Morphologic and immunophenotypic characteristics of malignant lymphomas in SIV‐infected rhesus macaques

Abstract

Eight cases of extranodal non-Hodgkin's lymphoma in simian immunodeficiency virus (SIV)-infected rhesus macaques, aged 4-9 years, were phenotypically and immunologically characterized, using the updated Kiel classification, in order to determine both the differences and the similarities between these types of lymphoma in immunodeficient rhesus macaques (Macaca mulatta) and man. The high-grade malignant tumors were of B-cell origin, with a predilection for extranodal growth in viscera and periorbital tissues. Immunophenotypical characterization showed that the monkey lymphomas were similar in many aspects to human immunodeficiency virus-associated lymphomas. The number of Ki67 positive cells varied from case to case and ranged from 50 to 90%. A serological screening for the simian equivalent of the Epstein-Barr virus (sEBV) by immunofluorescence assay revealed a prevalence of 92% of the sEBV antibodies in our cohort. The presence of Ebstein-Barr virus nuclear antigen (EBNA-2) could be demonstrated by immunohistochemistry in four out of eight cases. In situ hybridization revealed the presence of small EBV-encoded RNAs (EBER-1, EBER-2) in six of the eight cases. Further studies should define the precise role of herpesvirus infection for lymphomagenesis in SIV-induced immunodeficiency.

From the working group "Experimental Pathology" to the department "Pathology Unit" – historical development in retrospect

“…At the beginning of 1994, Dr. Kerstin Mätz-Rensing joined the working group as the first research assistant, and spontaneous nonhuman primate disease increasingly became the subject of research. Special emphasis was laid on the establishment of immunohistochemical markers for nonhuman primate tissue, which were used in different studies on the pathogenesis of the intestinal SIV infection, but also for tumor differentiation and classification in nonhuman primates Didier et al, 1999;Mätz-Rensing et al, 1999b;Kaup et al, 2001;Kahnt et al, 2002). Beside pathomorphological methods, new in vivo experimental techniques were also implemented.…”

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].…”

Intracranial Lymphomas in Simian Retrovirus-Positive Macaca fascicularis

“…3,5,6,8 In HIV-infected humans and SIV-infected macaques, lymphoma occurs late in the progression of the disease. 1,5,6 Histologically, these lymphomas were classified as immunoblastic. 6 Immunoblastic lymphoma with plasmacytic differentiation makes up 60% of AIDS-related primary brain lymphomas, and 100% of these cases are of the B-cell phenotype.…”

“…3,5,6 The incidence of naturally occurring lymphoma in cynomolgus monkeys (Macaca fascicularis) and rhesus monkeys (Macaca mulatta) is low. 5,6 However, the incidence in experimentally SIV-infected animals ranges from 3.8% to 19% in rhesus 5,6 and from 31% to 38% in cynomolgus monkeys. 3,5 EBV-like lymphocryptovirus sequences are detected in most lymphomas of rhesus macaques, and less often in lymphomas of cynomolgus macaques.…”

“…3,5,6 The common sites of lymphoma in acquired immunodeficiency syndrome (AIDS) patients are CNS, gastrointestinal tract, and bone marrow. 1,5,6 As in HIV-associated lymphoma, the sites of involvement in SIV-infected macaques are extranodal, as was seen in the monkeys presented herein. 3,5,6,8 In HIV-infected humans and SIV-infected macaques, lymphoma occurs late in the progression of the disease.…”