Part 11

Although the notes fail to discuss the gross appearance of the bone marrow, the amount of alteration in its microscopy and the relatively small output of pigment in the liver, seem to substantiate the determination of aplastic anemia; it is unfortunate that the blood smears could not be used in the decision. At all events the condition of the intestinal tract, of the heart, liver, spleen, and adrenal, justify us in classing the case as one of primary anemia. The next and last instance is of the same type, although I am inclined now to differ from the diagnoses made at the autopsy table, that of aplastic anemia, and to place it in the hemolytic variety. The rapidity of the fatal attack, the redness of the marrow, the excessive pigmentation, and the prominence of recent degenerative lesions in the organs are much more like the changes of a primary hemolytic intoxication than of an aplastic anemia.

Gray Fox (_Canis cinereo_). ♂ Weight four pounds, adult, was in the exhibition two years, but in good condition until two weeks before death, when it stopped eating and rapidly fell away.

DIAGNOSIS.—(Aplastic) Primary anemia. Zenker’s Hyaline of heart and skeletal muscles. Mucoid degeneration of bone marrow. Congestion of bone marrow. Atrophy of hemopoietic elements in bone marrow.

Hemosiderin pigmentation of liver. Atrophy of liver. Congestion of liver. Congestion and fatty infiltration of kidney. Patulous lumina in adrenal and absence of pars glomerulosa.

External appearance of coat good. Decomposition advanced in intestines. Skin and subcutaneous tissue faintly yellow. Poorly developed, dark muscles and fat. Respiratory tract normal throughout. Pericardium glistening, transparent, and pale, with no adhesions. Heart a little too pale, consistency slightly soft. Normal or slightly increased size of liver, with smooth surface and sharp edges, consistency friable, and of a brownish red with rusty coloring. Spleen normal. Kidney normal in size, shape, location, and consistency. Capsule strips easily, and of a faintly yellow, under general red, coloring. Adrenal normal. Mouth and teeth normal. Stomach, serosa and wall normal. Mucosa shiny, autolytic, muddy red. Ileum, agminated follicles swollen. Feces from colon examined microscopically. Pancreas normal. Bone marrow tibia and femur gelatinous and red, not slightest trace of yellow. Blood films from heart’s blood show poikilocytosis and anisocytosis; only one nucleated red.

Microscopic Notes.—Heart has torn but normal pericardium. No abnormalities of interstitial tissue or vessels. Fibres of normal width but show transverse markings irregularly since cytoplasm becomes hyaline and swollen in many places along its course. Nuclei prominent, slightly pyknotic. Zenker’s Hyaline.

Bone marrow consists of a matrix of granular or fibrillar mucoid tissue within the delicate reticulum of which highly developed capillaries are placed, together with stellate spindle and sealring cells. In a few places only are myelocytes recognizable and then in decreased numbers. Plasma cells sometimes found containing much blood pigment.

Liver.—Capsule normal; perilobular fibrous tissue only slightly overgrown, moderately infiltrated with lymphocytes and heavily with blood pigment. Arteries, ducts, veins, normal. Parenchymal cell a little smaller than normal with nuclei of normal type, and crowded with fine granules of blood pigment. Latter lie in usual pericanalicular position. Blood capillaries narrow, moderately congested and Kupffer’s cells also contain abundant pigment granules.

Thyroid.—Interstitial framework shows no fibrosis or cellular infiltrates. Blood vessels normal. Acini fairly uniform in size, none ever attaining large proportions, but some being distinctly below normal. They are uniformly filled with a very pale pink hyaline material which in some way gradually increases in color intensity toward one side, attaining in a few examples usual intensity of colloid. Lining epithelium is low cuboidal, shows no special hyperplastic features or atrophy.

Kidney.—Capsule normal. Interstitial tissue normal. Blood vessels slightly congested. Tubular epithelium granular, disintegrated and frequently contains numerous fat globules and obscured nuclei. Lumina of about normal size containing variable quantities of pink granular detritus. Glomerular tufts normal in size and appearance. Subcapsular space and Bowman’s capsule normal.

Adrenal.—Capsule and pericapsular tissue normal. Parenchymal cells throughout poor or practically free of vacuoles, such appearing in only limited portion of pars vesicularis. Interstitial framework and vessels normal. Structure of columns in pars vesicularis is peculiar in that they extend quite to capsule with no intervening pars glomerulosa, and again in that most peripheral parts are expanded at times showing a lumen, while deeper parts show broad cells extending fully across the column. Pars reticularis contains no pigment and medullary cells quite normal. Skeletal muscles show comparatively few fibres with transverse markings. Most are swollen, hyaline, lumpy, and have pyknotic nuclei. Interstitial parts show no inflammatory change.

Tissues treated by Prussian blue test for iron. Kidney, adrenal, heart found to contain none. Spleen, liver contain abundance. That in spleen responds to test showing that it is all iron containing. Two kinds of pigment found in liver. In periphery of lobule as much contains iron as that which does not, while in deeper parts iron predominates. Many times both kinds are recognized in one cell. On the whole it is the finest granules which contain more iron (are bluer) while iron free pigment occurs in bile canaliculæ. That in Kupffer’s cells stains strongly blue.

SUMMARY OF PRIMARY ANEMIAS.

A review of these instances of grave anemia brings one to the conclusion that there is a strong similarity to the disease in man. Perhaps we have constructed a picture that is too narrow for the animal kingdom in general, but surely these few instances deserve to be distinguished from the secondary cases already presented if for no other reason than that no associated etiological condition was exposed. It was hoped in studying the anemias of lower animals, and this hope extends over all the subject of this book, to be able to throw some light upon causation. The thought of incorrect diet came at once, but we are confronted with the paucity of cases among our records. Moreover, secondary anemia from digestive and dietetic troubles is clear, but how we can use this argument for an essential change in hematopoiesis and natural hematolysis, is far from evident. It will be noticed that I have studiously avoided grouping any case with parasites among the primary cases, nor will there be found any evidence of generalized infectious disease. Most of the reported instances of pernicious anemia in the lower animals have been associated with one or other of these factors, although certain authors (Kitt, Hutyra and Marek) maintain that a causeless variety probably exists.

LEUCEMIA.

This condition is fairly well recognized by veterinarians as occurring among domesticated animals, but in the records of this Garden it has occurred rarely, indeed only once in a mammal and but five times in birds. It is interesting that, in the wealth of material at the disposal of Plimmer and his associates, only one case, a polecat with lymphatic leucemia, is noted, and but very few avian instances. Herewith is submitted the protocol of our single mammalian case; perhaps we have missed others of a mild grade dying during the early stages because their resistance to infection was reduced. Unfortunately, perhaps because of the postmortem changes, but more likely because it appeared at first as if we had to do with a case of generalized tuberculosis, the bone marrow in this case was not examined. Nevertheless the infiltrative character of the lesions, the absence of distinct tumors and the numerous mononuclears in the blood as seen in sections seem to justify a diagnosis of leucemia, in all probability of the lymphatic type. There follows this case one with similar gross and microscopic picture which has no visible increase of leucocytes, but a very distinct myeloid picture in many places.

Common Opossum (_Didelphys virginianus_). ♂ Adult. No evidence of illness. Found dead. Lymphatic leucemia (involving all viscera and lymph nodes). Diffuse nephritis. Both lungs have become entirely involved in a firm, gray-yellow mass not adherent to any serous surface. Practically no normal lung tissue is left. This seems like tuberculosis but no tubercle bacilli could be found in a good smear. Estimation of the normal cubic capacity of an opossum lung was made to be about five cubic inches. In this case not over one-half cubic inch remained respirable. Bronchial lymphatic glands were enlarged, firm, yellow gray, with no recognizable lymphatic tissue. Heart muscle was firm and flaccid, pale and striated. Liver very large, firm and tough, with smooth surface and sharp edges. Color pale brown. Section surface glistening, dry, smooth, opaque. Common bile duct patulous. Spleen, slightly increased, firm, tough consistency, capsule smooth. Section surface, smooth, firm, brown-red, pale pulp, prominent follicles, and trabeculæ faintly visible. Right kidney, slightly decreased, normal in shape. Capsule smooth, strips with difficulty, tears surface. Surface, granular, color brown, consistency firm. Thickness of cortex, narrow irregular, markings irregular and obscure. Small mass of fibrous material in cortex about 3 × 3 mm. like those in lungs. There are also numerous pale yellow gray areas in cortex and outer medulla, round and streaky, distorting the striated architecture. Right adrenal converted to a yellow gray mass like lungs. The mesenteric and retroperitoneal lymph nodes are firm, gray-yellow. This includes those under diaphragm and around cœliac axis.

The histology of the organs may be described together. The infiltrate described is a densely packed mass of large cells with large, well staining nuclei and a very narrow rim of protoplasm. It is not limited by any definite wall or septa. It has no interstitial tissue. There is no blood supply in the densest masses but the walls of the blood vessels remain intact wherever the mass surrounds them. In the lungs it has involved all structures indiscriminately, and has destroyed practically all of the respiratory surface. It seems to follow by preference the peribronchial space. A few glands may be seen in the centre of this mass, but they are rapidly undergoing degeneration. In the liver the infiltrate is chiefly beneath the capsule extending inward but a very short distance. There are no large masses as in other organs but small infiltrates are seen at the portal areas. The spleen shows a diffuse excess of pulp cells and many of the cells above described, the difference being only in the size of the nucleus which is smaller in the pulp cells. There are very small round cells relatively. Follicles are absent, connective tissue not altered. Note states follicles prominent; this is due to nodal hyperplasia of the large mononuclears above described. The parenchyma in the kidney is anemic, the epithelium is slightly pigmented but this is probably not abnormal. Between the tubules especially of the outer layer of the medulla and medullary ray but also in the cortex and around the glomeruli are diffuse, irregular, infiltrating masses of the cells as described above. In some places in the kidney hyaline casts are being formed probably due to the degeneration of the epithelium by pressure. There are a few distentions of the tubules. The capsular space is free. In the neighborhood of the collections the capsules are a trifle thicker than normal. Lymph nodes, similar to spleen in that most of the bodies are thoroughly overrun with the large mononuclears. The sinuses, both marginal and internal, are practically obliterated by these cells. In the blood vessels of the lungs and liver there are many large mononuclears, perhaps not as large a number as might be seen in leucemia, but decidedly in excess of normal.

Common Marmoset (_Callithrix jacchus_). ♂ Adult. Had cage paralysis for two months before death and declined gradually from that time.

DIAGNOSIS.—Bronchopneumonia. Myeloid hyperplasia of bone marrow. Myeloma in pancreas. Fatty degeneration of liver. Constipation. Nematodes in cecum. Animal is thin, skin bare in spots. Both lungs are pale pink with large areas of deep red consolidation. Heart is dilated, increased in size with firm, red-brown muscle. Liver is firm, red-brown, with smooth surface and sharp edges. Section surface is glistening, smooth and moist. Lobular outlines are clear by reason of pale lines. The gall-bladder is normal in size and contains fluid pale green bile; duct patulous. Spleen is normal in size, smooth capsule, soft, purple pulp, follicles small and faint, trabeculæ fairly prominent. Kidneys normal in size and shape. Capsule smooth. Section surface smooth and brown and firm. The glistening section surface has a narrow cortex, swells slightly, with prominent striæ. Intestines throughout are pale on serosa. Wall thin. Mucosa flat, pale pink. Contents creamy mucus in the upper intestine. Large intestine contains large masses of very firm feces. Cecum is distended with feces and a great quantity of nematode worms. They are not attached to mucosa nor does mucosa seem altered because of their presence. Skeleton and muscles.—Long bones of extremities break easily, but with snap. Skull can be dented with fingers. Bone marrow of femur bright red.

MICROSCOPICAL NOTES.—Liver shows moderate degree of fatty degeneration with capillary congestion. Kidneys negative. Some postmortem change in last two organs. Spleen, marked congestion. Hyperplasia of large lymph cell type, particularly in follicular centres. Blood destruction moderate. Bone marrow seen in condition of marked activity of myeloid type. Aside from enormous crowding of strands there does not seem to be any atypical cell. Intestines show practically no change. Same condition holds in pancreas. In several places in pancreatic ducts cross sections of nematodes may be found. In among lobules of pancreas is a well encapsulated cellular mass without particular architecture. It consists of cells of large lymphocyte or endothelioid series. There are numerous cells of size and staining characters of small lymphocytes. There are no megalocytes but there are some indistinguishable from myelocytes. This may be an intrapancreatic lymph node. One small lymph node found in section; it shows a picture quite like the marrow except for megalocytes. Blood vessels do not show an excess of leucocytes in free or coagulated blood.

Perhaps this latter case belongs to the aleucemic leucemias or pseudoleucemias. These two conditions are recognized by the difference in circulating leucocytes, a piece of information not at our disposal. The whole subject of hemato-lymphatic affection must remain unsettled in so far as a diagnostic name is concerned, for in very few cases has the blood of our animals at autopsy been in a state permitting reliable observations upon stained smears, because of coagulation, lysis or decomposition. After considering a few more of the diseases of the blood and marrow, the lymphatic apparatus will be considered. But there is a borderland to which a word might be devoted at this time, that group to which various names—Hodgkin’s disease, pseudoleucemia, general adenopathy, adenie, aleucemic leucemia—have been applied and which has been accepted as occurring in the domesticated animals. Since I have been occupied for several years in a study of this clinicopathological complex in the human being, such cases have been searched for most diligently, but without success. The New York Zoological Park records a case of Hodgkin’s disease, without specifications, in 1901, and at the London Garden a pseudoleucemia was found. The paucity of leucemia and of the aleucemic adenopathies in lower animals and their relative frequency in man excite speculation as to their interdependence; but more of this under the lymphatics.

AVIAN LEUCEMIA.

The class Aves is rather better represented in the group of leucemias, but here the well known infectious disease may confuse the picture. The birds affected were Psittaci 3 (1 parrot, 1 parrakeet, and 1 amazon), Herodiones (stork) 1, and Galli (Gambel’s quail), 1. There was no close association of these cases either in time or housing. One of the parrots and the stork had a picture suggesting that given by Warthin for avian leucemia while the remainder presented greater evidence of a generalized infection, such as Moore described, associated with the finding of the B. sanguinarium; this organism was isolated once, but no secondary cases succeeded upon the death of this bird. It seems hardly profitable to quote protocols of this relatively unimportant condition, especially since it is fairly well known.

The separation of the two groups just specified might be discussed, however, for it is by no means certain that they are or are not different. When a pathological picture of leucemia gives a decided impression of an acute infection there are very prominent involvements of the viscera but no lymph nodal masses. On the other hand, in the cases with nodular masses corresponding to the scanty lymph tissue of birds, there is much less infiltrative involvement of viscera and less parenchymatous degeneration. This suggests that they are different processes, but an analogous contrast may be found in the pathologic anatomy of acute and chronic leucemia in man, and I am inclined to view them as stages of the same disease. In one of our infectious cases noted above the lesion was certainly myelogenic for the infiltrate in the organs and the cells in blood smears showed an enormous number of eosinophilic and basophilic polynuclears greatly in excess of normal. The study of two of our cases confirms the picture as given for lymphatic and myeloic leucosis by Ellermann[18], but material corresponding to his lymphoidocytes or erythroleucotic group has not come to our attention. Cells with deeply staining basophilic protoplasm and a lymphoid nucleus are certainly to be found with reasonable ease in the avian marrow normally and, more than this, can be detected by careful search in nearly all cellular infiltrates of organs not leucemic in nature. Perhaps, as Ellermann states, they are collateral stages in normal erythrogenesis.

THE BONE MARROW.

Since the foregoing conditions so vitally concern the bone marrow, it is but natural to give to this structure a separate consideration. From what is known of the origin, physiology, anatomy and regeneration of the marrow from the work of Ponfick, of Neusser, Bunting, Selling, Werigo and many others, it seems highly probable that the principal conclusions reached in the study of human medicine and experimental pathology, apply to the whole group of animals here under discussion. The peculiar arrangement already mentioned as encountered in the marrow of birds differs little if any from the erythropoietic centres seen in man after experimental anemia, although it may be somewhat more orderly. Myeloblasts or megakaryocytes are not numerously present in any order, but seem more prominent in the mammals than in birds. In so far as the mononuclear groups are concerned, one can state with reasonable certainty that they differ little throughout the animal kingdom. They occur in islands, strands, or infiltrate—like groups, are mixed granular and non-granular in character and, with exception of the frankly oxyphilic cells, are distinctly basic in tinctorial affinity. In a case probably myeloma, soon to be discussed, there is not a single acidophilic or multinucleated cell to be found in two sections. As might be expected from the greater eosinophilic content of the circulating blood in the Aves, greater numbers of such cells are to be found in the marrow and they are, understandingly enough, sometimes found in distinct nodes and groups containing mono- and polynuclear varieties. Concerning the platelets, no sufficient data are at our disposal to warrant a general statement. In the avian marrow they can be made out quite clearly, as in the blood, and have a greater diameter and a sharper, more chromatic nucleus than in the higher mammalian blood. Mast cells are quite common in lower mammals and birds, in whose blood they maintain an appreciable percentage, while in the marrow they stand out clearly. It is noteworthy, in the light of Graham’s statement that the hemic basophile is but a degeneration form of the eosinophile, that in the bird’s marrow, large mono- and polynuclear cells with both kinds of granules easily may be found by Romanowsky stain. An increase of eosinophiles, seen in avian as well as in human parasitism, is not necessarily accompanied by basophilia.

Hyperplasia and atrophy of marrow in the lower mammals follow much the same conditions as in higher groups. During acute general infections, as by the paracolon bacillus in carnivores, it is common to find a distinct increase in the mononuclear centres, while in suppurative lesions a polynucleosis results. The bird, however, responds less readily with leucocytes, judged by cross sections of blood vessels and the activity of the marrow. The latter may show a myeloid picture, but mononuclears without granules, with deeply staining nucleus and protoplasm, are usually more numerous; two cases recently studied, one of tuberculosis and one of pneumonia with general congestion, had similar bone marrow— pale homogeneous red with distinct mononucleosis, more outspoken, however, in the former case. Pigment is not common in the avian marrow.

The relation of the marrow to general conditions has been mentioned in the foregoing pages, but perhaps the following diagnoses will illustrate other connections seen among our records:

Bactrian Camel (_Camelus bactrianus_).—Hydatid disease of lung and liver. Hemorrhagic enteritis. Atrophic bone marrow. Calcified areas in thyroid.

American Gray Wolf (_Canis mexicanus_).—Cretinoid. Hemorrhagic external pachymeningitis with craniotabes. Secondary hyperplasia of thyroid with colloid. Chronic lymphatic hyperplasia. Chronic interstitial nephritis. Chronic enteritis. Osteogenesis imperfecta. Hemorrhagic bone marrow. Concentric hypertrophy and dilatation of heart.

MYELOMA.

Perhaps no pathological condition has given rise to more varied opinions than the tumor-like hyperplasias of the bone marrow, growths resembling bone sarcoma with and without giant cells—myeloma, chloroma, pseudoleucemia ossium and many others. In brief only two cases occur in our series which could be admitted to this category. There have been osteomata, but they were so clearly local tumors that they cannot be included in myeloid neoplasms that are assumed to be systemic in nature. Here is not the place to engage in a discussion of the correct classification and nomenclature since there are included only the aleucemic newgrowths usually assumed to originate from blood-making cells. The first case seems to be a myeloma because of the involvement of many bones and the infiltrates in the liver. Judging by the cross section of blood vessels there is no leucemia, but of course this is not final, although somewhat supported by the normal size of the spleen and lymph nodes; lymphatic structures need not be enlarged in myeloid leucemia although they usually are.