Veterinary Pathology

Sheep in New Zealand develop small intestinal adenocarcinomas more frequently than sheep elsewhere in the world. This high rate of neoplasm development could be due to a genetic predisposition or due to an environmental carcinogen. Differentiation between a genetic and an environmental factor is important as, if an environmental carcinogen is present, people could be exposed directly or by consuming sheep meat. In humans, germline defects in the mismatch repair (MMR) genes cause hereditary nonpolyposis colorectal cancer (HNPCC). Affected people are predisposed to neoplasm development, most commonly colonic adenocarcinomas. It was hypothesized that MMR defects are common within the New Zealand sheep flock, and these defects predispose New Zealand sheep to intestinal neoplasia. To investigate this, immunohistochemistry was used to evaluate the expression of the MMR proteins MSH2, MSH6, MLH1, and PMS2 within 49 ovine intestinal adenocarcinomas. Neoplastic cells within all sheep tumors expressed MSH2, MSH6, and MLH1. Expression of PMS2 could not be assessed, most likely because of insufficient affinity of the anti-human PMS2 antibody to ovine PMS2. The consistent expression of MSH2, MSH6, and MLH1 within the ovine intestinal adenocarcinomas does not support the hypothesis that defects in the MMR genes are common in New Zealand sheep.

Scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. This study documents incubation periods, pathologic findings, and distribution of abnormal prion proteins (PrP^Sc) by immunohistochemistry in tissues of genetically susceptible sheep inoculated with US sheep scrapie agent. Four-month-old Suffolk lambs (QQ at codon 171) were inoculated by 1 of 3 different routes (nasal, peritoneal, and conjunctival) with an inoculum (No. 13–7) consisting of a pool of scrapie-affected sheep brains. Except for 3 sheep, all inoculated animals were euthanized when advanced clinical signs of scrapie were observed between 19 and 46 months postinoculation (MPI). Spongiform lesions in the brains and labeling of PrP^Sc in central nervous system and lymphoid tissues were present in these sheep. One intranasally inoculated sheep euthanized at 12 MPI had presence of PrP^Sc that was confined to the pharyngeal tonsil. These results indicate that the upper respiratory tract, specifically the pharyngeal tonsil, may serve as a portal of entry for prion protein in scrapie-infected environments.

Kidney samples with interstitial nephritis from 26 pigs affected by postweaning multisystemic wasting syndrome (PMWS) were selected. A histologic evaluation was carried out to describe the type of inflammation and its relationship with viral load, as assessed by in situ hybridization (ISH). Of 26 cases, 10 revealed a tubulointerstitial, lymphoplasmacytic nephritis, 11 an interstitial granulomatous nephritis, and 5 both types of inflammation (mixed type). In 4 cases of granulomatous inflammation, the pattern was not classically nodular, and a population of macrophages and lymphocytes was present (interstitial lymphohistiocytic nephritis). ISH confirmed the presence of porcine circovirus type 2 (PCV2) nucleic acid in all cases. The epithelium of the renal tubules was the most constantly ISH-positive structure. In tubulointerstitial nephritis, the higher the number of positive inflammatory cells, the more severe the inflammation. The ISH reaction was more heterogeneous and unpredictable in granulomatous nephritis, with some epithelioid and giant cells positive by ISH. To quantify macrophages distributed in the three patterns of nephritis, immunohistochemical methods using anti-major histocompatibility complex II (anti-MHC-II) and anti-lysozyme antibodies were undertaken, and semiquantitative evaluation was carried out. MHC-II was mainly expressed by lymphocytes in tubulointerstitial nephritis, but did not always stain macrophages in cases of granulomatous (including lymphohistiocytic) nephritis; the anti-lysozyme antibody revealed macrophages when present in tissues. The amount of PCV2 nucleic acid was not apparently associated with the pattern of inflammation (tubulointerstitial or granulomatous). PCV2 load seems to reflect the severity of the lymphoplasmacytic inflammation but not that of granulomatous and lympho histiocytic types.

Toxicity following ingestion of the vagrant, foliose lichen Xanthoparmelia chlorochroa was identified as the putative etiology in the death of an estimated 400–500 elk on the Red Rim-Daley Wildlife Habitat Management Area in Wyoming during the winter of 2004. A single, unsubstantiated report in 1939 attributed toxicity of X. chlorochroa in cattle and sheep to usnic acid, a common lichen secondary metabolite. To test the hypothesis that usnic acid is the proximate cause of death in animals poisoned by lichen, domestic sheep were dosed PO with (+)-usnic acid. Clinical signs in symptomatic ewes included lethargy, anorexia, and signs indicative of abdominal discomfort. Serum creatine kinase, aspartate aminotransferase, and lactate dehydrogenase activities were considerably elevated in symptomatic sheep. Similarly, only symptomatic ewes exhibited appreciable postmortem lesions consisting of severe degenerative appendicular skeletal myopathy. The median toxic dose (ED₅₀) of (+)-usnic acid in domestic sheep was estimated to be between 485 and 647 mg/kg/day for 7 days.

Functional evaluation of the pars intermedia (PI) is required for the early diagnosis of equine pituitary PI dysfunction (PPID), yet most assays target the hypothalamic-pituitary-adrenal axis, which regulates the pars anterior. In contrast, the PI is regulated by dopaminergic tone from hypothalamic neurons. Loss of dopaminergic inhibition is hypothesized to cause the PI hypertrophy and hyperplasia that result in the clinical manifestations of PPID. Domperidone, a dopamine receptor antagonist, should exacerbate the loss of dopaminergic inhibition in horses with PPID and increase the release of endogenous adrenocorticotrophic hormone (eACTH) by PI melanotrophs. To test this, plasma eACTH concentration was determined in horses with or without clinical signs of PPID at 0, 4, and 8 hours after oral administration of 3.3 mg domperidone/kg. Pituitary glands were evaluated postmortem by histologic grading and morphometry. In the 33 horses, median age, plasma ACTH concentration 8 hours after domperidone, and PI area in median sagittal sections were associated with histologic grade as follows: pituitary grade 1 (normal), n = 3, 7.5 years, 20.0 pg/ml, 0.16 cm²; grade 2 (focal hypertrophy or hyperplasia), n = 9, 14.5 years, 27.1 pg/ml, 0.27 cm²; grade 3 (diffuse adenomatous hyperplasia), n = 5, 21.0 years, 64.4 pg/ml, 0.48 cm²; grade 4 (microadenomas), n = 12, 23.3 years, 128.0 pg/ml, 0.87 cm²; grade 5 (adenoma), n = 4, 24.9 years, 720.5 pg/ml, 2.1 cm². Results suggest that horses with pituitary histologic grade ≥3 respond to domperidone with increased plasma ACTH concentration.

We report a case of multiple glomus tumors associated with bovine papillomavirus type 2 (BPV-2) infection in the urinary bladder of a 13-year-old cow suffering from severe chronic enzootic hematuria. Macroscopically, multiple submucosal reddish nodules were seen swelling the vesical mucosa. Histologically, neoplastic proliferation was characterized by the presence of numerous blood vessels. These were lined by normal endothelial cells surrounded by round epithelioid cells with central nuclei, prominent nucleoli, acidophilic cytoplasm, and well-defined cytoplasmic borders. Tumor cells were distributed around open vascular lumina and in perivascular spaces. They were immunohistochemically positive for actin and vimentin and negative for cytokeratins, desmin, and factor VIII-related antigen. On the basis of these findings, this tumor was diagnosed as glomus tumor, a neoplasm not previously reported in cattle and exceedingly rare in animals. BPV-2 DNA was amplified from the formalin-fixed, paraffin-processed tissue specimens obtained by laser capture microdissection. This report widens the spectrum of mesenchymal tumors of the bovine urinary bladder. Finally, the microscopic pattern of tumor described here shares striking morphologic and immunohistochemical similarities with the angiomatous form of glomus tumor known to occur in man.

A 6-year-old, sterile, Blanca Celtibérica breed adult doe was referred to our faculty. The doe had external female genitalia, a short anogenital distance, and normally shaped udders. Masculinization signs in the head shape and male behavior were also noted at the time of referral. Genetic analysis demonstrated normal 2n = 60 XX karyotype and an absence of the sex-determining region Y (SRY). The animal was homozygous for a DNA deletion responsible for the Polled Intersex Syndrome (PIS). A uterus and 2 uterine horns were present at the postmortem examination. Gartner's ducts and degenerated Wolffian derivatives persisted. There were 2 intra-abdominal testicle-like structures, one of which consisted of epididymal and deferent ducts. An advanced Leydig cell tumor, resulting in almost total destruction of the intratesticular structures, was also observed. Leydig cell tumors usually produce testosterone. Thus, these histologic findings are compatible with the evident virilization.

Melanosis of the urinary bladder is a very rare condition characterized by an abnormal black or brownish-black pigmentation of the organ. The pigmentary disorder can involve both the urothelial cell layers and/or the submucosa. The biologic potential of the melanosis of urinary bladder remains unknown because only a few cases have been reported in medical literature. So far melanosis of the urinary bladder is not known to occur in cattle. Here we describe the first case of melanosis of the urinary bladder in an inbred red-spotted, 7-year-old cow. Light, ultrastructural, and immunohistochemic investigations demonstrated melanin pigment in the submucosa and lamina propria but not the urothelium of the bladder. In addition, biochemical characterization of the pigment-laden cells demonstrated that the pigment of this disorder consisted mainly of eumelanin, thus corroborating the morphologic studies. Finally, virologic examination revealed the presence of bovine papillomavirus type 2.

An outbreak of acute, fatal, hemorrhagic pneumonia was observed in more than 1,000 mixed breed dogs in a single animal shelter. The Department of Anatomic Pathology at the University of California at Davis School of Veterinary Medicine performed necropsies on dogs that were found moribund in acute respiratory distress or found dead with evidence of nasal bleeding. All dogs had hemothorax and an acute, fibrinosuppurative pneumonia. Large numbers of gram-positive cocci were observed within the lungs of all dogs and within septic thromboemboli of remote organs in about 50% of cases. Bacterial cultures from the dogs and their environment revealed widespread beta-hemolytic Streptococus equi subspecies zooepidemicus (Lancefield Group C). Extensive diagnostic testing failed to reveal the consistent presence of copathogens in individual cases. The clinical, epidemiologic, molecular biologic, and pathologic data indicate that a single clone of S. zooepidemicus was the cause of an acutely fatal respiratory infection in these dogs.

A B-cell, Burkitt-type lymphoma, diffusely affecting the peripheral nerves and intramuscular nerve branches was diagnosed in a 4-year-old domestic shorthair cat with a chronic progressive history of flaccid tetraparesis and generalized muscle atrophy. There was no evidence of cranial nerve, central nervous system, radicular, bone marrow, splenic, or lymph node involvement. The cat tested negative for feline retroviruses and a wide variety of herpes viruses, including Epstein-Barr virus. The clinical manifestation of this case was similar to the chronic polyneuropathic variant of human diffuse neurolymphomatosis; a condition most commonly caused by an axonopathy resulting from infiltration of peripheral nerves with non-Hodgkin's lymphoma.

A 5-year-old female neutered Boxer dog was diagnosed with extensive odontogenic cysts that affected the left and right mandibles. Rostral mandibular swelling was detectable clinically, and bilateral cystic mandibular lesions were identified radiographically. The dog's owners elected for euthanasia. A full postmortem was performed. Cystic cavities were confirmed in the body of each mandible, extending from the incisor teeth to the mid premolar region. Incisor, canine, and premolar tooth roots indented each cavity. Histologic examination of the cystic cavities reflected an inner lining of attenuated stratified squamous epithelium overlying a fibrous layer infiltrated by a mixed, predominantly mononuclear, inflammatory infiltrate.

A cranial cervical mass was surgically removed from a dog. On histologic examination, the mass was consistent with an esophageal duplication cyst, a condition rare in humans and not reported in the dog.

Central neurocytoma is a rare, prognostically favorable neuronal tumor of the human central nervous system, typically located intraventricularly near the foramen of Monro. Extraventricular cerebral neurocytomas and spinal tumors have also been reported. To date, however, neurocytomas have not been documented in domestic animal species. In this report, we describe a spinal cord tumor in a dog. The microscopic examination revealed tumor cells forming loosely packed clusters in some areas and palisades in other areas. In addition, they showed fine fibrillary neuropil-like areas of different sizes, sometimes resembling the “rosettes” of pineocytomas, as well as ependymoma-like perivascular pseudorosettes. The tumor cells had scant eosinophilic cytoplasm, with perinuclear halos, closely resembling the appearance of oligodendroglioma. Immunohistochemical staining showed expression of synaptophysin and neuron-specific enolase by tumor cells and pronounced in fibrillary areas. On the basis of histomorphology and immunohistochemical reactivity, the present tumor was diagnosed as extraventricular neurocytoma.

An aged male vervet monkey showed severe cardiac arrhythmia for more than 3 years. A multifocal amyloid consisting of transthyretin was deposited in all areas of the heart wall, especially in the extracellular stroma among muscle fibers and external tunica of arterioles. Moreover, the amyloid was deposited in the stroma and arterioles of other systemic organs except the liver and spleen. These characteristics are consistent with senile systemic amyloidosis in humans. A second amyloid consisting of amyloid β protein was in senile plaques and cerebral amyloid angiopathy in the cerebral cortex. A third amyloid consisting of islet amyloid polypeptide was deposited in islets of the pancreas. Apolipoprotein E and amyloid P component colocalized with the 3 amyloids. Thus, 3 different aging-related amyloids were found in an aged vervet monkey. In particular, to our knowledge, this is the first report on spontaneous transthyretin amyloidosis in animals.

An adult pet rabbit (Oryctolagus cuniculus) presented with a progressively enlarging left testicle. Because neoplasia was suspected, the testicle was removed. Pathologic evaluation (exfoliative cytology, histopathology, immunohistochemistry, electron microscopy) indicated that the tumor was an intratesticular granular cell tumor. Granular cell tumor has not been described in rabbits before and has not been described in the testes of animals or postnatal humans. Granular cell tumor should be included as a differential diagnosis of testicular tumors, particularly Leydig cell tumor, because of potential histologic similarities.

A 3-year-old female rabbit (Oryctolagus cuniculi) presented with apathy and indisposition for 2–3 days. Palpation revealed a mass in the caudal abdomen, namely, in the wall of the uterus. Ovariohysterectomy was performed, and the tissues were submitted for histopathologic examination. The mass consisted of 3 different (trophoblastic, syncytiotrophoblastic, and cytotrophoblastic) neoplastic cell types originating from the uterus. Immunohistochemistry was positive for cytokeratin in all 3 neoplastic cell types, and the syncytiotrophoblasts were positive also for human chorionic gonadotropin. Together these features allow the diagnosis choriocarcinoma. This report documents the first case of a spontaneous choriocarcinoma in a rabbit.

Necropsy of a 17-month-old male common marmoset (Callithrix jacchus) with a history of increased abdominal girth resulted in the finding of a unilateral polycystic renal neoplasm. Detailed histopathologic and immunohistochemical investigations revealed different tissue types within the tumor including stromal connective tissue and fusiform mesenchymal cell formations surrounding blastemal cells as well as different developmental stages of organ-specific epithelial cells accompanied by extensive cyst formation. Metastases were not observed. In consideration of the macroscopic, histologic, and immunohistochemical findings, the tumor was classified as a nephroblastoma closely resembling the so-called Wilms' tumor, a malignant embryonic renal tumor frequently observed in humans, especially in young children. In contrast, this tumor entity has rarely been observed in nonhuman primates. This report represents the first documented case of a cystic variant of nephroblastoma in a nonhuman primate.

Inflammatory or degenerative pathology involving the vertebral bodies and/or ventral intervertebral joints has been described in numerous species, both captive and free ranging, including mammals, birds, and snakes, although never in amphibians. We described 15 cases of a newly recognized spinal arthropathy in adult cane toads (Chaunus [Bufo] marinus), an invasive species in Australia. Grossly appreciable lesions consisted primarily of ventral proliferation of bone and cartilage that resulted in ankylosis. Histologic examination of the entire vertebral columns of the 15 affected toads revealed 13 toads to have lesions at multiple intervertebral sites, totalling 41 intervertebral joints with lesions. Most lesions involved bone and cartilage proliferation that resulted in fusion of the joint, with (n = 15) or without (n = 9) associated pyogranulomatous inflammation. In the remaining 17 affected joints, histologic lesions were characterized by degeneration of articular cartilage without joint fusion. In addition, in one of these joints, there was also hemorrhage and pyogranulomatous inflammation. Bacterial culture of affected joints in 9 toads and grossly normal joints in 4 control toads resulted in isolation of Ochrobactrum anthropi in 7 affected toads but in none of the controls (P < .01). We proposed an interaction between degenerative and bacterial etiologies in the pathogenesis of this condition. Invasive toads may be predisposed to this condition because of their large size; increased rates of movement; and, possibly, immunosuppression resulting from inhabiting a novel environment.

A progressive wart-like syndrome in both captive and wild populations of the Western barred bandicoot (WBB) is hindering conservation efforts to prevent the extinction of this endangered marsupial. In this study, 42 WBBs exhibiting the papillomatosis and carcinomatosis syndrome were examined. The disease was characterized by multicentric proliferative lesions involving cutaneous and mucosal surfaces, which were seen clinically to increase in size with time. Grossly and histologically the smaller skin lesions resembled papillomas, whereas the larger lesions were most commonly observed to be squamous cell carcinomas. Large amphophilic intranuclear inclusion bodies were observed in hyperplastic conjunctival lesions of 8 WBBs under light microscopy. Conjunctival lesions from 2 WBBs examined using transmission electron microscopy contained a crystalline array of spherical electrondense particles of 45-nm diameter, within the nucleus of conjunctival epithelial cells, consistent with a papillomavirus or polyomavirus. Conjunctival samples from 3 bandicoots that contained intranuclear inclusion bodies also demonstrated a positive immunohistochemical reaction after indirect immunohis-tochemistry for papillomavirus structural antigens. Ultrastructural and/or immunohistochemical evidence of an etiologic agent was not identified in the nonconjunctival lesions examined. Here we describe the gross, histopathologic, ultrastructural, and immunohistochemical findings of a papillomatosis and carcinomatosis syndrome recently identified in the WBB.

A 13–year-old neutered male lion was presented with a primary neoplasm arising from the left mandibular salivary gland associated with metastases to regional lymph nodes, thoracic viscera (lungs, heart, esophagus, and diaphragm), and kidney. Histologic and immunohistochemical investigations led to a diagnosis of a high-grade mucoepidermoid carcinoma of the mandibular salivary gland. In this case report, we point out the importance of the immunohistochemical characterization for differential diagnosis between various types of carcinomas of the salivary gland.