AIDS-RELATED PRIMARY BRAIN LYMPHOMA - IMM UNOPHENOTYPICAL AND MOLECULAR-GENETIC CHARACTERIZATION OF STEREOTAXIC BIOPSIES AND OF AUTOPSY ANDCEREBROSPINAL-FLUID SAMPLES

In this study we present morphological, cytological, immunophenotypica l, and molecular genetic features of ten cases of AIDS-related primary brain lymphomas obtained as sterotactic biopsies, autopsy specimens, or cerebrospinal fluid samples. Histologically, a very characteristic perivascular and diffuse lymphomatous spread in the brain parenchyma w as observed. By applying a highly sensitive in situ hybridization tech nique (ISH) using digoxigenin-labeled antisense riboprobes, abundant E pstein-Barr virus (EBV)-encoded small nuclear RNAs (EBER) transcripts could be demonstrated in each case studied. A combination of ISH with immunohistochemical staining for latent membrane protein (LMP-1) and E BV nuclear antigen-2 (EBNA-2) showed different patterns of EBV latency with a predominance of the broad spectrum (EBER(+)/EBNA-2(+)/LMP-1(+) ). Clonal rearrangements of immuno-globulin heavy chain (IgH) genes we re demonstrated in four cases using a sensitive polymerase chain react ion. In one patient the rearrangement pattern suggested biclonal lymph oproliferation. Our observations confirm the implication of the EBV in the etiology of AIDS-related primary malignant lymphomas of the brain . The demonstration of EBV gene products and clonal IgH rearrangements even in small biopsy samples is a useful tool for distinguishing betw een reactive and neoplastic lymphocytic infiltrates, which are frequen tly observed in brain and cerebrospinal fluid specimens obtained from AIDS patients. Clonal rearrangements of immuno-globulin heavy chain (I gH) genes were demonstrated in four cases using a sensitive polymerase chain reaction. In one patient the rearrangement pattern suggested bi clonal lymphoproliferation. Our observations confirm the implication o f the EBV in the etiology of AIDS-related primary malignant lymphomas of the brain. The demonstration of EBV gene products and clonal IgH re arrangements even in small biopsy samples is a useful tool for disting uishing between reactive and neoplastic lymphocytic infiltrates, which are frequently observed in brain and cerebrospinal fluid specimens ob tained from AIDS patients.