Veterinary Pathology

Andrews, A. G.; Dysko, R. C.; Spilman, S. C.; Kunkel, R. G.; Brammer, D. W.; Johnson, K. J.

doi: 10.1177/030098589403100301pmid: 8053123

A spontaneous, severely pruritic ulcerative dermatitis was initially observed in 33/201 (16.4%) aged C57BL/6NNia mice obtained from the National Institute of Aging. This ulcerative dermatis also developed in 21/98 (21%) aged C57BL/6 mice in a subsequent experimental group obtained from the same source. The average age of onset in the initial group was 20 months. These animals were negative for ectoparasite infestation and primary bacterial or fungal infection. The lesions varied from acute epidermal excoriation and ulceration to chronic ulceration with marked dermal fibrosis. In the affected animals, leukocytoclastic vasculitis was present in the dermis in both areas of ulceration and areas covered by normal intact epidermis. Immunofluorescent staining of the skin was positive for deposition of IgG, IgM, and fibrinogen in the dermal vessels of the affected mice. Leukocytoclastic vasculitis was not observed in unaffected animals, nor were deposits of immunoglobulin or fibrinogen present in the skin of the control animals. This study provides strong evidence that the ulcerative dermatitis is caused by an immune complex-induced vasculitis. The elucidation of the pathogenesis of this disease is important because of the significant percentage of animals affected and because the C57BL/6 mouse may be a useful model to study human vasculitides.

Dillberger, J. E.; Loudy, D. E.; Adler, R. R.; Gass, J. H.

doi: 10.1177/030098589403100302pmid: 8053124

Red blood cell parasites were identified electron microscopically in five anemic adult female cynomolgus monkeys (Macaca fascicularis), two of which died during anemic episodes. Organisms typically were 0.3–0.5-μm round, oval, or reniform bodies on the surface or within vacuoles of erythrocytes. Based on their size, location in the erythrocyte, and internal ultrastructural features, organisms were classified as Hemobartonella-like. The relationship between the organisms and the anemias in these monkeys was unclear. This report adds rickettsial erythrocyte infections to the list of latent infections that can complicate research studies with cynomolgus monkeys.

Gröne, A.; Werkmeister, J. R.; Steinmeyer, C. L.; Capen, C. C.; Rosol, T. J.

doi: 10.1177/030098589403100303pmid: 8053125

Two polyclonal antibodies, directed against N-terminal amino acids (1–36) or the midregion (amino acids 34–53) of parathyroid hormone-related protein (PTHrP), were used to localize PTHrP in a variety of normal and neoplastic canine tissues. Parathyroid hormone (PTH) immunoreactivity was demonstrated using anti-bovine PTH (amino acids 14–34). The following tissues (among others) stained strongly positive for PTHrP: all layers of epidermal keratinocytes, with the most intense staining of the basal layer; hair follicle keratinocytes; myoepithelial cells of dermal apocrine glands, mammary glands, and apocrine glands of the anal sac; anal sac epithelium; mammary duct epithelium; and thyroid C cells. Adenocarcinomas of the anal sac stained moderately positive (5/22 dogs), weakly positive (11/22 dogs), or did not stain (6/22 dogs). Most parathyroid gland adenomas stained moderately (2/6 dogs) or weakly positive (3/6 dogs) for PTHrP. Squamous cell carcinomas (6/6 dogs) stained strongly positive. Lymphomas stained weakly positive (2/10 dogs) or did not stain (8/10 dogs). There was no consistent relationship between the staining intensity of the tumors and serum calcium concentrations of the dogs. The anti-PTH antibodies stained only parathyroid chief cells strongly positive. Concentrations of PTHrP were measured by radioimmunoassay in protein extracts from an adenocarcinoma derived from the apocrine glands of the anal sac, pancreas, kidney, liver, heart, thyroid, adrenal, and parathyroid glands. PTHrP concentrations varied from undetectable up to 150 pg/mg in normal tissues as compared with 2,000 pg/mg in apocrine adenocarcinoma of the anal sac. These findings demonstrate the widespread localization of PTHrP in normal and neoplastic canine tissues and suggest a physiological role for PTHrP as a paracrine or autocrine factor.

Braund, K. G.; Toivio-Kinnucan, M.; Vallat, J. M.; Mehta, J. R.; Levesque, D. C.

doi: 10.1177/030098589403100304pmid: 8053126

A polyneuropathy recognized in mature Rottweiler dogs is characterized by paraparesis that progresses to tetraparesis, spinal hyporeflexia and hypotonia, and appendicular muscle atrophy. Although signs may appear acutely, the course tends to be gradually progressive (up to 12 months or longer in some dogs) and may be relapsing. Nerve and muscle biopsies were examined from eight affected Rottweilers (six male and two female) between ages 1.5 and 4 years. Pronounced neurogenic atrophy was present in skeletal muscle samples. Changes in sensory and motor peripheral nerves included loss of myelinated nerve fibers, axonal necrosis, and variable numbers of fibers with inappropriately thin myelin sheaths. Ultrastructural findings included myelinated fibers showing myelinoaxonal necrosis, demyelinated fibers often associated with macrophage infiltration, many axons with myelinlike membranous profiles, increased endoneurial collagen, occasional axonal atrophy, and numerous Büngner bands. Lesions in unmyelinated fibers included increased numbers of Schwann cell profiles and loss of axons in Schwann cell subunits. Morphologic and morphometric studies indicated preferential loss of medium (5.5–8 μm) and large (8.5–12.5 μm) fibers, which was more severe in distal parts of nerves than in more proximal regions and nerve roots. The cause was not determined; however, histopathologic studies suggest this condition is a dying-back distal sensorimotor polyneuropathy that has morphologic and morphometric similarities to hereditary motor and sensory neuropathy (HMSN) type II in humans.

Gavier-Widén, D.

doi: 10.1177/030098589403100305pmid: 8053127

Liver lesions were studied in 40 free-living adult European brown hares (Lepus europaeus) and varying hares (Lepus timidus) of both sexes that had died in Sweden with the viral infection European brown hare syndrome (EBHS). The lesions were characterized by their histopathologic, immunohistochemical, and electron microscopic findings. Periportal to massive coagulation necrosis was a distinctive feature of EBHS. Lytic necrosis, inflammation, fatty degeneration, and cholangitis occurred variably. Accumulation of basophilic granules in the cytoplasm of hepatocytes was commonly observed; these lesions corresponded ultrastructurally to mitochondrial calcification. Viral antigen was revealed in the cytoplasm and nucleus of hepatocytes and in the cytoplasm of macrophages.

Brooks, D. E.; Ginn, P. E.; Miller, T. R.; Bramson, L.; Jacobson, E. R.

doi: 10.1177/030098589403100306pmid: 8053128

Histologic evaluation of four eyes from three stranded juvenile green turtles (Chelonia mydas) from Florida, USA revealed ocular fibropapillomas composed of an overlying hyperplastic epithelium, various amounts of a thickened, well vascularized, collagenous stroma, and a moderate-to-dense population of reactive fibroblasts. The histologic morphology of the ocular fibropapillomas varied depending on whether the eyelid, conjunctiva, limbus, or cornea was the primary site of tumor origin. Fibropapillomas arising from the limbus, conjunctiva, or eyelid tended to be polyploid or pedunculated with a high degree of arborization. They often filled the conjunctival fornices and extended externally to be ulcerated on the distal aspects. Corneal fibropapillomas were more sessile and multinodular with less arborization. Some corneal tumors consisted primarily of a broad fibrovascular stroma and mild epithelial hyperplasia, whereas others had a markedly hyperplastic epithelium supported by stalks of fibrovascular stromal tissue. In green turtles ocular fibropapillomas may be locally invasive and associated with severe blindness and systemic debilitation.

Ackermann, M. R.; DeBey, B. M.; Stabel, T. J.; Gold, J. H.; Register, K. B.; Meehan, J. T.

doi: 10.1177/030098589403100307pmid: 8053129

A commercially acquired anti-human macrophage antibody (anti-CD68; EBM11) was used in an immunocytochemical technique to detect macrophages in formalin-fixed, paraffin-embedded tissues from cattle, pigs, humans, rats, turkeys, dogs, and cats. In healthy cattle, the antibody labeled alveolar macrophages, pulmonary intravascular cells (presumably intravascular macrophages), and macrophage-like cells in other tissues. In bovine lungs infected with Pasteurella haemolytica, EBM11 antibody labeled 95% of alveolar macrophages and macrophages within alveolar septa but only 0–2% of streaming or “oat” leukocytes. Alveolar macrophages were also stained by EBM11 in pigs but not in rats, turkeys, dogs, and cats. The antibody also stained macrophage aggregates in the mesenteric lymph nodes and intestinal lamina propria of Mycobacterium paratuberculosis-infected cattle. This study shows that the anti-CD68 (EBM11) antibody is a useful marker of macrophages in normal bovine tissues or tissues from areas of acute or chronic inflammation that have been routinely processed. The study also adds strength to the growing evidence suggesting that streaming leukocytes seen in pneumonic pasteurellosis are neutrophils.

Okada, H.; Merryman, J. I.; Rosol, T. J.; Capen, C. C.

doi: 10.1177/030098589403100308pmid: 8053130

Immunohistochemical and ultrastructural investigations of thyroid C cells were conducted in male nude (athymic) mice bearing a serially transplantable canine adenocarcinoma (CAC-8) model of humoral hypercalcemia of malignancy following subcutaneous administration of gallium nitrate. The following four groups were investigated: 1) vehicle-treated non-tumor-bearing control mice; 2) non-tumor-bearing mice treated with gallium nitrate; 3) vehicle-treated hypercalcemic mice bearing CAC-8; and 4) CAC-8 tumor-bearing mice treated with gallium nitrate. Gallium nitrate-treated tumor-bearing mice had a significant decrease in serum calcium as compared with tumor-bearing controls. C cells of non-tumor-bearing mice stained intensely for calcitonin and calcitonin gene-related peptide and weakly for chromogranin A and neuron-specific enolase. In C cells of both vehicle- and gallium-treated tumor-bearing mice, immunoreactive staining was decreased for calcitonin, calcitonin gene-related peptide, and chromogranin A, whereas there was a moderate increase in staining for neuron-specific enolase. Ultrastructurally, thyroid C cells in hypercalcemic tumor-bearing control and gallium-treated mice were hypertrophic and markedly degranulated as compared with those of non-tumor-bearing controls. Hypertrophic C cells contained few mature secretory granules, a well-developed Golgi apparatus, and lamellar arrays of rough endoplasmic reticulum. There was no evidence of C-cell hyperplasia. Immunohistochemical and ultrastructural findings revealed that C cells in mice with cancer-associated hypercalcemia were primarily in the actively synthesizing phase of the secretory cycle and had diminished immunoreactivity for calcitonin, calcitonin gene-related peptide, and chromogranin A. Gallium nitrate did not alter immunohistochemical or ultrastructural features of chronically stimulated C cells even though serum calcium was reduced.

Belknap, E. B.; Collins, J. K.; Ayers, V. K.; Schultheiss, P. C.

doi: 10.1177/030098589403100309pmid: 8053131

A type of bovine herpesvirus, BHV-1.3, causes encephalitis in calves, whereas BHV-1.1 causes respiratory disease. Three colostrum-deprived calves and two colostrum-fed calves were inoculated with BHV-1.3 by intranasal aerosolization. Two colostrum-deprived calves were inoculated with BHV-1.1 by intranasal aerosolization. BHV-1.3-inoculated calves demonstrated severe encephalitis with minimal respiratory lesions, and BHV-1.1-inoculated calves demonstrated severe respiratory lesions and no clinical signs of neurologic disease. Calves fed colostrum that contained virus neutralizing antibodies were protected against neurologic disease. Colostrum-fed BHV-1.3-inoculated calves did not develop disease although they did become infected; virus was shed in respiratory secretions for 10–13 days postinoculation, similar to infected colostrum-deprived calves. BHV-1.3 was reactivated from a latent state from one colostrum-fed calf after administration of dexamethasone 60 days postinoculation. Histopathologic examination of the three colostrum-deprived BHV-1.3-inoculated calves revealed severe lesions of encephalitis. One of the two BHV-1.1-inoculated calves had one focal lesion of encephalitis. Virus was isolated from brain tissue of colostrum-deprived BHV-1.3-inoculated calves and from one BHV-1.1-inoculated calf. Immunohistochemical staining for BHV-1 antigen was observed in neurons from the colostrum-deprived BHV-1.3-inoculated calves.

Herbert, R. A.; Stegelmeier, B. S.; Gillett, N. A.; Rebar, A. H.; Carlton, W. W.; Singh, G.; Hahn, F. F.

doi: 10.1177/030098589403100310pmid: 8053132

Immunohistochemistry and transmission electron microscopy were used to clarify the cellular origin for plutonium-239-induced pulmonary proliferative (preneoplastic) epithelial lesions and epithelial neoplasms in F344 rats. Examples of each histologic type of proliferative lesion and neoplasm were stained by the avidin-biotin complex immunoperoxidase method using antibodies to rat surfactant apoprotein and Clara cell antigen. Rat surfactant apoprotein immunostaining was detected in type II pneumocytes in sections of normal lung, in the cells of the proliferative lesions classified histologically as alveolar epithelial hyperplasia (51) and mixed foci (alveolar epithelial hyperplasia with fibrosis) (30), and in adenomas (2), adenocarcinomas (3), and adenosquamous carcinomas (2). With the exception of one adenosquamous carcinoma, Clara cell antigen immunostaining was not detected in any of the pulmonary lesions but was detected in nonciliated cuboidal epithelial (Clara) cells in normal bronchioles. The epithelial cells of the proliferative lesions and neoplasms had ultrastructural features consistent with type II pneumocytes, i.e., the presence of cytoplasmic lamellar and multivesicular bodies. The results of these studies indicate that the majority of plutonium-induced proliferative epithelial lesions and neoplasms in the rat originate from alveolar type II pneumocytes.