Immunophenotypic and molecular analyses of acquired immune deficiency syndrome-related and Epstein-Barr virus-associated lymphomas: A comparative study

Antonino Carbone, Riccardo Dolcetti, Annunziata Gloghini, Roberta Maestro, Emanuela Vaccher, Dario Di Luca, Umberto Tirelli, Mauro Boiocchi

Research output: Contribution to journalArticle

Abstract

Limited information is currently available on the molecular and immunophenogenotypic characteristics of CD30-positive anaplastic large cell (ALC) lymphomas occurring in human immunodeficiency virus (HIV)-infected individuals. To address this issue, the authors have undertaken a combined analysis of these lymphomas in comparison with other Epstein-Barr virus (EBV)-associated tumors in the setting of HIV infection. Twenty-one AIDS- related lymphomas, including five CD30-positive ALC and 11 small noncleaved cell (SNCC) lymphomas, and five Hodgkin's disease (HD) specimens were characterized regarding the immunophenogenotypic features, the frequency and subtype distribution of EBV (as defined by in situ hybridization [ISH], Southern blot, and a polymerase chain reaction [PCR] amplification of the EBV nuclear antigen-2 [EBNA-2] region), and viral antigen expression (latent membrane protein-1 [LMP-1], EBNA-2, and Bam HI Z fragment, Epstein-Barr virus replication activator [ZEBRA]). The same series of samples was also investigated for the presence of DNA sequences of the human herpesvirus-6 (HHV-6), and for alterations of the tumor suppressor gene p53. Combined immunophenotypic and immunogenotypic analyses showed a derivation from anomalously matured B cells in four of five CD30-positive ALC lymphomas, whereas SNCC showed features of mature B cells; no evidence of immunoglobulin or TCR gene rearrangement could be obtained in HD cases. Combined ISH and Southern blot analyses revealed that EBV was more strictly associated with HD (five of five) and CD30-positive ALC lymphomas (four of five) than with SNCC lymphomas (four of 11). EBV-positive samples from CD30-positive ALC lymphomas carried type 1 EBV (two of two specimens tested), whereas both EBV subtypes were observed in SNCC lymphomas and HD samples. All three forms of viral latent gene expression were found in the EBV positive CD30-positive ALC lymphomas. SNCC specimens did not express LMP-1 or EBNA-2, whereas HD specimens expressed LMP-1 (four of five tested) but no EBNA-2. Immunostaining for ZEBRA was consistently negative. HHV-6 DNA sequences were detected by PCR in one SNCC of the 19 specimens analyzed. Three out of five CD30-positive ALC lymphoma specimens and six of 10 SNCC showed nuclear staining for p53. No mutation was detected in any of the three CD30-positive ALC lymphomas analyzed, whereas an aberrant SSCP pattern was found in all the four SNCC samples tested. At variance with SNCC lymphomas, AIDS-related B-cell CD30- positive 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, HHV-6 probably does not represent a relevant factor involved in the pathogenesis of CD30- positive ALC and other HIV related lymphomas.

Original languageEnglish
Pages (from-to)133-146
Number of pages14
JournalHuman Pathology
Volume27
Issue number2
DOIs
Publication statusPublished - 1996

Keywords

  • acquired immunodeficiency syndrome-related lymphomas
  • CD30 positive anaplastic large cell lymphomas
  • Epstein-Barr virus

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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