Intracranial Lymphomas in Simian Retrovirus-Positive Macaca fascicularis

Abstract

Abstract. Two young adult Macaca fascicularis each had unilateral mydriasis and ptosis. Both animals were euthanatized, monkey No. 1 for progressive neurologic signs and monkey No. 2 because of a positive intradermal tuberculin test. At necropsy, each animal had a single intracranial mass on the ventral surface of the midbrain, surrounding the oculomotor nerve. Histologically, both masses were immunoblastic lymphomas. Immunohistochemical staining revealed the neoplasms to be of B-cell origin. Simian retrovirus (SRV) was isolated from both monkeys, but simian immunodeficiency virus was not found. Both animals lacked antibody to SRV. Both animals had antibodies to Epstein-Barr-like virus (EBV), but EBV antigens were not found by immunohistochemistry. Polymerase chain reaction analysis for integrated EBV DNA was unproductive. One of the animals (monkey No. 2) had a pulmonary infection with Mycobacterium avium, suggesting that immunosuppression was present. These cases represent a unique and previously undescribed type of solitary lymphoma in SRV-infected macaques.

Characterization of Spontaneous Malignant Lymphomas in Japanese Macaques (Macaca fuscata)

“…While T-cell lymphomas have also been reported in pig-tailed macaques, 3,27 they appear to be much less common than B-cell lymphomas in cynomolgus and rhesus macaques. Although there are many reports on B-cell lymphomas in cynomolgus and rhesus macaques, 4,11,14,[20][21][22][23][24]28 T-cell lymphomas have not been reported in these macaque species, except for 1 case in a rhesus macaque diagnosed with CD8-positive leukemia by flow cytometry. Identifying the cause of lymphoma in each macaque would help in understanding the differences in the tumor phenotype.…”

Simian Retrovirus Infections: Potential Confounding Variables in Primate Toxicology Studies

“…Common clinical findings in SRV-infected macaques include diarrhea, weight loss, splenomegaly, lymphadenopathy, anemia, neutropenia, lymphopenia and occasional neoplastic disease, including cutaneous fibrosarcoma and retroperitoneal fibromatosis (RF) (13, 25, 39, 40, 48 59). In SRV-infected cynomolgus macaques, but not in other species of macaque, rare B-cell lymphomas have been reported (13,51). There is now accumulating evidence that the fibromatosis and lymphomas are due to 2 different herpesvirus cofactors secondary to immune modulation of SRV-infection in macaques.…”

“…There is now accumulating evidence that the fibromatosis and lymphomas are due to 2 different herpesvirus cofactors secondary to immune modulation of SRV-infection in macaques. The etiologic agent of RF is thought to be a macaque rhadinovirus (gammaherpesvirus), the macaque counter-part of human Kaposi's sarcoma virus (human herpesvirus-8) (53), while the rare B-cell lymphomas observed in SRV-infected cynomolgus are likely due to coinfection with an EBV-like lymphocryptovirus (51). Clinical findings identified in a retrospective case review of SRVinfected rhesus and cynomolgus macaques at the California National Primate Research Center (CNPRC) are presented in Table 3 (N Lerche, unpublished data).…”

Malignant NK/T-Cell Lymphoma Associated with Simian Epstein-Barr Virus Infection in a Japanese Macaque (Macaca fuscata)

“…Analyses of CD markers also help us to classify non-Hodgkin lymphoma in non-human primates and provide more information about the lymphomagenesis [3,21,22]. There has been so far only one report on lymphoma with CD marker analyses for the Japanese macaque (Macaca fuscata) [31].…”

“…The procedure has been described previously [13]. As for the sEBV infection status, the presence of anti-sEBV VCA antibody and anti-sEBV early antigen (sEA) antibody were used as markers for the sEBV infection and the possible presence of sEBV associated cell proliferative diseases, respectively [22]. P3HR-1 cells [8] treated with 4 mM n-butyric acid (Wako Chem., Japan) and 20 ng/ml 12-tetradecanoylphorbol-13-acetate (TPA) (Sigma, USA) for 48 h, and Raji cells [23] treated with 20 ng/ml TPA for 5 days were fixed with acetone and used as target antigens of sEBV VCA and sEA, respectively.…”