[Primary brain lymphoma in acquired immunodeficiency syndrome. Immunophenotype and molecular pathologic characterization in stereotactic biopsy, autopsy and cerebrospinal fluid cytology].
In this study we present morphological, cytological, immunophenotypical, 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 was observed. By applying a highly sensitive in situ hybridization technique (ISH) using digoxigenin-labeled antisense riboprobes, abundant Epstein-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 EBV 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 immunoglobulin heavy chain (IgH) genes were demonstrated in four cases using a sensitive polymerase chain reaction. In one patient the rearrangement pattern suggested biclonal lymphoproliferation. 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 between reactive and neoplastic lymphocytic infiltrates, which are frequently observed in brain and cerebrospinal fluid specimens obtained from AIDS patients.
Schmitt-Gräff
A
A
Institut für Pathologie und Neuropathologie, Universitätsklinikum Benjamin Franklin, Berlin.
Hummel
M
M
Anagnostopoulos
I
I
Stoltenburg
G
G
Stein
H
H
D000328:Adult; D001921:Brain / Q000276:immunology / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D002555:Cerebrospinal Fluid / Q000166:cytology*; D015321:Gene Rearrangement / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016130:Immunophenotyping; D016483:Lymphoma, AIDS-Related / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D016133:Polymerase Chain Reaction
D007143:Immunoglobulin Heavy Chains
Primäre Hirnlymphome bei erworbenem Immundefektsyndrom. Immunphänotypische und molekularpathologische Charakterisierung in der stereotaktischen Biopsie, Autopsie und Liquorzytologie.