JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1350931): Unknown age and gender owl monkey
HISTORY: This owl monkey was housed in a cage next to a squirrel monkey
HISTOPATHOLOGIC DESCRIPTION: Liver: Diffusely infiltrating portal areas and sinusoids, separating, surrounding and replacing adjacent hepatocytes, and surrounding central veins is an unencapsulated, infiltrative neoplasm composed of round cells arranged in sheets. Neoplastic cells have variably distinct borders, scant amounts of eosinophilic granular cytoplasm, with a round to oval, vesiculate nucleus and 1 - 3 magenta nucleoli. The mitotic count averages 1-2 per 40x fields. Neoplastic cells are frequently within the lumen of blood vessels and sinusoids. Multifocally there is a moderate amount of single cell necrosis and low numbers of neutrophils. Diffusely, remaining hepatocytes are distended with one or more round clear vacuoles up to 20 µm in diameter (lipid) that often contain small amounts of pale green-brown granular intracytoplasmic pigment (hemosiderin or bile).
MORPHOLOGIC DIAGNOSIS: Liver: Lymphoma, owl monkey (Aotus trivirgatus), nonhuman primate
ETIOLOGIC DIAGNOSIS: Herpesviral lymphoma
CAUSE: Herpesvirus saimiri (Saimiriine herpesvirus 2)
- Family Herpesviridae, subfamily Gammaherpesvirinae, genus Rhadinovirus
- Herpesvirus saimiri (HSV) causes asymptomatic infections in the natural host [squirrel monkey (Saimiri sciureus)] and fatal lymphoproliferative diseases (lymphoma, lymphocytic leukemia) in susceptible species
- Susceptible species include rabbits and New World primates [marmosets (Callithrix sp), tamarins (Saguinus sp), cebus monkeys (Cebus sp), owl monkeys (Aotus sp), spider monkeys (Ateles sp), howler monkeys (Alouatta sp)]
- HSV is used in research on the mechanisms of viral oncogenesis
- In squirrel monkeys, the virus persists as latent infection in T lymphocytes
- A majority of squirrel monkeys have HSV antibodies; transmission is horizontal through oropharyngeal secretions
- HSV produces cell protein homologues thought to be important in the pathogenic persistence in the natural host to include: D-type cyclins, interleukin-17, and complement cascade and apoptosis pathway inhibitors
- In susceptible species, HSV causes neoplastic transformation of T lymphocytes
- Based on pathogenic phenotypes and different alleles, three subgroups are assigned: A, B, and C
- Highly oncogenic subgroup C produces two oncoproteins: Saimiri transformation-associated protein of Virus strain C488 (StpC) and Tip - thought to be essential for neoplastic transformation
- StpC: Induces mitogen activated protein kinase and nuclear factor kappa B (NFκB) activation
- Tip: Important in signal transduction and activation of transcription factors
TYPICAL CLINICAL FINDINGS:
- Lymphocytic leukemia may or may not be present
- Clinical course varies between and within susceptible species
- Can develop lymphoma as soon as three weeks after infection
- Generalized lymphadenopathy and/or hepatosplenomegaly are typical
- Terminal anorexia, lethargy, weight loss, and CNS signs in animals with brain involvement
- Three patterns / outcomes
- Survival less than 40 days with development of disseminated lymphoma; necrosis and replacement of organs
- Survival between 50 -150 days with a less aggressive form involving multiple organs and associated lymphocytic leukemia
- Survival over 150 days with a well-differentiated lymphocytic lymphoma
TYPICAL GROSS FINDINGS:
- Multifocal nodules in the liver, spleen; occasionally solitary nodules in the kidney, orbit, and abdominal cavity
- Enlargement of lymph nodes, spleen, thymus, kidney, adrenal gland with gray-white homogenous tissue that displaces and effaces normal parenchyma
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Sheets of neoplastic T lymphocytes with scant eosinophilic cytoplasm, large pleomorphic occasionally indented nuclei, distinct nucleoli, and frequent mitoses
- More aggressive form: Large pleomorphic neoplastic cells that resemble histiocytes with a high mitotic rate; often large areas of necrosis
- Less aggressive form: Neoplastic cells more closely resemble normal lymphocytes; most likely associated with leukemia
- In liver, there are frequently portal infiltrates that extend into hepatic lobules
- In kidney, neoplastic cells generally are confined to the cortex
- In lymph nodes, spleen and thymus, neoplastic infiltrates are generally diffuse
- Other Gammaviruses
- Ovine herpesvirus type 2 (OvHV-2): Natural host is the sheep; infected cattle develop malignant catarrhal fever (genus Macavirus)
- Alcelaphine herpesvirus type 1: Natural host is the wildebeest; infected cattle and buffalo develop malignant catarrhal fever (genus Macavirus)
- Leporid herpesvirus-3 (Herpesvirus sylvilagus): Inoculation in young cottontail rabbits causes lymphoproliferative disease; lymphoid hyperplasia to lymphoma
- Equid herpesvirus-2 (EHV-2): Low pathogenicity; upper and lower respiratory disease and keratoconjunctivitis in foals (genus Percavirus)
- Equid herpesvirus-5 (EHV-5): Associated with equine multinodular pulmonary fibrosis (genus Percavirus)
- Other Rhadinoviruses:
- Retroperitoneal fibromatosis herpesvirus (RFHV): Causes disease in association with simian retrovirus-2 (type D retrovirus); related to HHV-8
- Bovine herpesvirus-4 (BHV-4): Mammary pustular dermatitis; milder disease than localized form of bovine herpesvirus-2 (bovine herpes mammillitis virus)
- Murid herpesvirus-4 (MuHV-4): Mouse herpesvirus strain 68
- Other lymphotrophic herpesviruses:
- Epstein-Barr virus (Human herpesvirus 4): Burkitt's lymphoma, infectious mononucleosis, nasopharyngeal carcinoma, hairy leukoplakia
- Callitrichine herpesvirus-3 (Marmoset lymphocryptovirus): Induces a rapidly fatal lymphoma (principally B cell) or chronic mononucleosis-type disease in Marmosets
- Macacine herpesvirus-4 (Cercopithecine herpesvirus-15 / Rhesus lymphocryptovirus): Rhesus EBV-like virus; in rhesus monkeys, SIV associated lymphoma (B-cell origin) with concurrent infection with rhesus lymphocryptovirus in 94% of affected monkeys
- Marek's disease virus (Gallid herpesvirus 2): Atypical lymphoid proliferations in several tissues (T cell lymphoma), liver, kidney, eyes, peripheral nerves
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