Ja. Digiuseppe et al., EPSTEIN-BARR-VIRUS AND PROGRESSION OF NON-HODGKINS-LYMPHOMA TO KI-1-POSITIVE, ANAPLASTIC LARGE-CELL PHENOTYPE, Modern pathology, 8(5), 1995, pp. 553-559
Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a
variety of lymphoproliferative disorders (LPDs) including endemic Burk
itt's lymphoma, Hodgkin's disease (HD), HIV-associated non-Hodgkin's l
ymphomas (NHLs), and LPDs arising in immunosuppressed transplant patie
nts. More recently, EBV has been associated with Ki-1-positive anaplas
tic large cell lymphoma (ALCL), a recently described NHL that shares w
ith HD expression of the CD30 antigen Ki-1, Because EBV has been shown
to induce Ki-1 expression in vitro, and ALCL has been diagnosed in pa
tients with prior or concurrent HD or NHL, it has been proposed that E
BV may mediate progression of a ''primary'' lymphoma to a ''secondary'
' ALCL. We report a case in which an AIDS-associated, Ki-1-negative, l
arge-cell immunoblastic lymphoma progressed to a Ki-1-positive ALCL. A
nalysis of the immunoglobulin heavy chain locus revealed a clonal rela
tionship between these morphologically and immunophenotypically distin
ct tumors. Although EBV was absent from the original large-cell immuno
blastic lymphoma as assessed by in situ hybridization for EBV-encoded
small RNA1 (EBER1), polymerase chain reaction for EBNA-1, immunocytoch
emistry for latent membrane protein 1, and Southern blot hybridization
for EBV terminal repeat sequences, all four techniques confirmed the
presence of EBV in the secondary ALCL. Moreover, analysis of EBV termi
nal repeat sequences indicated that the ALCL resulted from expansion o
f a single EBV-infected clone. These data suggest that EBV may mediate
progression of NHL to Ki-1-positive ALCL, and that in some instances,
EBV may be involved in the later stages of clonal progression of NHL.