High Incidence of BCL-6 Gene Abnormalities in Primary Central Nervous System Diffuse Large B-Cell Lymphoma in Immunocompetent Patients
SE Martin, EM Hattab, MA Al-Abbadi, RA Stohler, GH Vance, M Czader. Indiana University School of Medicine, Indianapolis, IN; James H. Quillen Veterans Affairs Medical Center, Mountain Home, TN
Background: Primary central nervous system diffuse large B-cell lymphomas (PCNSL) are rare neoplasms characterized by a dismal prognosis. Despite emerging consensus that they arise from lymphoid cells at the post-germinal center stage of differentiation, the majority of the cases of PCNSL are positive for BCL-6, a marker selectively expressed by germinal center B cells. B-cell-6 is a proto-oncogene that codes for a zinc finger transcription repressor required for germinal center formation and function. We have studied the incidence of BCL-6 gene rearrangements in a well characterized group of PCNSL.
Design: Twenty-two cases of PCNSL were studied. Immunostains for CD10, BCL-6 and MUM-1 were used to determine germinal center vs. post-germinal center cell origin. In-situ hybridization for EBER was performed in each case. Fluorescence in-situ hybridization was performed in formalin fixed, paraffin embedded tissue using breakapart probe for BCL-6, and dual color/dual fusion probes for MYC/IGH and IGH/BCL2. Survival was calculated using a Kaplan-Meier method.
Results: Thirteen patients were female. Median age at diagnosis was 64 years (range 13-80). None of the patients had history of immunodeficiency. Eighteen cases were of post-germinal center cell phenotype. BCL-6 immunostain was positive in 20 cases. One case was positive for EBER. Eight cases (36%) showed rearrangements of BCL-6 gene. Additional three cases showed numerical abnormalities of BCL-6 (2 monosomy and 1 trisomy). The remaining 11 cases had normal BCL-6 signal. The majority of cases with BCL-6 rearrangement lacked MYC/IGH and IGH/BCL2 translocations with only one case being positive for IgH/BCL2 fusion. Two cases with rearranged BCL-6 showed trisomy/tetrasomy of BCL-2 gene, and one showed evidence of genomic instability with trisomy/tetrasomy for all studied probes. Even though there was a trend for shorter survival in patients with BCL-6 gene rearrangements, Kaplan-Meier analysis did not reach statistical significance.
Conclusions: High incidence of abnormalities of the BCL-6 gene was detected by FISH analysis in PCNSL in immunocompetent individuals. The majority of cases were of post-germinal center cell origin and were EBV negative.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 235, Tuesday Afternoon