Veterinary Pathology

McCaskey, P. C.; Rigsby, W. E.; Hinton, D. M.; Friedlander, L.; Hurst, V. J.

doi: 10.1177/030098589102800201pmid: 2063521

A variety of tissues from 20 cattle slaughtered at federally inspected facilities contained abundant light green to greenish-yellow material. Gross lesions were most common in the liver and hepatic lymph nodes. Less frequent lesions were present in the mediastinal, renal, intercostal, and gastric lymph nodes. The material was most prominent in the portal triads, and in the medullary sinuses of the lymph nodes, at times occupying up to one half of the nodal mass. Renal calculi were present in one animal.Histologically, the condition was characterized by the intracytoplasmic accumulation of innumerable brown, acicular crystals in hepatocytes, macrophages, and renal tubular epithelial cells. Less frequent large aggregates of extracellular crystals were found in the lumens of renal tubules and in portal triads. Crystals were highly birefringent when examined using polarized light. The crystals were identified as 2,8 dihydroxyadenine using X-ray diffraction, electron diffraction, infrared spectroscopy, and mass spectrometry.In mammals, adenine is normally converted to adenylate by the enzyme adenine phosphoribosyltransferase. When adenine phosphoribosyltransferase is absent, deficient, or inhibited, adenine is oxidized to 2,8 dihydroxyadenine, which is extremely insoluble at physiological pH. In human beings, an autosomal recessive disease known as 2,8 dihydroxyadeninuria is caused by a deficiency of adenine phosphoribosyltransferase.

Barr, B. C.; Anderson, M. L.; Dubey, J. P.; Conrad, P. A.

doi: 10.1177/030098589102800202pmid: 2063512

Eighty bovine fetuses with presumed protozoal infections from a previous 2-year retrospective study were examined by immunohistochemistry using antisera against Neospora caninum. In 66 (83%) of the fetuses, protozoa were found that reacted positively with anti-N. caninum sera. In three (4%) additional fetuses, protozoa identified as Sarcocystis species did not react, and in two fetuses (3%) single protozoal clusters were found only in hematoxylin and cosin-stained slides. A group of 20 fetuses were chosen for further evaluation. They included 14 fetuses from the first group of 80 fetuses plus six additional fetuses that had large numbers of protozoa in the fetal brain. The 20 fetuses were examined immunohistochemically with antisera to N. caninum, Hammondia hammondi, and Toxoplasma gondii. Protozoa from 3/20 fetuses, identified as Sarcocystis species, failed to react with any antisera. In 16/20 fetuses protozoa reacted positively to antisera against N. caninum, and in most cases reacted to H. hammondi, and weakly to one or more of the antisera against T. gondii. Thickwalled protozoal tissue cysts were found in the brain of four of these 16 fetuses by transmissiosn electron microscopy. The cyst wall morphology was comparable to N. caninum. The results suggested that a single protozoal parasite of unknown identity was responsible for most of the bovine abortions. By immunohistochemistry, the unknown protozoon reacted most strongly and consistently to N. caninum antisera, but was antigenically distinct from N. caninum. Ultrastructurally, tissue cysts found in four fetuses most closely resembled Neospora caninum.

Sheahan, B. J.; Caffrey, J. F.; Gunn, H. M.; Keating, J. N.

doi: 10.1177/030098589102800203pmid: 2063513

Degenerative lesions in the spinal cord white matter of 12 English Foxhounds and two Harriers between 3 and 6 years old were associated with a diet composed mainly of ruminant stomachs. Lesions were present throughout the length of the spinal cord and were more severe in ventral and lateral columns than in dorsal columns. Degenerate fibers were accompanied by astrocytic proliferation. Changes suggestive of a primary myelinopathy included vacuolated myelin sheaths around apparently intact axons and thick-thin transitions in myelin sheath thickness. Mixed sensory and motor peripheral nerves and muscle histochemical fiber type profiles appeared normal. Similarities were noted with the changes described in subacute combined degeneration of the spinal cord in human beings, a neuropathy caused by methionine and methylation deficiency in patients with vitamin B12 deficiency. Mean serum methionine levels were significantly lower (P > 0.01) and mean liver methionine synthetase levels were significantly greater (P > 0.01) in affected dogs restored to a balanced diet than in age-matched controls maintained on the balanced diet. The elevated methionine synthetase levels possibly reflected compensatory reactions to the associated dietary change.

Rowland, P. H.; Valentine, B. A.; Stebbins, K. E.; Smith, C. A.

doi: 10.1177/030098589102800204pmid: 1712141

Cutaneous plasmacytomas associated with local deposition of amyloid were diagnosed by light microscopy in a series of six older dogs (mean age 10.7 years) consisting of two Cocker Spaniels, a Poodle, a Weimeraner, and two mixed-breed dogs. The neoplasms occurred on the digits (2 dogs), forelimb (2 dogs), lip (1 dog), and ear (1 dog). In most cases, groups of neoplastic plasma cells were widely separated by large homogeneous islands of amyloid. The neoplastic cells had characteristic plasmacytoid features, but the degree of pleomorphism varied greatly between different neoplasms. In four of the six tumors, the diagnosis of plasmacytoma was confirmed by the demonstration of a monoclonal plasma cell population using immunofluorescent staining for anti-canine immunoglobulins. In these tumors, the neoplastic cells reacted with only one class of immunoglobulins (IgG). The amyloid did not react with any of the reagents used. The suspicion that the amyloid was of immunoglobulin origin (primary amyloid) was supported by its retention of birefringence under polarized light after treatment with potassium permanganate and staining with Congo red.

Suter, M. M.; Pantano, D. M.; Flanders, J. A.; Augustin-Voss, H. G.; Dougherty, E. P.; Varvayanis, M.

doi: 10.1177/030098589102800205pmid: 2063514

Neoplastic canine keratinocytes derived from a spontaneous oral squamous cell carcinoma were maintained in culture for more than 45 passages. The presence of desmosomes and keratin filaments was demonstrated by electron microscopy and immunohistochemistry. The keratinocytes were grown in two different culture conditions to induce variations in the stage of differentiation, i.e., in submerged cultures and at the air-liquid interface. For comparison, normal canine keratinocytes were grown under the same conditions. Anisocytosis was present in neoplastic cultures grown submerged in medium. Grown at the air-liquid interface, neoplastic keratinocytes differentiated into a well-organized, multilayered stratified squamous epithelium analogous to normal keratinocytes. Rare areas of irregular growth and formation of whorls were detected. Expression of lectin binding sites and specific cell surface antigens of neoplastic and normal keratinocytes demonstrated marked similarities between the two cell lines. Neoplastic cells lacked certain surface antigens that are present on normal cells. Squamous cell carcinoma cells grew faster than normal canine keratinocytes as demonstrated by growth curve evaluation. Neoplastic keratinocytes responded to growth stimulation by epidermal growth factor and cholera toxin as do normal keratinocytes. Neoplastic cells grown in medium lacking these factors proliferated faster than growth factor stimulated normal keratinocytes.

Cardy, R. H.

doi: 10.1177/030098589102800206pmid: 1676552

Sexual dimorphism is a routinely encountered but previously unreported feature of the normal rat mammary gland. Forty male and 40 female F344 rats, 19 weeks of age, were examined retrospectively to document histologic differences that are very apparent when mammary glands of males and females of the same age are compared.Development of the mammary gland starts in utero, and there is reported to be little morphologic difference between males and females at birth. By 19 weeks of age, however, the differences are very noticeable. The mammary glands of females, comprised of scattered tubular ducts and alveolar structures that have distinct lumina lined, usually, by a single layer of cuboidal epithelium, are characterized as tubuloalveolar. In young males, mammary tissue is generally more florid than in females of the same age. There are, scattered within the hypodermis, larger, more contiguous, lobular groups of cells that are distinct for their lack of obvious tubular or ductal orientation. The cells, arranged into alveoli, are generally characterized by abundant, foamy, eosinophilic cytoplasm containing distinct, variably-sized vacuoles. Alveolar lumina are mostly indistinct but may contain evidence of secretory activity.To emphasize the importance of this difference, selected results of a routine toxicity study are discussed in which the mammary glands of male rats, exposed for 52 weeks to cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methyl-aminobenzamide, a reported dopamine antagonist, underwent distinctive histomorphologic changes. As a result of exposure to this compound, the lobuloalveolar structure described as normal for male rats assumed characteristics of a tubuloalveolar morphology indistinguishable from that seen in the unexposed females. Female mammary glands were unaffected by exposure to the same material.

Hamilton, H. L.; Cooley, A. J.; Adams, J. L.; Czuprynski, C. J.

doi: 10.1177/030098589102800207pmid: 2063515

In this study, a paratuberculosis (Johne's disease) model was developed by intragastrically dosing gnotobiotic athymic nude mice with Mycobacterium paratuberculosis. The mice infrequently shed bacilli from their intestinal tracts during the first 4 months after inoculation. Following this time, increasing numbers of M. paratuberculosis (greater than 4.0 log10 bacilli per fecal pellet by 40 weeks) were recovered from the feces of the 12 mice that remained in the isolator. A similar pattern of recovery of M. paratuberculosis was obtained from the ileum, cecum, colon, and liver. Histopathologic lesions and acid-fast bacilli were rare during the first 4 months of infection and then, with time, increased in prevalence and severity. Mice maintained for 7 months or longer exhibited severe granulomatous inflammation and large numbers of acid-fast bacilli in the gastrointestinal tract and liver (up to 105 log10, colony forming units per gram wet weight). Five mice maintained for 7 months or more developed clinical signs consistent with those seen in paratuberculosis (weight loss, chronic diarrhea); three of these mice eventually died or became moribund and were euthanatized. M. paratuberculosis monoassociated mice released increased levels of tumor necrosis factor activity into their sera, as compared to uninfected control mice, when they were injected with bacterial Iipopolysaccharide. The clinical signs, fecal shedding of M. paratuberculosis, granuloma formation, and progressive bacillary multiplication observed with these mice are consistent with naturally occurring M. paratuberculosis infection of ruminants (Johne's disease). This model will be useful for future studies of immunoregulation and antimicrobial therapy of paratuberculosis.

Novilla, M. N.; Sandusky, G. E.; Hoover, D. M.; Ray, S. E.; Wightman, K. A.

doi: 10.1177/030098589102800208pmid: 2063516

Sixty, proliferative, endocardial lesions were diagnosed in 19,304 rats, for an overall incidence of 0.3%. This population consisted of 10,127 Fischer 344,8,737 Wistar, 200 Sprague-Dawley, and 240 Long Evans rats from chronic/oncogenicity studies reported at Lilly Research Laboratories from 1976 to 1988. Of the 60 proliferative lesions, 44 were classified as endocardial hyperplasia, 15 as endocardial schwannomas, and one as an endocardial sarcoma for prevalence rates of 0.2%, 0.08%, and 0.005%, respectively. Affected rats ranged in age from 42 to 110 weeks. There were no sex or treatment-related differences in the prevalence of the rat endocardial proliferative lesions. A review of endocardial lesions in 18 of 233 Wistar rats treated with carbamate derivatives revealed endocardial hyperplasia in 12 rats, schwannomas in five rats, and a sarcoma in one rat. One of the 12 rats with endocardial hyperplasia also had an intramural schwannoma. Of 200 Wistar rats given N-nitroso-N-methylurca, two had endocardial hyperplasia, and one had an endocardial schwannoma, Morphologic features were similar in either spontaneous or ireatment-associated hyperplasia or neoplasia of the rat endocardium. Probable Schwann cell origin of the endocardial proliferative lesions was indicated by positive immunohistochemical staining for S-100 antigen in 10/12 spontaneous and 11/14 careinogen-associated endocardial hyperplastic lesions. Further, 15/16 spontaneous and 6/7 carcinogen-associated neoplasms were immunoreactive to S-100. No tumor metastasis was recorded in either the spontaneously affected or carcinogen-treated rats.

Brown, C. C.; Mariner, J. C.; Olander, H. J.

doi: 10.1177/030098589102800209pmid: 2063517

Ten goats were inoculated with peste des petits ruminants virus, a paramyxovirus closely related to rinderpest virus. All goats developed severe clinical disease, 8/10 having coughing or dyspnea as prominent clinical signs. In addition, all of the goats had stomatitis and diarrhea. Histopathologic and immunohistochemical studies were done only on the respiratory tracts. Pathologic changes ranged from mild multifocal bronchiolitis and bronchitis to severe bronchointerstitial pneumonia. Lesions were more severe in anteroventral than caudal lobes. The histologic nature of the viral process in the goat lungs had many features in common with the processes of pneumonia in dogs, due to canine distemper, or pneumonia in human beings, due to measles virus. Immunohistochemical staining of formalin-fixed, paraffin-embedded respiratory tract tissue was performed using an indirect system with rabbit anti-rinderpest virus serum, biotinylated anti-rabbit antibody, streptavidin-alkaline phosphatase, and nitroblue tetrazolium chromogen. Staining was sensitive, highlighting the presence of viral antigen in both lung and trachea of all goats. Viral antigen was found in both cytoplasm and nucleus of tracheal, bronchial, and bronchiolar epithelial cells, type II pneumocytes, syncytial cells, and alveolar macrophages. In general, the amount of staining correlated directly with the severity of the inflammatory process.

Poulet, F. M.; Valentine, B. A.; Scott, D. W.

doi: 10.1177/030098589102800210pmid: 2063518