Proliferation rate and outcome in children with T-cell rich B-cell lymphoma: a clinicopathologic study from the NHL-BFM-study group.

T-cell rich B-cell lymphoma (TCRBCL) is considered a rare variant of aggressive B-cell lymphoma characterized by few neoplastic cells and a large reactive infiltrate with striking similarities to nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL). In childhood, these tumors occur even less frequently. Biopsy specimens at diagnosis from 16 children (13 boys) with a median age of 12 years (range, 7 to 18) were immunophenotyped. The proliferation rate was assessed with monoclonal antibodies against Ki-67 and repp86 antigens and additional clonality analyses were performed. Ten patients had localized disease and only two had B symptoms. All patients showed high Ki-67 expression (median: 80%, range 40% to 90%), but low repp86 expression (median: 25%, range 10% to 50%). PCR-based clonality studies of the hypervariable CDR III region of the immunoglobuline heavy chain and the T-cell receptor gamma-chain genes demonstrated predominant clones in nine and five patients, respectively. Three patients had previous or concomitant NLPHL and two of them received initial treatment for Hodgkin's disease. All patients achieved remission after a brief polychemotherapy regimen. Two patients subsequently relapsed and one was rescued by salvage therapy including autologous stem cell transplantation. At a median follow-up of 23 months, 15 patients (94%) are alive. The striking contrast between the proliferation rates determined by Ki-67 and repp86 expression points to a possible arrest in the G1 cell cycle phase because repp86 expression is restricted to the S, G2 and M cell cycle phases. This G1 arrest may explain the paradoxon of high Ki-67 expression in a paucicellular lymphoma with a favorable prognosis in young patients.