IMMUNOPHENOTYPIC AND MOLECULAR ANALYSES OF ACQUIRED IMMUNE-DEFICIENCYSYNDROME-RELATED AND EPSTEIN-BARR-VIRUS ASSOCIATED LYMPHOMAS - COMPARATIVE-STUDY

Limited information is currently available on the molecular and immuno phenogenotypic characteristics of CD30-positive anaplastic large cell (ALC) lymphomas occurring in human immunodeficiency virus (HIV)-infect ed individuals. To address this issue, the authors have undertaken a c ombined analysis of these lymphomas in comparison with other Epstein-B arr virus (EBV)-associated tumors in the setting of HIV infection. Twe nty-one AIDS-related lymphomas, including five CD30-positive ALC and 1 1 small noncleaved cell (SNCC) lymphomas, and five Hodgkin's disease ( HD) specimens were characterized regarding the immunophenogenotypic fe atures, the frequency and subtype distribution of EBV (as defined by i n situ hybridization [ISH], Southern blot, and a polymerase chain reac tion [PCR] amplification of the EBV nuclear antigen-2 [EBNA-2] region) , and viral antigen expression (latent membrane protein-1 [LMP-1], EBN A-2, and Bam HI Z fragment, Epstein-Barr virus replication activator [ ZEBRA]). The same series of samples was also investigated for the pres ence of DNA sequences of the human herpesvirus-6 (HHV-6), and for alte rations of the tumor suppressor gene p53. Combined immunophenotypic an d immunogenotypic analyses showed a derivation from anomalously mature d B cells in four of five CD30-positive ALC lymphomas, whereas SNCC sh owed features of mature B cells; no evidence of immunoglobulin or TCR gene rearrangement could be obtained in HD cases. Combined ISH and Sou thern blot analyses revealed that EBV was more strictly associated wit h HD (five of five) and CD30-positive ALC lymphomas (four of five) tha n with SNCC lymphomas (four of 11). EBV-positive samples from CD30-pos itive ALC lymphomas carried type 1 EBV (two of two specimens tested), whereas both EBV subtypes were observed in SNCC lymphomas and HD sampl es. All three forms of veal latent gene expression were found in the E BV positive CD30-positive ALC lymphomas. SNCC specimens did not expres s LMP-1 or EBNA-2, whereas HD specimens expressed LMP-1 (four of five tested) but no EBNA-2. Immunostaining for ZEBRA was consistently negat ive. HHV-6 DNA sequences were detected by PCR in one SNCC of the 19 sp ecimens analyzed. Three out of five CD30-positive ALC lymphoma specime ns and six of 10 SNCC showed nuclear staining for p53. No mutation was detected in any of the three CD30-positive ALC lymphomas analyzed, wh ereas an aberrant SSCP pattern was found in all the four SNCC samples tested. At variance with SNCC lymphomas, AIDS-related B-cell CD30-posi tive ALC lymphomas are strictly associated with EBV infection and may also express the broad lymphoblastoid cell line-like (LMP-1-positive, EBNA-2-positive) pattern, and lack p53 genetic lesions. Unlike EBV, HH V-6 probably does not represent a relevant factor involved in the path ogenesis of CD30-positive ALC and other HIV related lymphomas. Copyrig ht (C) 1996 by W.B. Saunders Company.