic mus- cle cell in longitud- inal sec- tion. Separated and atro- phic mus- cle cell in transverse section. Epicar- dium. 1* ? '■ Fig. 43. — Cor adiposum — adipose heart. Heart suffering from fatty infiltration of tiTe intermuscular connective tissue, with resulting sepa- ration and atrophy of the muscular fibers. Magnified 25 diameters. 107 v["TrnM:/,nv ooi f i c- rrrnArr ACUTE FIBRINOUS PERICARDITIS. Diagnosis of the Organ.— The section, as seen in the drawing (Fig. 44) is composed of two compact lamina, bound together by a loose tissue of very atypical appearance. At the extreme inferior portion the fibers of the myocardium, with their central nuclei can be recognized. Covering the myocardium there is a thin layer of adipose tissue between it and a thick fibrous band — the pericardium. The presence of these structures enables us to recognize the outer surface of the heart. Diagnosis of the Lesion. — In the lower part of the drawing, in the adipose tissue, there are some large vessels, about which are collections of small cells. The epicardial layer is reduced to the condition of granulation tissue, a type of inflammatory tissue with dilated capillaries and lymphocytes, of which the whole forms a dark layer above the subepicardial adipose tissue. The endothelium limiting the pericardium is replaced by a fine fibrillar tissue which takes the red color of the eosin with avidity — this is fibrin. The extreme upper edge of the drawing represents the parietal layer of the pericardium. It is formed of parallel bands and fasciculi of connective tissue, accompanied by vessels and nerves. At its middle portion one finds granulation tissue and infiltration comparable to that in the epicardium. The endo- thelium of the parietal layer, like that of the visceral layer has given place to a fibrinous exudate. Between the two principal structures in the drawing— the epicardium and the pericardium— and binding them together, there is a broad zone of lamellar tissue formed of fibrillas with a few nuclei. These are false membranes of fibrin. At certain points the fibrin is organizing as is shown by the appearance of a few new vessels. The organization is, however, only beginning as the patient died of the pericarditis before permanent adhesions had time to form. Resume.— Acute fibrinous pericarditis. Information derived from the bacteriological laboratory showed that the disease was caused by the pneumococcus. 108 Layer of vascular connective tissue. Granulation tissue. Fibrin undergo- ing organization. Fibrin. Epicardium. Subepicardial layer of adipose tissue. Vessel with peri- vascular infiltra- |^^^ tion Fibrous sac of the pericar- dium. Fibrinous exudate. Epicard- ium and sub-epi- cardial tissue. Myocar- dium. Fig. 44. — Acute fibrinous pericarditis. Stained with hematoxylon and eosin. Magnified lO diameters. Pneumococcic acute serofibrinous pericarditis with resolving exudate. 109 ULCERO-VEGETATIVE ENDOCARDITIS. Diagnosis of the Organ.— The section can easily be recog- nifeed as the wall of the heart by the features already pointed out. By knowing the normal thickness of the ventricular walls it can easily be guessed that the section includes the entire cardiac wall. Three portions are selected for special examina- tion and are indicated by the three small rectangles shown in the drawing (A). Diagnosis of the Lesion.— To facilitate the examination the selected portions will be considered from above downward. 1. The peripheral, or epicardial portion (Fig. 45, B). Passing from the outer portion of the section toward the deeper tissues, we find first the epicardium, a dense fibrillar tissue of considerable thickness. Below it there is a layer of adipose tissue and below it the muscle of the myocardium. The only abnormality is the presence in the adipose and muscular tissues of a considerable number of inflammatory small round cells. 2. The central or myocardial portion (Fig. 45, C), In this one sees, at once, the presence of strands of dense homogeneous connective tissue — plaques and bands of fibrous myocarditis. To the left in the drawing there is an arteriole with a very thick wall. Above and to the right the fibers of the myocardium are dissociated and separated from one another by fine bands of sclerosis. Examination with a high power may, in well-fixed and prepared tissues, permit the various stages of the muscular degeneration to be made out. They are charac- terized by a homogeneous staining of the protoplasm, dis- appearance of the striae and of the nucleus, etc. 3. The part shown in Fig. 45 (D) corresponds to the endo- cardial surface. As the surface is approached the entire tissue is found to be infiltrated with cells of various types: lympho- cytes, mononuclears and polymorphonuclears. The last-men- tioned are rather rare. At the extreme lower portion of the section, the lower ragged edge in the drawing, the color becomes dark blue. This is granulation tissue in which numerous mononuclear and polymorphonuclear cells well advanced in degeneration can be seen. There are also numerous small reddish bands with a finely fibrillar appearance composed of fibrinous exudate. All of the endothelial covering has dis- appeared, and the lesion forms a true ulceration. Resume. — Acute ulcerative endocarditis. The section shows the ventricular wall of the heart, in which the disturbance is almost limited to the endocardial surface. 110 B Visceral layer of the peri- cardium. Sub-epi- cardial layer o£ fibrous and adipose Ulcerated and necro- tic endo- cardium. Fig. 45. — Ulcero-vegetative endocarditis. Stained with hematoxylon and eosin. Entire thickness of the ventricular wall twice magnified, with small rectangles showing where fragments B, C and D were taken for further examination. Ill FATTY DEGENERATION OF THE HEART MUSCLE. The section is a longitudinal one passing through the wall of the heart of a case of "tabby-mottling," occurring in pernicious anemia. Diagnosis of the Organ.— This should not be dif&cult. The tissue is composed of longitudinal bundles of a fibrillar structure with distinct longitudinal and transverse striations (not shown in such distinctly diseased parts as that selected for the drawing). It is also composed of irregularly quadrilateral segments that can be recognized as cardiac muscle cells, both by the occasional anastomosing fasciculi and the centrally placed nuclei. Diagnosis of the Lesion. — Examination under a high mag- nification shows that in many of the fibers the original trans- versely striated fibrillar structure and the nuclei have dis- appeared, and in their place are collections of granules which are colored black with the osmic acid. These are fatty drop- lets, the result of the degeneration of the muscle following malnutrition or intoxication. Their presence, together with the degenerative changes with which they are associated, explains the yellow^rgray speckled appearance of the wall of the heart. Resume.— Fatty degeneration of the muscle fibers of the ventricular wall— fatty degeneration of the heart. 112 Fatty granules stained black by osmic acid. Fig. 46. — Fatty degeneration of the heart muscle. From a case of pernicious anemia. Stained with osmic acid. Magnified 750'diameters. 113 OBLITERATIVE ENDARTERITIS. Endarteritis Obliterans. Diagnosis of the Organ.— The section is of a tube whose wall is divisible into an external zone that stains a deep red—tunica media— a.nd an internal zone of paler co\or— tunica interna — separated by a thin undulating membrane, the internal limiting membrane, a landmark important both in making the diagnosis of the organ and of the lesion. Outside of this elastic hmifing membrane the unstriated muscular fibers can be recognized by their elongated nuclei. To bring out the elastic fibers recourse must be had to staining by one of the specific stains of Mallory or Weigert, or the orcein stain. In the lumen of the tube there are a number of red blood corpuscles that confirm the suspicion that the tube is a bloodvessel. The external tunic, the adventitia lacking in this section, being represented only by the connective tissue forming the stroma of the organ in which the vessel was contained. The distinctness of the undulating membrane shows that the vessel is an artery; in this case a visceral artery of middle size. Diagnosis of^^the Lesion. — The inner coat is very thick. Instead of being Composed of an endothelium with a thin layer of subjacent connective tissue, it has undergone an enormous thickening through h5rperplasia of the tunic beneath the endo- thelium which forms a very thick stratified connective tissue, with occasional elongated nuclei, particularly numerous in the neighborhood of the lumen. In proportion, as we remove from the lumen toward the muscular coat, the nuclei little by little lose their staining properties and become as pale as the surrounding tissue. The connective tissue of the endarterium becomes structureless, colorless and devoid of fibrillar structure— hyaline degeneration — which frequently complicates areas of endarteritis in the visceral vessels, as well as occurring in atheromatous degeneration of the aorta and great peripheral arterial vessels. The tunica media— the musculo-elastic tunic— does not show any notable alterations. The lumen of the artery, though diminished in size is not yet closed. Resume.— Arteritis chiefly confined to the internal tunic, hence endarteritis, and with a tendency to obliteration. 114 Greatly thickened internal tunic. Lumen of the artery with"- blood. Fraying out of the internal coat (arte- fact) Periarte- rial tissue (sclerosed kidney) . Median musculo- elastic tissue. Internal limiting mem- brane. Vessel of the renal paren- chyma. Fig. 47. — Endarteritis obliterans. Stained with hematoxylon and eosin. Magnified loo diameters. Section of an artery in the kidney of a case of chronic interstitial nephritis with pronounced vascular lesions. The great thickening of the inner coat, inside of the festooned line of the internal limiting membrane, effecting an incomplete obliteration of the lumen of the vessel, is to be carefully noted. 115 ENDARTERITIS OBLITERANS. Stained with Orcein. Diagnosis of the Organ. — Again we have to do with a trans- verse section of a cyhndrical tube, slightly flattened and having a lumen that is slightly excentric. The drawing A represents one-half of the entire section. At first glance it is difficult to make a diagnosis of the organ because of the special method of staining adopted (orcein); nevertheless, the circular character of the organ, the absence of epithelium and of lymphoid tissue, and above all the -presence of the sinuous blue-black line— elastica — permit one to recognize an artery. The sinuous line pointed out is nothing more than the internal elastic limiting lamina separating the endarterium from the mesarterium. The elastic fibers become more and more thick until they form a dense feltwork. They consist of long black filaments running parallel with one another and showing distinct undulations. Diagnosis of the Lesion.— There are no notable disturbances in either the external or middle tunics. All of the pathological alterations take place inside of the internal limiting elastics, that is to say, in the endarterium. Instead of consisting of an endothelial layer superimposed upon a thin layer of con- nective tissue, as can be seen in the right-hand lower comer of the drawing (Fig. 48, A), it has undergone enormous thickening in the form of a hyperplasia of the subendothelial fibrillar layer. At certain points, and especially at the internal limiting elastic membrane, the endarterium assumes a pale areolar and frag- mented appearance— hyaline degeneration corresponding to the beginning of the formation of an atheromatous area (Fig. 48, B). The lumen of the artery is extremely diminished and seems to have undergone an excentric displacement. This appear- ance is due to the fact that the plaque of endarteritis does not extend all around the vessel. The lumen still permits the passage of blood, but it is so reduced that except for the anas- tomotic branches, the territory of its distribution is menaced by ischemic gangrene. 'Resvan.e. — Endarteritis obliterans of the superior mesenteric artery. It resulted in an infarct of the intestine and the death of a woman aged seventy years. 116 Point represented in Fig. B Adventitia Elastic fibers of the tunica media Muscle fibers of the tunica media. Disso- ciated elastic fibers of the mesar- terium. Elastic _ layer. 1' -'a.'.iJi''''., '■ ■•■-,i-:i.vV' , »'l B Magnified ISO diameters . Internal elastic layer. s Uh' IV. Fig. 48. — Endarteritis obliterans. Stained with orcein. Partly obliterated superior mesenteric artery of a woman aged seventy years. ARTERIAL ATHEROMA. Diagnosis of the Organ.— One can recognize the organ as a fragment of the wall of a large vessel of which the middle tunic is formed of muscle and elastic fibers (the elastic fibers are not visible in this case because the specimen has not been a appropriately stained) without a distinct internal limiting membrane. Such a structure is characteristic of the aorta or pulmonary artery. The external tunic is composed of a loose connective tissue containing a number of vessels, though the middle and internal tunics contain none. Diagnosis of the Lesion.— In Fig. 49, A, the lower drawing, if one follows the section from left to right, he finds a certain point at which the inner tunic seems to separate from the middle one, and the endarteritis assumes greater and greater importance. From inside out, that is to say, from below upward, one notes the presence of an unaltered endothelium, an inner tunic slightly thickened, but of a colorless necrotic appearance^ passing into the principal lesion — the area of arteriosclerosis — which is subjacent. This area is composed of a pale zone of friable appearance in which there are elongated spindle-shaped crystals of fatty acids, and perhaps some lozenge-shaped crystals of cholesterin. These crystals have been subjected to the action of various reagents — alcohol, xylol, etc., in the course of the preparation of the section, and nothing is now left but the spaces in which the crystals were originally contained. Besides the crystals which prove the presence of fatty degeneration of the deeper layers of the intima, some much-altered leukocytes (macro- phages), some globules of fat and above all some bluish masses which indicate the beginning of calcareous infiltration are still to be found in the area. The internal tunic separating the area from the lumen of the vessel is very much thinned, and almost ready to rupture and liberate the contents of atheromatous swelling into the torrent of the circulation. Outside of the atheromatous area (above in the drawing) one notes the integrity of the middle coat of the artery. It is with difficulty that one sees the dis- appearance of some of the smooth muscular fibers separated by hyahne tissue (tiger appearance of the mesarterium). Finally, the adventitia (not visible here) is intact and the vasa vasorum are normal. Resume. — Chronic arteritis with atheromatous degeneration such as one often sees at the source of one of the larger branches of the aorta — arterial atheroma. 118 Middle coat. Athero- matous focus. Crystals __]«''"'''^ of fatty ' acids. -^ Internal coat. I Tui Atheroma Tun lica media.— tous focus. Lca interna. . B Athero- matous focus. Newly formed vessels. Fig. 49. — Atheroma of an artery. Section of the wall of an atheromatous abdominal aorta of an old man. A. — General view of the specimen twice natural size. The portion between the vertical lines on the right side, is that selected for higher magnification in B. B. — This shows an atheromatous focus with crystals of fatty acids and plates of cholesterin. It is limited above by the middle tunic, below by the internal tunic. The external tunic does not show, having been torn of in removal of the tissue at the autopsy. 119 CALCIFIED ARTERY. This is a common affection of the peripheral arteries of elderly people and may occur independently of endarteritis or in association with it. It is most common in the arteries of the extremities, but this particular section is from the cancerous breast of an old woman. Diagnosis of the Organ.— The greater part of the section consists of a tissue whose architecture bears no correspondence to that of any normal structure of the body and therefore may not be within the knowledge of the student. It is cancer or carcinoma, and with it we have nothing to do at present. That which concerns us now is the striking, dark-blue struct- ure that occupies the greater part of the center of the drawing and forms a circle with an irregular central opening. It impresses one as a section of some tubular structure. It is bounded externally by concentrically arranged parallel con- nective-tissue fibers, which as one advances toward the center, here and there, in the better-preserved parts, abut against unstriated muscle cells. The central opening is limited by a thin, flattened cellular structure— endothelium. A brief re- flection enables the student to recognize the adventitia, the media and the intima of a bloodvessel, and taking into con- sideration the thickness of the middle coat to diagnose an artery. Diagnosis of the Lesion.— In the upper part of the sketch, when the wall of the artery is least affected and when the lesion is probably youngest — it will be seen that the middle coat is the chief seat of disturbance, and is partly replaced by masses of dark blue, at certain points in which there are colorless deposits of a highly refracting, crystalline substance. This is of calcific nature and constitutes calcification of the middle coat of the vessel. The calcareous material when crystalline remains uncolored; when amorphous, absorbs the hematoxylon, and as it increases the alkalinity of the adjacent muscular tissue causes it also to absorb the hematoxylon so that all about the mineral deposits the tissue becomes intensely dark blue in color. In the lower part of the section of the vessel a much greater deposit occurs, distending the tissue so as to make it encroach upon the lumen which is diminished in consequence. At this point it is impossible to say that there may not have been endarteritis in association with the medium calcification, and, indeed, the two processes not infrequently occur in the same vessels, though they are independent of one another. 120 Such changes in the arterial walls makes them inelastic, brittle and subject to traumatic injury and rupture, as well as diminishing their conducting powers. The parts supplied by such arteries are, therefore, apt to fall into a state of mal- nutrition, and in the case of the extremities of the body into senile gangrene. Naturally the danger is greater when the calcification of the middle coat is accompanied by endarteritis by which the the lumen is further obstructed and the conducting power of the vessel further diminished. Resume. — Calcification of the middle coat of the artery — a condition which, when extreme and widespread, gives rise to the condition often described as "pipe-stem" arteries. Vein. - Adventi- tia. Fig. 50. — Calcified artery. The artery occurs in a mammary gland almost completely destroyed by carcinoma. The disease of the vessel wall, however, is independent of the tumor and probably antedates it. Stained with hematoxylin and eosin. Magnified 50 diameters. 121 OBLITERATIVE PHLEBITIS. Phlegmasia Alba Dolens. Diagnosis of the Organs. — The section is of a tube with its wall and contents (Fig. 51, A). The smooth muscular and elastic fibers in the wall form a ring of considerable density, lined on the inside with a pale edging and on the outside by a cellular layer, showing that in all probability we have to do with a vessel. The thinness of the wall, the absence of an internal elastic limiting membrane, make us suspect that the vessel is a vein. Compare it with the section of the artery shown in drawing (Fig. 45). Diagnosis of the Lesion. — The lumen of the vessel is obstructed by a clot— thrombosis (Fig. 51, B). In following the wall of the vein from outside inward we encounter the following: 1. The adventitia, or external tunic, a loose cellular tissue with numerous vessels. There are no alterations here apart from a mild inflammatory infiltration suggesting a deeper lesion. 2. The middle tunic, musculo-elastic, of comparative thin- ness also seems to be intact. It does not show the mottled appearance of chronic arteritis. 3. The internal tunic, on the contrary, shows important altera- tions in all points comparable to those of chronic endarteritis (thickening of the connective tissue layers). However, the inflammatory process is a great deal more acute and terminates in the formation of a clot that obstructs the lumen of the vessel. The lesion of the wall of the vessel has produced the clot (thrombosis). The venous endothelium resting upon stratified subendothelial connective tissue has disappeared and the internal tunic is continuous with the thrombus. The latter is formed by red blood corpuscles still distinct, and by bands of fibrin containing inflammatory cells in the meshes. The center of the thrombus has become fragmented in the course of treatment with the reagents and the form of the rent, the distinct hnes of the openings, and the absence of red blood corpuscles show their artificial nature. Resume. — Obliterating or thrombosing phlebitis, commonly observed in phlebitis of the limhs— phlegmasia alba dolens. 122 Fibrin and inflam- • matory cells. '>. ^ . "Jj^-. 1 J f . %J i.- Clot. ■^i £^^'^>F ■ « *n ^ 3, T 1 ■ L ^* 1 *!. -h B Lacerated internal 'coat (artefact) Middle coat. Perivas- cular tissue. Tunica ex 1 1 Tunica meili i Tunica interni — ■ Clot. Fig. 51. — Obliterative phlebitis. Stained with hematoxylon and eosin. A. — Transverse section of the femoral vein of a case of phlegmasia alba dolens, twice natural size. B. — The portion of the tissue shown in the square, magnified 2o diameters. A large thrombus is attached to the diseased internal coat of the vessel. 123 NORMAL BLOOD.i The examination of a drop of blood spread upon a slide and stained with hematoxylon and eosin shows two kinds of cells: 1. Small circular masses colored in a homogeneous manner by the eosin and entirely without a nucleus— the red blood corpuscles. 2. Other protoplasmic masses, a little larger than the red blood corpuscles and containing a nucleus staining blue with the hematoxylon and having finely granular cytoplasm— white blood corpuscles, or leukocytes. (A third cellular component of the blood is the platelets, but to demonstrate them it is necessary to use a special stain— Ehriich's, Wright's, Jenner's or Leishmann's stains. These, therefore, do not show in this slide, and do not appear in the drawing.) The Red Corpuscles.— These have the form of small bicon- cave-biconvex disks whose shape can be most easily recognized by gently varying the focus. Certain of the corpuscles are badly fixed or have been injured in the process of spreading upon the sUde, and some of them may show no definite form. The size of the corpuscles is very regular (diameter, 7 to 8 mm.) and knowledge of this may be of use in roughly estimating the size of other objects with which they may be associated. The White Corpuscles. —These at once divide themselves into two classes according to the presence or absence of granules in their cytoplasm: (a) The granular leukocytes have multilobulated nuclei, hence are often spoken of as polynuclear, but are more correctly called polymorphonuclear leukocytes. Their cytoplasm contains fine granules whose staining affinities are somewhat variable according to the elements studied. Some have granules that are almost colorless— neutrophiles. Others have granules that are strongly stained with the red of the eosin— eosinophiles. In order to recognize a third variety of the polynuclears, the basophils, it is necessary to employ a special method of staining with polychrome blue. But the basophils are exceptional in the normal blood, and only become numerous in certain in- flammatory reactions and the leukemias. (6) Non-granular leukocytes have homogeneous protoplasm and spherical or incurved nuclei without the definite con- strictions of the polymorphonuclears. Some are about the ' In this country it is not customary to make examinations of blood corpuscles except in spreads stained by Wright's method, by which all of the elements, including the platelets are brought out. We suppose the author knew this, but introduced the hematoxylin and eosin preparation in order that the beginner might have a marked comparison between the corpuscles as they occur in the blood, and as he may find them in the tissues. (Trans.) 124 size of the red blood corpuscles. The spherical nucleus occupies almost the entire cell, the cytoplasm itself scarcely appearing, being reduced to a narrow peripheral coronet. These are the lymphocytes (small lymphocytes). Others, eight or ten times larger, with abundant protoplasm and slightly indented nuclei are the middle-sized or large mononuclears (large lymphocytes). Between the two are numerous transition forms. Poly- morpho- nuclear neutro- phile. Red blood corpuscle. Fig. 52. — Normal blood. A drop of fresh blood is thinly spread upon a clean slide, dried and fixed with alcohol-ether, and stained with hematoxylon and eosin, and examined under the oil-immersion lens. Magnified 570 diameters. A single polymorphonuclear leukocyte and many red blood corpuscles are seen. The blood platelets are not visible in this preparation, requiring special stains to bring them out. Of the 6000 leukocytes found in i c.mm. of blood the different varieties occur normally in the following proportions: Polynuclear neutrophiles Lymphocytes .... Mononuclear and transition forms Eosiuophiles 65 per cent • IS 20 " I or 3 " 125 LEUKOCYTOSIS. - ,_ Polynuclears. The specimen is a spread drop of blood, dried and stained with hematoxylon and-eosin. In it are found the same ele- ments as were- seen in -t^- preceding figure — red blood corpuscles, polymorphonuclearSj.-^jjlymphocytes, large and middle-sized mononuclears'." '; But that which, ^mstinguishes this preparation from the preceding and gives it a quite different appearance is the much larger proportion of white blood cells. The increase is so con- siderable as to make it possible to appreciate the leukocytes without having recourse to methods of enumeration. As the increase consists almost entirely of the polymorphonuclear neutrophilic cells it is clear that we have to do with a poly- nucleosis or leukocytosis. Such a condition betrays a general reaction of defense against an acute inflammatory process. The discovery of leukocytosis is often of clinical and diag- nostic importance. In the course of an acute appendicitis, for example, it can serve to reveal transformation from the latent state to peri-appendicular abscess and to indicate neces- sity for operation. If, instead of concerning the polymorphonuclear neutrophils the increase in number affects the: 1. Eosinophils, it is called eosinophilia. This is observed parasitic affections (hydatid cysts, intestinal parasites). 2. Mononuclears— if the large or middle-sized mononuclears are increased — mononucleosis — it usually indicates the presence of some special form of infection such as variola or vaccinia. Differential Diagnosis.— By the examination of stained blood films one should be able to differentiate between leukemia and leukocytosis: (ffl) Through the great number of lymphocytes in leukemia of the lymphatic type. {b) Through the presence of new elements of the myeloid series (myelocytes) in the myeloid variety. 126 Poly- morpho- nuclear. Red blood corpuscle. Fig. 53. — Leukocytosis. A spread of blood taken from a pneumonic patient at the period of acme. Fixation with alcohol-ether, staining with hematoxylon and eosin. Magnified 570 diameters. There are eight polymorphonuclears in the field. A count of the blood corpuscles made at the same time showed 24.000 leukocytes of which 85 per cent were polymorphonuclears. 127 MYELOGENIC LEUKEMIA. The drawing, like the preceding, shows a spread of dry blood as it appears under the oil-immersion objective. The enormous number of white blood cells as compared with the red blood cells, as well as the varying types of leukocytes, give the specimen a very characteristic appearance which should at once make one think of leukemia. This can be confirmed by a blood count, which will show that the number of the red blood corpuscles is not increased, while that of the white blood corpuscles is. The leukocytes are of different types: (a) Leukocytes with polylobed nuclei and finely granular cytoplasm — polymorpho- nuclear neutrophils, (b) Mononuclears with pale nuclei, some showing fine protoplasmic granulations. These are called myelocytes because under normal conditions they are only found in the marrow of the bones, (c) Some lymphocytes or small mononuclears with very little protoplasm and nuclei rich in chromatin, (d) Eosinophils, more numerous than in the normal state, as they are easily found, (e) White blood cells with atypical karyokinetic figures in the nuclei. Finally, there are cells of an entirely abnormal type, the normoblasts or nucleated red blood corpuscles. These are cells not found in the normal blood, belonging solely in the bone marrow from which the adult red blood cells are derived. The morphological alterations of the red blood corpuscles should also be pointed out. They consist of deformity- elongation, oval or rectangular shape— and constitute what is described as poikilocytosis. There are also anomaUes referable to artefacts in making the preparation, and indicate no more than fragiUty of the red blood corpuscles. {Crenation, or chestnut-burr appearance, not shown in the drawings, usually uniformly affects all of the red blood corpuscles in a field.) Resume.— The augmentation in the number of white blood corpuscles (which sometimes gives the fluid blood a truly milky appearance) beyond the limits occurring in infection, and the preservation of the red corpuscles, suggest the diagnosis of leukemia. The presence of the cells of the bone marrow series—granular myelocytes and normoblasts— permit one to differentiate between the myelogenic leukemia and lym- phatic leukemia in which the augmentation in number is in the Ijmiphocytes. 128 Red blood corpuscle. Poly- morpho- nuclear neutro- phile. Karyo- kinesis of leuko- cyte. Eosino- phile. Normo- blasts (nucleated red blood cor- puscles) . Mononu- clear. Mono- nuclear. Lympho- cytes. Myelo- cyte with granular cyto- plasm. Fig. 54. — Blood of myelogenic leukemia. Spread fixed with alcohol-ether, stained with hematoxylon and eosin, and examined under a magnification of 570 diameters. Note the great number of white as compared with red cells; the various types of white corpuscles — polymorphonuclear neutrophiles, eosinophiles, middle-sized mononuclears, lymphocytes, granular myelocytes, leukocytes with karyokinetic figures, and lastly the nucleated red corpuscles or normoblasts. 129 ACUTE LYMPHATIC LEUKEMIA. As in the preparation of myelogenic leukemia, one is struck with the enormous proportion of white relatively to the red cells. Besides this, a preliminary blood count of both red and white cells shows that the number of leukocytes has increased in considerable proportions (from 20 to 200,000, according to the case). But the white corpuscles are all lymphocytes, of which there are two types: 1. The small lymphocytes, with very Httle cytoplasm forming a narrow coronet about an ovoid nucleus. 2. The large lymphocytes, or macrolymphocytes, which are much larger cells with larger and often irregular nuclei and relatively abundant protoplasm. These two different forms of leukocytes result from two different reactions in the lymphatic tissues. The small lympho- cytes express a chronic disturbance — chronic lymphatic leukemia. The large lymphocytes represent a younger type of element, less differentiated than that which circulates in the blood, indicating, as in the present case, an acute reaction — acute lymphatic leukemia. There are intermediates between these extreme types, but in this case the large lymphocytes being a great deal more numer- ous than the others, we have to do with a case of acute leukemia. In leukemia both the red corpuscles and the leukocytes are very fragile, so that as the blood is spread for staining, they are easily deformed and crushed. In the preceding drawing there are numerous fragments of cells that must not be mistaken for blood platelets, which, as has been said, do not show in smears stained with hematoxylon and eosin, but require special staining (Wright's stain). Some normoblasts and plasmocytes can also be found in the preparation. Resume. — The formidable increase in the number of white blood corpuscles and the relative preservation in the number of the red corpuscles is sufficient to suggest the diagnosis of leukemia. The occurrence of lymphoid cells (lymphocytes and above all large lymphocytes) is suffecient to enable the diagnosis of acute lymphatic leukemia to be made. 130 Small lym- phocyte. Large lym- phocytes. Red blood corpuscle. Fig. 55. — Acute lymphatic leulcemia. Fixed with alcohol-ether, stained with hematoxylon and eosin. Magnified 600 diameters. The great number of lymphocytes, especially large lymphocytes is to be observed as characteristic of acute lymphatic leukemia. 131 NORMAL KIDNEY. Kidney of an Executed Criminal. Diagnosis of the Organ.— The section of the kidney, includ- ing both cortex and medulla, appears to be divided into two distinct portions. The one, darker, and at the periphery, contains in its interior a number of small rounded masses. These are the characteristic elements of kidney structure, the glomerules, or Malpighian bodies, which should always be looked for with care in order to make the diagnosis of the organ, and to recognize its cortical substance. The other paler portion consists of tiny tubules, sometimes cut transversely, sometimes longitudinally and arranged in a radiating fashion: this is the medulla, much less characteristic than the cortex for making the diagnosis of the organ. I. In the cortical substance the glomerules, or Malpighian bodies, are of much the same size in the normal kidney; some, however, being cut tangentially, appear smaller. The Mal- pighian bodies consist of two parts: one central, the vascular tuft; the other, peripheral, the capsule of Bowman. The vascular tuft is a sort of undifferentiated plasmodium, that is to say, a protoplasmic mass not divided into cells, in the substance of which one perceives a great number of nuclei and numerous capillaries containing red blood corpuscles. About it there is a narrow space limited on the outside by the capsule of Bowman. It has a delicate endothelial (epithelial?) lining. Here and there in the section it may be possible to find glomeruli that show the vascular pole, formed of two vessels, the afferent artery and efferent vein, or the urinary pole, at which the uriniferous tubule begins. The glomerules are surrounded by a large number of tubules of unequal diameter sometimes cut transversely, sometimes longitudinally. Examination under the low power enables one to recognize two principal types: Secretory tubes (convoluted and irregu- lar tubes) and excretory tubes, ascending and descending loops of Henle. (a) The secretory tubes: These, known as the convoluted tubules, are recognized by a lining of granular epithelium, more or less acidophilic and peculiarly fragile. It is very common for kidney tissue taken from autopsy cases to show cadaveric alterations in a variety of forms such as desquamation and protoplasmic 132 Malpig- hian bodies or glomer- ules. Cortical substance. Tubules "^^f"^^ ^^^^^^^'^'''^I'^^i^.^^^^^^MI^^ Medullary or excretory -^^^^^^.gi^v^^^^^^^^^ substance, tubules cut »»»»-^^«»^' • j:vx>._-iiB«v^,^i .i~«iiH«fMciaiiiHmsiMo«i»s»HM parallel. Excretory tubules cut trans- versely. Fig. 56. — Normal kidney. Stained with hematoxylon and eosin. Magnified 40 diameters. The greater part of the drawing shows the renal cortex in which a great many Malpighian bodies or glomerules can he seen among the convoluted tubules. The capsule has been torn of and does not appear in the section. The lower right-hand corner shows the medullary substance with its excretory tubules cut transversely 133 fragmentation ; one must be careful not to mistake them for path- ological lesions. They can usually be recognized through uniform occurrence in all parts of the section. Such cadaveric changes begin to make their appearance a few hours after death. The cells of the secretory tubules are mostly cubical, possess a nucleus situated basally and show in well-fixed specimens, even with the ordinary stains, a fine fringe upon the centrally directed surface — the so-called rodded epithelium. (b) The excretory tubules: These are of two varieties. The first differ from the convoluted tubules by an epithelium with more distinctly basophilic staining reactions, in a much better state of preservation, as they are much less fragile. The cells have a bluish cast and darker nuclei than those of the secretory tubules. They comprise the larger or ascending limbs of Henle's loop. The others are fine tubules lined with an extremely flattened epithelium resembling endothelium, and have a general appearance not unlike capillaries, but are easily differ- entiated from them through the complete absence of red blood corpuscles from their interiors. They correspond to the descend- ing limb of Henle's loop or to the loop itself. 2. In the medullary substance are found nothing but the transverse and longitudinal sections of tubules of various kinds —excretory tubules, ascending and descending limbs of Henle's loops just studied in the cortical portion, and much larger collecting tubes lined with tall cubical epithelium— the collect- ing tubes of Bellini. 3. Besides these epithelial components one sees the fine vascular and connective tissue of the organ. The connective tissue consists sometimes of a young tissue rich in cells— more frequently of collagenous fibers. The vessels, always large and abundant, are of the adult type. Such is the picture presented by a histological section of the normal kidney, and such are the landmarks that one must know to recognize the parenchyma with which one chiefly has to do in recognizing the pathological alterations. With regard to the renal lobule, represented by the unity of the uriniferous tubule, it is impossible to gain information through study of the different parts of a section. It is a con- ception acquired through the study of tissues specially prepared by injection methods. In the pathological-histological study of the kidney, that which is of most importance is the recognition of the excretory and the secretory structures. 134 Capsule of Bowman. B Descend- ing limb of Henle's loop. Capillary containing blood. Ascending limb of Henle's loop. Duct or tubule of Bellini. Capillary, Fig. 57. — Normal kidney. Stained with hematoxylon and eosin. Magnified 250 diameters. Above A, the cortical substance is shown. In it are a Mal- pighian body, convoluted tubules and some excretory tubules. Below B, the medullary substance is shown with its various excre- tory tubules cut transversely. 135 SUBACUTE NEPHRITIS. Variolous Nephritis. Diagnosis of the Organ.— Upon examining the section with a low-power lens it is easy to recognize the Malpighian bodies whose capillary tufts are characteristic and at once enable the organ to be diagnosed. Diagnosis of the Lesion.— The lesions presented in the section are very varied. To understand them it will be necessary to study in detail the glandular parenchyma (glomerules and convoluted tubule) and the stroma or interstitial tissue. At the upper part of the section, shown in the drawing (Fig. 58), there is a thick layer of connective tissue containing some fat cells. It is the capsule of the organ which, in this case, is abnormally thick and contains a few small lymphocytic col- lections (inflammatory cells). This thickening of the capsule with inflammatory infiltration denotes a long-standing inflam- matory process. Below the capsule the cortical substance shows extremely complex alterations affecting both the glomerules and tubules (glomerulo-nephritis) . (a) The glomerules have a very variable size and structure. The next drawing (Fig. 59) shows two different portions from the section, taken at random, and shown under a higher mag- nification. One (A) shows a glomerule whose capsule of Bow- man is greatly thickened through stratified layers of connective tissue composed of coUagen fibers, among which are numerous long bluish nuclei. In the center of the capsule the vascular elements of the glomerulus show with some exaggeration because of the large number of red blood corpuscles they contain, and by which the nuclei of the plasmodium are obscured (con- gestion). On the left-hand side of Fig. 59, A, there is a glom- erular lesion of an entirely different kind. The sclerosis of the capsule has invaded the entire glomerule and the capillary structure can no longer be seen. The vascular strophy and the thickening of the capsule of Bowman have terminated in a glomerulo-capsular symphysis, and the formation of a rounded mass of fibrous substance to which the term "wafer" is some- times applied. This is another indication that the lesion is old. Throughout the section there are all stages between the two types of lesion described. (b) In the intervals between the glomerules the secretory 136 Capsule. Inflamma- tory in- filtration. ^ Fibroid glomerule. Vessel with peri- pheral sclerosis. Inflammed stroma. Glomer- ules in different stages o£ sclerosis. Inflam- matory infiltra- tion. Fig. 58. — Subacute nephritis. Stained with hematoxylon and eosin. Magnified 40 diameters. Below the thickened capsule shown at the top of the drawing, the kidney substance shows a variety of glomerular and tubular lesions (jglomerulo-nephritis) . Between the glomerules and the tubules there is considerable infiltration of inflammatory cells. 137 tubes show lesions more or less important. In Fig. 59, B, on the next page, the cylindrico-cubical epithelium is disposed around an opening sometimes potential, sometimfes com- pletely disappeared. The lumen is found stuffed with des- quamated cells with pycnotic nuclei crowded pell-mell into the center of a cavity more or less sinuous. Here and there, as in the right side of the Fig. 59, B, the desquamation of the epithelium is less marked, but the tubes tend to dilatation and cystic transformation. The lumen becomes a kind of cavity that is filled with hyaline fluid that stains distinctly with the eosin dye and is lined by flattened epithelium. These lesions of the tubule comprise desquamative and exuda- tive tubulitis and are certainly not postmortem alterations or artefacts due to bad fixation of the tissue. Such cystic appear- ances are never found under such circumstances. (c) Besides the lesions of the parenchyma there are less marked alterations of the stroma characterized by an enor- mous infiltration of small round cells (bluish) placed imme- diately beneath the capsule (Fig. 58). These cells infiltrate more or less everjrwhere between the glomerules and about the tubules, accumulating here and there in masses more or less distinct and clear cut. Finally are to be noted small interstitial hemorrhages, easily recognized by their brownish color with occasional traces of pigmentary change. In addition to all this, the walls of the bloodvessels are thickened through stratifications of young connective tissue. The medullary substances, not shown in the drawing, is not distinctly affected. In the excretory tubules, however, collec- tions of desquamated cells indicate lesions further up the tubules. In some of these cells the details of nuclear structure can still be seen; others have undergone hyaline change. Resume.— Nephritis of the subacute variety, affecting at the same time the glomerules and the tubules (glomerulo- nephritis in different stages) and the stroma. In consequence it is a mixed nephritis, as is usually the case if of sufficient duration to effect changes of the interstitial tissue which always requires more time than the injury to the epithelium. Hence the old division into interstitial and paranchymatous nephritis is too artificial to he valid. This type of subacute nephritis is common after scarlatina and variola. 138 Glomerule with con- gested capillary tuft, and thickened capsule. Connec- tive tissue stroma. Diseased i'foSii secretory tubule. Normal excretory tubules. Convo- luted tubules in a state of cystic dila- tation, and con- taining tube- casts. Secretory tubules. Fig. 59. — Subacute nephritis. Stained with hematoxylon and eosin. Magnified 250 diameters. Nephritis from a case of smallpox. A. — Two inflammed glomerules in (liferent stages of disease. B. — Diseased convoluted tubules with desquamated epithelium, cystic dilatation and tube casts. 139 CHRONIC NEPHRITIS. Bright's Disease. Diagnosis of the Organ.— The diagnosis of the organ is easily made, thanks to the characteristic aspect of the glomerules. Diagnosis of the Lesion.— As in the preceding case it is necessary to study the changes in both epithelial and con- nective tissue elements. A. The Malpighian bodies, or glomerules, present alterations much like those of the subacute form of the disease, but more distinct. The progressive transformation of the glomeruli into fibrous masses (wafers) is marked. At first the capillary tuft retracts toward one pole, only occupying a part of the capsular cavity, then it unites itself with the capsule of Bowman and finally degenerates altogether and becomes a mass of collagenous material. B. The convoluted tubules do not show any disturbance that can be attributed to cadaveric change, but under the capsule of the kidney they undergo a dilatation that is quite marked and explains the little bosselations that appear upon the surface of the kidneys of cases of Bright's disease, and remain as small pale spots when the capsule of the organ is torn off. The drawing shows two of these granulations separated by a slight groove, at the bottom of which an infiltration of blue cells (lymphocytes) can be seen. The ectasia of the convoluted tubules in the neighborhood of these granulations is referable to functional activity of the organ (compensatory hypertrophy). C. The stroma also shows important changes. The masses of bluish cells between the glomerules and the tubules some- times indicate an inflammatory reaction of chronic nature, sometimes a terminal process— an addition of a subacute nephritis to a chronic sclerotic one. The vessels have extremely thick walls ; their lumen is corre- spondingly diminished, and almost obstructed by the enormous proliferation of the middle and internal coats. In the medullary substance, not shown in the drawing, the lumina of the collecting tubes is obstructed by rounded masses of homogeneous substance — tube casts. Resvane. — Nephritis, whose lesions affect chiefly the glom- erules and stroma, and relatively spare the convoluted tubules. The stroma and parenchyma are both affected, again showing the artificial character of the old division into interstitial and parenchymatous nephritis. 140 Dilated tubules forming a "granu- lation ot Bright." Fibroid glomer- ules. (' ' Granu- lation of Bright" Majpig- hian body Thickened capsule of Bowmann. Arteriole with endarter- itis. Fig. 60. — Chronic nephritis. Stained with hematoxylon and eosin. Magnified 45 diameters. Section of a small sclerotic kidney of Bright' s disease. At the upper edge two of the so-called granulations of Bright project upon the surface beneath the capsule. The glomerular and peri- vascular sclerosis is striking. 141 PYEMIC NEPHRITIS. Embolic Nephritis. Diagnosis of the Organ.— This is relatively difficult because of the extent of the lesions. At certain points, however, as in the lower part of the drawing, it is possible to discover some glomerules and convoluted tubules. Diagnosis of the Lesion.— Under a low-power lens one is at once struck by the pale color of the renal elements. The cellular limits are indistinct, both those of the tubules and the glomerules. The nuclei have often disappeared from the cells. The tubules are often filled with amorphous eosinophilic masses. This necrotic aspect of the parenchyma is in accord with the vascular alterations. The preparation is mottled with dark bluish patches which are even visible to the naked eye. These are abscesses and can be seen in the upper part of the drawing. With a higher magnification they are seen to be made up of acidophilic cells with oval or multilobed nuclei (mononuclear and polymorphonuclear leukocytes). The acido- phihc quality of the protoplasm and the pycnosis of the nuclei indicate a marked cellular degeneration — pus. At the periph- eral limit of the abscess the necrosis is particularly marked by a zone of hyaline amorphous substance in which one can recognize tubules and glomerules. The abscesses are formed by a diffuse infiltration of inflammatory cells, mononuclear and polymorphonuclear cells, some of which lie between the tubules and some in the thickness of their walls. In addition to these microscopic abscesses there are much smaller dark spots extremely irregular in form having a finely granular appearance and distributed without any order through- out the specimen. These are masses of bacteria mostly com- posed of great numbers of cocci that can be rendered more distinctly visible by special methods of staining, especially Gram's stain. They are microbic emboli brought by the blood from sources outside of the kidney. In the center of the drawing is a glomerule containing such a microbic embolus. Thus is explained the origin of the abscesses. The paren- chymatous necrosis is due to the presence of the areas of sup- puration and to the vascular thrombosis. Resume. — Pyemic nephritis, with numerous abscesses and microbic emboli, such as occur in septicemia, and result from embolism. 142 B ^^ Abscess. ^ ■ ■0« . V - T yji^ Flattened excretory tubules. A Medullary Microor- ganismal "^#^5 *■■■■*■■■ .V - >-->■< - V _-' a. « !k,X,^ '^ ** embolus. Convo- luted tubules. Embolic and foci of suppuration. Fig. 61. — Pyemic nephritis. Stained with hematoxylon and eosin. Embolic nephritis in a boy, aged fourteen years, dying from septico-pyemia following acute osteomyelitis of the tibia. A. — The fragment of the kidney as it appears when twice mag- nified. B. — Numerous abscesses and microorganismal emboli ate seen in the upper part of the drawing, with necrotic renal tissue below. Magnification 30 diameters. 143 ASCENDING PYELONEPHRITIS. Urinary Nephritis. Diagnosis of the Organs. —Under the low power it is easy to recognize the Malpighian bodies, the convoluted tubules and the collecting tubes of the kidney. Diagnosis of the Lesion.— One is at once struck by the dissociation of the histological elements and by the diminution of the staining affinity of the cellular elements. A.— In the cortex (Fig. 62, C) the convoluted tubules present alterations analogous with those described in connection with the subacute nephritis. In the interior of more or less irregular cavities desquamated epithelial cells are mixed with many smaller cells : mononuclears and more rarely polymorphonuclear cells. The glomerules are less numerous, being crowded out by the inflammatory infiltration which dissociates all of the structures. Those that persist show varying congestion and capsular pro- liferation. An enormous number of blue cells diffusely infil- trate the entire stroma; in addition to which there are numer- ous dilated capillaries and small discrete interstitial hemorrhages. B. — In the medulla (Fig 62, B) the parallel excretory tubules with their lining of cubical cells are relatively intact. Inside of them are two kinds of elements: pus cells, i. e., polymorpho- nuclear and mononuclear leukocytes more or less degenerated with acidophilic protoplasm and pycnotic nuclei; and desqua- mated epithelial cells. The radiating appearance of the collect- ing tubules filled with pus and degenerated epithelium is char- acteristic of a nephritis of ascending origin (radiating nephritis of cystitis, prostatitis and urinary obstruction). In the inter- spaces between the tubules the stroma assumes a hyaline aspect: fine connective- tissue fibrillae infiltrated with edema- tous fluid, and here and there, with numerous inflammatory cells sometimes difficult to distinguish from the nuclei of the fixed connective-tissue cells. In the medulla, as in the cortex, there are numerous capillary vessels, dilated and sometimes ruptured (interstitial hemorrhages). Resume. — Ascending radiating nephritis with parenchyma- tous changes (desquamation of the cells) as well as important interstitial changes. 144 Medullary substance. Cortical substance rggirxj/ . ^ ^-^ Area {* shown in Fig. B. i^ B Abnormal excretory tubules. Hyalin stroma. Excretory tubules containing pus. Vessel. Area shown in Fig. C. »-&?^ c Secretory tubule. Infiltrated stroma. Secretory tubules containing poly- morpho- nuclear cells. Dilated capillary. .Excretory tubule. Fig. 62. — Ascending pyelonephritis. Stained with hematoxylon and eosin. Pyelonephritis follouinng a gunshot wound of the dorsal spinal cord with paraplegia and retention of urine. The infection following the repeated catheterizations was the cause of death. A. — Appearance of a fragment of the kidney magnified 5 diam- eters. B. — Medullary substance. Magnified 100 diameters. C. — Cortical substance. Magnified 100 diameters. 10 145 TUBERCULOUS PYELONEPHRITIS. Tuberculosis of the Kidney. The section has been made in the neighborhood of a tuber- culous cavity or excavation. It is divisible into three zones; an upper which is the edge of the excavation, a middle in which the kidney tissue is relatively undisturbed, and a lower. Diagnosis of the Organs. —This can easily be made by noting the presence in the middle zone of Malpighian bodies and convoluted tubules. Diagnosis of the Lesion.— To accomplish this it will be necessary to separately examine the upper and lower thirds. I. Upper Third.— This is the wall of the tuberculous excava- tion. It is composed of a caseous mass of a blue-violet color that is quite characteristic and has an undifferentiated appear- ance in which remnants of nuclei can be seen. It also shows numerous fractures or cracks that are caused by retraction effected by the reagents used in the preparation of the specimen for histolqgical examination. At the periphery of the caseous mass some epithelioid cells are seen with stretched-out nuclei and pale and abundant protoplasm, and, above all, lymphocytes forming a dense bluish layer at the extreme edge of the wall of the excavation, and extending into the parenchyma. II. Middle Third.— This shows the parenchyma variously disturbed by disease. Above, near the edge of the excavation, the tubules are deformed and compressed: lower down they are normal in appearance. In the secretory tubules desquama- tion of the epithelium is quite pronounced (tubulitis). The glomerules are but little altered (congestion) but the stroma presents an important lymphocytic infiltration with edema. In the lumen of some of the excretory tubules there are reddish hyaline masses (tube casts). The diminished staining power of all of the elements is to be noted. III. Lower Third. — This contains miliary tubercles which can be recognized by their rounded form, by the presence of giant cells with nuclei arranged in horseshoe form, by their caseous centers and by the epithelioid and lymphoid cells at their peripheries. It is easy to understand that with the occurrence of added caseation evacuation into a calyx might occur and thus begin a new open excavation. Resniae.— Pyelonephritis, not unlike the preceding case in the epithelial desquamation, the infiltration of the stroma and the marked cellular necrosis but differing from it in the presence of the miliary tubercles and the excavation. 146 Sclerosed glomerule. Lymphoid cells. Malpig- hian glomemle. Stroma. Miliary tubercle. Fig. 63. — Tuberculous pyelonephritis. Stained with hematoxylon and eosin. Magnified loo diameters. The upper third of the section shows a part of the wall of a tuberculous cavity of which the liquefied center cannot be seen. The middle part is composed of diseased renal tissue. The lower part contains a miliary tubercle with two giant cells. 147 AMYLOID INFILTRATION OF THE KIDNEY. From a Case of Chronic Pulmonary Tuberculosis. Diagnosis of the Organ.— This is very easy to make by a more extended study of the section than the Umited field shown in the drawing permits. Under a low power the structure of the organ is found to be tubular, divisible into a cortical portion in which the tubules twist and turn among them- selves, and a medullary part in which they occur in parallel formations— pyramids. Regularly distributed in the portions of the cortex lying between narrow, fairly equidistant, radiat- ing, parallel, hnear formations composed of excretory tubules and vessels— the medullary rays or pyramids of Ferrein— are rounded structures, which though so changed by disease that they no longer have the strawberry appearance, are recogniz- able of the glomerular or Malpighian bodies. We thus arrive at the diagnosis of kidney. Diagnosis of the Lesion.— The examination just completed has shown the absence of gross abnormalities; so for future study the higher-power lenses must be used. With such mag- nification, changes, such as are represented in the drawing, are readily found. They embrace abnormalities of both glomeruli! and tubules. 1. The Glomerular Disturbance— A diseased glomerule occu- pies the greater part of the center of the drawing. Instead of appearing as a nucleated plasmodium, as is normal, it is found to be largely composed of structureless, pink-colored, waxy substance in which a few cells and nuclei are caught, and between the masses of which some of the original structure survives. This is amyloid substance as can easily be determined by the application of the microchemic tests already described. Attention to the general arrangement of the amyloid material shows it to be deposited in a distribution corresponding to the letter S. This suggests that its seat of primary infiltration has been about the little vessels of the glomerules. This is in complete correspondence with its usual method of infiltration. Beginning its appearance about the small vessels, it gradually infiltrates the surrounding tissue, crowding its proper cells and causing them to atrophy. 2. The Tubular Disturbance. — These occur in association with the amyloid disease but are in no sense a part of it. Though it is rare for a kidney affected with amyloid disease to be otherwise normal, it may be possible. The amyloid infiltra- 148 tion is the result of certain chronic nutritive, or toxic, disturb- ance which may result in numerous and diversified associated changes. It is common, for example, to find fibrosis associated with amyloid. In this particular case the toxic disturbance of the patient's blood has manifested itself in tubular changes which assume various appearances that may be looked upon as indicating differing degrees of cell destruction. At the lower right-hand portion of the drawing are two transverse sections of convoluted uriniferous tubules (secretory tubules) that are fairly normal in appearance. In the upper left-hand portion there is a section of a similar tubule whose epithelial lining is transformed into an nuclear granular mass— com- plete distraction, or necrosis of the epithelium. Below it is a section of a slightly dilated tubule whose cells contain an excessive number of granules (cloudy swelling) among which are some very large granules and small spheres of translucent homogeneous substance much like the amyloid, but failing to give the microchemic reaction with iodine and gentian violet. These are hyaline. In some of the other tubules cells may be observed to lie free in the lumina of the tubules (desquamation) . These cellular and tubular changes are not the result of post- mortem autolysis for they lack uniformity. They are the results of disease — tubular nephritis. Resume. — Kidney whose glomerules show homogeneous, waxy, perivascular deposits {amyloid), and whose tubules show destruction and desquamation of the epithelium in varying in- tensity — tubular nephritis. Amyloid substance. Fig. 64. — Amyloid infiltration of a renal glomerula. From a patient dead of chronic pulmonary tuberculosis. Magnified 250 diameters. Stained witli hematoxylin and eosin. 149 BENIGN HYPERNEPHROMA. Diagnosis of the Organ.— The section shown in the drawing divides itself into two distinct portions, which have different staining afi&nities. In the lower, Mapighian bodies and tubules leave no doubt as to the organ concerned. This portion is separated from that above by a thick band of vascular con- nective tissue which is the capsule of the kidney. Diagnosis of the Lesion.— This constitutes the upper part of the drawing and is a tumor. When looked at closely it consists of nests of pale cells separated from one another by strands of connective tissue or by capillaries. The arrangement is irregular and the absence of parallel columns is particularly noticeable. The cells when examined under a higher power are found to have a transparent proto- plasm, and slightly excentric nucleus and a slightly reticulated or vacuolated protoplasm recalling that of the spongiocytes of the zona fascicularis of the adrenal body. Like them these cells are crowded with fine fatty granules (lipoid, neutral fats). Between the cell nests is a fine trellis work of collagen fibers. Newly formed capillaries are extremely numerous and are in intimate contact with the cells of the tumor, as in the adrenal. The structure of these capillaries is normal: the endothelium reposes upon a thin layer of connective tissue. In the part of the drawing representing the kidney, attention must again be called to the fibrous capsule, which separates it from the tumor, and the compression of the tubules in its immediate vicinity. We have here to do with a well-circumscribed definitely limited tumor of glandular origin, that is to say, with an adenoma — a benign tumor. But the apjjearance of the cells recalls the spongiocytes of the adrenal, and on this account it has been supposed that the tumor arises from debris of an embryonal vestige of that organ included in the kidney sub- stance, from which it derives the name hypernephroma. Resume.— It is an epithelial tumor starting from the tubules of the kidney and in which the cells, in part or altogether, take the pale appearance. It is possible sometimes to follow the transition of the kidney cells to the transparent cells. Sometimes in this case we have to do with a benign tumor, localized and encapsulated and not giving metastasis: adenoma with pale cells — benign hypernephroma. Sometimes, one finds the characteristics of malignant tumors of the kidney— some with dark cells (epithelioma with dark cells), others with pale ceil?,— hypernephroma malignum. 150 Adenoma. Kidney. Fig. 65. — Benign hypernepliroma. Stained with hematoxylon and eosin. A small sulphur yellow encapsulated benign tumor unexpectedly found at autopsy. ^.Separation between the tumor and the renal parenchyma, magnified 80 diameters. B.Spongiocytic cells of the neoplasm magnified 450 diameters. 151 NORMAL TESTICLE. Testis of a Dog. A section perpendicular to the long axis of the testis with its epididymis and surrounded by the tunica vaginalis (Fig. 66, A). The Testicle.— I. The seminiferous tubules (shown in the lower part of drawing, Fig. 66, B) are limited by a basement membrane upon which are placed two principal types of cells arranged in several layers. Some stain deeply and show a distinct contour and very distinct nuclei. They are the cells of Sertoli, very well shown here (dog's testis), but a great deal less distinct in human tissue. They are recognized by their somewhat peculiar nuclei flanked by a nucleolus and juxta- nuclear bodies. These are the so-called supporting cells. The other cells, varying according to the layer examined, belong to the seminal line and include several strata passing from the periphery to the lumen of the tubule. (a) The spermatogonia, rounded voluminous cells with large nuclei, in direct contact with the basement membrane. (6) The spermatocytes, cells whose nuclei show numerous mitotic figures indicating cellular activity. (c) The spermatids, a great deal smaller, with large nuclei and very dense protoplasm. (d) The spermatozoa, elongated cells with a swelling at one end (head) and a caudal membrane (tail). 2. Between the seminiferous tubules a mass of large cells with finely granular protoplasm can be seen. These are the interstitial cells which seem to play a role in the internal secre- tion of the organ. 3. The intermediate zone, which separates the seminiferous tubules from the tubules of the epididymis, contains the vessels of the organ and its ducts are lined with cubical epithelium. The Epididymis. — The tubules of the epididymis are com- posed of a rather thick basement membrane, upon which is arranged a single layer of cylindrical epithelium with pale protoplasm, and vibratory cilia that show very well. In the center of the lumen are collections of the spermatic secretion in which spermatozoa can be seen. The structure of the seminiferous tubules with their stratified epithelium and highly specialized cells easily enables them to be differentiated from those of the epididymis. 152 Epididymis. "" ' j\ -'-!-^^is^'& Body o£ . . "~}s.^-^MSr Highmore. '^UMm- Testicle. B Epididy- mis. Tunica albuginia. Testis. Basement membrane. Epithelial cells with vibratory cilia. Spermatozoa. Straight tubules or ducts. Spermatogonia. Spermatids. Spermatozoa. Interstitial cells. Fig. 66.— Normal testis of a dog. Stained with hematoxylon and eosin. A -Transverse section of the entire testis and epydidymis seen "t-p2t/rr£S the square, magnified .00 diameters, and' showing the epididymis above and the testis below. 153 TUBERCULOSIS OF THE TESTIS. Diagnosis of the Organ.— The drawing represents a group of tubules limited by a fairly thick lamina of connective tissue and lined on the inside by a stratified epithelium in a number of layers, which a high power shows to be composed of elements characteristic of the testis, and of its seminiferous tubules. None of the tubes has the structure characteristic of the epi- didymis. The tissue then includes only the testis. Diagnosis of the Lesion.— The tubules are more widely sepa- rated and less numerous than normal. At certain points (upper left-hand portion of the drawing) the glandular ele- ments of the organ have almost completely disappeared and their place is taken by a new combination which upon careful examination can be recognized as that of the miliary tubercle. That is to say: 1. A giant cell centrally situated and recognizable by its acidophilic cytoplasm and the coronet of peripherally arranged nuclei. 2. The epithelioid cells surrounding the giant cell with their usual transparent protoplasm and elongated nuclei. 3. The lymphoid cells more deeply colored. Elsewhere— in the interiors of the seminiferous tubules themselves — miliary tubercles may be found with similar giant cells in the centers, epithelioid cells around them and seemingly derived from the cells of the seminiferous series by metaplasia. There is no caseation. It is, therefore, an early tuberculosis in which the cheesy change has not had time to develop. Between the seminiferous tubules the inflammatory elements are mostly of the lymphoid tjrpe; some are, however, epithelioid. As a contingent lesion the thiclaiess of the basement mem- brane is to be noted. In this case it is very distinct and the modification of the seminal cells, which lose their differentia- tion, tend to give it an undifferentiated aspect. Resume.— An inflammatory lesion of the testis of tuberculous type— tuberculosis of the testis. Most frequently these lesions are associated with similar ones in the epididymis— ore Ai- epididymitis. 154 Zone of sclerosed seminif- erous tubules. Seminif- erous tubules with thickened walls. Fig. 67. — Tuberculosis of the testis. Stained with hematoxylon and eosin. Magnified 200 diameters. Tuberculous testis of an adult, removed at operation. The seminiferous tubules still show distinctly in the lower part of the drawing; miliary tubercles are seen above. 155 CANCER OF THE TESTICLE. Seminal Epithelioma: Seminoma. Diagnosis of the Organ.— When the drawing is examined with a low power it is found to be polymorphic and requires to be separately studied in its various parts. From above downward three different portions can be noted: The zone A can easily be recognized as the testicle with its seminiferous tubules, showing their usual stratification and cellular elements of the seminal series— spermatogonia, sper- matocytes in division and spermatozoa. There is no trace of the epididymis. The zone B contains an enormous mass of bluish cells com- pressed one upon another. At first view these recall the appearance of lymphocytes and seem to be of inflammatory nature and more or less conjunctivo-vascular. Diagnosis of the Lesion.— Under a higher magnification, and provided that the fixation of the tissue was good to begin with, these cells show, through their peripheral layer of pale protoplasm and large nuclei, their probable derivation from those of the seminal line. Elsewhere (left-hand side of the drawing) the transform3,tion of the seminiferous tubules into these masses of pseudolymphoid cells can be followed: the tubes seem to melt, the basement membrane disappears and the epithelial cells mix with the neighboring stroma. Thus is conceived to take place the transformation of the seminiferous tubule and the origin of a tumor which bears the name semi- noma. Elsewhere, between the seminiferous or cancerous tubules, there are extensive hemorrhagic areas such as are of frequent occurrence in these tumors. The zone C is separated from the p;receding by a thick band of connective tissue. It is formed of very fine fibrillje with scattered nuclei, or may be formed of a layer of homogeneous tissue recalling edematous fluid. In the substance of this mucous (myxoid) stroma there are elongated nuclei and cystic spaces, sometimes empty, some- times filled with edematous fluid, lined with epithelial cells comparable to those of the cell nests described above. This appearance of the tumor with its hyaline stroma and cystic spaces is entirely atypical. Resum6. — Malignant tumor or cancer of the testicle. In the least modified parts one recognizes a tumor of seminiferous origin — seminoma. 156 Seminif- Cancerous transfor- mation of the tubules. Inter- stitial hemor- rhage. T"^ f Connec tive tissue ^ partition. Epithe- lial cell nests. Mucoid stroma. Cystic cavity. <9,«^ •"il" ^ A Normal seminif- erous tubules. B Semin- oma. c Atypical epithe- lioma (mucoid) . Fig. 68. — Seminoma of the testis. Stained with hematoxylgn and eosin. Magnified 50 diameters. A rapidly growing tumor surgically removed jrom a man, aged fifty years. The drawing shows two different appearances of cancer of the testis. At the upper part the "seminoma" is shown with still recognizable seminiferous tubules; below the tumor has become atypical and myxoid through degeneration of the stroma. 157 HYPERTROPHY OF THE PROSTATE. Adenoma of the Prostate. Diagnosis of the Organ.— The tissue has a glandular appear- ance. The acini limited on the outside by a dehcate basement membrane (condensation of the connective-tissue stroma) are lined by a single layer of cubical epithelium. The lumen is filled with a finely granular substance: the prostatic fluid coagulated by the reagents. In the interior of some of the acini there are peculiar formations of an ovoid form, and apparently made up of concentric stratifications of some amorphous material — protein concretions, corpora amylocia, or sympexions, of the prostate. Some of the narrow spaces are excretory ducts of the gland. The stroma, which is very important, is composed of pale connective tissue with numerous smooth muscle fibers, appear- ing as reddish stripes upon the rose-pink background of the connective tissue. These fibers also differ from the connective tissue through their elongated nuclei swollen at the ends. The glandular acini, the sympexions and the vascular con- nective tissue stroma enable the diagnosis of the prostate gland to be made. Differential Diagnosis. — The mammary gland is the only organ with which the prostate can be confused, and is to be differentiated through its acini in which there is a double row of epithelial cells (myoepithelial cells), its stroma rich in adipose vesicles and the absence of muscular fibers in the stroma. Diagnosis of the Lesions. — The chief characteristic is the great irregularity of the acini. In many places there are veri- table microcysts lined with flattened epithelium. In propor- tion as the cavities are distended the epithelial lining is flattened until finally it may resemble endothelium. In certain of the acini, as in the center of the drawing, the epithelium becomes stratified, and even sends little vegetations into the interior of the cavity. Such epithelial proliferation, limited to the tubes, belong to the variety of benign glandular tumors known as adenoma. The stroma, equally hyperplastic, includes numerous smooth muscular fibers and connective-tissue fibers. Resume. — An adenoma, or benign tumor, of the prostate gland, a condition called in the cUnic hypertrophy oj the prostate. 158 Adenoma- tous acinus. Cyst. Sub- normal Cyst. Sympex- ion in the interior of a cyst. Normal acini. Fig. 69. — Hypertrophy of the prostate gland. Stained with hematoxylon and eosin. Magnified 30 diameters. A portion of the hypertropkied prostate surgically removed from a man aged fifty-five years. Numerous microscopic cysts are formed from the dilatation of the prostatic glandular acini. In some the epithelium is proliferating. Few or no ducts are seen. Smooth muscular fibers can he seen in the stroma. 159 EPITHELIOMA OF THE PROSTATE. Diagnosis of the Organ.— This is scarcely possible to make unless there are, in some part of the section, prostatic acini with sympexions and smooth muscle fibers in the stroma. Diagnosis of the Lesion.— The greater part of the drawing (lower part of the drawing. Fig. 70) has a very different appear- ance from that of the prostate gland. Everywhere are groups of dark staining epithehal cells arranged more or less regularly in strands that lose themselves in the depths of a dense con- nective tissue. Some of the groups vaguely recall the appear- ance of acini, but the architectural confusion is marked. In the intermediate zone, that part of the drawing between the more healthy part and the cancer, one can see the trans- formation of the glandular into the neoplasmic formation. At certain points the 'glandular epithelium proliferates and finishes by rupturing the basement membrane of the acinus and dis- seminating its cells in the stroma. Even in the part of the section described as more healthy, one can see at various points the neoplasmic transformation of the glandular acini. The muscular and connective tissue of the gland shows very distinctly between the tubules. Schematically the section can be divided into three portions or zones which correspond to three different stages in the devel- opment of the tumor. Zone A , where the gland is nearly healthy, some of its tubules beginning to proliferate; the beginning of the development of the tumor. Zone B, in which the cancer is developed. It assumes the form of a typical epithelioma, that is to say, the arrangement of the glandular elements in acini is preserved for the most part. Zone C, in which the tumor is infiltrating. Here it has become entirely atypical because of its degree of malignancy. It is impossible here to determine from what type of epithelium the tumor is derived. Resume. — An epithelioma developed from the prostate gland, comparable to what is observed in the breast— typical epithelioma in parts, atypical epithelioma elsewhere. 160 Normal glandular Zone of transition. Cancer acini. Cancer masses. Fig. 70. — Cancer of the prostate Staining with hematoxylon and eosin. Magnified 50 diameters. The tissue was operatively removed from a man aged seventy years. In the upper part A, the structure of the prostate is still recognizable. In the middle part B, the neoplasmic development is beginning. In the lower part C, the cancer is well developed and is recognized either as atypical acini with thickened epithelial linings or as atypical epithelial cell infiltration. 161 NORMAL OVARY. Ovary of a Cat. The section embraces almost the entire organ and is com- posed of a rather uniform tissue, paler at the center and darker about the borders. Each portion requires separate study. ■ 1. In the central zowe— the medullary portion— the matrix is composed of an abundant connective tissue, peculiarly rich in cells and, therefore, of an embryonal type— fibroblastic— through which pass, in serpentine fashion, numerous blood- vessels—some of which are cut transversely, some longitudinally. The veins among them can be recognized by their flattened condition, the arteries by their rounded sections. There are also a great number of capillaries. 2. The peripheral layer —cortical zone— includes an epithelial covering composed of cells resting upon a dense stroma in which appear numerous clear dots— enormous cells almost visible to the naked eye— the ovules characteristic of the ovary. The surface epithelium, or germinal epithelium, is composed of cells of cuboidal form and rests directly upon the subjacent stroma. At various points it grows down into the depths of the tissue in the form of peculiar invaginations, the cell cords of Valentine- Pflueger, which give origin to the primordial follicles. Each of these follicles is formed of a protoplasmic mass with a central nucleus and is limited externally by an intercellular layer. The primordial follicles are distributed in the zone immediately beneath the germinal epithelium. More deeply the Graafian follicles, or ovisacs, are developed from the primordial follicles. Each appears as a cavity filled with a finely granular substance — liquor folliculi; at the periphery there is a thick membrane — the zona pellucida; in the center, according to the thickness of the section, a very large nucleus, the germinal vesicle, provided with a very large nucleolus — the germinal spot. At the periphery of the ovisac there are cells more or less polygonal in shape, forming a thick investiture of concentric formation — the memhrana granulosa. The ripening of the ovules in the ovisacs, or Graafian follicles, takes place from the time of puberty to the menopause {ovo- genesis). At the time of each menstrual period an ovule, arrived at maturity, ruptures its protecting membrane, escapes from the follicle and is caught in the infundibuliform extremity of a Fallopian tube where it is either fertilized by a spermatozoon, or eliminated externally with the menstrual blood. That which remains of the ovisac after its rupture forms the corpus luteum. 162 Pfliiger's tubes. ■ Stroma. Ovisac. Mem- brana granulosa Ovisac cut ^ tangenti- ally. Artery. Fig. 71. — Normal ovary. Stained with hematoxylon and eosin. Ovary of an adult cat. A shows the entire organ magnified 3 diameters. B shows the fragment of the cortical substance within the square in A, magnified 100 diameters. It shows the details of cortical structure above and of medullary structure below. 163 FIBROUS CORPUS LUTEUM. Senile Ovary. The section is made perpendicularly to the long diameter of the ovary (A). Diagnosis of the Organ.— This is attended with some diffi- culty, but can be arrived at by observing the division of the structure into the central or medullary zone rich in vessels, continuous with the pedicle of the organ and the peripheral zone, or cortex. In the cortex there are few or no Graafian folHcles, but there are numerous larger structures visible even to the naked eye; the corpora lutea, with an undulating outline; specific forma- tions of the ovary which enable the organ to be recognized. If the section be examined under a higher magnification the germinal epithelium, which usually covers the surface of the ovary, will be found to have almost entirely disappeared. This atrophied epithelium no longer dips down into the stroma, and there is an entire absence of primordial follicles or ovisacs. The cortical substance below is no longer composed of fibro- blastic connective tissue. A little lower down the homogeneous masses of the corpora lutea are found. Each is formed of an undifferentiated material, a veritable cicatricial mass in the depths of which are some fine strands of connective tissue with nucleated cells. These are the corpora albicantes, resulting from the sclerosis and hyaline transformation of the corpora lutea of menstruation. In consequence of their retraction and atrophy these elements undergo characteristic transformations. Elsewhere (Fig. 72, C) a different type of the corpus luteum, younger, much more rare in senile ovaries, is formed of poly- hedral cells with pale granular protoplasm (lutein cells), with large nuclei arranged about the bloodvessels — an arrangement that recalls the structure of the glands of internal secretion, especially the adrenal. The cortical stroma is composed of spindle-shaped connective- tissue cells (fibroblasts) arranged in whorls. In the most vascular part of the organ (medullary substance) there are many bloodvessels in a state of hyaline degeneration. Resume.— The disappearance of the germinal epithelium, the ovules and the follicles and the presence of cicatricial corpora lutea and vessels with hyaline walls, in the absence of any signs of pathological change, lead to the conclusion that the diagnosis of senile ovary is justified. 164 Corpora fib SET Vascular pedicle Corpus luteum. Vestige of germinal epithe- lium. Arteriole with , /, hyaline ■wall. Corpus fibrosum. Fibro- blastic tissue. Lutein cells of recent corpus luteum. Fig. 72. — Ovary with corpora fibrosa. Stained with hematoxylon and eosin. Longitudinal section through the entire ovary of a woman, aged seventy years. A, entire section magnified 3 diameters. B, part of the cortex magnified 100 diameters, corresponding to the part included in the little square in A. It shows the structural details of a corpus luteum- corpus fibrosum. C, magnified 150 diameters, the details of structure of a fresh corpus luteum. 165 SCLEROCYSTIC OVARY. The section passes through the long axis of an ovary and consists of a swollen part and a pedicle. With the naked eye or with a hand lens a series of cavities can be seen arranged about the periphery of the organ. Diagnosis of the Organ. — Examination with a low-power lens shows the characteristic elements of the ovary. That is to say: 1. A connective tissue rich in fibroblasts which surrounds each of the cystic cavities and separates them one from another. 2. Here and there, in the thickness of this connective tissue, are primordial ovules or Graafian follicles with their large central germinal vesicles, the zona pellucida, colored rose with the eosin dye and their granular membrane. These are some- what rare and may be absent altogether. 3. The corpora lutea of oval shape. Some have undulating outlines and homogeneous structure and are old, hyaline and sclerotic. Others, more rare, are composed of large pale cells filled with fatty granules and are more recent corpora lutea. Under a higher-power magnification one notes the disappear- ance of the germinal epithelium which can only occasionally be found. The cysts, variable in size and number, contain a homogeneous mucilaginous substance that colors rose red with the eosin dye. It sometimes entirely, sometimes only partly, fills the space on account of retraction or fragmentation effected by the reagents or manipulations to which the specimen has been subjected. Fig. 73 (B) shows the details of the structure of the walls of the cysts, as well as the mode of their formation. Below and to the left there is an entire small cyst, arising through trans- formation of an ovisac with its granular center, and its wall formed of polyhedral cells in many layers, derived from the membrana granulosa of the ovisac. To the right, and above, is a portion of a larger cyst of which the wall is still formed by cells arranged in numerous layers. Below, and to the right, in consequence of further distention with fluid, the epithelial lining of a cyst is reduced to a single layer of flattened cells. Between these different cysts the stroma is represented by collaginous fibers with a small number of young connective- tissue cells and numerous capillary vessels of which the walls are composed of a single layer of endothelial cells. Resume.— Cystic transformation of the ovary, or sderocystic ovary, supposed to result from chronic inflammation. 166 Stratified epithe- lium. Stroma. Flattened cyst wall. Cystic ovisacs. Fig. 73. — Sclerocystic ovary. Stained with hematoxylon and eosin. Sclerocystic ovary of a woman aged seventy years. A. — Entire section, cut longitudinally and magnified 3 diameters. B. — Showing the structure and formation of the cysts, separated from one another by a richly vascular connective tissue. Magni- fied 80 diameters. 167 NOFtMAL UTERUS. A histological section of the body of the uterus, passing through the entire thickness of the organ, and including two distinct zones: the one. quite thick— the muscularis, or muscu- lar wall; the other much thinner, the mucous membrane, or endometrium. Diagnosis of the Organ. —Examined under a low-power lens (Fig. 71, A), the muscularis is seen to be composed of a very thick layer of smooth fibers— the greater part cut transversely, others longitudinally or obliquely. This gives the wall of the uterus its characteristically plexiform appearance. The mucosa, very thick, is formed by a simple epithelium, lining the whole interior as a narrow band composed of tall cylindrical cells with clear slightly acidophilic protoplasm. The nuclei stained deep blue, the long diameters corresponding to those of the cells, are somewhat close together at the basal portions. By the ordinary method of preparation it is diffi- cult to distinguish the vibratory cilia with which the epithelial cells are provided. At many points the epithelium dips down in the form of "glove fingers" and penetrates into the depth of the subjacent tissue. The cells lining these prolongations are of the same character as those of the primitive epithelial cells (Fig. 74, B). They are not active glandular cells with dense and finely gran- ular protoplasm, but simple invaginations of the mucosa — glanduliform invaginations. The mucous corium, which is very abundant, is formed almost entirely of young connective-tissue cells (fixed cells and leukocytes) which must not be taken as an indication of a pathological state. The nature of the epithelium, the glandibuliform depressions of the mucosa and the thick plexiform subjacent muscular layer, are sufficient to enable the diagnosis of the body of the uterus to be made (the neck is covered -mXh a stratified squamous epithelium in its vaginal part). Differential Diagnosis. — Sections of the alimentary canal— stomach, small intestine and colon — ought not be confused with what has just been described, for in them all besides the difference in the epithelium there is always a thick layer of connective tissue — the submucosa, which is missing here. 168 Epithe- lium. Mucosa. Muscle. B Columnar epithe- lium. Corium with interstitial cells. iv Glanduli- ^ — form de- pression. Fig. 74. — Normal uterine mucosa. A portion of normal uterus removed at surgical operation from a woman, forty years of age. A. — The entire thickness of the mucosa and part of the muscu- laris magnified 20 diameters. B. — The part included in the little square in A magnified 200 diameters, and showing the structural details of the glanduliform depressions. 169 FIBROMYOMA OF THE UTERUS. Diagnosis of the Organ. — In actual practice it is difficult to make the diagnosis of both the organ and the lesion if one is to do so from the examination of the sections alone. He should always have information from the clinic or autopsy to guide him. Nevertheless it is possible to arrive at a reasonable degree of accuracy without it. In the section there is a part in which it is possible to recognize the uterine mucosa elsewhere and much changed, and in which scarcely any of the glanduli- form invaginations exist. In the corium yolmg connective-tissue cells and leukocytes are to be found as usual. Immediately below the mucosa there is a narrow band of pale connective tissue. Diagnosis of the Lesion.— The greater part of the section, as shown in the drawing (Fig. 75, A), is formed by a lai;ge mass of dark staining elements arranged in whorls. Under a higher power lens these are found to be composed of elongated cells grouped in bundles cut transversely, obliquely and longitudinally. Their dense protoplasm is strongly colored with the eosin, and each shows in the center an elongated nucleus of a rod shape, not pointed at the extremities. These are unstriped muscle fibers such as are encountered in the thickness of the uterine wall. That which differentiates this muscular tissue from that of the normal uterine wall is the marked disposition to occur in whorls, with disarrangement of the fibers. In some areas, in the substance of the muscular mass, rose- red patches are formed by connective tissue rich in collagen, with fusiform nuclei a little shorter than the muscle nuclei— Hhrous fasciculi. Such an appearance corresponds with that of a benign tumor —a myoma or fibromyoma— according to the proportion of con- nective to muscular tissue present. With greater precision, the tumor is a submucous intraparietal myoma, easily enucleable. Resume.— A benign tumor— a Mfenwe^firomyomo- developed in the wall of the uterus and formed chiefly of unstriated mus- cular fibers. Such common muscular tumors of the uterus frequently xm- dergo a mahgnant degeneration and terminate in myosarcoma with frequent interstitial hemorrhage, monstrous nuclei, necrotic zones and metastases. 170 Pseudo- glandular crypts. Vessels. f V Sub- mucous cellular tissue. Fibro- myoma. Smooth muscle fibers cut longitu- dinally. Fig. 75. — Fibromyoma of the uterus. Stained with hematoxylon and eosin. Intramural fibromyoma of a uterus which showed in addition an enormous submucous sloughing fibromyoma. Removed at operation. A. — The uterine wall with the enucleable intramural fibromyoma, magnified 25 diameters. B.^yl portion of the tumor magnified 200 diameters. 171 CANCER OF THE BODY OF THE UTERUS. Diagnosis of the Organ. ^It is extremely difficult if not impossible to say what organ the section comes from. The diagnosis has to be presumptive. The greater part of the tissue, upon careful examination, proves to consist of a musculo-connective-tissue matrix, par- ticularly rich in smooth muscle fibers which makes us think of the uterus, the bladder or the prostate. The abundance and disorderly arrangement of the ppeudoglandular formation with which the tissue abounds, some of which are united while others are separate, gives the impression of a neoplasm— a tumor of the type of columnar glandular epithelium. Diagnosis of the Lesion.— The spaces, or epithelial cavities, are lined with tall cylindrical epithelial cells with abundant protoplasm, and nuclei also elongated and deeply stained. They are arranged parallel and in several layers, thus constitut- ing a stratified epithelium. Under a higher power magnifica- tion (Fig. 76, B) the cells, which line the spaces are found to retain their tiny filaments — vibratory cilia. In a nest full of epithelial cells the cylindrical form may be lost, the arrangement in parallel rows has disappeared and the cells, side by side, sometimes contain nuclei of monstrous size with abnormal karyokinetic figures. Finally, the substance of the protoplasm frequently contains little dark chromatin granules (pseudo- coccidia). In the centers of the glandular tubules small masses of amorphous substance with more or less nuclear debris (cellu- lar necrosis), sometimes less altered desquamated epithelial cells can be found. The stroma is formed of connective tissue and smooth muscu- lar fibers. The paler connective tissue is chiefly represented by fibroblasts with elongated protoplasm and fusiform nuclei and by some fixed connective-tissue cells. The smooth muscular fibers (more deeply stained with the red) have nuclei that are not pointed at the ends. There are some masses of round cells especially formed about the blood- vessels — small areas of inflammatory infiltration. Resume.— It is a neoplasm of the columnar epithelial glandu- lar type; a tumor because of the architectural confusion of the tissues and a malignant tumor because of the atypical character of the cells. This epithelial tumor, or epithelioma, is developed from the mucosa of the fundus of the uterus and penetrates the entire thickness of its wall. The lymphocytic infiltration is explained by the fact that the tumor was ulcerated. 172 Smooth muscle fibers Pseudo- glandular prolifera- tion. Stroma. Inflam- matory infiltra- tion. Cancer cell nests. Vessels j^^^t^^^^.M Neoplastic epithel al nests ^J^Viy-^ B Neo- plasmic acinus. Fig. 76. — Cylindrical epithelioma of the body of the uterus. Stained with hematoxylon and eosin. A.— Section of a fragment of the body of the uterus taken from a part of the muscular wall infiltrated with cancer nests. Magnified 20 diameters. B.—The same showing the pseudoglandular appearance of the tumor formed of cylindrical cells containing nuclear monstrosities. 173 CANCER OF THE NECK OF THE UTERUS. Epithelioma Spinocellulare. Diagnosis of the Organ. — An examination of the section under a low-power lens enables a presumptive diagnosis to be made. The left-hand part of the drawing shows a stratified squamous epithelium supported upon a musculo-connective tissue. The superficial layers are not cornified and the corium does not contain fat cells. It is then a Malpighian (squamous) mucous membrane. The arrangement of the smooth muscle fibers below the squamous epithelium makes one think of the neck of the uterus. This, however, refers to the vaginal portion only, for the neighboring portion of the isthmus is covered with a single layer of columnar epithelial cells. This opinion, however, should be confirmed by information from the clinic or the report of the autopsy. Diagnosis of the Lesion.— If the epithelium be followed from one side to the other (Fig. 77, A) it will be seen that the basal layers become less undulating and thicket! into a condi- tion of acanthosis. Further to the right the epithelial covering disappears— an ulceration. In the corium there are epithelial prolongations that deeply invade the musculo-connective tissue of the organ. It is, therefore, a tumor and a squamous-cell carcinoma of the vaginal portion of the neck of the uterus. The drawing B gives the histological details of the tumor. It is formed of cells more or less resembhng those of the squamous mucous membranes — epithelioma spinocellulare. In the center of the drawing there is a bloodvessel— an arteriole— whose tunica musculo-elastica is much thickened. About it in the perivascular space is some protoplasmic debris, some of which is multinucleated. This is the debris of cancer cells which have invaded the perivascular lymph spaces and might have been transported to other parts of the body. In the upper right-hand part of drawing B there is another lymph vessel stuffed full of cancer cells. Such invasion of the lymph vessels is common in epitheliomas in general. In the neck of the uterus it explains the peculiar tendency of the tumor to extend widely and early reach the cellular tissue at the base of the broad ligament, especially the periurethral parametrium. One should be particular to notice the presence of numerous monstrous nuclei and the frequent cellular divisions which evince the malignant nature of the tumor and the tendency of its tissues to proliferate and to degenerate. Resume. — Epithelioma spinocellulare of the vaginal portion of the neck of the uterus. 174 Stratified squamous epithelium. Cancer cells in a perivascu- lar lymph space. Arteriole, Degener- ated zone. Ulcerated epithe- lium. Dilated capillary. Epithelial columns. Cancerous lymphan- gitis. Mon- strous nuclei. Fig. 77. — Squamous cell carcinoma of tine neck of the uterus. Stained with hematoxylon and eosin. A. — Vaginal portion of the neck, magnified 25 diameters. B. — Cancer masses with nuclear monstrosities. 175 ULCERATIVE METRITIS OF THE NECK OF THE UTERUS. Diagnosis of the Organ.— This should be made by noting the simultaneous presence of a very thick mucosa covered by columnar cells and a muscularis separated froni one another by a corium of a pseudolymphoid appearance. These together with the unstriated and plexiform character of the muscularis, and the fact that the mucosa sends extensions consisting of young cellular connective tissue deeply into a corium, make the diagnosis of uterus with certainty. The somewhat disso- ciated appearance of the muscular fibers makes one think of the neck of the uterus. Diagnosis of the Lesion.— The section is drawn under a low- power magnification. Fig. 78, A, shows in the right-hand upper portion a thick mucosa, in the depths of which there are numer- ous glandular crypts. These are sometimes cut perpendicu- larly, sometimes parallel, and show as cavities with sinuous walls. At the left of the section the mucosa disappears; it is an ulceration. In the depths of the mucosa the glands are greatly dilated, forming cysts' with mucous or mucopurulent contents; these are called the cysts or follicles of Nabotk. They are formed through the inflammatory obliteration of the orifices of the glandular crypts and are extremely common in the uterus. But a diagnosis of metritis must not be made upon their presence alone. Under a higher magnification (Fig. 78, B) the details of the inflammatory lesion of the corium can be studied. The epithelium consists of tall cylindrical cells, covering the surface of the neck and descending deeply into the glandular depres- sion. The mucous corium is formed, in the normal state, of a stroma full of young connective-tissue cells of a pseudolymphoid appearance. This infiltration is strongly emphasized in the present case and at two points the cells are approximated so as to form definite inflammatory masses. Going hand in hand with this lymphatic hyperplasia there is an unusual number of capillaries. The unstriated muscle shows no pathological alteration. Resume.— The hypertrophy of the mucous membrane, its ulceration at certain points, the cysts, the infiltration and the deformity of the glands make the diagnosis of ulcerative metritis of the neck of the uterus. Hypertrophic subacute metritis with diffuse glandular and periglandular lesions of the mucosa. 176 Ulceration. Nabothian M follicle. ~\* Epithe- lium. Tubular glands. Gland. Corium. J — Muscle. B Glandular orifice. Ulceration. Capillary. — Corium. Gland. • m ^m^ •wffiy ) Fig. 78. — Ulcerative cervical metritis. Stained with hematoxylon and eosin. A. — Portion oj the section magnified lo diameters, showing the general topography of the structure and the ulceration of the mucosa. B. — A glanduliform depression with lesions of the ulcerated epithelium, of the corium, and the inflammatory infiltration, magni- fied iqo Wameters. ■' 12 177 ACUTE SALPINGITIS. Diagnosis of the Organ.— A circular section (Fig. 79, A) with irregular spaces in the center. Under a low-power lens the peripheral part of the section is found to be made up of inter- lacing smooth muscle fibers cut longitudinally and transversely. Here and there are dark spots. Inside of the muscular coat is a mucosa with its multiple tubules deformed and ramifying in so peculiar a manner as to give the impression of a veritable labyrinth— an appearance that is only to be encountered in the infundibuliform Fallopian tube with its multiple mucous folds. In this case the secondary and even the tertiary folds have lost some of their epithelial covering as the result of inflammation, and have become soldered together. It is thus that the peculiar diminished and divided appearance of the interior of the tube is brought about. Diagnosis of the Lesion (Fig. 79, B).— The muscularis, which is covered on the outside by a peritoneal endothelium which is imperfect, is composed of bundles of fibers indefinitely mixed together. The normal arrangement in two layers, one circular and one longitudinal, does not obtain here, or, at least, is not visible. In the entire thickness of the walls, but especially near to the external surface, there are numerous dilated vessels, and about them an inflammatory infiltration compbsed of round cells- leukocytes. These same cells are separately disseminated throughout the smooth muscle tissue of the wall. Further inside the mucosa is very much altered. The vibra- tory cilia have entirely disappeared. All that can be seen is that the epithelium on the mucosa occurs in a single layer and is frequently interrupted through desquamation. This appearance is particularly distinct in the spaces or pseudo- glandular cavities which result from the adhesion of the various folds. In the interior of these cavities degenerated poly- nucleated leukocytes are mixed with the desquamated epithe- lium, all bathed in a serous fluid which in case of obstruction can occasion the distention of the tube and the occurrence of the condition known as pyosalpinx. Resume.— Acute inflammation with preponderating lesions in the mucosa— acMte salpingitis. By special methods of staining it may be possible to demonstrate the presence of microorganisms, the most frequent and specific being the gonococcus; less specific the more common microorganisms of suppuration, the staphylococcus or the streptococcus. 178 1 ular wall. 1 nfiltration. Circular muscle fibers Connec tive tissue fibers Pseudo- glands containing pus. Pus. :^^^^^>?jt^#-S ■ £f_^ •<.? \ o:^ S^S."" -*v ^- H 4.^ ,_j?*^.i>-^ Inflam- matory infiltra- tion. Circular muscle fibers. Longi- tudinal muscle fibers. Pseudo- gland. Granula- tion tissue replacing the mucosa. Fig. 79. — Acute gonococcic salpingitis. 179 FIBROADENOMA OF THE BREAST. Diagnosis of the Organ.— At the right-hand part of Fig. 80, A, there is a connective tissue in which are a number of small duct-like structures, some of which are grouped as acini about little ducts (galactophorous ducts) which appear as small slits or crevices in the tissue, each lined with epitheUum. There are also occasional groups of fatty vacuoles. This arrangement of acini in groups about galactophorous ducts, in a stroma fibrous and fatty, is characteristic of the mammary gland. Differential Diagnosis.— One single other organ can be mis- taken for Ae mammary gland— that is the prostate. But in its stroma there is no fatty substance, but instead an admixture of smooth muscle fibers and in the acini there are nitrogenous concrements or sympexions. Moreover, under a high power it is easy to recognize, in well-fixed tissue, two rows of nuclei, as there are both glandular cells and myoepithelial cells. Diagnosis of the Lesion.— One cannot help being struck by the architectural confusion of the remaining half of the drawing (left-hand portion of Fig. 80, A). There are no acini; every- where there is a starred appearance, formed by attenuated ductules, the extremities of which are variously evaginated and exvaginated. The lumina are lined by an epithelium that appears to be partly desquamated on account of bad fixation. These structures are derived from the proliferated acini. A matrix of a special variety of connective tissue surrounds and separates the glandular formations. The most internal part of this tissue, with a pale tint, has undergone mucoid degenera- tion. The proliferation and development of this tissue, which has crowded out the acini and compressed their walls, explains in large measure the peculiar appearance of its epithelial struct- ures. At the periphery of the neoplastic nodule, and separating it from the mammary tissue proper, there is a delicate connec- tive-tissue wall that definitely circumscribes the neoplasm. It is to be noted that the mammary tissue proper does not have a normal appearance; the acini are small and compressed in a sclerosed matricial tissue. Resum6.— Tumor of the breast following the abnormal development and proliferation of the connective- tissue stroma; a benign tumor, or fibroadenoma: (i) Because of its distinct circumscription arid independence from the organ in which it develops; (2) because the basement menibrane is not broken through so that processes of the epithelium can escape into the stroma; (3) because the connective tissue is of adult type, with few cells. 180 Connec- tive tissue capsule of the tumor. Desqua- mated epithe- lium. Fig. 80. — Pericanalicular fibro-adenoma of the breast. Stained with hematoxylon and eosin. A benign emicleable tumor, movable beneath the skin, removed from the breast of a woman aged thirty years. A.—Showing the line of separation between the tumor and the breast, magnified 12 diameters. B.— 4 portion of the tumor, magnified 150 diameters. 181 CANCER OF THE BREAST. The drawing, which represents in its totality a section of a considerable extent of breast tissue, enables one to follow in a methodical fashion the mode of development of cancer of the breast. Toward the upper right-hand corner of the drawing (Fig. 8i, A) a few rare glandular acini are almost lostan the very dense fibrous tissue, but permit one to recognize 'the tissue of the breast, and from an organ affected with chronic mammi- tis (mastitis). In the lower right-hand portion of the section (Fig. 8r, A) there are numerous cystic formations of varying size — beginning intracanalicula,r epithelioma. Finally, at the lower left-hand corner (Fig. 8i, A)there is an extensive infiltra- tive mass of nests and processes, composed of cells that color deeply with the nuclear stains — atypical epithelioma. Let the different portions be studied in detail: 1. Fig. 8i, B, represents No. i of Fig. 8i, A, drawn under a higher power. The glandular acini are lost in a stroma of dense connective tissue formed chiefly of collagen fibers with only occasional nuclei and few if any fatty vesicles. The acini are dissociated, isolated or extinguished by the proliferation of the connective tissue (sclerosis). In the center there are longi- tudinal sections of two galactophorous ducts. The use of the higher power shows distinctly the characteristic structure of a glandibular epithelium: cells resting upon a peripheral basement membrane, a simple condensation of the connective- tissue stroma, but whose topographical interest from the point of view of tumor study is great. If the structure of the mammary acini is still recognizable their scarcity coincides with the density of the stroma resulting from a diffuse inflam- mation — chronic mammitis. 2. The following figure (Fig. 82, C) shows the details of No. 2 of Fig. 81, A. Here are larger or smaller cysts, sometimes even visible to the naked eye. The contours are very irregular and the wall formed of epithelial cells in numerous layers limited on the outside by the basement membrane. The cells are of the cuboidal, sometimes cylindrical, form and have nuclei of various size, rich in chromatin; some of them are monstrous and show mitotic figures. The mucosa that lines the cysts grows into the interior, forming numerous prolongations (invagi- nations). Sometimes these are provided with a connective- tissue axis that enables them to project into the cavity of the 182 Cancerous, infiltration No. 3. Zone of atypical epithe-i lioma.f '» Galacto- phorous duct. Sub- normal acinus. Fig. 81. — Epithelioma of the breast. Stained with hematoxylon and eosin. Cancer of the breast of a woman, aged forty-five years, removed at surgical operation. A. — The entire section magnified 5 diameters. B. — Zone of chronic fibrous mastitis, magnified 75 diameters. 183 cyst. These intracanilicular invaginations or processes can take on a considerable development. In the thickness of their walls there may be innumerable minute cysts— secondary intra- parietal cysts. The cavities contain a structureless mass of coagulated material, usually of a finely granular nature, in which there are apt to be numerous desquamated epithelial cells from the alveolar walls, in an advanced state of degenera- tion, with nuclei in a state of pycnosis. The presence of intracanalicular buds, the stratification of the epithelial bed and the numerous atypical cells make the aspect of the tumor very suspicious from the point of view of malignancy. It can be already affirmed that we have to do with an intracanalicular epithelioma or dendritic epithelioma. In order to confirm the diagnosis one studies with care the condition of the basement membrane, an important element not only from the diagnostic point of view, but also from the point of view of prognosis. Insomuch as the basement mem- brane appears to be intact, one has to do with a malignant tumor still limited, with little chance of lymphatic metastasis after ablation by the surgeon. Here, on the contrary, though the basement membrane appears to be intact, one already finds neoplasmic cells (cancerous emboli) outside of certain of the cysts in the interior of the vessels. 3. In Fig. 82, D (No. 5 of the drawing A), the cancerous infiltration is established. Only at rare points does one find cystic glandular formations; elsewhere there are httle masses or fine strands of cells, with an occasional large nest of cells distributed, throughout the stroma. Only occasional circular groupings distinctly recall the glandular arrangement of the neoplasm— atypical or infiltrating epithehoma. The stroma of the tumor is an adult connective tissue infiltrated with small round cells which indicate an infection added through ulceration of the tumor. Resume.— In this specimen all of the stages in the develop- ment of a glandular tumor can be followed from the precan- cerous stage (chronic mammitis) to the formation of an atypical epithelioma. It ought not be imagined that one easily finds, as in this case, all of these various stages in a single histological preparation of cancer of the breast. It is usually necessary and, therefore better, to prepare several fragments from the material removed at operation in order to make the diagnosis of the tumor. 184 Cancer exudate Vegeta- tion with connec- tive tissue axis. Cyst cavity. Epithelial wall. Epithelial . processes. Fig. 82. — Epithelioma of tine breast. Stained with hematoxylon and eosin. Same case as Fig. 8i, magnified 75 diameters. C. — Zone of intracanalicular epithelioma with cystic formations and vegetations {point No. 2, Fig. 81). D. — Zone of atypical infiltrating epithelioma {point No. 3, Fig. 81). 185 HEMIPLEGIA OF CEREBRAL ORIGIN. Descending Degeneration of the Pyramidal Tract. In order to be able to interpret the sections which follow and to appreciate their lesions it is indispensable to have at least an elementary idea of the technic employed in the study of the pathology of the nervous system. The tissues of the central nervous system are fixed in forma- line (io:ioo) and after hardening are cut into sections either frozen or after embedding in celloidin or paraffine. The staining of the sections is achieved through a variety of methods according to the particular information that it is desirable to gain. This may have reference to the nerve cells, the myelin sheaths, the neuroglia or the fibrovascular tissue. The cellular elements visible in sections stained with hema- toxylon and eosin are particularly well brought out by the method of Nissl (fixation in alcohol and staining in polychrome blue) which colors the protoplasmic granulations of the nerve cells blue. When it is desirable to demonstrate the myelin sheaths of the nerve fibers and bring out fresh or old degeneration of the fibers the methods of Weigert, Weigert-Pal or Na;geotte are appropriate. The myeUn sheaths which surround the axis- cylinders are colored blue by the method of Nageotte; intense black by the methods of Weigert and Weigert-Pal. The cells stain badly by these methods and appear brown upon a yellowish field. The tracts of nerve fibers stained intensely black, cut longi- tudinally or transversely in the sections and contrasting with the brown background are highly characteristic of sections of the central nervous system stained by the methods of Weigert or Weigert-Pal. But it only applies to healthy nerve fibers with intact myelin sheaths. The degenerated sheaths whose continuity has been interrupted (Wallerian degeneration) do not stain. The employment of the Weigert method, therefore, result in the demonstration of dark areas — healthy nerve tracts — and pale areas — degenerated nerve tracts. These methods are, therefore, only adapted to the study of the white matter which is composed entirely of nerve fibers and should not be employed when it is desired to determine the condition of the gray matter and nuclei. But care must be taken not to confuse cell aggre- gations, which stain palely, with fiber degeneration, and the beginner will do well to begin by assuring himself of the absence of 186 -o ^ g 1 ■ii S §s § 5S ClQ ^ -S -?i< . XI "S » ■d 8-^ ^ <> i « =j ^ I 189 The drawing (Fig. 84) is sharply limited on the right and left by two straight lines which correspond to cuts made by the knife in diminishing the extent of nervous tissue to be sectioned. The tissue shown in the drawing includes the middle cere- bellar peduncles which have been divided for the removal of the cerebellum. It thus forms an antero-posterior section of the annular protuberance, or pons, at its middle portion. The anterior rounded part corresponds to the foot, the posterior slightly flattened part to the floor of the fourth ventricle. In the foot are a number of thick fasciculi of fibers cut longi- tudinally, mixed up with little cells— the pontine nuclei. These fibers form a thick bundle on each side which are cut trans- versely: they are the ponto-cerebellar fibers and enter into the composition of the middle cerebellar peduncles and participate in the accessory motor paths. In the middle and a little behind these are two large transversely cut bundles of fibers — the pyramidal tracts, of which the left is degenerated. Behind these, in the posterior part of the pons, there are various structures: fibers and masses of gray matter more or less rich in cells (nuclei of the cranial nerves). The principal of the structures are as follows: the median ribbon of Feil on each side of the median line ; the posterior longitudinal fasci- culus; the acoustic stria and the arciform fibers in the white substances; the pontine olive also called the superior olive, a little mass of gray matter placed at the anterior part of the anterior portion of the pons. It only shows to the left of the median line; the section being a little oblique does not pass through it on the right side. In fine, the only lesion that is to be found in the section is the degeneration of the pyramidal tract of the left side following closely upon that seen in the last section. Fig. 85 represents a section of the medulla at its middle part where it passes through the olivary bodies, flattened layers of gray substance having an undulating arrangement and bend- ing so as to make a kind of horse-shoe, the opening in which is directed toward the median line, and a little posteriorly. These bodies, which attract immediate attention, facilitate the diag- nosis of the organ and approximately indicate the height at which the section was cut. Between the olives and extending backward almost to the floor of the fourth ventricle is a layer of transversely cut fibers, the inter-olivary layer or sensory tract (median tract of Reil) . A little to the outer side of the sensory tract are the fibers of the great hypoglossal nerve, the XII 190 o tfl .2 ■0 it u w 3 ■0 1 1 TJ « > s S^- ■j d) L 1 ig 3 ^^ 'q •0 +3 'y to _4^ CO w to --S 8 g 191 cranial nerve, which arises from a nucleus situated immediately below the floor of the bulb, near the middle line, to pass out a little in front and outside of the p)T:amidal tract, which makes a slight projection in front of the section on each side of the median hne. At the inferior angle of the section is a thick layer of trans- versely cut fibers: the restiform body, with, at its internal part, the vestibular nucleus of Deiters. Between the nucleus of Deiters and the hypoglossal nucleus there is an isolated bundle: the solitary fasciculus, a sensory root of mixed nerves, notably of the tenth pair, or pneumo- gastrics, of which the posterior nucleus, nucleus of the gray wing may be seen imder the floor of the fourth ventricle, imme- diately outside of the nucleus of the twelfth nerve, and the anterior nucleus, or ambiguous nucleus at the middle of the reticulated structure of the bulb. Some oblique fibers directed forward and outward can be distinguished between the two nuclei of the tenth nerve: they are the radicular fibers of the pneumogastric, which are on their way to emerge at some dis- tance outside of and behind the swelling of the olivary body. Finally, in front and above in the drawing are the two pyra- mids containing the pyramidal tracts. On the left the p3rramid is somewhat diminished in size, and is of a gray color; degen- eration of the pyramidal tract on the left side, following upon those described above. In the right pyramid there is a fine band of gray matter bounded anteriorly and internally by the pyramidal tract, which should not be mistaken for degenera- tion. It is a special gray formation: the arciform nucleus of the bulb, in which the cells can be seen with a higher lens. The three sections which follow are of the spinal cord and have as common characteristics an ovoid shape, central gray matter arranged in the form of a letter H, and surrounding white matter almost entirely made up of transversely cut fibers. As representation of spinal-cord structure, the cervical spinal cord (Fig. 86) will first be considered. The section is divided into symmetrical halves, in front by a broad and deep fissure, reaching downward to the transverse branch of the H, into which penetrate the meninges and the vessels, and behind by an incomplete fissure continued by a narrow septum of neuroglia. On each side of the cord the gray and white matter are clearly differentiated. The gray matter is expanded into large masses anteriorly, and contains large multipolar nerve cells easily visible under a low-power lens : the radicular cells. The posterior horn is slender and reaches to the periphery of the section where it 192 •a a a o "^ ■O ffl lU u ■S >> • JO Q, 4J H ca a '' - ^ fe g o ■4-3 w c8 ^ 1 o " d < S3 -4J s C ■d < "^ S "fc* o *-* ci jl i i lU S t3 1 II: .2 ^-s O S3 M •i o § fe « Is 11 •o 8 1 'q. r ^ ^ CO cS t5 ^ "is CM O K "^ '> a . ^^ .2 ■0 8 -S •^ *o t-i R\ *S ^•h S Righfhemiplegia. The s the degeneration of the d 13 193 is continued into the posterior nerve root; at the extremity of these horns are the zones of Lissauer. The two halves of gray matter are united by a transverse branch, the gray commissure, in the middle of which is the central canal, hned with the cuboidal cells of the ependyma. The peculiar shape of the anterior horn, the presence of a little lateral point at the base of each (lateral horn), together with the shape and large size of the section enable the cervical cord to be recognized. On each side of the anterior surface, at some distance outside of the deep anterior median fissure, there is a slight and indis- tinct depression : the anterior collateral fissure, through which the anterior radicular _,fibers — anterior nerve roots — ^pass out. The white matter is thus divided into three columns : anterior, lateral and posterior. ' " The posterior columns are composed entirely of posterior roots: the anterior and lateral are combined under the name antero-lateral columns, and include all the remainder of the cord. The posterior column is further divided into two por- tions, indistinctly separatedijin sections of normal tissue, the differentiation being based chiefly upon the study of its degen- eration: an internal fasciculus , the column of Goll and an exter- nal fasciculus, the column of Burdach. In the antero-lateral column, in addition to the association fibers that connect at different levels, there are the following: 1. On each side of the anterior median fissure, a narrow band corresponding to the direct pyramidal tract. 2. In the remainder of the antero-lateral column there are three important fascicuU, the crossed pyramidal tract, directly against the gray matter, the direct cerebellar tract, and a fasciculus of Gowers thrust out toward the periphery. The cord is surrounded by a layer of pia mater that contains vessels not only belonging to the membrane itself but also those that penetrate into the substance of the cord to form its fibro-vascular axes. Alongside of and external to the posterior horn of gray matter, on the right side, is a large decolorized zone that does not appear on the other side. It is a degenerative lesion which evidently involves the entire crossed pyramidal tract, hmited solely to the fibers of the crossed pyramidal tract and showing its topography. In the other half of the cord there is a narrow pale degenerated zone in front and along side of the anterior median fissure, representing the left direct pyramidal tract. 194 o D '•3 -d ■« 1 S ■d 195 This degeneration, crossed on the right and direct on the left, is in accord with what we have observed at higher altitudes : peduncles, pons and bulb. It enables one to demonstrate the decussation of the fibers of the pyramidal tract which takes place at the bulb, a few fibers remaining in the spinal cord on the homolateral side (direct pyramidal tract), but the greater part passing to the other side (crossed pyramidal tract). Fig. 87 shows a section of the dorsal cord, which can be recognized by its relatively small size, the narrow and attenu- ated anterior and posterior horns, and above all by the presence of an oval mass of gray matter: the column of Clark, character- istic of the dorsal cord, on the internal surface of the posterior horn, in the neighborhood of the gray commissure. The same degenerated tracts are found here as in the cervical cord; to the left in the anterior column, the direct pyramidal tract: on the right, in the lateral column, the crossed pyramidal tract, the shape and size of which are a little different from those seen in the other sections. Fig. 88 represents a section of the lumbar cord in its middle part. It is recognized by the swollen appearance of the ante- rior horns of the gray matter, rounded and a little projected externally; by the absence of the lateral horn, and the irregularly circular shape of the section There is no longer degeneration of the left anterior column because the direct pyramidal tract disappears at the inferior part of the dorsal cord. But the degeneration in the lateral bundle can still be distinctly seen on the right side in the crossed pjTamidal tract. Resume. — Descending degeneration of the motor nerves, affecting the pyramidal tract in its entire length, can be traced through different attitudes of the cerebrospinal axis. It is the only lesion observed in the sections. The case was one of softening in the motor area of Rolando in the left cerebral hemisphere with descending degeneration of the pyramidal fibers, which in the cord are found partly on the left side, but in greater part on the right side, because of the decussation of the greater part of the pyramidal tracts in the medulla. Thus is explained why lesions of the left hemisphere (region of Rolando) occasion motor symptoms (hemiplegia) of the right side of the body. Resume. — Hemiplegia following a lesion of the left hemisphere. 196 ^ •« S; t~, ^ « •»-i- s s r "2 o ■| ^1 o « ►^ 00 u " S 00 T3 S <£.1S a 1 :^-i U. +3 • ^S -*A >> J •'w' So ?^ 5 to ight hem shows de onger an ^t1 e s 197 TABES DORSALIS. Diagnosis of the Organ. — The cervical spinal cord can be easily recognized by its oval and laterally extended shape, the size of the anterior cornua, their quadrilateral form which depends upon the presence of the lateral horn, and by the depth of the anterior median fissure. Diagnosis of the Lesion.— That which at once strikes the observer is the small size of the posterior horns of the gray matter which are atrophied, though not degenerated in their entire extent. Areas of healthy dark-colored fibers separate the degenerated pale areas. The most degenerated portions on each side form a hand corresponding to the external part of the columns of Burdach. This little tract bifurcates at its postero-external part in the form of a fork whose two branches surroimd an almost normal zone, the external band of Pierret. The more interior part of the posterior column, or column of Goll, is a great deal less degenerated than the column of Bur- doch. The posterior nerve roots, cut transversely or longi- tudinally are completely degenerated. Their entrance into the cord, the zone of Lissauer, is equally affected and appears bleached. The external fasciculus being an ascending prolonga- tion of the posterior nerve roots, having penetrated lower down, the lesion passes through the posterior roots in their intramed- ullary as in their extramedullary course {posterior radiculitis). The zones that remain intact correspond to the territory of endogenous fibers, i. e., to those fibers that have their cells of origin in the gray substance of the spinal cord. These endo- genous zones consist at first of a kind of blackish arch situated immediately behind the gray commissure and extending along the posterior horns — the cornu-commissural zone. Between the branches of the fork of the external fasciculus the postero- external field is found: equally a territory of endogenous fibers. Thus the distribution of the endogenous zones, relatively simple at this level of the cervical cord, is limited to the cornu- commissural zone and the postero-external fields. The meninges in this case are slightly adherent to the sclerosed zones in the neighborhood of the posterior columns. Other methods of staining — hematoxylon and eosin — would show a slight infiltration of inflammatory cells in the meninges. Resume. — Tabes dorsalis: that is to say, of degeneration with sclerosis of the nerve roots and posterior columns. The disease is not very far advanced, as the degenerative process still respects the areas of the endogenous fibers. 198 ° S3 ^ s s ^il ^.3 ^ ^ ^ e^^ •(f* i 1 od of atax st, the zone ■ of Goll, cd •5» C "5 ■'3 e per Pier, lumn ^ ^^^-i d 8 S ta ■§ _« ■'^ §■§ 1 ■5 CO ■0 w 05 s eof t to the ■■grity is to ^7 cas tedi inte nes U-l II 6« 1 00 □1 d of a is limit The ural zo u. 1 1 pinal cor columns ve roots, -commiss >. al s rior ner rnu- ^ -d ID .V « ts ■i n of the cervi on of the post the posterior zones and c ts -^ .-^ Secti enerat nd to xterna tM tS ^ 199 DISSEMINATED SCLEROSlS. Diagnosis of the Organ. — The oval shape of the section, in which, in spite of the lesions, the gray medullary matter with its large triangular anterior horn and slender posterior horn, reaching to the periphery, can be seen, shows it to be a section of the spinal cord at the altitude of the cervical en- largement. Diagnosis of the Lesion. — One is struck by the extent and asymmetry of the decolorized zones which are irregularly distributed throughout the section. These pale patches, of which three are situated in the heart of the antero-lateral and posterior columns, are shaped like wedges forcing themselves into the periphery of the medullary mass. Under a higher magnification, these pale areas do not show any traces of myeline sheaths, but are entirely degenerated. The distribu- tion of the patches is devoid of system: the degenerated zones do not correspond with either tracts of nerve fibers (direct or crossed pyramidal) or even with the gray matter. The patch to the right, forexample, affects the entire antero- lateral column except its anterior angle and some few fibers of the direct pyramidal. It also equally affects the gray matter, but seems to spare the nerve cells which show with great dis- tinctness as brown upon the white background. It is impossible any longer to recognize the network of fibers surrounding the nerve cells in the anterior horn. Toward the inner side and in front the patch of sclerosis encroaches a little at the bottom of the anterior median fissure, upon the anterior column of the opposite side of the cord. There is no invasion of the poste- rior column except the part immediately contiguous to the gray commissure. It is an old lesion — neurogliar sclerosis — of which the details ought to be shown by elective stains. If the lesion were fresh sclerotic patches, when stained by the Marchi method with osmic acid, fatty vesicles enclosed in the interior of macro- phages (compound granular cells should show). Resume. — The presence of the patches of sclerosed degen- erated tissue, without system, occurring in both the white and gray matter, make the diagnosis of disseminated sclerosis. 200 ■a u y o _o J •S "3 ^ u4 °^ S , . CJ rt W ft 03 PL. M a •a o 4^ « s s « to so JU -1 ■8 •; v/*^ . tous stroma. . Fig. 98. — Parenchymatous goiter. (Goiter with small acini.) Stained with hematoxylon and eosin. Magnified 50 diameters. The tissue was removed at autopsy from the neck of an old woman. In the upper part of the drawing the goiter is character- ized by the presence of a large number of small acini mostly empty of colloid; in the lower part the acini are dissociated by edema and hyaline degeneration of the stroma. 217 THE NORMAL ADRENAL BODY. A histological section of the adrenal or suprarenal body made perpendicularly to the transverse axis, and presenting to the naked eye the characteristic elongated appearance, and under slight magnification two concentric layers of different staining intensity. These two layers correspond to the cortex and medulla of the adrenal body. The following details of histo- logical structure make the diagnosis clear. A. The Cortical Zone. — This is composed of three layers, recognizable under a low power, which passing from the surface to the center are: 1. The Zona Glomerulosa. — This is the most superficial layer, and lies immediately beneath the connective-tissue capsule. It is composed of cellular masses, scarcely acini, composed of cells with dark protoplasm and darker nuclei. This zone, easily enough recognizable in man, forms a dark line at the periphery of the section. Its cells are of an undifferentiated type, that is to say, their protoplasm is homogeneous and scarcely tinted by the eosin. 2. The Zona Fasciculata, which forms the greater part of the Fig. 99, B, is formed of parallel columns of cells between which the capillary vessels, easily recognized by the presence of red blood corpuscles, are in intimate contact with the ceUs. This layer is composed essentially to spongiocytes, or cells in the clear protoplasm of which is an extremely fine meshwork. This appearance is caused by the fact that the cells are filled with fat (neutral fat or lipoid) dissolved out by the usual histological reagents, with the resulting pale and reticulated appearance. At the bottom of the drawing there are some cells of undiffer- entiated type with dark granular protoplasm. 3. The Zona Reticularis. — Here the spongiocytes completely disappear and the cells have an undifferentiated appearance, and granular protoplasm; they form an extensive network, in the meshes of which are numerous capillaries. Here and there are a few cells containing granular pigment. The zona reticu- laris is a particularly vascular layer. The three layers of cells represent different stages in the development of the same cell, whence the variability in the thickness of the layers in different parts of the section, accord- ing as the gland is in a state of activity or repose. 218 Cortex. Central vein. ••tiif. *^&f <* Medulla. Reticu- lated layer. Fascicular layer. Glomeru- lar layer. Capsule, m'^-^^^^''^ B Capsule. Glomeru- lar layer. Fascicular layer with spongio- cytes. Undiffer, fe entiated cells. Capillary. Fig. 99.— Normal adrenal body. Stained with hematoxylon and eosin. A. — Transverse section of the entire adrenal gland magnified 15 diameters. The medullary substance occupies the center, the corti- cal substance being seen above and below. B. — Glomerular and fasciculate layers seen under a magnifica- tion of 200 diameters. Above is the capsule of the organ; below the drawing continues with Fig. 100, C. 219 B. The Medullary Zone. — This, forming the central part of the organ, differs from the preceding in its appearance and by staining a deep blue-violet color in sections stained with hema- toxylon and eosin. It consists of an extensive epithelial net- work in which the elements are separated by capillary blood- vessels. It is broader than the zona reticularis with which it is continuous without distinct separations. The cells have a dark granular protoplasm that takes the hematoxylon strongly: chromaffine cells — so-called because they are distinctly browned by salts of chromic add. The center of the medulla contains numerous vessels, of which the central veins are large and have thick walls. Lastly it must be pointed out that the medullary substance contains rare and disseminated lymphoid collections. The stroma of the gland is formed of fine collagenous fibrillae and of young connective-tissue cells, the former rare except at the periphery of the organ where they are condensed to form its capsule. Here and there at the periphery of the section, but at points not shown in the drawing, are small cellular masses composed of spongiocytes or undifferentiated cells well isolated from the remainder of the gland by surrounding connective tissue. Such epithelial islands occur in the greater number of adrenal glands, and when the number is not excessive have no patho- logical signification. In the periglandular connective tissue it is always possible to find small groups of cells deeply stained with hematoxylon, and of the nervous type. These are ganghonic nerve cells belonging to the sympathetic nervous system. Resume. — The histological appearance of the suprarenal gland with its differentiated cell layers and the absence of any ducts is characteristic and easy to differentiate from other blood vascular glands. 220 Capillary. Pigmented cells. Fig. 100. — Normal adrenal gland. Stained with hematoxylon and eosin. Magnified 200 diameters. C. — The zona reticularis below the zona fasciculata shown in the preceding drawing, with its cells in irregular anastomosing columns. Some of the cells have a finely granular -protoplasm, others contain pigmentary granules. D. — The medullary substance. It consists of columns of large cells whose protoplasm contains granules of adrenalin. These granules turn brown upon the application of salts of chromium and are therefore called chromuffine cells. 221 HYPERPLASTIC ADRENAL. Diagnosis of the Organ. — The section passes through all three layers of the adrenal. Above, beneath the connective- tissue capsule, the glomerular layer is scarcely visible; in the center is the zona fasciculata, below this is the zona radicu- laris, with its undifferentiated cells, and at the bottom is the medullary portion. Diagnosis of the Lesion. — One is at once struck by the great thickness of the cortex, which is almost entirely formed of the spongiocytes. Under a higher power lens it is possible to recognize the vacuolar or reticular character of the cells as in the normal adrenal, but the nuclei are larger and sometimes in a state of division. Toward the right hand in the drawing, the arrangement of the fasciculi has the nprmal appearance; the cells are arranged in long parallel columns in a radiating manner. To the left, the cellular tubes have lost all regularity of direction, some- times paralleling the surface of the organ, and tending to arrange themselves in a concentric fashion (adenomatous hyperplasia). The zona reticularis, at the right inferior portion of the draw- ing, is formed of undifferentiated cells in short columns. Finally here and there one sees some pigment cells. On the exterior of the capsule, at points not shown here, are some large oval masses formed of spongiocytes. The medulla, which is partly shown in the lower part of the drawing, does not show anything abnormal. The connective-tissue stroma appears to be a httle better developed than normal. One can see very distinctly the thin connective-tissue separations between the columns of cells. So far as the capillaries are concerned, especially in the fas- ciculus, they are scarcely visible, being compressed between the hypertrophied columns of cells. Resume. — The usual histological picture is modified by the great thickness of the cortex, especially in the zona fasciculata in which the spongiocytes are greatly augmented in number and in size. This appearance betrays a condition of hyper- plasia and corresponds anatomically with general enlargement of the gland, which instead of weighing 4 to 6 grams may reach 10 grams. From the point of view of physiology it signifies excessive function. It is found in cases of Bright's disease and arteriosclerosis. 222 Zona reticu- laris. Fig. 101. — Hyperplastic adrenal gland. Stained with hematoxylon and eosin. Magnified i oo diameters. The cortical area is greatly thickened, especially in the zona jasciculata, which is almost entirely composed of spongiocytes. Toward the right of the figure the columns of cells are regularly arranged and parallel; toward the left they are confused, and show the beginning of an adenomatous transformation. 223 HYPOPLASTIC ADRENAL BODY. Diagnosis of the Organ. — The adrenal body is easily recog- nized through its division into two layers, the cortex and the medulla, the former with its three portions. Diagnosis of the Lesion. — One is immediately struck by the diminished thickness of the cortical portion. Comparing this drawing with the preceding, it is found that the thickness of the cortex is diminished by about one-half. 1. The glomerular layer: This is scarcely visible, but one should not draw conclusions from this alone. 2. The fascicular layer: This shows the cells well arranged in long columns, but they have almost lost their spongiocytic aspect; scarcely a trace of the vacuoles being seen in their protoplasm. The cells are small, retracted and shrunken. In some of them the nuclei show no chromatic structural details and have become pycnotic. At occasional points, as in the central and upper parts of the drawing, there are oval areas with ill-defined limits, which form pale patches. These have an adenomatous aspect, and are composed of less differentiated cells than those we have been describing, but without vacuolar structure as in the normal spongiocytes. In addition to the cellular alterations a slight sclerosis dissoci- ates the cell columns; some fine connective-tissue bands isolate the cells from one another. 3. The reticular layer: This also contains retracted cells poor in pigment, but whose lesional appearance is less distinct than in the fascicular layer. In regard to the lesions of the medulla, they are of slight importance. Resume. — The histological picture is the reverse of that shown in the last specimen. It is hypoplasia of the adrenal generalized throughout the entire gland, and characterized by the absence of the spongiocytes and the return of the cells to the imdifferentiated condition, and by the slight sclerosis that dissociates the cellular elements. This hypoplasia corresponds anatomically to a diminution in the size of the gland, which may not weigh more than 2 or 3 grams, and physiologically to a condition of hypofunctionation. It is seen in infectious diseases and in the cachexias of cancer and tuberculosis. 224 Vessels. Medul-f lary cells. \ f Connec- tive tissue capsule. Medulla Vessels. Fig. 102. — Hypoplastic adrenal gland. Stained with hematoxylon and eosin. Magnified 500 diameters. The connective-tissue capsule of the gland is thickened, and fine strands descend from it between the cellular elements which they separate {sclerosis). The cells of the zona fasciculata have lost the spongiocytic appearance, and are smaller and darker in appear- ance: undiferentiated cells. 15 225 NORMAL HYPOPHYSIS CEREBRI. A microscopic section passing through the hypophysis close to the center of the organ, in an antero-posterior direction and having a very peculiar and characteristic appearance. When examined under a low-power lens (Fig. 103, A), the section divides itself into two distinctly limited portions: one, the larger, is red-violet and rounded, and forms nearly the whole of the section; the other pale rose-red, scarcely colored, ovoid and very small. One of the poles of this latter is partly included in a recess in one edge of the former. Such a histological appearance is truly unique and at once permits the assumption, even without microscopical examina- tion, that we have to do with a section of the hj^ophysis. The hypophysis is then composed of two lobes, the one a great deal larger than the other and stained blue-violet, the glandular or anterior lobe; the other much smaller, and stained rose-red, the posterior or nervous lobe. These lobes form in a certain fashion two kinds of glands pressed together, of which the origin and function are different. Between them is a connecting portion, the intermediate lobe. Under a higher power the histological detaUs of the different portions can be studied. I. The Glandular Lobe (Fig. 103, B). — This is formed of a series of cellular elements grouped in different ways. Some- times the cells form little masses separated from one another by the connective tissue and vessels of the gland; sometimes and more rarely, the arrangement takes the form of acini and recalls more clearly a glandular structure (Fig. 103, C). The columns or masses include two types of glandular cells; some have a clear protoplasm scarcely stained, so that it is only the nucleus that indicates the presence of the cell — chromophobic cells — others have protoplasm that stains with avidity and is finely granular — chromophilic cells. Among the latter the greater number stain violet (hema- toxylon), and are called basophilic; the others, less numerous, take the eosin and are called eosinophihc. It is probable that these different staining reactions of the granules of the proto- plasm express different functional conditions of the cells. It is, however, important to remember that in the normal hypoph- ysis the chromophobic and chromophylic cells occur in about equal numbers and that the basophiles are less numerous than the eosinophiles. 226 'TS-Jfc 3P^ Inter- mediate _j lobule. 1 Glandular lobule. Nervous lobule. Colloid acini. Capillary. Chromo- philic Capillary. Chromo- philic cells. Chromo- philic " cells.l Capillary. Fig. 103. — Normal hypophysis. A. — Vertical section of the entire organ showing its three lobes magnified 5 diameters. B. — Section of the glandular lobe showing the different types of cells, magnified 250 diameters. C. — Another section of the glandular lobe showing two acini filled with colloid. 227 In the acinous formations (Fig. 103, C) the cells, chiefly chromophylic, line small cavities in which a colloid substance exactly comparable to that of the thyroid body is found. Such acinous formations are not common, however, in the normal hypophysis. Between the different cellular components is a fine connective tissue in slender fasciculi, forming the stroma of the gland. Numerous capillary vessels are in intimate contact with the cells. One sees in this the chief characteristic of the glands of internal secretion, which together with the absence of ducts, easily enables the diagnosis to be made. II. The Nervous Lobe. — This presents an individual structure that in no way resembles a parenchymatous gland. It is formed (Fig. 104, D) of fine collagenous fibers and a great number of neuroglia fibrillae, impossible to differentiate by the ordinary methods of staining, but made very distinct by the special and specific method of Lhermite. In the depths of this fibrillar stroma are numerous nuclei, and finally, here and there some masses of pigmented cells the origin and nature of which are badly known. III. The Intermediate Lobe. — This includes a series of cystic formations of very varied number. They are acini lined by cubical cells filled with a colloid material, sometimes retracted and fissured, sometimes colored rose-red by the eosin, sometimes bluish by the hematoxylon, and whose morphological appear- ances recall the vesicles of the thyroid body. Between the cysts are cells of the glandular type of the anterior lobe. Resume. — The structure of the hypophysis is sufficiently characteristic for its tissue to be easily recognized in a micro- scopic section. That which is most diflScult is to appreciate its normal or abnormal condition. A large number of chromophile as opposed to the chromo- phobe cells, frequent acinous formation and a quantity of the colloid substance, added to the increase in the size of the organ, suggest a gland in a state of hypersecretion: glandular hyper- plasia. Opposed characters indicate the opposed condition: glandular hypoplasia. 228 Pigment- ary cells. Capillary. Fig. 104. — Normal hypophysis. D. — The nervous lobe, magnified 200 diameters, showing its fibers of collagen and neuroglia and nervous cells. E. — The intermediate lobe, magnified 100 diameters, with its colloid cysts and glandular cells. Below a fragment of the nervous lobe. 229 SCLEROSIS OF THE THYMUS. Diagnosis of the Organ. — Examination of the section with a low power lens shows a dense tissue divided into lobxiles by broad bands of connective tissue that support the bloodvessels (Fig. los, A). With a medium power magnification (Fig. 105, B), the lobules are found to resemble the lymphoid organs, the spleen, the tonsils and the lymph nodes, being composed of a reticulum in the meshes of which are an infinite number of lymphocytes. At certain points the reticulum can be seen to be composed of fibrillary prolongations anastomosing among themselves. The lymphocytes are small cells in which it is often impossible to distinguish more than a nucleus surrounded by a thin coronet of scarcely visible protoplasm. There are, however, occasional mononuclear cells with abundant pale red protoplasm. But that which enables the organ to be immediately recog- nized is the presence of numerous small pale masses composed of flattened cells arranged one upon another like the skins of an onion, vaguely recalling the pearly bodies of the squamous- cell carcinoma, known as the corpuscles of Hassal, and charac- teristic of the thymus. Diagnosis of the Lesion. — The thymus under examination differs from the normal by the presence of broad and dense connective-tissue trabeculae that send fine divisions into the interior of the lobes. Resume. — It is a chronic inflammation of the thymus or a chronic sclerotic ihymitis, characterized by: 1. Excess of the connective tissue. 2. Architectural transformation which no longer permits the differentiation of the lymphoid elements into cortical and medullary zones. 230 A Sclerosed tissue ~y I phatic tissue. S¥ Vessels. B Sclerosed corpuscle of Hassal. Vessels. Corpus- cles of Hassal. Capillar- ies. Fig. 105. — Sclerosed thymus gland. Stained with hematoxylon and eosin. Portion of a large, firm, sclerosed thymus gland taken at autopsy from an infant. A. — Entire section magnified 5 diameters. B. — A portion of the same, magnified 150 diameters, showing the corpuscles of Hassal and the sclerotic bands. 231 NORMAL FIBROBLASTIC CONNECTIVE TISSUE. In this section we will consider the different stages in the development of normal and pathological connective tissue. Drawing A represents an embryonal connective tissue, essen- tially composed of cells, the fibroblasts, distinctly visible but not distinctly differentiated. They have abundant protoplasm and pale nuclei relatively rich in chromatin, which at certain points may show a tendency to lobulation which is assumed to be an indication of activity. Between these cells, arranged in parallel fashion, are opaque, undulating, striated bands of variable size, composed of delicate fibrillse of collagen. At the left-hand lower corner of the drawing is shown a mononuclear cell, derived either from the blood, or from the fibroblasts through metaplasia, Such a purely fibroblastic appearance is typical of the embry- onal connective tissues, in which there is relatively little collagen. Similar poverty of collagen fibers is also observed in certain mahgnant tumors of connective-tissue origin, the fibrosarcoma or spindle-cell sarcomas. In them, however, are atypical cellular and nuclear formations not found in the normal embry- onal connective tissue. Drawing B shows a more highly developed connective tissue. The fibroblastic cells have become flattened, are without envel- opes, and mold themselves to the spaces between the collagen fibers. The nuclei are a great deal darker, the mass of chroma- tin being condensed. The thickness of the collagen fibers has greatly augmented. The origin of the coUagen fibers is disputed. It is, however, admitted that the fundamental amorphous substance that will later give origin to the collagen is a part of the primitive con- nective-tissue cell, which, through differentiation may give origin to either collagen or elastic fibers. In Drawing C the development of the connective tissue has reached an adult stage. The nuclei and bodies of the fibro- blastic cells are reduced to a sinuous line of chromatin. The collagen fibers have become much larger and more prominent, and show marked undulation. The fibroblasts seem to have been smothered by the coUagen. 232 Mononu- clear cell. Collogen fiber. Nucleus o£ fibro- blast. Collogen fiber. Interstice -|-^ Fibro- blast. Nucleus of a fibro- blast greatly flattened. Nucleus. Collagen fiber. Fig. 106. — Normal fibroblastic tissue. Stained with hematoxylon and eosin. Magnified 1500 diameters. A. — Connective tissue from an embryo, showing numerous cells and few collagen fibers. B. — Embryonal connective tissue in a stage of further develop- ment, showing equality in the proportion of cells and fibers. C. — Adult connective tissue. It contains only rare nuclei smothered in the collagenous proliferation. 233 FIBROSARCOMA. Spindle-cell Sarcoma. Dense tissue, in which the cells are arranged in whorls about the vasculo-connective-tissue axes and occasional red-colored patches betray the presence of small hemorrhages. This is all that can be learned, under a low power, from the topographical study of a histological section taken from a fibrosarcoma. The appearance xmder a higher power lens is shown in Fig. 107. In the center of the drawing is a section of a capillary whose walls are partly formed of elongated cells with fusiform nuclei. But these cannot be found on the right-hand side of the right-hand limb of the capillary, where the cells of the tumor seem to form the actual wall of the vessel. The capillary contains a few white mononuclear and polymorphonuclear leukocytes. The greater portion of the section is composed of cells with elongated bodies pointed at the ends — young fibroblasts of the connective tissue — arranged side by side to form parallel fasciculi of cells cut transversely which gives them a rounded appearance with central or peripheral nuclei. The vegetating nuclei, sometimes constricted at the center, like an hour-glass, and the arrangement of the chromatin in equatorial plates, denote a great reproductive activity. A tissue presenting a uniform structure of this kind is in all probability a tumor of the connective tissue. But the diagnosis should always be confirmed by information received from the clinic or autopsy. Resume. — A tumor of the connective tissue composed of fibro- blasts: a fibrosarcoma or spindle-cell sarcoma. It is regarded as a sarcoma, that is to say, a malignant tumor, rather than as a fibroma, which is a benign tumor of the connective tissue : I. Because it is extremely rich in atypical cells with mon- strous nuclei and karyokinetic figures which indicate its tendency to malignant development. II. Because it contains numerous newly formed vessels whose walls appear to be cut into the substance of the tumor. 234 Fibro- blasts cut longitu- dinally Capillary with poly- morpho- nuclear cells. Mons- trous nuclei. Fig. 107. — Fibrosarcoma. Stained with hematoxylon and eosin. Magnified 225 diameters. A fibrosarcoma of the nose, not yet having given rise to metastasis at the time it was removed at operation. Note the imperfect char- acter of the central capillary and the numerous cellular mon- strosities. The histological structure of the fibrosarcoma explains its anatomical characteristics; its softness, its vascularity, and its tendency to hemorrhage. Certain inflammatory processes may aford histological pictures very similar to this, but the uniformity of the structure seen here ought to make us incline toward the diagnosis of tum.or in the absence of clinical information. 235 ROUND-CELL SARCOMA. Sarcoma globo-cellulare. The tumor is formed almost entirely of cells of variable size and shape, whose general contour is polygonal or circular, whose protoplasm is abundant and without prolongations, whose nuclei are rich in chromatin, and which contain large nucleoli. Sometimes the nuclei are small, sometimes very large, actively multiplying and showing atypical mitotic figures or they may even be multiple — giant cells. The stroma consists of occasional fibrillae and abundant vessels, with thin walls composed only of endothelium, and often formed by the cells of the neoplasm itself. Such a histological picture does not correspond to that of any known organ and one is brought to the diagnosis of tumor, which it is always well to confirm by information from the clinic or autopsy. It is a tumor of the connective-tissue type in which the occurrence of cell monstros- ities betrays the malignant character. It is then a malignant tumor of the connective tissue, that is, a sarcoma. Inasmuch as the cells are roimd, a round-cell sarcoma, or sarcoma globo-cellulare, or, if the form of the cells is very variable, a polymorphous sarcoma. Differential Diagnosis. — Round-cell sarcoma must be dis- tinguished from: (a) Lymphadenoma, or lymphocytoma, which is recognized by the presence of a fine reticulum in the meshes of which atypical lymphocytes are contained. (b) Atypical epithelioma, which can frequently impose itself upon us as a sarcoma. The differential diagnosis is based upon the fact that the connective tissue and the neoplasmic cells are quite independent of one another in the epithelial tumors, and vessels present a normal wall quite independent of the tissue of the tumor. (c) Inflammatory pseudo-tumors, "proud flesh," "granula- tion tissue," which present cells of very polymorphous char- acter, and in which it is usually possible to find the specific lesion — miliary tubercle, syphilitic plasmoma, etc. Resume. — It is a malignant tumor, round or polymorphous- cell sarcoma, developed in the subcutaneous tissue. 236 Capillary bounded by tvimor cells. Fig. 108. — Round-cell sarcoma. Stained with hematoxylon and eosin. Magnified 50 diameters. A sarcoma with extremely polymorphous cells developed in the cellular tissue of the thigh, and removed by surgical operation. It is a tumor in which the atypical nature oj the cells and numerous nuclei showing mitotic change testify to extreme malignancy. 237 LYMPHADENOMA. Lymphocytoma. At the center of the drawing, Fig. 109, there is a triangular section of a capillary vessel. From each of its angles, con- nective-tissue prolongations extend and circumscribe areas in which are cells and a reticulum. 1. The cells, pressed one against the other, are lymphocytes, the greater number of which are about the normal size, though some are large, with a greater amount of protoplasm, and nuclei sometimes of monstrous size, bUobed and showing abnormal karyokinetic figures. 2. The reticulum is often difficult to see, and is formed of connective-tissue fibrillEe, that stain a rose color and form an immense network that seems to be in contact with the cells either by continuity or contiguity. Such a histological picture — and, of course, it is understood that the rest of the section has the same general appearance — enables one to recognize the lymphoid tissue, and after eliminat- ing the normal lymphoid organs, to arrive at the diagnosis of a lymphoid tumor. Differential Diagnosis. — The following are to be excluded: (o) The Spleen. — This organ is easily recognized by the presence of the Malpighian corpuscles, little collections of lymphoid tissue in the center of which there is usually a vessel, and by its fibromuscular trabeculae. (J) The Lymph Node. — These are composed, especially at the periphery, of a pale tissue (sinus lymphaticus) and a dark central or medullary substance with lymph follicles having germinative centers. Lymph nodes subject to chronic inflam- mation are often difficult to differentiate because of the dis- turbance of the normal architecture. One then has to look with care for such signs of inflammation as sclerosis, poly- morphonuclear leukocytes, or for caseous centers with giant cells. (c) The Thymus, which is easily recognized through the presence of the corpuscles of Hassal, formations roughly looking like the bulb of an onion. Resume. — It is a tumor of a lymphoid structure — lymphocy- toma, or lymphadenoma — a tissue not occurring in the normal organism. It is further an atjrpical tumor, in which nuclear monstrosities betray malignant character — malignant lymphocytoma. 238 Normal lympho- cyte. Capillary. Reticulum Fig. 109. — Lymphocytoma. Stained with hematoxylon and eosin. Magnified 225 diameters. This tumor was about the size of an egg, and grew in the subcu- taneous cellular tissue of the scapular region. It was surgically removed. The reticulum containing lymphocytes in its meshes is to be carefully noted. This network is of extreme importance in the diferential diagnosis of the tumor. The presence of cell monstrosities, though not numerous, betrays malignant tendency of the tumor. 239 OSTEOSARCOMA. Osteogenetic Sarcoma. The section, examined under a low-power lens, shows a number of long columns stained a rose-red color with the eosin (osseous trabeculas), between which are pale blue carti- laginous masses and connective tissue composed of elongated cells. 1. The Osseous Trabecules. — These are recognized by their undifferentiated and structureless substance (ossein), in which the cells or osteoplasts, of which no more than the nuclei can be distinguished, lie in spaces. Most of the trabeculas are surrounded by a border of large cells — osteoblasts. These osseous formations do not have a medullary cavity containing red blood corpuscles and hemopoietic cells, or concentric arrangements forming lamellae about a Haver- sian canal like the normal bone. They consist rather of tissue in process of ossification than of fully formed bony tissue. 2. The Cartilaginous Masses. — These are composed of homo- geneous structureless pale masses of chondrin, in which are cartilage cells with pale nuclei, two or three in a space. 3. The Fibroblastic Tissue. — This is seen in the left-hand upper part of the drawing and consists of fusiform cells resem- bling those of the fibrosarcoma. Examination under the higher power will show cellular monstrosities. Study of the remainder of the section which is found to show the same structure everywhere supplemented by informa- tion from the clinic or autopsy brings us to the conclusion that we have to do with a tumor of the connective tissues or fibro- sarcoma. But it is a fibrosarcoma of a special structure, inasmuch as it contains bone and cartilage. The young connective tissue has manifested a peculiar property called metaplasia, by which, in the embryonal state, it transforms itself into other tissues — bone and cartilage. Resume. — It is a fibrosarcoma giving origin to bone and cartilage : ossifying or osteogenetic sarcoma, observed exclusively in connection with bones. 240 Fibro sarcoma tous tissue ,]^^ ' d¥>y u ^.^^ , f ., J Fig. 110. — Osteosarcoma. Stained with hematoxylon and eosin. Magnified 50 diameters. Osteosarcoma of the extremity of the femur of a young girl aged fourteen years. Amputation at the hip-joint; no return. It is an osteogenetic sarcoma showing in the middle of sarcomatous tissue fine osseous trabecula and numerous masses of cartilage which indicate the osteogenic property. 16 241 EPULIS. Giant-cell Sarcoma. Examining under a low-power lens from above downward, one sees the following: A dark line of stratified epithelium which corresponds to the external surface of the structure: a dense mass in which are a large number of large cells, multi- nucleated cells, the myeloplaxes a deep part containing long, rose-red homogeneous osseous trabeculse. 1. The Superficial Epithelium. — This is of the squamous type: a deep basal germinal layer formed of parallel cells, arranged upon a basement membrane, and supporting polyhedral cells with the intercellular filaments of Ranvier, and surface cells filled with granules of eleidin, but nowhere showing a horny formation. This type of epithelium is found in the mouth, esophagus, vulva, glans penis, anus, etc. Beneath the epithelium there is a loose layer of connective tissue, the corium, which contains the vessels. 2. The Dense Tissue Below the Corium. — This is formed of fusiform cells compactly placed one upon another, fibroblasts, analogous to those of fibrosarcoma, but without monstrosities, and without abnormal mitotic figures. Here and there are large giant cells, or myeloplaxes — large cells with somewhat baso- philic protoplasm, and nuclei in varying numbers, grouped in masses in the center or at the periphery. The myeloplaxes must not be confused with the giant cells of tuberculosis, whose protoplasm is distinctly acidophihc, and whose nuclei form a peripheral coronet like a horseshoe. 3. The Osseous Trabecule. — These are formed of lamellae of rose-red structureless material: ossein containing osteoplasts. Bordering these trabeculae are the osteoblasts which form the bone. The absence of organization in the osseous trabeculae (concehtric arrangement about Haversian canals) suggests that the structure is a neoplasm. Resume. — The superficial part of the section is composed of a squamous mucous membrane. The tumor is a fibroblastic tissue like that of fibrosarcoma, but with the addition of the myeloplaxes and the osseous elements. It is osteosarcoma of the gum, a tumor described under the name of epulis. 242 Squamous epithe- lium. Corium . Tissue with tnyelo- plaxes. Newly- formed bone. Cells con- taining eleidin. Cells of ^ i^ the rete ■ . ' ii mucosum. Basal cells. Corium. 3 giant cells or myelo- plaxes. Fig. 111. — Epulis. (Giant-cell tumor of the gum.) Stained with hematoxylon and eosin. Magnified 80 diameters. Epithelium and corium covering a fibroblastic tissue with giant cells and containing in the center some osseous lamella. It was a tumor arising from the gum of the mandible in a child of eight years that caused the loss of two teeth. It was surgically removed. No return. 243 SQUAMOUS CELL CARCINOMA WITH EPITHELIAL PEARLS. Lobulated Squamous Epithelioma. Diagnosis of the Organ. — Let the section be examined with a low-power lens, beginning at the left. The dark upper border consists of a squamous epithelium with a horny layer in which can be distinguished: (a) The germinative layer. (b) The Malpighian layers {rete mucosum), composed of large cells of polyhedral shape, arranged in several layers upon the basal layer. (c) The granular layer, composed of cells filled with granules of eleidin. {d) The horny layer, composed of cornified cells — fine des- quamating lamellae of keratin. Keratinization of the superficial layers of a squamous epi- thelium can occur in leukoplakia of the buccal or vaginal mucosa ; but at one extremity of the section (not shown on the drawing) the connective tissue subjacent to this epithelium is found to contain fat cells, which enable the tissue to be recognized as the skin. Diagnosis of the Lesion. — At the other extremity of the draw- ing, as the cutaneous epithelium is followed from left to right, there appear in the derm, enormous dark-colored masses that descend deeply and are separated more or less completely by islets and bands of connective tissue. They are not in con- tinuity with the suprajacent epithehum, though of a very analogous structure. They are formed, at the periphery, of cells whose appearance recalls the basal epithehum, and at the center,, of polyhedral cells with intercellular spines, of the type of the cells of the Malpighian layer. But that which gives the tissue a pathognomonic appearance is the presence, in the centers of the large cell nests, of enormous spherical masses, frequently malformed, of an ovoid shape, the epithelial pearls. They are like onions and are formed of concentric laminae of cornified epithelium. Between the epithelial masses is a loose connective tissue which disappears little by little as they grow, until only narrow bands remain. This relation between the stroma and the cells is peculiar to mahgnant tumors developed from squamous epithelium. The section is one of squamous epithelioma, lobu- lated, and containing epithelial pearls. The epithelium which 244 Derm, Epithe- J' lium. Korny layer. Rete mu- cosum. Epithelial pearls. Infiltra- tion o£ neoplas- mic cells. Vessels Fig. 112. — Epithelioma spinocellulare. (Squamous-cell carcinoma with epithelial peai'ls.) Stained with hematoxylon and eosin. Magnified 40 diameters. A cutaneous epithelioma of which a fragment was obtained at autopsy. Beneath the cutaneous epithelium with its horny layer there are numerous cancer-cell nests, some of which contain epithelial pearls. 245 covers the tumor is not ulcerated: it is the infiltrating, not the ulcero-vegetating variety, in which the cancer masses form enormous buds that ulcerate at the surface and bleed upon the slightest touch. A moderate magnification permits both the diagnosis of the tissue and the lesion to be made: a higher magnification enables the cytological details to be studied. The epithelial cells contain numerous mitotic figures. In the neighborhood of the epithelial pearls important trans- formations of the cells can be seen and serve to explain their formation. The rose-red center of a young pearl (Fig. 113) is composed of polyhedral epithelial cells connected together by protoplasmic filaments, the intercellular bridges of Ranvier, which give a stippled appearance to the interspaces. The nuclei stain well and are provided with distinct nucleoli. But in proportion as one passes toward the center of the pearl, the cells become flattened, attenuated and frayed out from one another; their protoplasm becomes paler and here and there small cavities with small masses of chromatin in the center are seen. This appearance is known as dyskeratosis, and has often been mistaken for parasitic inclusions in the cells. It is, however, due to nuclear malformation through fragmentation. Occasional cells show small dark blue dots which take the hematoxylon stain intensely; they are granules of eleidin and precede the keratinic transformation of the epithelial cells. The cells flatten more and more, become pale, almost acidophilic, the nucleus disappears, and nothing remains but a mass of hyaline keratinized substance surrounded by flattened cells arranged one upon another like the skins of an onion. Between the cells and grouped around the epithelial pearls, occasional polymorphonuclear cells, plasma cells and lympho- cytes indicate secondary infection, suggesting that there is an ulceration of the tumor at some point not shown in the drawing, or to be found in the section. Resume. — A tumor developed from the squamous epithelium and recalhng the structure and transformations of the epiderm: squamous-cell epithelioma with epithelial pearls. A malignant tumor, because of its destructive invasion, the presence of the atypical cells and the frequent occurrence of metastasis to the regional lymph nodes. 246 Cells con- taining Nuclear Lympho- eleidin Cornified frag- cytes. granules, center. ments. Plasma- Squamous cytes. cells. Pseudo- parasites. Spinous cells. Fig. 113. — Epithelial pearl in an epithelioma of the tongue. Stained with hematoxylon and eosin. Magnified 425 diameters. It is one of the epithelial pearls found in the preceding section. In this pearl the keratinic change is only beginning and is far from the large formations that can almost be seen with the naked eye. 247 CARCINOMA BASOCELLULARE. Tubular Squamous-cell Carcinoma — Rodent ulcer. Diagnosis of the Organ.— The preparation can be divided into two parts; that on the left, in which the organ can be recognized, and that on the right, which shows the lesion. In the left-hand portion are found elements characteristic of the skin: squamous epithelium with a uniform horny layer, supported upon a dense connective tissue in the thickness of which are numerous fat cells; sebaceous glands, with their large pale cells grouped in masses and filled with fine granules of fat; sudoriparous glands with a double row of nuclei in the fining, myoepitheUum; hairs cut obliquely and provided with an epithelial sheath. Diagnosis of the Lesion. — At the right-hand extremity of the drawing, beneath the epithelium, there appear in the connec- tive-tissue stroma below and without the leas.^ulceration, large masses of dark blue which the connective tissue divides into more or less distinct tubular formations. This infiltration of the corium by the epithelium, without distinct limits, indicates a mahgnant tumor, epithelioma. But the uniformity of the cells which compose its prolonga- tions -and the complete absence of epithefial pearls cause this tumor to appear quite different from the epithefioma shown in Fig. 112. Under a higher power magnification, the tumor is found to be composed chiefly of cells recalling those of the basal layers of the epiderm; cells uniform in their structure and not subject to keratinic change. Everywhere the protoplasm has the same staining quality, and nowhere do granules of eleidin occur in the cells. Occasional monstrous cells may be found. The absence of all keratinic transformation and the close resemblance of the cells of the neoplasm to those of the basal layer of the epiderm lead one to designate the tumor an epithe- lioma basocellulare. It is sometimes called tubular epithelioma because of the tube-like arrangement of its cell processes. The connective-tissue stroma shows an enormous infiltra- tion of leukocytes in consequence of suprajacent infection. Resume. — An epithelial tumor derived from the basal or germinal layers of the epithelium — an epithelioma basocellulare. 248 Trans- verse section of Interpapil- an elon- lary pro- gated Rete longation. papilla, mucosum. Horny Cancer layer. masses Sebaceous gland. Fig. 114. — Epithelioma basocellulare of the sl I t-i : (S &| ^ I I ^ o o J] J2 n o % ■H S I ^1 ■5 ^ I.S to -^ 1- S ■» "' ■d § '^ 8l 11 ^; S a a 13 S 'T3 -« -5; ■3 E^ ^ •^ "T?. «0 "5 'S ^-l ^rs» wS* f^ g'5 ^1 17 257 them, are a number of larger cells with finely granular proto- plasm, containing besides the nucleus, chromatin fragments and sometimes even a polymorphonuclear leukocyte. This is another manifestation of phagocytosis — pyophagocytosis — these cells being known as pyophages. The pol3Tiuclears and pyo- phages may be held by dehcate threads of fibrin or simply immersed in a fluid which constitutes the most internal part of the inflammatory nodule, the part completely liquefied, the pus of the abscess. Z'one 2 (Fig. 119, C).— Outside of the layer of the pyophages is a zone of organized tissue, rich in newly formed vessels, arid in large mononucleated cells of a form intermediate between the polynuclears and the pyophages. These are the large mononuclear cells, macrophages, some of which, in a state of degeneration, show protoplasm that is homogeneous and acido- philic and have pycnotic nuclei. Besides the macrophages there are a large number of cells of oval form with polar nuclei, the plasmacytes. These can multi- ply as is shown by the presence of several nuclei in some of them. The much dilated bloodvessels show a thickened endo- thehum. In a capillary, shown in the central part of the drawing, red blood corpuscles and two polymorphonuclear leukocytes indicate coexistent leukocytosis. Zone 3 (Fig. 119, D).— The upper part of this zone is a con- tinuation of the preceding. There are three capillaries and numerous mononuclears and plasmacytes. In the lower part the confines of the pyogenic membrane are reached. There are a number of fibroblasts that have formed collagen fibers. In the interstices are some large mononuclears and some plas- macytes. Resume.— In this section can be followed in detail all of the stages of an acute inflammation: cellular necrosis, extremely active phagocytosis, and finally the connective-tissue reaction. The abscess is sharply circumscribed by an important con- nective tissue reaction that tends to limit the extension of the suppuration and make it different from the diffuse phlegmon and the cold abscesses of tuberculosis. 258 Macro- phage. Plasma- cyte. In- flamed newly formed vessel. Poly- morpho- nuclear leukocytes. Mitosis. Capillary. Mononu- clear leuko- cytes. Capillary. Fig. 119. — Intradermic abscess. Plasma- cytes. C. — Zone 2 (Fig. ii8) showing the macrophagic reaction, the plasmacytes and the newly formed capillary vessels with swollen endothelium. D. — Zone 3 {Fig. 118) showing the fibroblastic reaction forming pyogenic membrane at the outer limits of the abscess. 259 SUBCUTANEOUS SPOROTRICHOTIC NODULE. Diagnosis of the Organ. — An examination of the specimen with the naked eye, and a low-power lens (Fig. 120, A), shows that the section passes through an entire subcutaneous nodule. The presence of squamous epithelium with its various layers of hair follicles and sebaceous glands are sufi&cient to make the diagnosis of the skin. Diagnosis of the Lesion.— In the thickness of the derm and subcutaneous tissue there is a dark blue colored nodule, in the center of which there is an irregular space. It is a circum- scribed new formation concerning the exact nature of which it will require a higher magnification to decide. The Central Zone (Fig. 120, B; No. i in Fig. 120. A).— This is a zone of suppuration as is shown by the large number of cells with polylobed nuclei, relatively abundant protoplasm colored dis- tinctly by the eosin, and without appreciable granules. They are polymorphonuclear leukocytes in a more or less marked condition of necrosis, and forming the pus cells or pyocytes. The fragmentation of the nuclei, the chromatolysis, the eosino- philia of the protoplasm are characteristic of pus cells and are the same as in the more common form of suppuration already studied. At the periphery of this central zone the lower part of Fig. 120, B, pyophages are mixed with the pyocytes. As in the abscess, the pyophages and polymorphonuclears may be held by a fine fibrinous reticulum, or be suspended in the fluid in the cavity. As the examination proceeds from the center to the periphery the pyophages become more and more rare until they disappear altogether, and a growing connective tissue is reached. It is composed of fibroblasts in process of metaplasia. The collagen fibers are nearly all absorbed, and scarcely anything remains except fine fibrillas more or less dissociated by edematous fluid. Between fibers and fibroblasts occasional polymorphonuclear cells with pycnotic nuclei may be found. The Intermediate Zone (Fig. 121, C; No. 2, Fig. 120, A).— This is the zone of epithelioid and giant cells. The drawing shows a number of cells with pale nuclei and scarcely stained protoplasm with peripheral prolongations, and two giant cells; one in the center of the figure, containing two nuclei, the other at the lower part— left-hand part— with a pale center in the early stage of necrosis, and a coronet of nuclei at the periphery. 260 B . 6 §4 0^6 Poly- ; morpho- nuclears. wMm- Connec- ' tive tissue cells. Fig. 120. — Subcutaneous sporotrichotic nodule. Stained with hematoxylon and eosin. A. — View of the entire section, magnified 3 diameters, showing in the little rectangles i, 2, 3 the areas jrom which the following drawings were made under a higher power. B. — Zone i, magnified 350 diameters, showing the pus cells in the center of the abscess, atid the zone of macrophages outside. 261 Scattered among these are also a number of mononuclear and polynuclear cells and occasional fibroblasts. Peripheral Zone (Fig. 121, D; No. 3, Fig. 120, A).— This cor- responds to the external limiting zone of the sporotrichotic nodule. In it appear plasmacytes which have an ovoid shape, basophilic cytoplasm, especially dark at the periphery and polar nuclei which are spherical and have a reticulated appearance, and large granules of chromatin pressed against the nuclear membrane or about the nucleolus which is usually quite distinct. The nuclei appear in the center or at the pole of the cells accord- ingly as they are cut tangentially or perpendicularly. Sometimes a plasmacyte may have two or three nuclei, indi- cating cellular division. There are also sections of capillaries, indicating vascularity. Their walls are formed of several layers of cells, the endothelium being tumified or swollen, unHke the normal condition in which they simply show a single layer of endothelial cells. In the most external zone (lower part of the Fig. 121, D), the pyogenic membrane is seen to form the external limit of the nodule. It is composed of fibroblasts and collagen fibers more or less dense, in the interspaces of which are a few lympho- cytes and polymorphonuclears. Resum6.— An intradermic inflammatory nodule composed of three zones of inflammatory reaction of different character: A central zone, composed of pus formed of degenerated poly- morphonuclear cells and pyophagous mononuclears of large size. A median zone with epithehoid and giant cells, recalling the lesions of miliary tuberculosis. A peripheral zone, intensely vascular, composed of lymphocytes and plasma cells. This histological structure is sufficiently characteristic to permit the diagnosis of sporotrichosis to be made. But besides this a bacteriological examination by cul- tures from the fresh material ought to be made, and should show the specific agent, the sporotrichium of Beurmann and Gougerot. 262 Poly- morpho- nuclears. Epithelial cells. > Tt n ce r/l Giant cells. s D Fibro. blasts. Fig. 121. — Subcutaneous sporotrichotic nodule. Plasma- cytes. Plasma- cyte. Capillary. Lympho- cyte. Collagen fibers. C. — Zone 2 showing giant cells and epithelioid cells. D. — Zone 3 showing the lymphocytic resection in the connective tissue and the vascularity of the pyogenic membrane. 263 BLOOD CAPILLARIES IN INFLAMMATION. The drawing shows a collection of blood capillaries such as are frequentiy met with in various normal and pathological conditions. Fig. 122, A and B, show two different stages in the embryo- genesis of blood capillaries. A is connective tissue taken from an embryo. In the middle of an extremely loose tissue of a myxoid appearance, and com- posed of undifferentiated connective-tissue cells, there is a section of a long tube, cut longitudinally at the left and trans- versely at the right. Such cellular tubes, from which the vascular system is developed, are the islands or cords of Wolf of the embryologists. In B is shown an embryonal capillary developed from a cord of Wolf, in the center of which is a lumen. Its walls consist of endothelial cells with large nuclei which project into the lumen in which there is a nucleated red blood corpuscle: normoblast. The connective tissue about the capillary has acquired a more dense appearance than that shown in Fig. 122, A. Capillaries with such embryonal appearance are frequently found in the adult in pathological conditions, especially in the course of inflammatory disturbances such as proud flesh. In Fig. 122, C, is shown a section of adult capillary in a dense connective tissue. The wall is formed of a single layer of endothelial cells very flattened, in which two fusiform nuclei can be seen; The lumen contains six or seven red blood corpuscles of the adult type. The connective tissue through which the capillary passes is sclerotic: in it there are very few cells (fibroblasts) and very many coUagen fibers. In Fig. 122, D, is shown a capillary in an inflamed tissue. Diapedesis of leukocytes is distinct. It consists in the passage of the polymorphonuclear and small mononuclear white blood corpuscles through the wall of the capillary vessel. In the drawing is shown the condition known as margination of leuko- cytes, that is to say, their attachment to the inner wall of the vessel, and their passage through it into the neighboring stroma. 264 WolfEan cord. Connec- tive tissue cell. Poly- morpho- _ nuclears. Red blood _ 1 1 1 corpuscles. Hj w 1 theliiun. Connec- m m tive tissue ■ fibers. ^p \if D Connective tissue fibres. Polymorpho- nuclears. Mononuclears. Endothelium. Mononuclear. Fig. 122. — Capillary bloodvessels. Stained with hematoxylon and eosin. Magnified 350 diameters. A. — Embryonal capillary showing the cords of Wolf. B. — Embryonal capillary containing a normoblast. C. — Adult capillary in sclerosed tissue. D. — Capillary in inflammed tissue showing the margination of leukocytes and diapedesis of white corpuscles. 265 SYPHILITIC CHANCRE. Diagnosis of the Organ.— If in this case it is not possible to determine with what organ one has to do, he can say very definitely that it is a squamous epithelium of which a basal germinative layer, a rete Malpighii and horny scales in process of desquamation can be recognized. No fat cells are found in the subjacent tissue, nor are there any sebaceous glands, sweat glands or hair follicles. It is the prepuce. Diagnosis of the Lesion.— Below the epithelial covering, inter- rupted over a considerable part of its extent, by an ulceration, there is a dark bluish mass which constitutes the principal lesion. It is shown by a blue stippling that indicates numerous cells and a large number of capillary vessels, all lost in a pale rose connective tissue. The stippling and the vessels are distinctly shown in Fig. 123, B. With such a magnification it is difiicult to determine further details, except a very definite collection of the cells about" the vessels. A much greater magnification, even an oil-immersion lens may be necessary to bring out the nature of the lesion. Let one of the capillaries with its perivascular infiltration (Fig. 124) be studied. In the center of the drawing is a capillary with a distinctly thickened wall and swollen endothehum projecting into the lumen, and partly obstructing it. The external wall is also proliferated and is composed of several layers of young con- nective-tissue cells. An intense vasculitis is expressed by the scantiness of the lumen in comparison with the thickness of the wall. About the capillary the infiltration consists of large oval cells with excentric nuclei — plasmacytes — which indicate a particular type of inflammatory reaction which is sometimes called "plas- moma peri vasculare." Though very numerous, the plasmacytes do not constitute the only cells in the inflammatory infiltration. There are also a considerable number of lymphocytes, and occasional, but rare, polymorphonuclears, and lastly forms intermediate between the plasmacytes, the lymphocytes and the mononuclears. The plasmoma characterizes the primary and secondary lesions of syphilis; but it is not specific as it is quite possible to find similar infiltrations of plasmacytes in other types of inflammation, as in sporotrichosis for example. 266 .,-i^KiA% » ^ Epithelium prepuce. Ulceration. Capillary with peri- vascular - infiltra- tion. * Epithe- lium. Stroma. Lymph- angitis. Capillaries. Fig. 123. — Syphilitic cliancre of tlie prepuce. Stained with hematoxylon and eosin. Operative removal of the prepuce in the early days of the develop- ment of the chancre. A. — Showing the entire ulceration, magnified 20 diameters. B. — Showing the inflammatory infiltration about the bloodvessels of the stroma, magnified 40 diameters. 267 The stroma contains large fibroblasts with normal appearmg nuclei, and protoplasm which has secreted an abundance of collagen fibrills, which give the lesion {the chancre) its induration. Resume.— Because of the nature of the cells that go to make up the cellular infiltration, and their arrangement about the bloodvessels as well as the importance of the vascular lesions, it is correct to make a diagnosis of primary or secondary syphilis; a diagnosis to be confirmed later by the discovery of the trepon- ema through the employment of one of the special methods of staining with silver salts. Plasma- cytes. Dividing plasma- cytes. Poly- morpho- nuclears. Fig. 124. — Syphilitic chancre of the prepuce. Stained with hematoxylon and eosin. Magnified 425 diameters. One of the capillaries shown in the preceding drawing is shown under a higher magnification to show the plasmacytic perivascular infiltration. Note the thickness of the wall of the capillary, in which the endothelial cells are swollen and surrounded by several layers of fibroblasts. About the capillary the tissue is infiltrated with a composition of inflammatory cells particularly rich in plasmacytes. 268 INDEX TO THE ILLUSTRATIONS. A Abscess, biliary, of liver. Fig. 32, P-85 embolic, of kidney, Fig. 61, p. 143; Fig. 62, p. 145 intradermic. Fig. 118, p. 257; Fig. 119, p. 259 Adrenal body, hyperplasia, Fig. loi, p. 223 hypoplasia, Fig. 102, p. 225 normal. Fig. 99, p. 2ig; Fig. 100, p. 221 Amyloid infiltration of kidney. Fig. 64, p. 149 of liver. Fig. 27, p. 75 of spleen. Fig. 38, p. 97 Angioma, cavernous, of liver, Fig. 31. ?■ 83 Appendix vermiformis, acute in- flammation with perforation Fig. 20, p. 61 chronic obliterative inflamma- tion, Fig. 21, p. 63 normal. Fig. 19, p. 59 Artery, atheroma. Fig. 49, p. 119 calcification of middle coat. Fig. 50, p. 121 endarteritis obliterans, Fig. 47, p. 115; Fig. 48, p. 117 Atheroma, artery. Fig. 49, p. 1 19 B Blood, acute lymphatic leukemia, Fig- 55. P- 131 leukocytosis. Fig. 53, p. 127 Blood, myelogenic leukemia, Fig. 54. P- 129 normal. Fig. 52, p. 125 Brain, hemiplegia, degeneration, annular protuberance (pons). Fig. 84, p. 189 cerebral peduncles, Pig. 83, p. 187 medulla, Fig. 85, p. 191 purulent cerebral meningitis, Fig. 93, p. 207 Breast, fibroadenoma, Fig. 80, p. Calcification, middle coat of artery, Pig. 50, p. 121 Capillary bloodvessels. Fig. 122, p. 265 Carcinoma basocellulare, Pig. 114, p. 249 of breast, Fig. 80, p. 181; Pig. 81. p. 185 cylindrical cell, of body of uterus. Pig. 76, p. 173 gland-cell, of pancreas, Fig. 36, P- 93 of prostate, Fig. 70, p. 161 of pylorus, Fig. 16, p. 53 secondary, of liver, Fig. 33, p. 87 in lymph node, Fig. 41, p. 103 spinocellulare, of skin, Fig. 112, P- 245 of tongue, Fig. 13, p. 47 squamous-cell, of neck of uterus, Fig. 77, p. 175 of testicle, Fig. 68, p. 156 270 INDEX TO THE ILLUSTRATIONS Cecum, cylindrical-cell carcinoma, Fig. 22, p. 65 Chancre of syphilis. Fig. 123, p. 267; Fig. 124, p. 268 Chorion-epithelioma, Fig. ii5, p. 253 Cirrhosis of liver, Laennec s annu- lar, atrophic form. Fig. 28, p. 77 Congestion, chronic passive, of liver. Fig. 23, p. 67; Fig. 24, p. 69 of spleen, Fig. 37, p. 95 of liver with fatty infiltration. Fig. 25, p. 71 Connective tissue, various stages of development. Fig. 106, p. 233 Corpora lutea in ovary. Fig. 72, p. 165 Cylindrical-cell carcinoma of ce- cum, Fig. 22, p. 65 D Deciduoma malignum, Fig. 116, P- 253 E EcHiNococcus cyst in liver, Fig. 34, P- 89 Embolism, septic, of kidney, Fig. 61, p. 143; Fig. 62, p. 145 Embryoma, sacrococcygeal tumor. Fig. 117, P- 255 Endocarditis, ulcero-vegetative. Fig. 45, p. Ill Epithelial pearl. Fig. 113, p. 247 Epulis, Fig. Ill, p. 243 F Fallopian tube, inflammation of (acute salpingitis). Fig. 79, p. 179 Fatty degeneration of liver. Fig. 26, p. 73 of muscle of heart. Fig. 46, p. 113 infiltration of liver, with conges- tion, Pig. 25, p. 71 Fibroadenoma of mammary gland, Fig. 80, p. 181 Fibroid of uterus, Fig. 75, p. 171 Fibromyoma of uterus. Pig. 75, p. 171 Goiter, colloid. Pig. 97, p. 215 parenchymatous. Fig. 98, p. 217 H Heart, acute fibrinous pericarditis, Pig. 44, p. 109 chronic myocarditis, Fig. 42, p. endocarditis, ulcero-vegetative form, Fig. 45, p. iii fatty infiltration (cor adiposum). Fig. 43, p. 107 metamorphosis of muscle, Fig. 46, p. 113 Hypernephroma of kidney, Fig. 65, P- 151 Hypophysis cerebri, normal, Fig. 103, p. 227 Ileum, tuberculous ulcer, Fig. 18, P- 57 . typhoid ulcer. Fig. 17, p. 55 Infarction, hemorrhagic of lung, Fig- 5. P- 31 Kidney, amyloid infiltration, Fig. 64, p. 149 chronic nephritis. Fig. 60, p. 141 hypernephroma or adenoma of, Pig. 65, p. 151 normal, Fig. 56, p. 133; Fig. 57, P- 135 pyemic nephritis, with abscesses, Fig. 61, p. 143; Pig. 62, p. 145 subacute nephritis (variolous ne- phritis), Fig. 58, p. 137; Fig. 59. P- 139 INDEX TO THE ILLUSTRATIONS 271 Kidney, tuberculous pyelonephri- tic, Fig. 63, p. 147 Leiomyoma, Fig. 75, p. 171 Liver, amyloid infiltration of, Fig. 27, P- 75 bile pigmentation of, from biliary obstruction. Fig. 29, p. 79 biliary abscess, with cirrhosis, Pig. 32, p. 85 cavernous angioma of, Fig. 31. p. 83 chronic passive congestion of, in heart disease, Fig. 23, p. 67; Fig. 24, p. 69 congestion and fatty infiltration, Fig. 25, p. 71 echinococcus cyst of. Pig. 34, p. 89 fatty degeneration. Fig. 26, p. 73 Laennec's aimular atrophic cir- rhosis of, Fig. 28, p. 77 malaria of, with hemozoin or melanin pigmentation. Pig. 30, p. 81 secondary carcinoma of. Fig. 33, p. 87 Lung, bronchopneumonia. Fig. 7, P- 35 emphysema and congestion, Pig. 3- P- 27 stained with acid orcein to show elastica. Fig. 4, p. 29 fibrinous or croupous pneumonia. Fig. 6, p. 33 hemorrhagic infarction of , Fig. 5, P- 31 massive caseous tuberculous pneumonia of, Fig. 11, p. 43 miliary tuberculosis of, Fig. 8, p. 37; Fig. 9, p. 39 normal. Fig. I, p. 23 stained with acid orcein to show elastica, Pig. 2, p. 25 tuberculous bronchopneumonia of. Fig. 10, p. 41 Lymph node, secondary carcinoma of. Pig. 41, p. 103 Lymph node, tuberculosis of. Fig. 40, p. lOI Lymphocytoma, Fig. 109, p. 239 M Mamma, carcinoma of. Fig. 80, p. 181; Fig. 81, p. 185 fibroadenoma of. Fig. 80, p. 181 Melanin, Fig. 115, p. 251 Mixed tumor, sacrococcygeal (em- bryoma). Fig. 117, p. 255 Nevus, Fig. 115, p. 251 Osteosarcoma, Pig. no, p. 241 Ovary, corpora lutea in. Fig. 72, p. 165 cystic and sclerotic. Fig. 73, p. 167 normal. Pig. 71, p. 163 Pancreas, carcinoma of. Fig. 36, P- 93 sclerosis or chronic inflammation of. Fig. 35, p. 91 Pericardium, acute fibrinous in- flammation of. Pig. 44, p. 109 Pigmentation, biliary, of liver, Fig. 29, p. 79 hemozoin or melanin, in liver, Fig. 30, p. 81 Pituitary body, normal, Pig. 103, p. 227; Fig. 104, p. 229 Pleura, tuberculosis of, with sero- fibrinous exudate, Fig. 12, p. 45 Prostate, carcinoma of, Pig. 70, p. 161 hypertrophy of. Pig. 69, p. 159 Psammoma of the meninges. Pig. 95. P- 2" 272 INDEX TO THE ILLUSTRATIONS Salpingitis, acute gonococcic form of, Fig. 79, p. 179 Sarcoma, giant-cell (epulis). Fig. Ill, p. 243 osteo-, Fig. no, p. 241 round-cell, Fig. 108, p. 237 spindle-cell (fibrosarcoma), Fig. 107, P- 235 Skin, abscess of. Fig. 118, p. 257; 119, p. 259 sporotrichosis, Fig. 120, p. 261; Fig. 121, p. 263 Spinal cord, acute anterior polio- myelitis. Fig. 92, p. 205 disseminated sclerosis, Fig. 90, p. 201 epidemic cerebrospinal men- ingitis of, Fig. 94, p. 209 hemiplegia, degeneration of pyramidal tracts, cervical region, Fig. 86, p. 193 dorsal region. Fig. 87, p. 195 lumbar region. Fig. 88, p. 197 syringomyelia. Fig. 91, p. 203 tabes dorsalis. Fig. 89, p. 199 Spleen, amyloid infiltration of, Fig. 38, p. 97 chronic passive congestion of. Fig- 37, P- 95 miliary tuberculosis of, Fig. 39, P- 99 Sporotrichosis of skin. Fig. 120, p. 261; Fig. 121, p. 263 Squamous-cell carcinomaof tongue. Fig. 13, p. 47 Stomach, carcinoma of pylorus. Fig. 16, p. 53 simple ulcer of pylorus. Fig. 15, p. 51 Syncytioma malignum. Fig. 116, p. 253 Syphilis, chancre, or primary sore, Fig. 123, p. 267; Fig. 124, p. 268 Testicle, carcinoma of. Fig. 68, p. 157 normal, of dog, Fig. 66, p. 153 tuberculosis of. Fig. 67, p. 155 Thrombosis following pulmonary embolism. Fig. 5, p- 3' . Thrombus in vein of obliterative phlebitis. Fig. 51, p- 123 Thymus, sclerotic. Fig. 105, p. 231 Thyroid gland goiter, colloid, Fig. 97, P- 215 parenchymatous, i'lg. 90, p. 217 normal. Fig. 96, p. 213 Tongue, carcinoma of, spinocellu- lare. Fig. 13, p. 47 tuberculosis of, Fig. 14, p. 49 Tuberculosis, bronchopneumonia Fig. 10, p. 41 of kidney, Fig. 63, p. 147 of lymph node, Fig. 40, p. loi massive caseous pneumonia. Fig. ii,P-43 miliary, of lung. Fig. 8, p. 37; Fig- 9, P- 39 of spleen, Fig. 39, p. 99 of pleura. Fig. 12, p. 45 of tongue. Fig. 14, p. 49 ulcer of small intestine. Pig. 18, P-57 Typhoid fever ulcer of intestine. Fig. 17, p. 55 U Ulcer, simple, of stomach, Fig. 15, P-51 tuberculous, of small intestine. Fig. 18, p. 57 typhoid, of intestine. Fig. 17, p. 55 Uterus, carcinoma of body of (adenocarcinoma; cylindri- cal-cell carcinoma). Fig. 76, P- 173 squamous-cell, of neck of, Fig. ^^ 77, P- 175 hbromyoma (fibroid). Pig. 75, p. 171 normal, Fig. 74, p. 169 ulcerative cervical metritis, Fig. 78, p. 177 V Vein, obliterative phlebitis Pie I 51, P- 123 ' *^' INDEX TO THE TEXT. AbbA condenser, 17 Abscess, biliary, of liver, 84 tntradermic, 256 Acid orcein stain, 21 Acanthosis, 48 Adenocarcinoma ot liver, 86 of pancreas, 92 Adrenal body, hyperplasia ot, 222 hypoplasia of, 224 normal histology of, 218 Atelectasis, 24 Alveolitis, catarrhal, 36 fibrinous, 24, 32, 34 hemorrhagic, 24, 26 ptirulent, 24, 32, 34, 36 serous, 24, 34, 36 Amyloid disease of kidney, 148 infiltration of spleen, 96 liver, 74 reaction, 74 substance, nature of, 96 Angioma, cavernous, of liver, 82 Anthracosis, 22 Artery, atheroma ot, 118 calcification of, 120 endarteritis obliterans of, 1 14 normal histology of, 1 14 pipe-stem, 120 Atheroma or artery, 118 Atrophy of liver cells, 74, 76 Bichloride of mercury, deposit from, 98 18 black Bile capillaries, normal, 66 Blood, myelogenic leukemia, 128 leukocytosis, 126 lymphatic leukemia, 130 normal histology of, 124 red corpuscles of, 124 basophils, 124 eosinophils, 124 lymphocytes, 124 polymorphonuclears, 124 white corpuscles of, 124 Brain, cerebrum,hemiplegia of, 186 descending degeneration of pyra- midal tract of, 186 purulent leptomeningitis of, 206 Breast, cancer of, 182 fibroadenoma of, 180 Bright's disease, 140 Bronchopneumonia, 34 tuberculous, 40 Calcification of arterial wall, 120 of artery, 120 psammoma of meninges, 210 Cancer ot breast, 182 of cervix uteri, 1 74 embolus, 86 of pancreas, 92 of prostate, 160 secondary, of liver, 86 in lymph node, 100 of testicle, 156 of uterine body, 172 Capillary vessels, 264 Carcinoma, basocellulare, 248 274 INDEX TO THE TEXT Carcinoma of cecum, 64 of pylorus, 52 spinocellulare, 46, 174,, 244 squamous cell of cervix uteri, 174 Caseation, 40, 42 Cecum,, cancer of, 64 Cerebrospinal meningitis, 208 Chancre, syphilitic, 266 Cholesterin in atheromatous artery, 118 Chondrin, 240 Chorion, epithelioma, 252 ChromafEne cells, 220 Chromatolysis, 256 Chromatophores, 250 Chromophobic cells, 226 Cirrhosis of liver, 76 Collagen, 232 Congestion, chronic passive, of spleen, 94 passive, of the liver, 66, 70 pulmonary, 26 Connective tissue, 232 Coradiposum, 106 Corpus luteum in the ovary, 164 Corpuscles of Hassal in thymus, 230 Corrosive sublimate, 20 Crenation of blood corpuscles, 128 Crystals of fatty acids in atheroma, 118 Cutting sections, 20 Cylindrical-cell carcinoma of ce- cum, 64 epithelioma of body of uterus, 172 of liver, 86 Cyst, echinococcus, of liver, 88 hydatid, of liver, 88 D Deciduoma, 252 Desquamation of epithelium, 32 Disseminated sclerosis, spinal cord, 200 Dyskeratosis, 246 E Echinococcus cyst of liver, 88 Embolism, microorganismal in kid- ney, 142 pulmonary, 30 Embolus, cancer, 86 Emphysema, 24 essential, 28 pulmonary, 26 Endarteritis obliterans, 114 ulcero-vegetative, no Eosin, 21 Eosinophilia, 88 Epididymis, normal histology of, 152 Epithelial pearls, 46 in carcinoma spinocellulare,244 Epulis, 242 Fallopian tube, acute inflamma- tion of, 178 False membranes, 32, 44 in acute pericarditis, 108 Fatty acid crystals in atheroma, 118 degeneration of liver, 73 infiltration of liver, 71 Fibin, 32, 44 Fibroadenoma of breast, 180 Fibroblasts, 232 Fibromyoma of uterus, 170 Fibrosis of c ardiac muscle, 104 Fixation, 19 Follicles of Naboth, 176 Formaldehyde, 20 G Gentian violet for amyloid test, .74. 96 Giant cells, foreign body, 38 in sporotrichosis, 260 of tuberculosis, 38 of tumors, 38 Gliosis in syringomyelia, 202 Goiter, colloid, 214 INDEX TO THE TEXT 275 Hassal, corpuscles of, in thymus, 230 Heart, acute fibrinous pericarditis of, 108 chronic myocarditis of, 104 endocarditis of, ulcero-vegeta- tive, no fatty degeneration of, 112 myocardial fragmentation of, 105 normal histology of, 104 obese, 106 in pernicious anemia, 112 tabby mottling, 112 Hematoidin, 30 Hematoxylon, 21 Hemiplegia, 186 Hemozoin, 80 Hepatization, red, 32 gray, 32 Hyaline bodies in psammoma, 210 degeneration of vessel, 114 Hydatid cyst of liver, 88 Hydromyelia, spinal cord, 202 Hypernephroma of kidney, 150 Hypertrophy of prostate, 158 Hypophysis cerebri, normal histol- ogy of, 226 I Imbedding, 20 Infarction, hemorrhagic, 30 Infiltration, amyloid, of liver, 74 fatty, of liver, 70 Inflammation, abscess of liver, 84 of skin, 256, 260 of alveoli of limg, 24, 32, 34, 36 endocarditis, no of Fallopian tube, 178 of kidney, 142, 144 of neck of uterus, 176 of pericardium, 108 proud flesh, 236 round-cell infiltration, 46 serofibrinous, 44 thrombosing, of vein, 122 ulcer of stomach, 50 Intestine, typhoid ulcer of ileum, 54 Iris diaphragm, 18 Keratinization of epithelial cells, 244 of epithelium, 46 Kidney, adenoma of, 150 amyloid infiltration of, 148 hypernephroma, benign, 150 glomerules, 132 Malpighian bodies of, 132 normal histology of, 132 pyramids of Ferrein, 148 subacute nephritis of, 136 tuberculous pyelonephritis, 146 Kupffer's cells, 80 Laennec's cirrhosis of liver, 76 Langerhans, islands of, in pancreas, 90 Langhans, cells of, 253 Large intestine, normal histology of, 64 Leiomyoma of uterus, 170 Leptomeningitis, purulent, 206 Leukemia, lymphatic, 130 myelogenic, 128 Leukocytes, acidophilic, 88 eosinophilic, 88 LeukoC3rtosis, 124 Leukoplakia, 46, 244 Liver, amyloid infiltration, 74 annular cirrhosis of, 77 atrophic cirrhosis of, 76 biliary abscess of, 84 pigmentation of, 78 bivenous cirrhosis of, 76 cavernous angioma of, 82 of chronic cardiac disease, 66 passive congestion of, 66 cirrhosis, 76, 84 echinococcus cyst of, 88 fatty and congested, 70 degeneration of, 72 infiltration of, 70 metamorphosis of, 72 hob-nail, 77 hydatid cyst of, 88 inverted lobule, 68 276 INDEX TO THE TEXT Liver, malarial pigmentation, 80 monocellular dislocation, 68, 70 normal histology of, 66 nutmeg, 68 pseudocanaliculi, 76, 84 secondary cancer of, 86 Lugol's solution for amyloid test, 74.96 Lung, bronchopneumonia of, 34 carbon particles in, 22 congestion of, 26 elastic tissue in, 22 embolism of, 30 emphysema of, 26 fibrinous pneumonia of, 32 infarction of, 30 massive caseous ppeumonia of,42 miliary tuberculosis of, 36 normal histology of, 22 serofibrinous pleuritis, 44 tuberculous bronchopneumonia, 40 Lymph node, normal histology of, 100 secondary cancer of, 100 tuberculosis of, 100 Lymphadenoma, 236, 238 Lymphocytoma, 238 M Macrophages, 30, 118, 256 Malaria, pigmentation of liver, 80 Malignant tumor, method of inva- sion, 52 metastasis of, 52 Malpighian corpuscle of spleen, 94 Mamma, cancer of, 182 fibroadenoma of, 180 Margination of leukocytes, 264 Medulla oblongata, 190 Melanin, 80, 250 Metaplasia, 240 Metritis, ulceration of cervix uteri, 176 Microphages, 256 Microscope, methods of using, 17 Mirror, 18 Mixed tumor of sacrococcygeal region, 254 Muscle, cardiac, 104 Myelocytes in leukemia, 128 Myeloplaxes, 242 Myocarditis, chronic, 104 N Nabothian follicles, 176 Nevus pjgmentosus, 250 of skin, 250 Nephritis, ascending radiating, 144 chronic, 140 desquamative tubulitis, 138 embolic, 142 exudative tubulitis, 138 mixed, 138 pyelo-, 144 pyemic, 142 subacute, 136 tuberculous pyelo-, 146 Neuronophagia in poliomyelitis, 204 Normoblasts, 128 Nutmeg liver, 68 O Objectives, 18 Orcein, elastic stain in endarteritis obliterans, 116 Organization of a thrombus, 30 Osmic acid stain for fat, 112 Ossein, 240 Osteoblasts, 240 Osteosarcoma, 240 Ovary, corpus luteum of, 164 normal histology of, 162 sclerocyclic, 166 Oxyuris, 60 Pancreas, adenocarcinoma of, 92 islands of Langerhans in, 90 normal histology of, 90 sclerosis of, 90 Periangiocholitis, 84 Pericarditis, acute fibrinous, 108 Phagocytes, mononuclear, in spleen, 94 INDEX TO THE TEXT 277 Phlebitis, obliterative, 122 thrombosing, 122 Phlegmasia alba dolens, 122 Pigmentation, biliary, of liver, 78 malarial, of liver, 80 Pituitary body, normal histology of, 226 Plasmocytes, 256, 266 Plasmoma, 266 Pleuritis, serofibrinous, 44 Pneumonia, fibrinous, 32 massive caseous, 42 Poikilocytes, 128 Poliomyelitis, anterior acute, 204 Prepuce, chancre of, 266 Prostate, 158 adenoma of, 158 cancer of, 160 hypertrophy of, 158 Proud flesh, 236 Psammoma, 210 Pycnosis, 34 Pyophages, 256 R Rodent ulcer, 248 Sacrococcygeal tumor, 254 Salpingitis, acute, 178 Sarcoma, fibre-, 234 giant-cell, 242 globo-cellulare, 236 osteogenetic, 240 osteosarcoma of gum, 242 round-cell, 236 spindle-cell, 234 Sclerosis of pancreas, 90 Seal-ring appearance of liver cells, 70 Section-cutting, 20 Sections, methods of interpreting, 17 Seminoma, 156 Skin, abscess of, 256 chancre of, 266 nevus of, 250 Skin, sporotrichosis of, 260 squamous-cell carcinoma of, 244, 248 Spinal cord, acute anterior polio- myelitis of,. 204 cervical, 192 disseminated sclerosis of, 200 dorsal, 194 epidemic cerebrospinal menin- gitis of, 208 lumbar, 196 syringomyelia of, 202 tabes dorsalis of, 198 Spleen, amyloid infiltration of, 96 chronic passive congestion of, 94 Malpighian corpuscle of, 94 normal histology of, 94 pulp of, red, 94 white, 94 tuberculosis of, 98 Spongioc3rtes, 218 Sporotrichosis, 260 Squamous-cell carcinoma of cervix uteri, 174 of skin, 244 of tongue, 46 Staining, 21 Stains for nervous tissue study, 186 Stomach, cancer of pylorus, 52 normal histology of, 50 ulcer of pyloris, 50 Small intestine, normal histology of, 54 tuberculous ulcer of, 56 Suprarenal gland, normal histology of, 218 Sympexions in prostate gland, 158 Syncytioma malignum, 252 Syphilis, chancre, 266 Syringomyelia of spinal cord, 202 Tabes dorsalis of spinal cord, 198 Testicle, cancer of, 156 normal histology of , 152 tuberculosis of, 152 Thrombus, organization of, 30 venous, 122 Thyroid gland, colloid goiter of , 2 14 278 INDEX TO THE TEXT Thyroid gland, fetal goiter of, 216 normal histology of, 212 parenchymatous goiter of, 216 sclerosis of, 230 Tongue, carcinoma spinocellulare of, 46 tuberculosis of, 48 Transmigration of leukocytes, 264 Tube casts in tubules of kidney, 140 Tuberculosis of kidney, 146 of lung, serofibrinous pleuritis, 44 of lymphatic node, 100 miliary, histology of, 36,38 of lung, 36 of spleen, 98 of testicle, 152 of tongue, 48 ulceration of intestine, 56 Tubular epithelioma, 248 Tumor, angioma, 82 carcinoma, adenocarcinoma, 86, 92 cylindrical-cell, 64, 86, 160, 172 gland-cell, 52, 92, 156, 182 secondary, 86, 100 spinocellulare, 46, 174,244 squamous-cell,carcinoma baso- cellulare, 248 chorion epithelioma, 252 deciduoma malignum, 252 hypernephroma, 150 lymphadenoma, 236,238 mixed, 254 nevus, 250 psammoma, 210 sarcoma, fibro-, 234 Tumor, sarcoma, giant-cell, 242 osteosarcoma, 240 round-cell. 236 spindle-cell, 234 syncytioma malignum, 252 Typhoid fever, intestinal ulcer, 54. U Ulcer of cervix uteri, 176 of pyloris, 50 tuberculous, of intestine, 56 Uterus, cancer of body, 172 of cervix, 174 fibromyoma of, 170 inflammation of muscle of neck of, 176 normal histology of, 168 Van Giesen's stain, 21 Vein, obliterative phlebitis, 12 2 Vermiform appendix, chronic oblit- erative appendicitis, 62 normal histology of, 58 perforative appendicitis, 60 Vomica, 38 W Wallerian degeneration of the central nervous system, 186 ■■■■HMMaM