A LABORATORY TEXT-BOOK OF PATHOLOGY FOR THE USE OF STUDENTS AND PRACTITIONERS OF MEDICINE BY HORACE J. B.S., M. D. DEMONSTRATOR OF PATHOLOGY IN THE MEDICAL COLLEGE OF OHIO (UNIVERSITY OF CINCINNATI) TiHUtb ©ne Ibunbreb anD ©wentE=one 11 (lustrations PHILADELPHIA P. BLAKISTON, SON & CO. IOI2 WALNUT STREET 1897 Copyright, 1897, By P. BLAKISTON, SON & CO. Press of Wm. F. Fell & Co., 1220-24 SANSOM ST., PHILADELPHIA. TO LEWIS A. STIMSON, M.D., PROFESSOR OF SURGERY IN THE UNIVERSITY MEDICAL COLLEGE OF NEW YORK ; SURGEON TO THE NEW YORK HOSPITAL AND TO THE HUDSON STREET HOUSE OF RELIEF, Zhis Dolume is 2>cC)icateC)t IN TOKEN OF HIGH APPRECIATION OF HIS GREAT KINDNESS AND OF HIS INVALUABLE INSTRUCTION DURING A SERVICE AS HOUSE SURGEON TO THE NEW YORK HOSPITAL, BY THE AUTHOR. PREFACE. The aim of this volume must be stated in clear terms in order that its limitations may be definitely understood, and that it may not go into the hands of the critic as a complete treatise on pathol- ogy. For the medical student the complete text-books of pathology are too full in their text, and more time is required for its mastery than the student can give to this one branch. Furthermore, in the most thorough laboratory courses given by the colleges, only the important pathological lesions are demonstrated, and the student must search through the complete treatise on pathology for the lesion he is studying. The aim of the present volume is to fur- nish the student with a text-book that he can have beside his microscope in the laboratory; a book that gives him a concise and accurate idea of the lesions, is brief in its text, yet omits none of the important pathological lesions, nor the mention of any part in a given tissue change. The method of illustrating by photomicrographs was adopted in order that the student might see in the diagram of the specimen to be studied a picture, not of clear-cut lines, diagrammatic arrange- ment, and magnified clearness of the point to be illustrated, but the actual picture that is given by the specimen under his microscope. In some cases it has been impossible to take a good photomicro- graph of the tissue described, and drawings have been introduced. It is a point of great regret to me that the number of these dia- grams must be limited by the exigencies of publication. The author wishes to express his hearty thanks to Dr. M. A. Brown for his careful reading of the manuscript, and for many V VI PREFACE. valuable suggestions which have added much to the value of the work; to Dr. L. J. Krouse for the specimens used in figures 12, 13, 16, 36, and 97 ; to Dr. D. I. Wolfstein for specimens used in figures 7 and 8; to P. Blakiston, Son & Co. for a uniform courtesy and care in the work of publication. Horace J. Whitacre. 2120 Auburn Ave. , Cincinnati, Ohio. November 12, i8g7. CONTENTS. INFLAMMATION. Exudative Inflammation, 9.—Necrotic Inflammation, 12.—Purulent Inflammation, 13.— Productive Inflammation, 14.—Healing, 15.—Granulation Tissue, 16.—Primary Union, 17.—Infectious Granulomata, 18.—Healing of Bone, 19.—Healing of Nerve, 21. INFECTIOUS GRANULOMATA. Tubercular Inflammation, 21.—Lupus, 25.—Syphilitic Inflammation, 26.—Leprosy, 27.— Glanders, 28.—Rhinoscleroma, 28.—Actinomycosis, 29. DEGENERATIONS. Necrosis, 29.—Cheesy Degeneration, 30.—Gangrene, 30.—Hypoplasia, 30.—Atro- phy, 30.—Cloudy Swelling, 31.—Fatty Degeneration, 31.—Fatty Infiltration, 31.— Mucous Degeneration, 31.—Colloid Degeneration, 32.—Amyloid Degeneration, 32.—Hyaline Degeneration, 33.—Calcification, 33.—Pigmentation, 34. TUMORS. Definition and Characteristics, 34.—Classification, 38.—Fibroma, 38.—Myxoma, 42.— Lipoma, 43.—Chondroma, 43.—Osteoma, 44.—Odontoma, 45.—Angioma, 45.— Myoma, 47.—Glioma, 48.—Neuroma, 49.—Lymphadenoma, 50.—Sarcoma, 50.— Epithelial Tumors, 58.—Adenoma, 58.—Carcinoma, 60.—Differential Table, 67.— Teratoma, 68. THE LIVER. Normal Structure, 69.—Acute Degeneration, 71.—Fatty Infiltration, 71.—Fatty De- generation, 72.—Amyloid Degeneration, 72.—Chronic Passive Hyperemia, 73.— Cirrhosis, 74.—Atrophic Cirrhosis, 74.—Hypertrophic Cirrhosis, 76.—Syphilitic Hepatitis, 77.—Tubercular Hepatitis, 77.—Acute Yellow Atrophy, 78.—Leukemia, 78.—Abscess, 78.—Pigmentation, 80.—Tumors, 80. THE RESPIRATORY SYSTEM. The Lung. Normal Structure, 82.—Acute Bronchitis, 84.—Chronic Bronchitis, 84.—Lobar Pneu- monia, 84.—Bronchopneumonia, 87.—Intra-alveolar Pneumonia, 89.—Pneumonia of Heart Disease, 90.—Interstitial Pneumonia, 90.—Syphilitic Pneumonia, 91.— Tubercular Pneumonia, 91.—Acute General Miliary Tuberculosis, 92.—Subacute Miliary Tuberculosis, 93.—Chronic Miliary Tuberculosis, 93.—Acute Phthisis, 93.— Chronic Phthisis, 95.—Emphysema, 96.—Atelectasis, 97. THE THYROID GLAND. Tumors, 98.—Myxedema, 99.—Exophthalmic Goiter, 99. VII VIII CONTENTS. THE SPLEEN. Normal Structure, 99.—Active Hyperemia, 101.—Chronic Venous Congestion, 101.— Infarct, 101.—Acute Splenitis, 101.—Chronic Splenitis, 102.—Leukemia, 102.— Hodgkin’s Disease, 103.—Waxy, 103. THE GASTROINTESTINAL CANAL. The Stomach. Normal Structure, 104.—Contents, 106.—Acute Gastritis, 106.—Toxic Gastritis, 106.— Phlegmonous Gastritis, 107.—Chronic Gastritis, 107.—Ulcer, 108.—Tumors, 109. The Small Intestine. Normal Structure, 109.—Acute Catarrhal Enteritis, 112.—Typhoid Fever, 112.—Tuber- cular Ulcer, 115.—Differential Table, 115. The Large Intestine. Acute Catarrhal Colitis, 116.—Chronic Colitis, 116.—Croupous Colitis, 117.—Follicular Colitis, 117.—Amebic Colitis, 118.—Necrotic Colitis, 118.—Vermiform Appendix, 118. HEART. Acute Degeneration, 119.—Fatty Degeneration, 120.—Fatty Infiltration, 121.—Brown Atrophy, 122.—Coronary Arteries, 122.—Acute Purulent Myocarditis, 122.—Acute Endocarditis, 123.—Chronic Endocarditis, 124. THE ARTERIES. Normal Structure, 125.—Chronic Endarteritis, 126.—The Aorta, 127.—The Smaller Arteries, 127. THE' KIDNEY. Normal Structure, 129.—Acute Congestion, 132.—Acute Degeneration, 132.—Acute Exudative Nephritis, 133.—Acute Productive Nephritis, 134.—Chronic Congestion, 136.—Chronic Degeneration, 137.—Chronic Nephritis, 137—Chronic Productive Nephritis with Exudation, 138.—Chronic Productive Nephritis :without Exudation, 140.—Suppurative Nephritis, 142.—Tubercular Nephritis, 143.—Cystic Kidney, 143.—Hydronephrosis, 144.—Waxy Kidney, 144.—Tumors, 144. ORGANS OF GENERATION. Endometritis, 144.—Chronic Endometritis, 145.—Septic Endometritis, 146.—Gonor- rheal Endometritis, 147.—Erosion of Cervix, 147.—Tumors of Uterus, 147.—Ovary, 149.—Tumors of Ovary, 150.—Salpingitis, 150. THE BLOOD. Normal Structure, 151.—Leukocytosis, 152.—Lymphocytosis, 153.—Eosinopliilia, 154.— Myelocytosis, 154.—Chlorosis, 154.—Pernicious Anemia, 156.—Leukemia, 157.— Hodgkin’s Disease, 159.—Changes in Special Diseases, 160.—Malaria, 161.— Filaria Sanguinis Hominis, 163.—SpirochetEe of Relapsing Fever, 163. APPENDIX, 164 INDEX, 165 LABORATORY TEXT-BOOK OF PATHOLOGY. INFLAMMATION. Inflammation is the name given to that pathological condition characterized by redness, swelling, increased local heat, pain, and altered functions in the tissues so affected. It is essentially a series of local tissue changes, combined with pathological exudations from the blood-vessels, and in chronic inflammations with the pro- duction of new cells and tissues. It is the response of a living tissue to an injury, be that injury mechanical, chemical, electrical, or parasitic in its nature, provided that its action be sufficient to cause circulatory disturbances with exudation, yet insufficient to cause a death of tissue or an arrest of circulation. I. Exudative Inflammation.—Before the stage of actual inflam- mation sets in there is always an active hyperemia of the tissues, the blood-vessels are dilated, and the blood-current is in conse- quence more rapid on account of the lessened resistance. There quickly supervenes a pathological modification in the structure of the walls of the blood-vessels themselves, and a slowing of the blood-current even to stagnation, accompanying or following which an exudation from the blood-vessels takes place, owing to an increased permeability of their walls. There also occurs an increase in the number of the polynuclear leukocytes in the blood of the inflamed organ, and these leukocytes rapidly collect in the peri- pheral plasma zone of the smaller veins. Here the cells roll along the vessel wall, become adherent, and are dragged into various shapes by the blood-current, or collect in marked accumulations. The important element in the pathological alteration of the vessel wall is a softening and widening of the cement lines between the 10 LABORATORY TEXT-BOOK OF PATHOLOGY. endothelial cells, this giving rise to weakened points in the vessel wall. Consequently, the adherent leukocytes, by virtue of their active ameboid movement, very soon begin to emigrate through the vessel walls in great numbers. The cell sends a minute process through a softened cement line of the veins and capillaries (not the arteries), a knob appears on the outside of the vessel, and the remainder of the cell follows, until finally its entire body is found in the surrounding tissues outside the vessel wall. This cell dies and forms a pus-cell, remains attached to the vessel and organizes into a living tissue cell, or it may wander off in the lymph-spaces. This phenomenon of emigration, it must be understood, is not a passive infiltration, but an active process accomplished by the ameboid movement of the cell, and made possible by the softening of the cement substance. If the inflammatory process be very severe, or if large numbers of leukocytes have emigrated, the cement lines become so perme- able that the red blood-cells are permitted to pass through in rapid succession, under the influence of pressure. This process is called diapedesis. Accompanying and usually preceding the emigration of white and red blood-cells a fluid exudate is poured out into the surrounding tissues, which represents the serum of the blood, modified in some unknown way as it passes through the vessel walls. The process is not one of filtration, but a disordered secretory function of the endothelium, brought about by the change in the vessel wall. This fluid contains a high percentage of albumin, and may also contain the fibrin ferment necessary to cause a coagulation of the exudate with the separation of fibrin. This will account for the serum and fibrin of inflammatory condi- tions. The fate of the various materials which have exuded in this way from the blood-vessels must necessarily be different in the various tissues of the body. In the arm, for example, the serum, fibrin, and red and white blood-cells will be poured out into the connective tissue in large amounts, render the structures edema- tous and boggy, and produce a condition called cellulitis. Serum secreted on a serous surface will form large collections of fluid in the body cavities, as in pleurisy with effusion. If the exudation is cast off on a mucous surface we have a catarrhal inflammation, as in pneumonia and bronchitis. These exudates on a mucous sur- face may coagulate and form a croupous exudate. INFLAMMATION. 11 It remains to account for the small round-cells which are found so abundantly in all inflamed tissues, because they constitute a very important feature in the lesion. They are, undoubtedly, entirely composed of the white blood-cells exuded from the vessels. The connective-tissue cells among which the exudate takes place pro- liferate a little later, but even then the newly-formed cells have not the features of lymphocytes. The leukocytes which are exuded may, in part, return unchanged to the blood by way of the lymph- channels; others take on very rapid proliferation, resulting in a great increase of cells in the tissues to form the small round-cells Fig. i.—Croupous Inflammation. The lower portion of the diagram shows the mucosa of the trachea infiltrated by pus-cells and its vessels are dilated. Above and separated from the mucosa by a clear space is the false mem- brane, made up of pus-cells, epithelial cells, and fibrin. spoken of above; while still others die and form pus-cells, which either collect to produce abscesses, are thrown off as an exudate or false membrane on free surfaces, or disintegrate and are absorbed. Such an exudate, collected in the tissues, may occlude the arteries and produce necrosis and disintegration. Much more frequently, however, the circulation is preserved, the exudate begins to soften with the recession of the inflammatory condition, and is either dis- integrated and absorbed or cast off on free mucous or serous sur- faces. The serum element is rapidly absorbed by the lymph- vessels, but when contained in serous cavities may remain for a long time. The red blood-cells lose their color, disintegrate, and 12 LABORATORY TEXT-BOOK OF PATHOLOGY. are absorbed. The fibrin is either present in such amount as to occlude the arteries and cause death of the tissues, or it softens and disappears, or may become organized into new connective tissue. Any one of the products of exudation may predominate and give rise to serous, fibrinous, purulent, or sanguineous inflammations. Serous exudation into tissues causes edema ; on a mucous surface, catarrhal inflammation. When plastic lymph is thrown out, we speak of the exudate as fibrinous. This exudate is more or less solid in consistency, and forms patches adherent to the surfaces from which it springs. When a fibrinous exudate is confined to a Fig. 2.—Purulent Myositis. Pus-cells are found in abundance between the muscle-fibers. serous cavity, there is usually more or less serous fluid present also, making the exudate serofibrinous. A hemorrhagic exudate most often occurs as a result of intense inflammatory reaction, and is usually associated with the for- mation of fibrin, as in pneumonia. An exudate made up mainly of leukocytes is found in the mucous membrane as a purulent catarrh, in the cavities of the body as empyema, and in connective tissue as purulent infiltration, abscess formation, idcers, etc. The exciting cause in any purulent inflammation is usually some one of the pus-forming bacteria. II. The term necrotic inflammation is one used to cover a INFLAMMATION. number of conditions where, added to the preceding phenomena of simple inflammation, there is also a death of tissue present as the characteristic element. (1) Purulent or suppurative inflammation is the most common, and perhaps the most important, of this variety. It is an inflamma- tion similar in every way to the simple inflammation just described, except that the exudate consists mainly of polynuclear leukocytes in excessive amounts, and these cells are called pus-cells. These pus-cells may infiltrate the tissues diffusely and be found crowded between the elements of the tissue, as, for instance, between the muscle-fibers in an interstitial myositrs, or they will be found closely packed in the tissues, to complete obliteration of the former structures. When there is such a collection of pus-cells, the tis- sues involved soon begin to look yellowish-white, then break down, liquefy, and form abscess cavities filled by pus-cells and broken-down tissue fragments. When the pus-cells collect in body cavities, as the pleura, joints, antrum of Highmore, etc., they form purulent effusions, or empyemata. Such suppurative inflammation, occurring in the skin or mucous membrane, forms ulcers; or, if the exudate be cast off on a mucous surface, it constitutes a purulent catarrh. When there is great transudation of serum along with the pus, it constitutes a seropurulent exudate, and if this exudate invades an extensive area, a phlegmon is produced. Likewise, on serous surfaces we may have a fibrinopurulent exudate. The suppurative inflammations are usually caused by the pres- ence in the tissues of the pus-forming bacteria, and most frequently by the Staphylococcus pyogenes aureus and Streptococcus pyo- genes. Chemical substances, however, such as turpentine, nitrate of silver, mercury, croton oil, sterilized cultures of bacteria, etc., may produce suppuration when introduced into the tissues, yet such an inflammation has none of the virulent characteristics of the bac- terial form. (2) The next variety of necrotic inflammation is one where suppuration does not follow the tissue necrosis, but the areas of dead tissue, which are of definite size, remain unchanged for a length of time, until they are either cast off in bulk or are slowly absorbed. Such a condition is caused by the action of caustic chemical sub- stances, arrest of the blood-supply to a part, high and low tempera- tures, and bacterial infection, such as that produced by the bacteria of typhoid fever, diphtheria, and dysentery. The diph- 13 14 LABORATORY TEXT-BOOK OF PATHOLOGY. theric form of inflammation occurs on mucous membranes as a coagulation necrosis, affecting both the exudate and the inflamed and indurated tissues. (3) The remaining type of necrotic inflammation is one in which the necrosis appears only after new inflammatory tissue has formed and existed for a long time, as in tuberculosis. Here the necrosis is called caseation. III. Productive Inflammation.—According to Dr. Delafield, we may have: (1) A simple, acute, productive inflammation where there is no exudation of serum, fibrin, or pus, but the products of inflammation are entirely represented by new connective-tissue Fig. 3.—Interstitial Inflammation in a Lymph-node. New connective tissue has formed through the node, until only a few islands of cells are left. cells, formed from the old. (2) A productive inflammation with exudation. The usual products of exudation are present, but there is also, from the start, a production of new tissue, which is first composed mainly of cells, but later develops fibers and vessels. This gives rise to the subacute and chronic types of inflammation. The exudate may be, and usually is, absorbed, but the new tissue is permanent, and its organization is usually progressive. The new tissue affects mainly the stroma. (3) There may be a chronic productive inflammation, with or without exudation, but with the formation of round-cell tissue, granulation tissue, or connective tissue. This is the type often called interstitial inflammation. HEALING. 15 Such productive inflammations are very slow in their progress, and tend to continue indefinitely. They are caused by slight but long-continued irritation, as from inhalation into the lungs of coal- dust; by long-continued action of the poisons of syphilis, gout, rheumatism, and alcohol; and by bacteria, in the case of tubercu- losis and other of the infective granulomata. Just the relationship between this type of inflammation and a simple fibrosis occurring in the repair after a simple inflammation, is not yet understood. HEALING. The process of healing or repair after simple inflammation or destruction of tissues must necessarily vary much: (i) With the nature of the causative agent, whether applied momentarily, as in trauma, or during a considerable period, as in bacterial action. (2) Again, it must be very different where there is slight loss of tissue, and where healing takes place by granulation and cicatrization, after extensive loss of substance. No matter what the organ or the character of the tissue destroyed, every extensive loss of sub- stance is replaced by connective tissue. Repair is best understood by studying an open wound of soft parts on the body surface, healing by granulation, and not infected by bacteria. After hemorrhage has ceased, the blood-vessels dilate, the tissues are swollen, serum, fibrin, and white blood-cells exude upon the sur- face and into the tissues, and fragments of tissue necrose. On the second or third day the surface is covered with small red papules, called granulations, and is bathed in an exudate rich in albumin and dead leukocytes or pus-cells. New blood-vessels begin to form at once on the surface of such a wound, by a growth of buds of solid protoplasm from the cells of the walls of old blood-vessels. These buds lengthen out, and are channeled by the blood-pressure from within the vessels, with a simultaneous appearance in the proto- plasm of nuclei to form endothelial cells. These new vessels contain circulating blood, form abundant anastomoses by giving off sprouts themselves, and, by their projection above the normal surface form the papillae which characterize a granulating surface. New connective tissue, of an embryonal type, has meanwhile been forming around these new blood-vessels, as a result of proliferation both from the fixed connective-tissue cells and from the walls of i6 LABORATORY TEXT-BOOK OF PATHOLOGY. the vessels. This tissue is made up of small round-cells, hyper- trophied connective-tissue cells, and round and polynuclear leuko- cytes closely packed together, the only partition being a fluid intercellular substance. From the small round-cells are very soon developed certain large polynuclear cells, with large, oval, clear nuclei, which stain less deeply than those of the other cells. These are the formative connective-tissue cells, and are called epithelioid cells, from their resemblance to epithelium. They increase rapidly in number, until they predominate over the round-cells, and are packed more or less closely together. Certain of these cells, and especially those cells representing hypertrophied connective-tissue Fig. 4.—Granulation Tissue from the Inner Wall of a Granulating Ovarian Cyst. cells, become much enlarged, and spindle-shaped, or branched, to form the fibroblasts, which seem to be especially concerned in the formation of connective-tissue fibers, and which remain as fixed connective-tissue cells. At a certain stage in their develop- ment these fibers appear in the intercellular substance as branches from the cells, or as a formation of fibrillae alongside of them. The round-cells not undergoing these changes seem to die, and are thrown off on the surface of the wound as pus-cells. With the formation of connective-tissue fibers the cells become progressively fewer in number, until the entire tissue is made up of fibers with a few flattened fusiform or branched cells, and we have the condi- tion known as a cicatrix. In other words, healing is complete. HEALING. 17 When the wound is in the skin, the formation of granulation tissue continues until the epithelium, by progressive extension over the granulation surface, has covered the entire surface of the latter. The difference between healing by first intention, or primary union, and healing by granulation in an open wound, although of great importance to the surgeon, is one entirely of degree. In an incised wound, where the parts are drawn accurately into apposi- tion, there is slight necrosis of tissue, and the area into which exudation may take place is of such paper thinness that granula- Fig. 5.—Exuberant Granulation Tissue. Blood-vessels with rapidly proliferating endothelium predominate and project above the surface. Many types of cells are found in the granulation tissue. tions can very quickly fill it. Every stage in the process of healing is identical with that described above, except that the amount of new tissue formed is very much less, and the resulting cicatrix is a mere line. When fibrin forms on an inflamed serous surface, granulation tissue very soon forms beneath it. The fibrin is penetrated from below by vessel sprouts, new tissue cells form, and the mass of fibrin is soon transformed into connective tissue. This results either in a thickening of the serous coat, or, when two serous surfaces are opposed, in adhesions by connective tissue bands. 18 LABORATORY TEXT-BOOK OF PATHOLOGY. Coagulated exudates in the lung may undergo the same organization, and produce the organized or indurated pneumonia. Thrombi and necrotic areas that can not be cast off externally, organize in the same way. Likewise, in abscess cavities and empyemata, the tissues surrounding the necrosed area begin to heal, form granulation tissue, and, with the absorption or evacuation of the pus, the cavity will be filled by new granulation tissue and eventually cicatrize. In some granulation surfaces the tissue growth does not keep pace with the formation of new blood-vessels, and the surface is one mass of thin-walled capillaries, projecting high above the surface. Flabby, pale granulations are formed and the wound Fig. 6. —Organized Thrombus in Anterior Tibial Artery. Man aged thirty-five, gave symptoms of slow but progressive gangrene of toes and foot. The lumen of the vessel is filled by a typical granulation tissue, rich in blood-vessels. does not heal. These are called exuberant granulations, or “proud flesh.” Certain chronic granulations form spongy, tumor-like growths, and are called fungous granulations or infectious granu- lomata. These are caused by a specific infection, as by the germs of tuberculosis, syphilis, leprosy, glanders and farcy, rhinoscleroma, and actinomycosis. Inflammation may pursue a chronic course (i) because the tis- sues may be unable to recover immediately from great loss of sub- stance, and regeneration must go on slowly. (2) There may be present a continued irritation, as is seen in the progressive connec- tive-tissue thickening in the lungs as the result of the inhalation of HEALING. 19 coal- or stone-dust, or as is seen in the formation of condylomata on parts constantly bathed with acrid discharges. (3) Chronic congestion plays an important part and acts, doubtless, by disturb- ing the nutrition of the parts. This is illustrated by the varicose ulcer of the leg or by chronic inflammation of any one of the viscera follow- ing a chronic congestion. (4) Infection by bacteria or molds, as is seen in gonorrheal and tubercular inflammation of mucous mem- branes. (5) Chronic intoxications which seem to affect mainly the liver and kidneys, as is seen in the poisoning of syphilis, alcohol, lead, etc. Healing of Bone Fractures. The healing of bone varies from that taking place in soft tissues, alone in the fact that the lime salts are present and the cicatrix is bone. With a fracture of a bone the periosteum and surrounding tissues are lacerated and blood is poured out between the ends of the bone and forms a fusiform tumor around the seat of injury. A simple exudative inflammation follows, with an infiltration of the tis- sues by leukocytes and serum ; the blood is absorbed, and in a very few days, with a subsidence of the inflammation, a soft granulation tissue is formed. This granulation tissue is formed (i) around the bone, and extending for some distance above and below the line of fracture, to form a spindle-shaped tumor, which will later become the ensheathing callus ; (2) it replaces the medulla for some distance up and down the canal, to form, later, the internal callus; and (3) it forms between the ends of the fragments, receiving its new capillary buds from the vessels of the Haversian canals, and gives place to the intermediary callus. The ends of the bone, meanwhile, have under- gone a rarefying osteitis and become soft and porous, and the granu- lation tissue entirely changes into cartilage or into firm connective tissue, called osteoid tissue. Ossification begins around the vessels in the angle between the torn up periosteum and the bone. Irregu- lar branching lamellae of bone form through the callus under the action of the osteoblasts, Haversian canals continuous with those of the bone form between the lamellae, and the ends of the fracture are surrounded by a mass of spongy bone, which lasts until healing is complete. Meanwhile, the medulla has been undergoing the same changes, and is also filled by newly-formed bone. The soft, rarefied ends of the bone show an enlargement of the Haversian canals, and are united by a mass of spongy bone. LABORATORY TEXT-BOOK OF PATHOLOGY. 20 When union is completed an absorption of the callus takes place. This begins first in the medullary canal, which again becomes per- Fig. 7.—Healing of Bone Fracture. Laminae of new bone are forming through the granulation or osteoid tissue. vious, and there is a gradual disappearance of all excess of bone and a return to .normal. With imperfect apposition of the ends of Fig. 8.—Healing of Bone Fracture. Two laminae of new bone are represented with osteoblasts along their borders. a fracture, angular deformity, etc., a large mass of callus remains permanently. TUBERCULAR INFLAMMATION. 21 Repair of Nerves. After the division of a nerve there is a degeneration in the entire peripheral portion, and also, to a limited degree, in the central end of the nerve, dependent undoubtedly upon the separation from their neurons. The medullary sheaths break up into droplets, which degenerate, become fatty, and after a time are absorbed, and the axis-cylinder shares in the destruction and complete absorption. The neurilemma and its nuclei, however, are preserved, and it is from these nuclei that regeneration takes place. By the seventh day an active proliferation sets up in these nuclei, and they are found free in the cavity of the internodal space; yet protoplasm soon collects around them, and a fusion of such cells forms a solid rod of proto- plasm, or an embryonic nerve-fiber. A new nerve-sheath is formed from the outer layers of the protoplasmic cord, and healing is complete. These changes of regeneration go on, provided the divided nerve-ends are reunited by suture or otherwise; but if they remain apart, the proliferation of nuclei is slow at the beginning, and finally ceases without forming the embryonic fiber. It will be observed that this regeneration is entirely from pre-existing nerve tissue, and not from the connective tissue of the perineurium and endoneurium. TUBERCULAR INFLAMMATION. Tubercular inflammation is a specific inflammatory process caused by the presence and growth of the tubercle bacillus. This is a disease affecting both man and animals, and consequently in any inhabited region immense numbers of bacilli are thrown off in the sputum and excreta and are spread broadcast. These germs retain all of their virulence, even when dried, and are ready to set up a local tubercular inflammation at their point of lodgment whenever they gain entrance into the body. They gain entrance most frequently, of course, to those places which are accessible from without, as, for instance, the lungs, intestines, and skin; yet there are many cases where the first indication of lesion is in some deep-lying tissue, as the testicles, lymph-nodes, bones, or joints, and we must infer that the germs gain entrance into the blood- and lymph-vessels through some imperceptible abrasion on the surface of the body and leave no evidence of infection at their point of entrance. 22 LABORATORY TEXT-BOOK OF PATHOLOGY. The tubercle bacillus sets up in the tissues a proliferation of the fixed connective-tissue cells, and an exudation of white blood-cells Fig. 9.—Typical Miliary Tubercle, from a Lymph-node in a Child. A giant-cell, epithelioid cells, and small round-cells are present. Fig. io.—Vessel Infection in Tuberculosis. The clear carrot-shaped space to the left represents a blood-vessel, in the wall of which tubercle bacilli have lodged to form the miliary tubercle. from the vessels with the formation ot circumscribed nodules of cells, which remain devoid of blood-vessels and after a time necrose. The first effect of the presence of the tubercle bacillus in the TUBERCULAR INFLAMMATION. 23 tissues is a stimulation of karyomitotic proliferation in the fixed connective-tissue cells, with the development of large mononuclear cells resembling epithelium and called epithelioid cells. At the same time one or more giant-cells, containing many large oval nuclei, are usually formed in the rapid proliferative process. These cells form more or less definitely circumscribed spheroidal masses around the bacilli, and are called tubercles or miliary tubercles. The reticulum of the normal tissues is pushed apart by the new forming cells, until a fine network alone separates the cells, or this reticulum of the tubercle is a new formation going on with the development of the cells. New blood-vessels do not form in this Fig. ii.—Bronchial Infection in Tuberculosis. A bronchus is shown in the center of the field, the walls of which are replaced by tubercle tissue. new tissue, and the old vessels are obliterated as the process invades them. Besides this obliteration set up in the blood-vessels of the tissues invaded by the tubercular process, there is a further altera- tion in the surrounding vessels, which results in an exudation, sooner or later, of large numbers of leukocytes, which latter also enter into the formation of the tubercle. The exudation of white blood-cells may be very limited and the miliary tubercle consist mainly of epithelioid and giant-cells with a few small round-cells ; or, on the other hand, it may take place very early, and in this case the small round-cells will characterize the tubercle throughout, and the large epithelioid cells will be either entirely absent or appear 24 LABORATORY TEXT-BOOK OF PATHOLOGY. only at a later stage. Such a completely formed tubercle appears in the tissues as a small, circumscribed, translucent collection of cells about the size of a millet-seed. When it has reached this development, however, retrograde changes take place by which the cells in the center of the tubercle undergo that form of necrosis known as cheesy degeneration, and the nodule becomes a cheesy mass surrounded by a zone of cells. The tubercle now has an opaque yellowish-white appearance. The subsequent history of such miliary tubercles varies considerably: (a) Secondary in- fection by the pus-forming bacteria may take place, with rapid breaking down and abscess formation; (b) fibrous tissue may form around the miliary tubercle and lead to its complete oblitera- tion and cure ; or (e) new tubercles may form about the primary focus through the lymph-channels, thus leading to extension of the disease and its diffusion throughout the organ. It is evident that there may be many types of miliary tubercles : 1. The tubercles may be wholly made up of small round-cells. 2. They may be entirely made up of large epithelioid cells. 3. There may be both epithelioid and round-cells uniformly inter- mingled, or the small round-cells may be arranged in a zone around a central collection of epithelioid cells. 4. Giant-cells may be, and usually are, mixed with the preceding types. 5. Caseation takes place in the center of any one of these forms. Diffuse Tubercular Inflammation.—When there is a very extensive infection by tubercle bacilli, the miliary tubercles will be very numerous. These extend, as has been explained, by the formation of other tubercles about the primary focus through the agency of the lymph-channels, and great numbers of tubercles run together in this way to form extensive areas of tubercle tissue in more or less advanced caseation. Such areas are found in the lungs, brain, serous membranes, lymph-nodes, kidneys, prostate, testicles, etc. Another type of diffuse tubercular inflammation is that which we find in an acute phthisis, where the predominant element is a severe inflammatory reaction to a very virulent infection, with the pouring out of large quantities of the products of simple inflammation. These products undergo very rapid caseation before the typical organized tissue of small round-cells has had time to form. Disseminated tuberculosis is the name sometimes given to LUPUS, 25 that form of the disease where one organ after another is infected from a primary focus. Thus, with a primary tuberculosis of the lung there may be a secondary tuberculosis of the liver alone, of the kidney alone, of the meninges, or of several organs simultane- ously, or of one organ after another. This dissemination occurs, of course, by a breaking through of the tubercle bacilli into the blood-current, whence they are carried to distant parts. LUPUS. Tuberculosis may occur in the skin as a result of direct infection, or about sinuses leading to areas of tubercular inflammation, but the typical skin tuberculosis is lupus. This is characterized by the appearance of multiple small, reddish-brown nodules of granulation tissue in the skin of the face, and, much less frequently, in the mucous membrane of the mouth, conjunctiva, vulva, and vagina. These nodules may run together, forming a more or less extensive area of infiltration ; the epithelium over them is increased exces- sively in amount, and the nodules break down and ulcerate, or they degenerate, absorb, and leave a white scar, without ulceration. The disease begins between the age of two years and puberty, and its course is always chronic. Microscopically, the nodules consist of small round-cells of granulation tissue, epithelioid cells, and often giant-cells. These cells are supported by a well-developed reticu- lum, and the nodule differs from a miliary tubercle of other parts in being rich in blood-vessels. The tubercle bacillus has been found constantly present in small numbers. The course of tuberculosis is usually chronic. Ulcers form if the broken-down nodule is on the skin, or cavities and systems of cavities, lined by a pyogenic membrane, form when the lesion is deep in the tissues. Extension may be by the lymph-channels, or foci may break into an artery, when the bacilli will be carried to distant parts, and form metastatic growths of tubercle tissue. It has been found by Prudden that dead tubercle bacilli set up the same pro- liferation of the tissues, with the formation of miliary tubercles identical in structure with those caused by living germs ; but coagu- lation necrosis and systemic intoxication are absent. 26 LABORATORY TEXT-BOOK OF PATHOLOGY. SYPHILITIC INFLAMMATION. Syphilitic inflammation occurs only in man. It bears a close analogy to tubercular inflammation, and is caused by a bacillus described by Lustgarten, which also resembles very much in its appearance the tubercle bacillus. The bacillus of syphilis, how- ever, produces the greatest variety of inflammatory reactions, ranging from a simple hyperemia to extensive tumor formation or connective- tissue growth. Infection takes place by direct or indirect transfer of the virus from one person to another, or it may be inherited. The primary focus of infection, or the hard chancre, or Hun- The skin surface is shown on the left and the surface of the ulcer on the right, with a round-cell infiltration deep into the tissues. Fig. i2.—Chancre of the Lip. terian induration, is a circumscribed area of dense, small round- cell infiltration in which are found a few epithelioid, and, some- what later in its development, giant-cells. The area is hard, and remains fibrous or breaks down, ulcerates, and heals by cicatrization. The secondary lesions consist of an inflammation of the lymph- nodes, skin, and mucous membranes. In these lesions there is a round-cell infiltration, associated with a hyperplasia of the fixed tissue cells. In the skin the papillae especially are infiltrated with cells and fluid exudates, the epithelium is increased in amount, is infiltrated by round-cells, and is gelatinous. The syphilitic lesions occurring in the internal organs and belonging to the tertiary stage LEPROSY. 27 are usually called gummata. These appear in the periosteum, brain, liver, spleen, testicles, etc., as grayish-white or grayish-red firm masses, with a cheesy center and a translucent outer zone. They are usually rich in small round-cells, and seem to be true granulation tissue, with new but poorly-formed blood-vessels. These gummata undergo coagulation necrosis or cheesy degenera- tion, and their peripheral portions merge into connective tissue, which surrounds the caseous masses. This connective tissue radiates in rays into the surrounding tissues. Syphilitic endarteritis constitutes an important lesion of syphi- litic inflammation. The changes which take place, especially in the Fig. 13.—Venereal Wart from the Vulva. There is a slender branching stalk of fibrous tissue, covered by thick layers of epithelial cells smaller arteries and veins of the brain, consist in a growth of new tissue, resembling granulation tissue, beneath the endothelium which leads to a gradual narrowing of the lumen. This tissue later becomes more fibrous; furthermore, the endothelium becomes altered and the blood coagulates to form thrombi, with resulting cerebral softening. LEPROSY. Leprosy is an infectious disease which is common in India and the hot countries, and there are isolated cases in other regions. It 28 LABORATORY TEXT-BOOK OF PATHOLOGY. is caused by the presence of the lepra bacillus, and is characterized by the formation in the skin of exposed parts (rarely in subcu- taneous tissue, viscera, etc.) of nodules or masses of granulation tissue, made up of small spheroidal cells, large round-cells, and branching cells supported by a stroma. These nodules are minute, or one inch in diameter; they push aside, are intermingled with, or cause an hypertrophy or an atrophy in the tissues invaded. The nodules remain a long time, or ulcerate, or form white cicatrices without ulceration. Certain nerve lesions are secondary to the disease. GLANDERS. This is an infectious disease affecting the nasal mucous mem- brane of the horse, which is caused by the Bacillus mallei, and may be communicated to man. Occurring in the skin of the horse, it is called farcy. The seat of infection in man is usually the skin, but it may be found in the mucous membrane, lungs, kidneys, testes, spleen, and liver. Small round and epithelioid cells (no giant-cells) infiltrate the tissues diffusely or are collected in circumscribed masses, which appear as small white foci, much resembling miliary tubercles, or as large-sized nodules. These soon break down, to form abscesses or ulcers when near the surface, and the skin will be covered with a pustular eruption, and the deeper structures con- tain abscesses of varying size. The nodules may pursue a very chronic course without abscess formation, and such persistent masses are differentiated from miliary tubercles by the absence of cheesy degeneration and giant-cells in the former. The bacillus is abundant in fresh nodules, but found with difficulty in the degen- erated nodule. RHINOSCLEROMA. This is a chronic inflammation of the mucous membrane of the nose, pharynx, and larynx, caused by the Bacillus rhinoscleromatis, and characterized by the formation of granulation tissue in nodules and masses, which soon become dense and cicatricial. DEGENERATIONS. 29 ACTINOMYCOSIS. Actinomycosis (ray fungus) is an infectious disease, caused by the actinomyces, which is a micro-organism belonging undoubtedly among the bacteria. The germ develops to form radiating fila- ments with club ends, hence the name “ ray fungus.” In cattle it constitutes “ lumpy jaw,” whereas in man a granulation tissue is formed around the fungous mass, making a tumor formation, which is characterized by early necrosis and sloughing, with abscess formation. Such tissue is found in the lungs, skin, lymph-nodes, gastro-intestinal canal, etc. The fungus is diagnostic, and appears as yellow masses, the size of a millet-seed, scattered through the new tissue and contained in the pus. DEGENERATIONS. In the tissues of the body are certain retrograde changes in the structure of the tissues, dependent upon general or local causes, and leading to a diminution in the size of any given organ, the destruction of its element, and an impairment or total loss of its function. There are many types of degeneration, each one of which will be taken up in order. Necrosis. Necrosis is a local death of tissue cells, with consequent cessa- tion in their function. It is caused by lack of nutrition, diminished oxygen supply, mechanical injury, high temperature, chemical agents, poisons, and trophic nerve disturbance. While these may be given as exciting causes, the effect produced, however, by their action, seems largely dependent upon the condition of the tissue at the time when such causes act. The cells may gradually lose their nuclei, break down, soften, and form a fluid, degenerated mass, or they will be swollen and granular, disintegrate, become pigmented by broken-down blood-cells, and contain bacteria. The surround- ing tissues are inflamed. Complete regeneration may take place in 30 LABORATORY TEXT-BOOK OF PATHOLOGY. the degenerated areas, or cicatrization, calcification, or cyst formation may follow. Coagulation Necrosis. In coagulation necrosis the cells become transparent, lose their nuclei, are shrunken and distorted. This is due either to certain chemical elements present (ferments or bacterial products), produc- ing coagulation of the albuminous constituents of both exudate and cell, or to normal body fluids flowing over the necrotic area. Cheesy Degeneration. Cheesy degeneration is a term used to designate that type of degeneration in which the cells lose their nuclei, become granular, fatty, or homogeneous, and run together to form masses resembling hard or soft cheese. This mass is made up of fatty and albuminous debris, of granules and indistinct fragments of tissue, but no cell outlines. It occurs in tubercular and syphilitic inflammation. Liquefaction Necrosis. In liquefaction necrosis the degenerated tissues are infiltrated by liquids, break down, and become fluid. Gangrene. Gangrene is death of tissue large enough to be seen with the naked eye. Dry gangrene results from a gradual stoppage of arterial supply, with unimpaired venous return, while in moist gangrene there is a sudden stoppage of arterial supply or of venous return, with decomposition and putrefaction of the necrotic tissues. Hypoplasia. Hypoplasia is a defective development of the entire body, of certain organs, or parts of organs. Atrophy. Atrophy is a diminution in the size of an organ, dependent upon a decrease in the size or entire disappearance of the structural elements composing it. It maybe a simple atrophy, with no change in the structure except the diminution in size of the elements; or it may be a degenerative atrophy, where the cells become granular or CLOUDY SWELLING.—MUCOUS DEGENERATION. 31 fatty, lose their nucleus, swell up, then degenerate, liquefy, and disappear. Atrophy may be senile, from impaired nutrition, inflam- mation, pressure, disease, or it may be neuropathic. Cloudy swelling, or parenchymatous degeneration, is a degener- ative process taking place in the parenchyma cells of organs, and is found in the acute infectious diseases, fever, burns, and poisoning from phosphorus, arsenic, and acids. The cells swell up, become cloudy, and filled with small albuminous granules, so that the normal structure and form of the cell is lost. It is a beginning disorganization of the cell protoplasm, and the cell may go on to complete disintegration or return to its normal condition. Such an organ appears gray and cloudy, anemic, and, in the more advanced cases, is doughy in consistency, and looks as though it had been boiled. Cloudy Swelling. Fatty Degeneration. Fatty degeneration is a degenerative process in which minute fat droplets are formed in the cell at the expense of its protoplasm. The fat droplets are very small, as a rule, but may coalesce to form larger drops. In far advanced cases the cells may be broken up into a cell detritus, composed of granules, fat droplets, and some- times cholesterin crystals. It is a process which is undoubtedly dependent upon a lessened food and oxygen supply to the organ, together with a lowered vitality on the part of the cell itself. Thus, in anemia from hemorrhage, or in certain diseases associated with profound anemia, and with many poisons, we are apt to find this condition. Fatty Infiltration. Fatty infiltration is a condition where the fat is formed outside the cell body and deposited in its protoplasm. The fat droplets are much larger than in fatty degeneration, as a rule, and the condition is less serious. Mucous or mucoid degeneration has its analogue in the normal physiological production of mucus in the epithelial cells of the mucous membrane and glands. Here the mucous cell becomes transparent, swells up, loses its granules, and discharges its mucus. Pathologically, the protoplasm of the epithelial cells and connective- tissue group may degenerate into this type of tissue, and take on Mucous Degeneration. 32 LABORATORY TEXT-BOOK OF PATHOLOGY. a translucent, gelatinous, and swollen appearance from conversion into mucus. In connective tissue the degeneration may be con- fined to the intercellular substance, and the cells suffer only secondarily, by pressure and lack of nutrition. The gelatinous substance found in such degeneration is of complex chemical composition, with mucin and pseudomucin as the important con- stituents, and it is precipitated by acetic acid. It occurs in mucous membrane, tumors, cartilage, and bone. Colloid Degeneration Colloid degeneration is a change closely related to the preceding form, but it takes place in the cell protoplasm alone, and not in the connective tissue. The colloid material collects in droplets ol varying size, and may cause complete degeneration of the cell. It has a homogeneous appearance similar to mucus, but is usually firmer and more consistent. It does not swell or dissolve in water and is not precipitated by acetic acid or alcohol. Colloid material normally exists in the thyroid gland, and this is the seat of its most frequent pathological formation. It also occurs in the renal tubules, the gastric mucous membrane, and the pituitary body of the brain. Amyloid, waxy, or lardaceous degeneration is a peculiar degen- erative process, where a firm, clear, albuminous substance, called amyloid material, is deposited in the walls of the blood-vessels and in the connective tissue of various organs of the body. The spleen, liver, kidney, intestinal tract, suprarenal capsules, lymph- nodes, and connective tissue are most frequently affected, and in the order named. The organ increases in size, becomes firm, and presents, on cut surface, clear, waxy areas, which may be seen with the naked eye when the process is extensive. Hence the name “ waxy liver ” and “ sago spleen.” When fresh tissue is treated with a solution of iodin and potassium iodid (Lugol’s solution), the amyloid areas are brought out in mahogany-red color. When sec- tions are stained deeply in a one per cent, aqueous solution of methyl-violet and mounted in glycerin, the amyloid material is stained a rose-red color, while the remaining tissues are stained deep-blue. Amyloid material is a firm, translucent, or glassy albu- minous material, which is clearly deposited in the walls of the arteries and capillaries and between the fibers of connective tissue. Amyloid Degeneration. HYALINE DEGENERATION.—CALCIFICATION. 33 The wall of the blood-vessel appears as a thickened ring with a pro- gressively narrowing lumen. The parenchyma cells of the organ are not invaded, and suffer only from pressure when the deposit is great. It occurs in cachectic conditions, especially with suppura- tion and bone disease, tuberculosis, syphilis, dysentery, leukemia, etc. The impaired nutrition of the cells in such conditions seems to favor the formation of amyloid material from certain materials contained in the blood. The name amyloid was given because of a supposed resemblance to starch, but it is now proven to be a nitrogenous and not a carbohydrate substance. Corpora amylacea are amyloid concretions found in the central nervous system and prostate gland. They occur both normally and under pathological conditions. These bodies, however, do not appear to belong to the type of progressive amyloid degeneration, although they do give the amyloid reactions. Some appear to be formed from the albumin of the affected tissues, while others are made up of degenerated epithelium. Hyaline Degeneration. Hyaline degeneration is a process closely allied to the preceding form, and occurring in the walls of the smaller blood-vessels and, occasionally, in connective tissue. It does not give the amyloid reaction. Hyaline material is a transparent, glassy substance, staining deeply with eosin and deposited immediately beneath the endothelium of the blood-vessels, thus rapidly diminishing their lumen, often to complete obliteration. Seat of Occurrence.—It occurs in the brain, lymph-nodes, ovaries, kidneys, eyes, etc., as a result of tubercular or syphilitic disease. A form of this degeneration, belonging to old age and occurring in the valves of the heart, blood-vessels, thyroid gland, and the stroma of tissues, has been called by Virchow sclerosis. Calcification. Calcification is a condition where granules of the phosphate and carbonate of calcium are deposited both in the cells and stroma of tissues. The cause is undoubtedly a preceding degenera- tive change of the tissues, leading to an attraction of lime salts to them. 34 LABORATORY TEXT-BOOK OF PATHOLOGY. Pigmentation. Pigment exists normally in the body in the rete Malpighii, the choroid, ganglion cells, red blood-cells, etc. Pigment may be deposited pathologically in the cells and stroma of many different tissues as yellow, brown, black, or red granules, but its origin and formation are no better understood than that taking place in nor- mal tissues. Pigment formed by the breaking down of red blood- cells may be in the form of red plates and needle crystals of hema- toidin, or it may be the yellow or brown iron-containing pigment hemosiderin, which gives rise to the condition called hemochroma- tosis. As a result of the action of the plasm odium malariae upon the blood, two very different pigments are formed. There is one which lies within the bodies of the plasmodia, is black in color, gives no iron reaction, and is very little understood, while the other, hemosiderin, is dissolved in the plasma of the blood as a result of the destruction of red blood-corpuscles, and is deposited later in liver, spleen, etc., to produce a malarial pigmentation of these organs. The yellow pigmentation of jaundice is a deposition in the tissues of yellow granules or crystals derived from bile in the blood. In many pathological conditions the pigment, which is normally formed in given amount within the cells, may increase— e. g., in the pigmentation of the skin in pregnancy and Addison's disease, in pigmented moles, and the blue-black pigmentation of melanotic tumors, etc. Instances of pigmentation due to intro- duction of pigment from without are found in the deep skin pigmentations following the use of large doses of nitrate of silver. Tattoo markings and the occurrence of coal-dust in the lungs will serve as further examples. A tumor, or neoplasm, or new growth, is a new formation of tissue, possessing an atypical structure, not exercising any function of service to the body, and presenting no typical limit of growth ; or it may be defined as an atypical new formation not the result of “ inflammation.” Tumors, as a rule, reproduce with more or less deviation the TUMORS. TUMORS. 35 structure of the part in which they primarily grow. They are characterized by an independent or lawless growth, their structure is without rule or uniformity, and their history is outside of any physiological limitation. The type of tissue in a tumor may be the same throughout its life history, or it may change to another type within its general class. Tumors are usually sharply circum- scribed and well defined from the surrounding tissues, yet, on the other hand, they may shade off so imperceptibly as to make it impossible to place a line of limitation. The new tissues grow imperceptibly, or with such rapidity that their vessels, stroma, and cells are imperfectly formed, thus subjecting such tissues to every retrograde or degenerative change. Tumors usually exist singly, but there may occur simultaneously great numbers of any given type of tumor scattered throughout the body. Different varieties of tumor may coexist entirely independent of one another, or, from one tumor, metastases may form in many distant parts of the body. All tumors develop by a proliferation or rapid karyomitosis in the cells of the tissue from which they spring, and by a formation of new blood-vessels. Subsequent growth of the tumor is principally by rapid division of the primary tumor cells, yet, less prominently, by the transformation into tumor tissue of the cells of the tissues invaded and of the white blood-cells. Tumors behave differently in their mode of growth, (i) They may grow equally in all their parts and entirely within themselves, so that the surrounding tissues are involved only by pressure. This is called central growth. (2) A tumor may grow mainly on the surface, by forcing its way into the intercellular spaces of the tissues about. The tissues thus invaded are also stimulated to proliferation, and a growth takes place both from tumor cell and normal tissue cells. This is called growth by peripheral infil- tration. (3) Tumor cells may be carried a short way by the blood- or lymph-vessels where they lodge, and develop into tumors which will soon fuse with the mother tumor. This constitutes dis- continuous peripheral growth in a tumor. When the tumor cells taken up by the blood- or lymph-vessels are carried to points distant from the primary growth, they lodge and develop into tumors identical in structure with the primary tumor, and we have that very important method of dissemination known as metastasis. When we consider the poorly-formed blood- 36 LABORATORY TEXT-BOOK OF PATHOLOGY. and lymph-vessels resulting from such rapid development, indeed, the formation of the very vessel wall, at times, by tumor cells, it is not surprising that metastases should form. One cell, detached, will be swept away in the current, lodge in some remote part, and, by rapid cell division, form a secondary or metastatic tumor. Metastasis through the lymph-vessels usually takes place in those vessels, and in the first set of lymph-nodes which receive lymph from the organ involved ; while that through the blood-vessels may occur in any remote organ of the body, but usually is found in the first set of capillaries through which the venous blood must pass in coming from the tumor; hence the frequency, indeed, almost the rule, of secondary tumors of the liver in carcinoma of the stomach. The retrograde or degenerative changes taking place in tumors are : fatty and myxomatous degeneration, hemorrhage with result- ing necrosis or pigmentation, calcification, cyst formation, and cicatrization. Germs may gain entrance and set up a simple or suppurative inflammation in the tumor, or superficial necroses may form ulcers. Tumors are divided clinically into the benign and malignant. If by malignancy we mean death-producing, then all tumors may be malignant if located in the right place; as, for instance, a brain tumor or a tumor of the larynx. There are, however, certain characteristics of malignant tumors which divide them sharply from the benign: (a) A rapid infiltration of the surrounding tissues without limitation; (b) their tendency to ulceration and necrosis; (c) a tendency to local recurrence when once removed, dependent undoubtedly upon a failure to remove all tumor cells; (d) the formation of metastatic growths in remote parts of the body; and (e) a condition of anemia, feebleness, and a diminished general nutrition which is commonly known as cachexia. The cachexia seems dependent, in part, upon a diminution in the nutritive supply, by the rapidly-growing tumor, but is, perhaps, most influenced by interfered nutrition and assimilation, due to the location of the growth (esophagus, stomach); or upon loss of sleep, from pain, from degeneration, with suppuration and ulceration. It may, furthermore, be due to various toxic agents produced by the tumor in its growth. Many causes are given for the development of tumors, (i) The most probable explanation is Cohnheim’s theory of misplaced or superfluous embryonic cells. According to this theory, certain TUMORS. 37 embryonic cells have failed to develop, and remain dormant, ready to start up in active growth at anytime. When this growth does begin, all the unrestrained activity and force of embryonic tissue is manifested in the midst of adult tissue, where the cells are under the limitation of growth expressed by physiological co-ordination. Nobody has seen such an embryonic cell, but the theory would seem to explain many points concerning tumors, such as their heredity, congenital nature, abnormal and atypical structure, their multiplicity, and their occurrence in tissues of entirely different structure. (2) Trauma certainly seems to be a cause in a certain small percentage of cases, because of the frequency of*the carci- nomata at points subjected to greatest irritation, as the mouth, pylorus, ileo-cecal valve, and anus. (3) They follow inflammation, especially where there is ulceration or scar formation. Such cases are found in cancer of the stomach, beginning in the edge of a simple ulcer, or in cancer of the gall-bladder, where gall-stones have produced ulceration. (4) There seems to be a balance of forces between the elements of any tissue. With the atrophy of one element, the restraining influence over the other is gone, and the remaining element grows without limitation. Such seems a cause of epithelioma where, in old age, the connective tissue atrophies and the epithelium grows unrestrainedly. (5) A bacterial origin is not proven. (6) Certain protozoa and other cell inclu- sions are given a place among causative agents, but such connec- tion is not established. Tumors are best classified according to their embryonic origin. The cells of the embryo are arranged in two layers, the archiblast and parablast. The archiblast divides (1) into an outer layer, or epiblast, which supplies the epithelium of the skin and its adnexa, the epithelium of the terminal portions of the alimentary canal, the nervous system, and the neuroglia; (2) into a middle layer, or mcsoblast, from which spring the smooth and striped muscle-fibers and the epithelium of the genito-urinary tract; and (3) into an inner layer, or hypoblast, which gives origin to the epithelium of the respiratory and alimentary tracts together with all the connected glands. The parablast develops later than the archiblast, but its origin is not fully understood. From it are formed all connective tissue, including cartilage, bone, teeth, and fat, the blood-vessels and blood-cells, the lymph-vessels and tissues, and the endothelial cells. 38 LABORATORY TEXT-BOOK OF PATHOLOGY. CLASSIFICATION OF TUMORS. I. Type of Fully-developed Connective Tissue. Physiological Type. Fibrillar connective tissue. Mucous tissue. Adipose tissue. Cartilage. Bone. Lymphoid tissue. Neuroglia. Tumors. Fibroma. Myxoma. Lipoma. Chondroma. Osteoma. Lymphoma. Glioma. Parablast II. Type of Embryonic Connective Tissue. Sarcoma in all of its varieties. III. Type of Higher Tissues. Muscle. Nerve. Blood-vessels. Lymphatic vessels. Myoma. Neuroma. Angioma. Lymphangioma. IV. Type of Epithelial Tissues. Archiblast Papillae of skin or mucous membrane. Glands, Papilloma. Adenoma. Carcinoma. V. Teratomata, or Congenital Mixed Tumors. Fig. 14.—Fibroma Durum. The entire structure of the tumor consists of wavy fibers of connective tissue, with very few blood-vessels. FIBROMA. The fibroma is a benign tumor composed of fibrillar connective tissue. Varieties.—1. The fibroma durum is a hard nodular tumor, tough in consistency, glistening white, and made up almost en- FIBROMA. 39 tirely of thick bundles of fibers in irregular arrangement. Among the fibers are a few flattened or spindle-shape cells and an occa- Fig. 15.—Fibroma Molle from the Nose. Large, branching cells are numerous; the connective-tissue fibers are loosely arranged, and blood-vessels are numerous. Fig. 16.—Papilloma of the Bladder. sional blood-vessel. Examples of tumors of this type are found in the fibromata of the periosteum, uterus, testes, etc. 2. In the fibroma molle, round-, spindle,-and branched-cells are abundant. The fibers are few in number, loosely arranged, and 40 LABORATORY TEXT-BOOK OF PATHOLOGY. separated by a gelatinous, albuminous material. The tumor is soft, translucent, grayish-white, and contains many blood-vessels. The nasal polypi represent soft fibroma. Fig. 17.—Intracanalicular Fibroma of the Breast. The clear bands represent the lumen of a former duct into which the fibrous projections have grown. Fig. 18.—Papilloma of the Ovary. Each stalk or branch of the tumor is covered by a single row of cuboidal cells. 3. When a fibroma forms in the skin or mucous membrane, it grows from the papillary layer, and the epithelial cells covering these papillae keep pace in their growth. This is called a papil- FIBROMA. 41 loma. The papilloma is often considered as a separate tumor of the epithelial type, and it would seem more accurate to classify it as such in cases of papilloma of the ovary, bladder, intestine, in condylomata, etc., where the connective-tissue element is merely a very thin branching stem and the main element in the tumor is epithelial cells. 4. Intracanalicular fibromata are tumors formed within the ducts of glands. Fibrous polypi of irregular shape grow from the walls of the ducts into their lumen. A single layer of epithelial cells covers these polypi, and on section there appears a solid mass Fig. 19.—Keloid from the Shoulder of a Negro, where it Occurred Without Previous Injury. The body of the section is of a firm fibrous structure, and its edge, which represents the surface of the tumor, presents a skin covering containing, in the deeper layer, the black pigment of the negro race. of connective tissue, divided up by irregular fissures which are lined by a single row of cuboidal cells. These tumors often grow to large size, and occur most frequently in the breast. 5. The pericanalicular fibroma is a type of tumor in which the fibrous tissue is deposited cylindrically about the duct but does not grow into the lumen. 6. Fibroma molluscum is a name given to multiple, soft, wart- like fibromata occurring in the skin. They are neurofibromata formed on or around the peripheral terminations of the cutaneous nerves. 7. Keloid is an irregular, radiating new formation of connective 42 LABORATORY TEXT-BOOK OF PATHOLOGY. tissue in the skin and subcutaneous tissue. It has the structure of a hard fibroma and looks like scar tissue, but occurs either sponta- neously or in a scar after injury. Keloids are common in the negro. MYXOMA. Connective tissue in its embryonic condition consists almost entirely of spheroidal cells with a small quantity of fluid lying between them. As development advances, these cells become fusi- Fig. 20.—Myxoma from the Nose. This specimen represents almost a pure myxoma. The blood-vessels (a, a) consist of a single row of endothelial cells. The dotted portions are homogeneous mucous tissue. form, branched, and irregular, the fluid increases in amount, and delicate fibrillae run through it. To this older form of embryonic connective tissue is given the name of mucous tissue. It is found normally in the vitreous of the eye and in the umbilical cord of the fetus. The myxoma is a benign tumor, composed of mucous tissue with irregular, fusiform, branching, and anastomosing cells, and a gelatinous intercellular substance which is coursed by fine fibrillae. They are soft, translucent, and usually very vascular. A white precipitate is formed when dilute acetic acid is applied to the cut surface. Few tumors are myxomatous throughout, but this tissue is often found in combination with others, forming thus fibromyxoma, lipomyxoma, chondromyxoma, and myxosarcoma. LIPOMA CHONDROMA. 43 Seat of Occurrence.—Myxomata develop in fat tissue, subcuta- neous and submucous tissue, in the marrow and periosteum of bone, in the breast, and in the parotid glands. Myxomata are essentially benign, but many myxomata of the nerves are certainly malignant, and other varieties are often con- sidered as relatively malignant tumors because of the frequency with which they change into sarcomata. Fig. 21.—Lipoma of the Buttock. LIPOMA. A lipoma is a benign tumor composed of fat tissue. The struc- ture of such a tumor varies in no way from normal fat tissue, except that the fat cells are usually larger and less regularly arranged. They are usually encapsulated. Associated with other tissues they form lipofibroma, lipomyxoma, angiolipoma, etc. Seat of Occurrence.—They occur in the subcutaneous tissue of the neck, buttocks, back, axilla, abdomen, thigh, and occasionally in the abdominal cavity, breast, and kidney. CHONDROMA. The chondroma is a hard, spherical, or knobbed tumor, made up of hyaline, elastic, or fibro-cartilage, but more frequently of a com- bination of the three. The number, size, form, and arrangement of 44 LABORATORY TEXT-BOOK OF PATHOLOGY. the cells varies greatly in the different tumors,—sometimes, indeed, in the same tumor,—but the uniformity in structure of normal cartilage is lost. The cells may be numerous or few, small or large, or both, and frequently are fusiform or branched. They have a capsule or not, and sometimes lie in groups in a mother capsule. With other tissues they form osteochondroma, myxochondroma, and chondrosarcoma. Seat of Occurrence.—They occur most frequently in places where cartilage normally exists, and are called ecchondroniata. When occurring in tissues other than cartilage—as, for instance, in the Fig. 22.—Chondroma. The dark band above represents the capsule of the tumor. Cartilage cells of every type are seen in the capsules, and fibrous tissue supports these capsules. periosteum, testicle, parotid, and mamma—they are called enchon- dromata. Clinically, they are benign, as a rule, but metastases sometimes form in the lung and heart. OSTEOMA. An osteoma is a tumor made up of bone. It may be soft and spongy, like cancellous tissue, or denser (eburneous), resembling compact bone, or very hard and dense, like ivory (ivory exostoses). If the new growth is diffusely spread out it is called a hyperos- ODONTOMA ANGIOMA. 45 tosis ; if confined to a limited area, an osteophyte, or, if of con- siderable size, an exostosis. Circumscribed bony growths inside of bones are called enostoses. Of the types of bony tumor not connected with old bone are: (1) Those surrounded by the perios- teum, yet separate from the bone; (2) those located near a bone ; (3) those located in muscles and tendons remote from bones; (4) those occurring in the lungs, meninges, diaphragm, skin, and parotid gland. ODONTOMA. Tumors containing dentine are sometimes formed from the pulp, during the development of the teeth. These are called odonto- mata. ANGIOMA. The true angioma includes those new growths in the structure of which blood- or lymph-vessels constitute such an important part as to determine the character of the tumor. Hence we have: (i) Hemangioma, or a blood-vessel tumor; (2) lymphangioma, or a lymph-vessel tumor. Hemangiomata are of four types : 1. The simple angioma, or angioma telangiectoides, is a circumscribed dilatation of pre- existing or newly-formed capillaries, with thin or thick walls. These walls are imbedded in a more or less abundant connective-tissue stroma. The dilatations are cylindrical, fusiform, and sacculated ; there is abundant anastomosis and a perfect tangle of intertwined vessels. These tumors are popularly known as strazvberry marks, or vascular nevi. 2. The simple hypertophic angioma is a form of tumor com- posed of dilated capillaries, but the capillary wall is disproportion- ately thick, and is rich in cells, like the wall of an arteriole. 3. In the cavernous angioma the structure is that of a system of wide, variously-shaped, intercommunicating cavities, separated from one another by mere connective-tissue partitions. They are dilatations of pre-existing vessels, and are lined with endothelium. The structure is that of the corpora cavernosa of the penis. They occur on the skin as raised patches of bluish-red color, in the liver, and, less frequently, in the brain, bone, spleen, kidney, uterus, etc. 46 LABORATORY TEXT-BOOK OF PATHOLOGY. 4. The cirsoid aneurysm is a condition where a whole system of arteries are dilated, tortuous, and thickened, forming one large Fig. 23.—Angioma Telangiectoides from the Back of a Child. The section shows a tangle of thickened blood-vessels imbedded in fat, which is seen as the clear spaces around the border. Fig. 24.—Angioma Cavernosum of the Liver. Liver tissue is shown below, and the large sinuses above marked off by fibrous septa represent the typical structure of such a tumor. mass. The tumor feels like a bunch of earthworms beneath the skin. Lymphangiomata are composed of old and new lymph-chan- MYOMA 47 nels, dilated to form either simple dilatations or cystic or cavernous spaces. They are identical in structure with hemangioma, except that one is filled with lymph and the other with blood ; furthermore, the walls of the lymphangioma are thinner and more delicate. Seat of Occurrence.—They occur in the skin of the scrotum, vulva, and neck. In the thigh they form the condition of elephan- tiasis ; in the tongue, that of macroglossia. Under the head of lymphangioma must be included certain other new formations occurring in the skin. They are : (a) The pigmented nevi, which appear as pale or dark-brown plaques on a level with the surface of the skin or as elevated warty growths; ib) lentigines, or permanent pinhead spots of brown or yellow pigment; (c) freckles ; and (d) the fleshy warts, which are well- defined non-pigmented elevations springing from the papillae and having smooth or uneven contour. They are covered by normal or hypertrophic epithelium. The structure common to all of these conditions is that of a connective-tissue framework inclosing masses of cells in groups or bands. These cells lie partly in the papillae, partly in the corium of the skin, and in the pigmented forms they contain pigment granules. The cells seem to be pathologically developed from the endothelium of the lymph-vessels ; hence their classification among the lymphangiomata. MYOMA. Myomata are tumors composed of newly-developed muscle- fibers. They are divided into leiomyomata, formed of smooth muscle-fibers, and rhabdomyomata, formed of striped muscle- fibers. Leiomyomata are characterized by fusiform smooth muscle cells, which are of uniform size, have elongated or rod-shaped nuclei, and are regularly arranged in bands or parallel lines. These cells are packed closely together, interlace in every direction, and are intermingled with a certain amount of connective tissue and a varying number of blood-vessels. When the connective tissue is in large amount, it is termed a fibromyoma. Seat of Occurrence.—They occur as nodular tumors in the uterus, intestinal tract, bladder, and prostate. The rhabdomyomata are very rare tumors, made up of striated 48 LABORATORY TEXT-BOOK OF PATHOLOGY. muscle tissue. The muscle-fibers of such a tumor are nucleated and ill-developed, slender, spindle, club-shaped, or round in form, and very irregularly arranged. They are variously striated in a longi- tudinal or transverse direction and are intermingled with connective tissue, which varies in amount in different tumors. The sarco- lemma is absent. Seat of Occurrence.—They occur in the kidney, testicle, and ovary as circumscribed nodules. Clinically, they are benign. Fig. 25.—Glioma from Brain. (Teasedpreparation) The diagram shows the delicate branches of the cells and the fibrous intercellular substance. Gliomata are tumors which grow from, and consist essentially of, the glia-(connective-tissue) cells of the central nervous system, the ganglion-cells taking no part in the tumor formation. The struc- ture is of an extremely delicate network of fibers, among which are imbedded numerous small round-cells with disproportionately large nuclei. The cell protoplasm is distinguished with difficulty, but teased preparations show great numbers of fine branching pro- cesses from the cells, which make up the delicate fibrillar net- work. The blood-vessels are highly developed. These tumors are soft and can not be sharply defined from the surrounding brain tissue in color or consistency. They are very frequently associated with other tumor tissues, as gliosarcoma, gliomyxoma, etc. Seat of Occurrence.—They occur in the retina, brain, and spinal GLIOMA. NEUROMA. 49 cord. The glioma occurring alone is benign, but that form found in the retina is very malignant and results fatally unless enuclea- tion is early. This leads to its classification as a sarcoma; indeed, it is claimed by some that all gliomata are neurogliar sarcomata. Neuroglioma ganglionare is a name applied to another tumor of the central nervous system. It is an ill-defined or circumscribed tumor made up of glia-cells, ganglion-cells, and nerve-fibers. The structure is usually that of a more or less dense glia tissue, with a few nerve-fibers and ganglion-cells scattered throughout it. It has the same clinical features as glioma. Fig. 26.—Amputation Neuroma from the Thigh NEUROMA. Most tumors described as neuromata are nothing more than fibromata of the nerves. Such, for example, are the tumors in the ends of amputated nerves, tumors in the course of nerves, and multiple tumors present in different parts of the body. In such neurofibromata there is a growth in the connective tissue of the outer, sometimes of the inner, layers of the endoneurium, so that the nerve-fibers and bundles lie inclosed in a connective-tissue mass. True neuromata are either ganglionic or fibrillar. The ganglionic type of neuromata is only occasionally found in certain terato- mata of the ovary, testicle, and sacral region. The cirsoid or plexi- form neuroma represents the fibrillar neuroma, and is made up of medullated nerve-fibers. The fibers reveal extensive fibromatosis, 50 LABORATORY TEXT-BOOK OF PATHOLOGY. from excessive growth of the endoneurium; but, aside from this, the nerve-fibers are not only greatly thickened and increased in number, but are increased in length and rendered tortuous, until we have a mass of curled and intertwined nerve bundles. Seat of Occurrence.—They occur in the head, body, and ex- tremities. Both neurofibromata and true neuromata sometimes take on a sarcomatous character. Hereditary transmission and congenital predisposition have been established in both forms. LYMPHADENOMA. Lyinphadenoma (or lymphoma) is a term applied to tumors arising from a proliferation of the lymphadenoid tissue already existing in certain organs of the body. Such proliferation may affect whole groups of lymph-nodes, the tonsil, and the spleen, as in the general diseases of leukemia and Hodgkin’s disease, or it may be limited to the tonsils, even to the pharyngeal tonsil, as in adenoids of children. Microscopically, there is an enormous increase in the number of uni- and polynuclear cells and in the reticular tissue. The character of the lymphatic tissue is preserved, but the normal relations of follicles, cords, and lymph-sinuses are lost. The cause of such development is unknown, but the fact that they are not hyper- trophic classes them as tumors. Seat of Occurrence.—The types are leukemia, pseudoleukemia (Hodgkin’s disease), and tonsillar tumors. SARCOMA. A sarcoma is a connective-tissue tumor in which the cellular elements are much more prominent, in both number and size, than the intercellular substance. This characteristic stamps them as undeveloped or embryonic connective-tissue tumors. All epithelial structure is completely absent or only accidentally present. The intercellular substance, however, is always present and in intimate relationship with the cells by direct fibrillar processes. This will be well illustrated by stating that should an attempt be made to pencil out the cells in water, it would be found impossible, be- cause each cell would hang to the intercellular connective tissue SARCOMA. 5 1 by a fine fibrillar process. The cells are most varied in shape and size, but the one type of cell usually predominates in a given tumor to furnish a suitable qualifying name. The blood-vessels form a constant and important element in the structure of sarcomata, and are intimately associated with both cells and intercellular substance. In fact the tumor cells oftentimes form the very walls of the blood-vessels, and from this intimate relationship it can easily be understood why metastases should form almost entirely through the transportation of sarcomatous cells by the blood-current. Cysts frequently form. The overlying skin is not involved. Fig. 27.—Small Round-cell Sarcoma. The clear space below the center of the diagram is a poorly-formed blood-vessel Clinically, their cellular character, vascularity, rapid growth, marked tendency to local recurrence, the formation of metastases, and the production of the cachectic state, all go to stamp the sarcoma as the most malignant of tumors. They occur in yoiith and early middle life, affecting organs and tissues which are de- veloping or in active function, while carcinoma belongs to later life and senescent tissues. The small round-cell sarcoma is made up of very small round-cells which have very little protoplasm, and a single, relatively large oval or round nucleus. The intercellular substance is usually scanty and delicately fibrillated or granular. The ves- sels are numerous, the tumors soft, juicy, and very malignant. 52 LABORATORY TEXT-BOOK OF PATHOLOGY. Such tumors occurring in lymph-nodes are called lymphosarcomata, and these differ in no way from lymphomata except that they in- vade the surrounding tissues and form metastases. Fig. 28. —Large Round-cell Sarcoma. The clear space in the center is a blood-vessel with detached endothelium Seat of Occurrence.—They occur in the periosteum, bone, lymph- glands, subcutaneous tissue, testicle, eye, ovary, etc. In the large round-cell sarcomata the cells are very large, abund- ant in protoplasm, and have from one to three very large round or oval nuclei. They usually have polymorphous cells as well. The intercellular substance is present in varying amount, the vessels are abundant, the tumor is firmer and less malignant than the preced- ing form. Fig. 29.—Small Spindle-cell Sarcoma. SARCOMA. 53 Seat of Occurrence.—They occur in much the same regions as the preceding, but are found especially in the subcutaneous tissue of the pharynx and posterior nares, forming small, firm, pale polypi. The small spindle-cell sarcoma is a firm, dense, and elastic tumor, less malignant and of more frequent occurrence than any other form. The intercellular element may be small in amount, or so abundant as to constitute a fibrosarcoma. The cells have a varying amount of protoplasm, are regularly formed, contain an oval nucleus, and are arranged either in bundles parallel to one another or they interlace intricately. . Seat of Occurrence.—They are found in the periosteum, subcuta- neous tissue, uterus, mamma, testicle, thyroid, etc. In the large spindle-cell type the cells are relatively thick, irregular, or bifurcated, the tumor is softer, pinker, and more vas- Fig. 30.—Large Spindle-cell Sarcoma. cular, the growth is more rapid, and metastases form early in the lymph-glands. Seat of Occurrence.—They occur most frequently in the skin. Melanosarcomata are usually of the spindle-cell type, but the characteristic point is the deposition around the nuclei of the cells, less frequently in the intercellular substance, of granules of brown or black melanin pigment. The pigment is dis- tributed through the tumor in streaks or patches and varies in amount. Seat of Occurrence.—Such pigmented tumors arise in connection with the choroid of the eye or moles of the skin. They are the most malignant of tumors and form rapid metastases. Myeloid or giant-cell sarcomata occur most frequently in con- nection with bone. They arise in the marrow and periosteum, form spheroidal or fusiform tumors of the small spindle variety, 54 LABORATORY TEXT-BOOK OF PATHOLOGY. and are characterized by the presence of numbers of large multi- nuclear or giant-cells. These giant-cells appear as irregular areas of delicate protoplasm containing from 10 to 20 or more nuclei. When Fig. 31.—Melanosarcoma Occurring in a Spindle-cell Tumor. The melanin pigment is deposited in streaks. Fig. 32.—Myeloid or Giant-cell Sarcoma of the Tibia, Large round-cells are associated with the giant-cells. they arise from the marrow they are apt to be very soft and vascular and cause resorption of the bone. The periosteal form is much denser. They grow very slowly and are the least malignant of sarcomata. SARCOMA. 55 Seat of Occurrence.—They occur most frequently in the lower jaw, lower end of the femur, and head of the tibia. Fig. 33.—Angiosarcoma. The vessel wall consists merely of endothelial cells, which are detached from the surrounding large round-cells of the tumor. Fig. 34.—Alveolar Sarcoma from the Superior Maxilla. The arrangement in alveoli seems dependent upon a growth of cells from the walls of lymph- vessels. In the angiosarcomata the tumor is almost wholly made up of a tangle of vessels whose walls are surrounded by heavy masses of proliferating round-cells, which extend even to the endothelium. 56 LABORATORY TEXT-BOOK OF PATHOLOGY. The vessels anastomose freely, are packed closely together, and may be fused in such a way that the tubular structure is wholly lost. They are called perithelial sarcomata. Scat of Occurrence.—They occur in the brain, testicle, lymphatic glands, breast, skin, and bone. Alveolar Sarcoma.—In certain sarcomata the intercellular sub- stance is more or less abundant and arranged in a wide-meshed net with masses of cells in the meshes. This gives to us the alveolar structure which is so characteristic of carcinoma. The cells, how- ever, do not lie loose in the meshes but are intimately related to the intercellular substance which sends fine trabeculae into the Fig. 35.—Endothelioma of the Dura Mater. Two blood-vessels are seen in the center and from the endothelial cells of these the surrounding mass of cells have proliferated. alveoli between the cells. In water, the cells of a carcinoma could be pencilled out of the alveolus, while in alveolar sarcoma the fibrillae would hold each cell in place. The new formation of blood- vessels and their arrangement are also diagnostic. Clinically, they are very malignant tumors. Seat of Occurrence.—They occur in the skin, lymph-nodes, bone, and the pia mater. The endothelioma is a tumor arising from a proliferation of the endothelial cells lining the lymph-vessels and lymph-spaces. The cells making up such a tumor are either of almost normal character, very large and thick, or even cylindrical and cuboidal. Sometimes SARCOMA. 57 the cells are packed together in dense and concentric masses of glistening appearance and contain cholesterin crystals, when they are called cholesteatoma. Arising from the lymph-vessels as they do, it can readily be seen that a tubular structure is often given to the tumor resembling carcinoma. The periphery of the tumor, however, will show a proliferation from the endothelium, which is diagnostic. Seat of Occurrence.—They occur in the pia and dura mater, pleura, periosteum, and mamma. Cylindroma.—This name is given to those sarcomata in which layers of flattened or cuboidal cells are arranged about a central homogeneous or striated cylinder of hyaline degeneration. Fig. 36.—Psammoma. The circular markings represent the calcareous deposits The myxosarcoma is one in which myxomatous change has taken place, but this must be considered a degeneration in a tumor rather than a separate type. The same is to be said of osteo- sarcoma, where bony trabeculae without regular lamellation and without Haversian canals form in the substance of a periosteal spindle-cell sarcoma. The chloroma is a lymphosarcoma arising in connection with the skull and presenting a bright green color on fresh section. The color is not understood. In certain sarcomata of the pineal body and choroid plexus, small, sand-like areas of calcification are often formed. Such tumors are called psammomata, or brain sand. 58 LABORATORY TEXT-BOOK OF PATHOLOGY. EPITHELIAL TUMORS. In the tumors described thus far there has been a connective- tissue origin or a development from the parablastic germ layer. We have now to consider certain new growths springing from some one of the archiblastic layers and having epithelial cells as their characteristic and predominant element. Such epithelial tumors have certain general characteristics in common. Besides the cellular element which characterizes these tumors, there is also a connective-tissue stroma which supports the cells and carries the vessels. The connective tissue is abundant or slight, and is usually arranged to form the walls of variously-shaped alveoli within which the epithelial cells lie. These cells, however, have no connection with the stroma, and are separated from one another by cement substance alone. Some of the tumors are benign (the adenomata), others are very malignant (the carcinomata and epitheliomata), while on the border line between these two a distinction oftentimes can not be made. ADENOMA. In the adenoma the reproduction of typical gland tissue is main- tained. The acini are regularly formed and usually have a lumen. The cells are arranged in a sjngle row upon a basement membrane of endothelial cells with a double contour, but are not of uniform shape, nor do they conform to the shape of the cells of the gland from which they originate. Simple hypertrophy of a gland, with increased connective tissue, does not constitute an adenoma. There must be a new formation of more or less typical gland tissue. Furthermore, there must be a lack of conformity to the gland tissue from which it originates, both in anatomical character and mode of growth. There must be a proliferation of epithelium, which is followed by the formation of gland sprouts, and these sprouts, penetrating into the surrounding tissue, cause a connective- tissue proliferation as well. These tumors are usually circumscribed, nodular, and of tough consistency, except in the papillary forms. Seat of Occurrence.—They occur in the mamma, ovary, liver, kidney, thyroid, prostate gland, and in the mucous membrane of the gastro-intestinal tract and uterus. In the adenoma papilliferum there is a rapid growth of con- ADENOMA. 59 nective-tissue papillae from the walls of the gland tubules beneath the epithelium. A correspondingly rapid growth of the epithelium in a single layer takes place to cover these outgrowths. Fig. 37.—Fibro-adenoma of the Breast. The clear areas represent gland acini, lined by a single row of cells Fig. 38.—Adenoma of the Breast. (High power.) In this tumor the gland tissue predominates and the stroma is loose and cellular. The multilocular cystoma, or glandular cystadenoma, is one of the most important forms of adenoma. They form very large tumors, made up of innumerable small and large cysts with 6o LABORATORY TEXT-BOOK OF PATHOLOGY. smooth glistening walls, and lined by a single row of columnar, and often ciliated epithelium. The fluid contained is clear or clouded, thin or thick, and tenacious. These tumors have their origin in an ingrowth of epithelium, covering the ovary into the stroma of the organ, and are characterized by a marked tendency to form cysts. Coincident with the formation of the cyst, or at a later date, minute or large cauliflower papillary excrescences may be formed within some or all of the cysts. They are then called papillary cystoma, and are regarded by some authors as a sepa- rate type of cystadenoma. Seat of Occurrence.—These tumors occur in the ovary, breast, testicle, kidney, or liver, and may take on a malignant form. Adenomata are differentiated with difficulty from many glandular hypertrophies occurring in the mucous membrane of the intestine and uterus. These seem to be atypical gland structures, developed as a result of great reproductive activity. The adenomata are benign tumors in general, but some of the adenomata of the stomach and intestines must be classed among the most malignant of tumors. Their rapidity of local extension, invading all adjacent tissues, the formation of metastases, and the production of cachexia would place them in this class. These have been called adenoma destruens or malignum. Their structure is that of very irregular tubular glands, with high col- umnar cells arranged in a single row on a basement membrane and supported by a very slight connective-tissue stroma. Further- more, certain adenomata begin as such, but later take on a true can- cerous nature. These are called adenocarcinoma. Thoma believes that a great number of carcinomata of the breast come from simple adenomata. CARCINOMA. Carcinomata are characterized by a perfectly atypical arrange- ment of the proliferating epithelial cells in variously-shaped alveoli, clusters, and columns, and by their tendency to unlimited growth The growth of carcinomatous cells undoubtedly proceeds from a rapid mitotic cell-division, taking place first in the old gland cells and later in the newly-developed tumor cells. The arrangement of the cells in alveoli varies greatly. There may be huge masses of cells surrounded by small bands of connective-tissue stroma, CARCINOMA. 6i alveoli containing small numbers of cells in no regular arrangement, long columns of cells extending into the tissues, or cells in groups of two or three wedged between dense bands of fibrous tissue. Never is there connective tissue between the cells within the alveoli. There is no typical and diagnostic cancer-cell. On the other hand, there is great polymorphism of cells, undoubtedly dependent upon their origin, rapidity of growth, and certain con- ditions of nutriment and pressure. Thus, in cancer of the intestine we may have cylindrical cells as the characteristic form in the tumor; of the skin, stratified epithelium; of the breast, cuboidal cells ; while in other parts of any one of these tumors may be found small round-cells, young cells, or cells distorted and flattened by pressure. It is the general character of the cells, together with the topography, seat, and clinical history of the tumor, upon which we base a diagnosis. These tumors possess all the characteristics of malignancy. Their peripheral extension seems to be chiefly through the lymph- spaces, but the septa and sheaths of nerves provide a very certain means of dissemination. Metastasis occurs through the lymph- channels as distinguished from sarcoma, where it takes place through the blood-current; and, consequently, the first lymph-nodes in the chain receiving lymph from the part involved will be earliest infected. Infection may be carried, however, by the blood-vessels, and from nodular tumors of identical structure in distant organs, as is evidenced by the regular appearance of secondary tumors of the liver in cases of cancer of the stomach where the portal vein is the carrier. Retrograde changes come on early. They consist in fatty degeneration, calcification, and, most frequently, necrosis with gan- grene and ulceration. The cause of cancer has not been arrived at as yet. By histo- logical investigation we find that the growth of cancer is due to a pathological penetration of epithelium into connective tissue. This may be due to diminished resistance of the connective tissue or to an increased proliferating power of the epithelium, but most probably it is due to both. As yet, no evidence justifies the assumption that parasites are the cause of the proliferation. That chronic irritation plays a part is shown by its occurrence at the orifices of organs and of the body, and in pipe-smokers, tar and paraffin workers. Epitheliomata arise from the cells of the stratified or squamous 62 LABORATORY TEXT-BOOK OF PATHOLOGY. epithelium of the skin and mucous membrane. The cell growth, instead of being upward from the limiting membrane toward the surface, has been reversed. The interpapillary cells have increased Fig. 39.—Epithelioma of the Lip. The skin surface is above and columns of epithelial cells descend deep into the tissues. Two typical “pearls” are seen. Many pearls are seen imbedded in separate masses of cells. Fig. 40.—Epithelioma of the Clitoris. in number, then broken through into the subcutaneous layers, and epithelial cells in columns and in nests are found in the tissues beneath the skin. The cells are of every variety found in the 63 CARCINOMA. normal skin, characteristic among which are the “ prickle cells.” The life history of the cell being the same and the growth being downward instead of upward, the thin, dry, horny epidermis cell is Fig. 41.—An Epithelial Pearl or Cell Nest. Showing the lamination and cellular character. Fig. 42.—Epithelial Pearl within a Mass of Cancer-cells from a Fungous Epithelioma of the Cervix. The fibrous strip below represents the slight stroma of the tumor. found deep in the tissues, and they are often packed together con- centrically, like the layers of an onion, to form the “epithelial pearls ” or “ cell nests.” The outermost cells of such a pearl have nuclei, 64 LABORATORY TEXT-BOOK OF PATHOLOGY. but these disappear as the center is approached, where we find only the flat, horny cells. Such pearls or nests are a characteristic feature. Giant-cells may be present. Metastatic infection of the lymph-nodes is early, except in the superficial form. Seat of Occurrence. — Epitheliomata occur most frequently at points of junction of the mucous membrane and skin,—as the lip, nose, labium, glans penis,—and are frequent in the mouth, esoph- agus, vagina, and cervix uteri. Certain superficial forms of epitheliomata (rodent ulcers) occurring on the face have some very different characteristics. Small, cuboidal cells seem to grow down in anastomosing columns Fig. 43.—Carcinoma Simplex of the Breast. The cells and stroma are about equal in amount, and the cells are arranged in alveoli in small masses. from the deep layers of the rete, to form what are sometimes called tubular epitheliomata. Their origin is claimed by some to be in the sweat glands. The cell masses grow very slowly (for years), and connective tissue may form the predominant element. They do not infect the lymph-nodes and are not very malignant. Seat of Occurrence.—They occur on the nose and other parts of the face. Carcinoma simplex, or gland-cell carcinoma, usually occurs in glands, and forms hard, nodular tumors. The cells have no con- stant characteristic shape, and are arranged in alveoli of different CARCINOMA. 65 shapes and sizes, which are formed by a strong connective-tissue stroma. The cut surface is of a grayish-white color. A scirrhous carcinoma is one in which the cellular element is Fig. 44.—Scirrhous Carcinoma of the Breast. The cancer-cells are arranged in collections, in rows, or are found singly in the dense fibrous tissue. The stroma is represented by mere lines between the masses of cells Fig. 45.—Medullary Carcinoma of the Breast. relatively small and the main mass of the tumor is made up of tough fibrous tissue. There is no strict line of division between this and carcinoma simplex, the difference being mainly one of degree. 66 LABORATORY TEXT-BOOK OF PATHOLOGY. Seat of Occurrence.—They occur in the breast, stomach, and sometimes in the testicle and ovary. In the medullary carcinoma there are very large numbers of Fig. 46.—Columnar-cell Carcinoma of the Stomach The newly-formed ducts are lined by high columnar cells. Fig. 47.—Colloid Carcinoma. The clear portions represent the areas of colloid degeneration, and only a few cancer-cells are left ill each acinus. cells, arranged in alveoli without a lumen. The stroma is delicate, and the consistency of the tumor soft and juicy. The cylindrical-cell carcinomata occur in the mucous mem 67 CARCINOMA. brane of the intestine and uterus; also in the gall-ducts and respira- tory passages. They form soft nodular or papillary tumors, which are rich in cells. The arrangement is of high cylindrical cells lining the regular alveoli, while the remainder of the cells are variously arranged. The comparatively complete development of the epithelial cells, and their arrangement in alveoli, often render it difficult to differentiate this tumor from benign adenoma, but, as a rule, the cells have in some part broken through the basement membrane and appear in irregular masses, infiltrating the deeper coats. Colloid carcinoma is a form in which the cancer-cells have undergone a colloid degeneration. This colloid material is de- posited in droplets or masses, giving the entire tumor a transparent appearance. When the degenerative process is extensive, the stroma about the alveoli shows very distinctly, and the term alveolar carcinoma is applied. Seat of Occurrence.—Such tumors occur in the intestine and breast, sometimes in the ovary. In the carcinoma myxomatodes the stroma of the tumor is made up of mucous tissue. It occurs in the intestine and mamma. DIFFERENTIAL DIAGNOSIS OF SARCOMA AND CARCINOMA. Sarcoma. Carcinoma. Occur. In youth and before forty. After forty years. Origin. Parablastic layer. Archiblastic layer. Stroma. Between each cell and con- nected with cells. Does not form alveoli. Forms alveoli surrounding masses of cells. Cells. Embryonic or granulation tis- sue. No epithelial cells. Epithelial cells of various shape and size. Intercellular Sub- stance. Stroma. Cement substance alone. Never stroma. Vessels. Embryonic, and in definite re- lation to cells which make up walls. Well developed. In walls of alveoli and never in contact with cells. Metastasis. By blood-vessels. By lymphatics. Carcinoma cylindroma is the name given to a type of cancer where a cylindrical hyaline degeneration has taken place in the center of the cell-nests and the cells are arranged about the degen- 68 LABORATORY TEXT-BOOK OF PATHOLOGY. erated area. They occur but rarely in the skin, intestine, and glands. Giant-cell carcinoma is the name given to certain tumors containing very large-sized cells. They are simply hypertrophic, multinuclear cells, or the enlargement may be dropsical. The black or brown melanin pigment of a melanocarcinoma is found partly in the stroma, partly in the cells, giving these tumors a blue-black appearance. Seat of Occurrence.—Such tumors occur in the skin, and always in a normally pigmented area. Leukoma, or leukoplakia, is a condition of the tongue which often precedes carcinoma. It appears as one or more white furry patches which are thickened and elevated above the general sur- face. Numerous deep fissures and ulcers appear from time to time, and later in the disease warts are apt to form. There is a thickening of the epidermis, a growth both upward and downward of the rete mucosum, an elongation downward of the interpapillary cells, and an infiltration or complete obliteration of the papillae by small round-cells. The condition undoubtedly precedes cancer. TERATOMA. Teratomata are certain tumors presenting a peculiar and compli- cated growth, and consist of tissues which do not normally occur at the site of the tumor. In a single tumor may be found sometimes fibrillar connective tissue, bone, cartilage, muscle, glands, pigment, etc. There are other tumors that not only have different tissues present, but even more or less complete organs, as skin, hair, teeth or a jaw-bone with teeth, formed pelvic bones, breasts, nerves, muscles, and portions of intestine. These are called dermoid tumors, and are apt to be cystic. Such tumors are undoubtedly explained on the supposition of misplaced germinal fragments or that fetal remains have persisted. The latter is certainly true of most of the dermoids, while others probably arise from the inclu- sion of a twin fetus. THE LIVER. 69 THE LIVER. Normal Structure. The liver is covered by peritoneum, except for a small area on the posterior surface, and is inclosed in a fibrous capsule. The portal vein, hepatic artery, and bile ducts enter the hilus of the organ sur- rounded by loose connective tissue (the capsule of Glisson), and these vessels, carried by the connective tissue, make up the framework of the organ. The liver is made up of vast numbers of lobules, which are identical in structure, and it will suffice to describe a single lobule. Fig. 48.—Pig's Liver. Showing the distinct marking of lobules with the interlobular vessels, the central vein, and the capillaries between. Each lobule has an oblong polyhedral shape and is formed by a collection of liver cells arranged around a single terminal radicle of the hepatic vein; hence in cross-section a lobule will always have this central or intralobular vein in its center. The liver cells making up such a lobule are irregular or polygonal in shape, have a granular body, and one or more large oval nuclei. Granules of brown pigment and glycogen and globules of fat are found in the cells. These liver cells are arranged in columns of a single row or many rows, which radiate at right angles from the central vein and are separated from one another by the blood and bile capillaries to be described later. 70 LABORATORY TEXT-BOOK OF PATHOLOGY. Now let us follow the three vessels, which entered the hilus of the liver, in their divisions and subdivisions until finally we arrive at the lobule we have been describing. These three vessels, now called interlobular vessels, will be found on its outside surface, still held together by connective tissue yet ready to break up into minute branches which will cover over the surface of the lobule like the net over a balloon. This much will be true of vein, artery, and duct, but from this point each vessel must be considered separately. The blood from the interlobular portal vein is emptied at once into the rich capillary network, which forms an irregular anasto- mosing series of channels between the columns of liver cells and has a direct course to the central or interlobular vein. It is thus evident that the portal blood enters the hilus of the liver, reaches the interlobular veins, then passes through the capillary network around the liver cells directly into the central vein, which is a branch of the hepatic, and from the latter into the vena cava. The hepatic artery carries arterial blood for the nourishment • of the elements of the organ. It also breaks up into capillaries on the surface of the lobule, but these capillaries empty into the portal venous capillaries at a point about midway between the sur- face and the center of the lobule, and their blood also passes on into the central vein. The larger gall passages have cylindrical epithelial cells and mucous glands, but in the interlobular bile ducts the glands are lost and the cells are flat or polygonal. At the surface of the lobule these ducts are continuous with the bile capillaries, which form a delicate network around each liver cell, yet at all times these capillaries are separated by a portion of the cell diameter from the blood capillaries. They have no walls, but seem to be formed by grooves in the liver cells. The lobule may be divided pathologically into three zones : (i) A peripheral one-third, or portal zone, which is the area of fatty infiltration. (2) The middle one-third, where the capillaries of the hepatic artery empty into the portal capillaries, and which is the area of amyloid degeneration. (3) The central zone around the central vein, or the area of chronic passive hyperemia. FATTY INFILTRATION OF THE LIVER. 7i ACUTE DEGENERATION OF THE LIVER. Acute degeneration of the liver (cloudy szvelling) takes place in the acute and infectious fevers, and in certain of the poisons. The liver is swollen, looks boiled, is friable, and the lobules are more distinct. The liver cells are swollen, opaque, filled with albu- minous granules, and may become fatty or necrotic, but usually return to normal. FATTY INFILTRATION OF THE LIVER. In fatty infiltration of the liver (fatty liver) the cells of the organ, especially in the periphery of the lobule, contain larger or smaller Fig. 49.—Fatty Infiltration of the Liver. The small clear circles represent the fat droplets, and it will be noted that these are in the periphery of the lobule. The central vein is seen in the center. droplets of fat, even to complete replacement of the cell body by fat, so that the original cell appears as a nucleated crescent at one side of the fat droplet. It most often occurs associated with other lesions, and especially cirrhosis. Such livers are much enlarged, their edges are rounded, the consistency firm; they pit on pres- sure, are yellowish in color, and the cut surface is greasy. The process may be uniformly distributed through the organ, occur only in patches, or, when it is in the earlier stages, it will be con- 72 LABORATORY TEXT-BOOK OF PATHOLOGY. fined to the periphery of the lobules, thus outlining them more distinctly. It occurs in chronic alcohol, phosphorous, and arsenic poisoning, and in conditions of malnutrition and general obesity. FATTY DEGENERATION OF THE LIVER. Fatty degeneration can not always be differentiated from fatty infiltration, but in the former the fat is formed from the protoplasm of the liver cell, the droplets, as a rule, are very small and abundant, the liver cells are angular and clearly in a state of degeneration. It Fig. 50.—F'atty Degeneration following Phosphorous Poisoning. begins in the periphery of the lobule, and usually follows acute degeneration, wasting disease, or acute phosphorous and arsenic poisoning. AMYLOID DEGENERATION OF THE LIVER. An amyloid or waxy liver is one in which an amyloid degenera- tion, general or local, has taken place in the blood-vessels of the liver. When the amyloid is small in amount, the liver is merely a little firmer; if moderate, translucent spots maybe seen, while in extensive degeneration the organ is much increased in size, smooth, CHRONIC PASSIVE HYPEREMIA. 73 tough, firm, inelastic, and translucent. The liver cells are not invaded by the amyloid material, but they may be much atrophied by pressure. The condition occurs in cachexia, especially of tuberculosis and chronic suppuration. Chronic passive hyperemia of the liver (;nutmeg liver) occurs in valvular heart disease, pericarditis with effusion, myocarditis, em- physema, pleuritic effusion, and intrathoracic tumors and aneu- CHRONIC PASSIVE HYPEREMIA. Fig. 51.—Chronic Passive Hyperemia of the Liver. In the center of the light-colored area is a central vein, and it will be observed that the liver cells are almost entirely destroyed by the dilated capillaries in this region. rysms, where the blood-pressure is raised in the vena cava and there is a damming back of the blood in the hepatic and central veins. The capillaries about the center of each lobule are permanently dilated and filled with blood, the liver cells in this region are atrophied and pigmented or have entirely disappeared, the cells of the intermediary zone are tinged yellow by bile, while the cells of the periphery undergo fatty infiltration. The liver is firm and red, mottled like a nutmeg, and normal or diminished in size. 74 LABORATORY TEXT-BOOK OF PATHOLOGY. CIRRHOSIS OF THE LIVER. Cirrhosis of the liver is a chronic disease characterized by an overgrowth of the connective tissue of the organ and a gradual destruction of the liver cells. This is dependent upon many excit- ing causes, and, furthermore, it affects the organ differently accord- ing to the element in the liver structure which is mainly involved. The following table will include all these variations : (rear. - 8.00 KIDNEY DISEASES. Thornton. Surg. of Kidney'. 1.50 Tyson. Bright’s Disease and Diabetes, Illus. - - MASSAGE. Kleen and Hartwell. - 2.25 Murrell. Massage. 5th Ed. 1.25 Ostrom. Massage. 87 Illus. 1.00 MATERIA MEDICA. Biddle. 13th Ed. Cloth, 4.00 Bracken. Materia Med. 2.75 Davis. Essentials of Materia Med. and Pres. Writing. 1.50 Gorgas. Dental. 5th Ed. 4.C0 Heller. Essentials of. - 1.50 Potter’s Compend of. 5th Ed. .80 ALL PRICES ARE NET. 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