The t(14;19)(q32;q13)-Positive B-Cell Leukemia: A Comprehensive Genetic and Clinicopathologic Study of Six Cases
YO Huh, RP Ketterling, F Vega, JE Kim, LJ Medeiros, LV Abruzzo. University of Texas M. D. Anderson Cancer Center, Houston; Mayo Clinic, Rochester
Background: The t(14;19)(q32;q13), involving the BCL3 locus at chromosome 19q13 and the immunoglobulin heavy chain gene locus at 14q32, is a rare recurrent cytogenetic abnormality in patients with B-cell neoplasms. B-cell neoplasms harboring t(14;19) have been most commonly reported in B-cell chronic lymphocytic leuekmia (CLL). However, a recent study reported that the t(14;19) is not restricted to CLL. We previously reported seven cases of small B-cell leukemia with t(14;19). These cases share many features with CLL but differ from CLL in their morphologic and immunophenotypic features.
Design: Over the past two years, six additional cases with t(14;19)(q32;q13) were identified at the Cytogenetics Laboratory. Clinical and laboratory findings were reviewed. The morphologic features of peripheral blood and bone marrow smears, clot and core biopsy specimens, and lymph nodes were examined. Immunohistochemical stains for ZAP-70, cyclin D1 and bcl3 were performed on bone marrow biopsy or clot section. Flow cytometric immnophenotyping was performed on bone marrow aspirates. Conventional cytogenetic analysis and FISH analysis for detecting IGH/BCL3 fusion was performed using a homebrew dual-color, dual fusion FISH probe. IgVH mutation anlysis was performed on the bone marrow specimen.
Results: The patient cohort included 4 men and 2 women, with a median age of 62 years (range 51-79). All had absolute lymphocytosis, 4 had lymphadenopathy, and 1 had splenomegaly. Lymphocytes in blood and bone marrow aspirate smears were predominantly small but cytologially atypical and demonstrated significant heterogeneity. Flow cytometric immunophenotyping showed an atypical immunophenotype with low CLL scores and positive CD38 in 5 of 6 cases. Immunohistochemical stain showed overexpression of bcl3 in all cases. ZAP-70 was positive in 3/6 cases. IgVH mutation analysis revealed unmutated gene in 5/6 cases. Conventional cytogenetic studies demonstrated trisomy 12 in 4 patients and additional cytogenetic changes were found in 5 patients. FISH analysis verified IGH/BCL3 fusion in all 5 cases tested.
Conclusions: All patients with t(14:19)(q32;q13)-positive B-cell neoplasms and IgH/BCL3 fusion in this study are small B-cell leukemias with atypical morphologic and immunophenotypic features and are frequently associated with additional chromosomal changes including trisomy 12. The IgVH genes are usually unmutated.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 115, Tuesday Morning