Intestinal stromal tumors in a simian immunodeficiency virus-infected, simian retrovirus-2 negative rhesus macaque (Macaca mulatta)

Multifocal submucosal stromal tumors were diagnosed in a 5.5-year-old rhesus macaque (Macaca mulatta) experimentally infected with simian immunodeficiency virus, strain SIVsmE660, and CD4+ T cell depleted. The animal was negative for simian retroviruses, SRV-1, -2, and -5. Polymerase chain reaction analysis of DNA from tumor and spleen tissue revealed abundant, preferential presence of retroperitoneal fibromatosis herpesvirus, the macaque homologue of the Kaposi sarcoma-associated herpesvirus (human herpesvirus-8), in the tumors. This was corroborated by demonstration of viral latent nuclear antigen-1 in the nuclei of a majority of the spindeloid tumor cells. Low levels of an additional macaque herpesvirus, rhesus rhadinovirus, were also detected in the spleen and tumor tissues. The spindeloid cells labeled positively for vimentin and CD117 but were negative for CD31, CD68, desmin, and smooth muscle cell actin. Collectively, these findings suggest a relation to but not absolute identity with simian mesenchymoproliferative disorders (MPD) or typical gastrointestinal stromal tumors (GISTs).     

Pulmonary cryptosporidiosis in simian immunodeficiency virus-infected rhesus macaques

Cryptosporidiosis is a common opportunistic infection in the gastrointestinal tract of human and nonhuman primates with AIDS. Pulmonary infection associated with Cryptosporidium spp. has not been previously reported in monkeys. Two macaques experimentally infected with simian immunodeficiency virus (SIV) had lesions containing cryptosporidial organisms involving the trachea, lungs, bile ducts, pancreas, and intestine. The pulmonary sections revealed moderate to severe bronchopneumonia associated with cryptosporidiosis. Numerous 2-4 microm oval Cryptosporidium spp. organisms were present in the cytoplasm of alveolar macrophages, multinucleated giant cells, and intestinal epithelial cells. Giant cells were positive for SIV by in situ hybridization. These are the first reported cases of cryptosporidiosis with involvement of pulmonary parenchyma in SIV-infected macaques.     

Hemophagocytic syndrome in a pancytopenic simian retrovirus-infected male rhesus macaque (Macaca mulatta)

Hemophagocytic syndrome (HPS) is a macrophage hyperactivation disorder triggered by disrupted T-cell macrophage cytokine interaction. HPS has been reported in humans, dogs, cats, and cattle, and it is infrequent and poorly characterized in animals. A 16-year-old male rhesus macaque was euthanized because of severe pancytopenia, including nonregenerative anemia (hematocrit = 5.5%), neutropenia (0.29 K/μl), and thrombocytopenia (21 K/μl). Bone marrow was hypocellular with normal maturation, myeloid hypoplasia, and few megakaryocytes. There were numerous morphologically normal macrophages (12% of nucleated cells), with 6% of nucleated cells being hemophagocytic macrophages in the bone marrow. Serology was negative, but polymerase chain reaction and immunohistochemistry were positive for simian retrovirus type 2. Blood and bone marrow findings were consistent with HPS. Cytopenias are common in simian retrovirus-infected macaques, but HPS has not been reported. An association between simian retrovirus infection and HPS is undetermined, but retrovirus-associated HPS has been observed in humans.     

Amebic meningoencephalitis caused by Acanthamoeba castellani in a dog

A natural infection of Acanthamoeba castellani, a free-living ameba, was determined to be the cause of acute, hemorrhagic, necrotizing amebic meningoencephalitis in a dog. This case is unique because previous reports of infection by the Acanthamoeba spp in dogs have not indicated its presence in the brain. Naturally developing meningoencephalitis by Acanthamoeba spp in the dog may have a pathogenesis similar to that of human beings. The ameba in this case also was observed in the lungs and kidneys, which are believed to be the primary sites of lesions in human beings that develop amebic meningoencephalitis from Acanthamoeba spp.     

Combined-type osteosarcoma in a rhesus macaque

A femoral mass from a 15-year-old rhesus macaque was evaluated. Grossly, the mass consisted of a large, osteolytic focus in the distal femur, a gelatinous core of neoplastic tissue in the medullary cavity, and an invasive mass-obliterating musculature of the thigh. On histopathologic evaluation, three neoplastic mesenchymal cell populations, osteoblasts, fibroblasts, and primitive mesenchymal cells were identified. The mass was diagnosed as a combined type osteosarcoma. To our knowledge, this is the first osteosarcoma in a rhesus macaque with this subclassification.     

Ulcerative cheilitis in a rhesus macaque

A 2-year-old, female, simian immunodeficiency virus E543-infected rhesus macaque (Macaca mulatta) was presented for necropsy following euthanasia due to a history of diarrhea, weight loss, and a small, round ulcer along the left labial commissure. Histopathologic examination of the ulcer revealed infiltration by large numbers of degenerate and nondegenerate neutrophils and macrophages admixed with syncytial epithelial cells. Rare epithelial cells contained herpetic inclusion bodies. These cells stained positive for Human herpesvirus 1 via immunohistochemistry, and DNA sequencing confirmed the presence of closely related Macacine herpesvirus 1 (B virus).     

Necrotizing meningoencephalitis associated with cortical hippocampal hamartia in a Pekingese dog

A 4-year-old male Pekingese dog was referred to the clinic with a history of recurrent seizures and progressive abnormal gait and behavior, which did not respond to treatment. At necropsy, a large cortical defect in the right temporo-parietal cortex, malacia of subcortical white matter, right basal nuclei, and capsula interna, as well as abnormalities of the right hippocampus were observed. Histological examination of the brain revealed moderate to severe nonsuppurative meningoencephalitis in the left cerebral hemisphere and extensive infarction-like lesions with milder inflammation in the right hemisphere. In the right hippocampus, the pyramidal cells were arranged in a gyrus-like pattern and intermingled with gemistocytic and fibrillary astrocytes. The histopathological features of the inflammatory lesions were consistent with necrotizing meningoencephalitis and resembled those described in so-called Pug dog encephalitis. The hippocampal changes were interpreted as dysplasia (monolateral hippocampal cortical hamartia), unrelated to clinical signs and necrotizing inflammatory lesions.     

Palmoplantar nonpustular psoriasiform dermatitis in a rhesus macaque

A case of psoriasiform dermatitis in an adult male rhesus macaque is reported. Appearing spontaneously, the condition presented the clinical and histopathological features of human palmoplantar nonpustular psoriasis. The animal developed multiple scaly plaques on his palms and soles, as well as nail hyperkeratosis and widening of the nail root. Microscopically, the skin lesions showed epidermal hyperkeratosis with multifocal parakeratosis, neutrophil microabscesses in the stratum corneum, a loss of granule cell layer under the microabscesses, acanthosis, and elongation of the rete ridges; the superficial dermis showed a dense inflammatory infiltrate containing lymphocytes, macrophages and neutrophils, as well as dilated and tortuous blood vessels. The lesions improved for 15 days after intramuscular corticosteroid depot therapy and worsened slightly afterwards. Later, a spontaneous, progressive remission coincided with the beginning of spring and lasted until the end of summer; the skin lesions practically disappeared during this period, and the nails looked nearly normal. During the next autumn and winter only nail hyperkeratosis was present. Serum analyses showed hyperproteinaemia and hyperglobulinaemia during the outbreak phase and normal values during remission. The clinical and histopathological features of this case, as well as its evolution, are compared with the three other reported cases of psoriasiform skin lesions in nonhuman primates. To the authors’ knowledge, this is the first report of a definite palmoplantar nonpustular psoriasiform dermatitis in a rhesus macaque.     

Pyogranulomatous meningoencephalitis due to Actinomyces sp. in a dog

Actinomyces sp. are commensal, filamentous, gram-positive, acid-fast-negative bacteria that can cause pyogranulomatous inflammation in animals and humans. Central nervous system (CNS) disease is a rare presentation of actinomycosis and is usually due to extension from infected wounds or seeding from distant sites. A dog with progressive, poorly localized neurologic signs had primary CNS actinomycosis without history or evidence of previous trauma or other organ involvement. Histologically, there was a severe pyogranulomatous meningoencephalitis with intralesional filamentous bacteria that were also visible on cytology of the cerebral spinal fluid (CSF) postmortem. Actinomyces sp. was cultured postmortem from the CSF, confirming the diagnosis. This case demonstrates that Actinomyces sp. can be a causative agent of primary CNS disease in dogs.     

Trichomonad gastritis in rhesus macaques (Macaca mulatta) infected with simian immunodeficiency virus

In a retrospective study, 51 cases of gastritis (14%) were identified from among 341 necropsies performed on simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta) at the New England Primate Research Center from 1993 to 2001. Protozoa were seen in the stomach of 13 monkeys (25%) with gastritis. Two histopathologic manifestations of gastritis were observed: seven cases of lymphoplasmacytic gastritis with trichomonad trophozoites within lumens of gastric glands and four cases of necrosuppurative gastritis containing intralesional periodic acid-Schiff-positive protozoa; two cases of gastritis had morphologic features of both types of gastritis. In instances of necrosuppurative and combined lymphoplasmacytic and necrosuppurative gastritis, protozoa were 4-35 microm in diameter and round to tear-shaped. Because of the unusual morphology of the protozoa in these latter cases, transmission electron microscopy and polymerase chain reaction (PCR) were used to further identify these organisms. The protozoa were definitively identified as Tritrichomonas in all cases on the basis of ultrastructural characteristics (flagella and undulating membranes) and amplification of a 347-bp product of the 5.8S ribosomal RNA gene of Tritrichomonas foetus, Tritrichomonas suis and Tritrichomonas mobilensis by PCR using DNA extracted from stomach tissue. On the basis of these observations, we conclude that Tritrichomonas can be a significant cofactor in the development of necrosuppurative gastritis in SIV-infected rhesus macaques.     

Pelvic endometriosis and simian foamy virus infection in a pigtailed macaque.

Pelvic endometriosis and simian foamy virus infection occurred in a pigtailed macaque. Diffuse omental, peritoneal, and intestinal implantation of endometrium resulted in massive adhesions between adjacent abdominal and pelvic viscera, with formation of a large mass in the right caudal quadrant of the abdomen. Simian foamy virus type 1 was isolated from ectopic endometrium and from the uterine wall but was considered to be merely epiphenomenal.     

Lentivirus-induced pulmonary lesions in rhesus monkeys (Macaca mulatta) infected with simian immunodeficiency virus.

Necropsy reports from 28 rhesus monkeys that had been experimentally infected with simian immunodeficiency virus (SIV) and that were free of cytomegalovirus were reviewed. Lung sections from 24 of these monkeys that had no etiologic agent other than SIV detected in the lung were studied in detail by histopathologic, immunohistochemical, and electron microscopic examination and by in situ hybridization. Fourteen of the monkeys were part of a serial euthanasia study, while others were euthanatized after they became moribund. The following lesions were detected: perivascular inflammation, vasculitis, interstitial pneumonia, syncytial cells, hemorrhage, fibrin exudation, and pleural fibrosis. Perivascular inflammation was the most frequent lesion and occurred as early as 2 weeks after inoculation. Severe pneumonia and numerous syncytial cells were seen only in animals euthanatized because they had become moribund. The lesions appeared to be directly due to SIV infection. SIV antigens, RNA, and virions were detected in syncytial cells and macrophages by immunohistochemical examination, in situ hybridization, and transmission electron microscopic examination, respectively. The amount of virus present was correlated with the severity of the lesions. The SIV-induced lesions were different from those of the lymphocytic interstitial pneumonia, which occurs in human immunodeficiency virus-infected children and in ovine lentivirus-infected sheep and goats.     

Necropsy findings in rhesus monkeys experimentally infected with cultured simian immunodeficiency virus (SIV)/delta

Lesions induced in rhesus monkeys by different isolates of simian immunodeficiency virus (SIV)/Delta were studied at necropsy. Four groups of monkeys were inoculated with SIV/Delta isolated from other experimentally infected rhesus monkeys, while one group was inoculated with SIV/Delta from an asymptomatic mangabey monkey. Three rhesus isolates and the mangabey isolate were virulent, killing 75-100% of infected monkeys. One rhesus isolate, which had been extensively passaged in vitro, was attenuated but was restored to virulence by single animal passage. Clinically, infected monkeys had lymphadenopathy, splenomegaly, diarrhea, and a rash. Most monkeys died of enteric disease. The following lesions were seen: weight loss, thymic atrophy, lymphoid atrophy, bone marrow hyperplasia, encephalitis, colitis, amyloidosis, hepatitis, glomerulosclerosis, and the presence of syncytial cells. One Rh Epstein-Barr virus (EBV)-related lymphoma occurred. Opportunistic agents were identified: cytomegalovirus, adenovirus, Cryptosporidia, and Pneumocystis. Shigella and Campylobacter often caused colitis.     

Chronic polymyositis associated with disseminated Sarcocystosis in a captive-born rhesus macaque

A 2-year-old, captive-born, clinically healthy male, rhesus macaque, was euthanatized as part of an experimental study. At necropsy, diffuse pale streaking of the trunk, lumbar, and limb muscles were noted macroscopically. On histology, numerous elongated cysts that contained crescent-shaped basophilic spores were found in the fibers of skeletal muscles. Scattered affected myofibers were degenerate and accompanied by eosinophilic-to-granulomatous inflammation. Sarcocysts had prominent villus-like projections with the morphology of a type 11 sarcocyst wall similar to Sarcocystis neurona but possessing many more villus microtubules than is reported for S. neurona. In addition, bradyzoites were very long, up to approximately 12 microm in length. The protozoa were consistent with a Sarcocystis sp., based on histology and ultrastructure, however, a definitive identification of the species was not possible. Nonspecific immunohistochemical crossreaction with Sarcocystis cruzi antisera was observed. The 18S ribosomal deoxyribonucleic acid sequence showed 91% similarity to Sarcocystis hominis, 90% similarity to Sarcocystis buffalonis, and 89% similarity to Sarcocystis hirsuta. Interestingly, the ITS1 sequence showed very little homology to any sequence in GenBank, suggesting that this is possibly a unique Sarcocystis sp. Sarcocystosis is often considered an incidental finding, particularly in wild-caught animals, with little clinical significance. However, as demonstrated in this report and others, disseminated sarcocystosis can occur in captive-born rhesus macaques with or without clinical signs. In some cases interference with research results can occur; including death in fulminant cases.