High-Grade B-Cell Lymphoma with Features Intermediate between Burkitt Lymphoma and Diffuse Large B-Cell Lymphoma (Grey Zone Lymphoma): A Clinicopathologic Analysis of 39 Cases
Anamarija Perry, Bhavana Dave, David Crockett, Pamela Althof, Lynette Smith, Patricia Aoun, Wing Chan, Kai Fu, Timothy Greiner, Philip Bierman, Gregory Bociek, James Armitage, Julie Vose, Dennis Weisenburger. University of Nebraska, Omaha, NE
Background: High-grade B-cell lymphoma with features intermediate between Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLCBL) represents a heterogeneous and poorly-characterized entity. Therefore, we investigated 39 cases of this grey zone lymphoma.
Design: We searched our database for the period of 1985 to 2010 for potential cases and these were reviewed by two hematopathologists. The following immunohistochemical stains were performed: CD3, CD10, CD20, BCL2, BCL6, MUM1, GCET1, FOXP1, C-MYC and Ki67. The tumors were assigned a germinal center B-cell-like (GCB) or non-GCB subtype according to Choi algorithm for cell of origin. Immunostains for BCL2, C-MYC and Ki67 were graded in increments of 10%, and the cutpoints of 30% and 50% were used for BCL2 and C-MYC, respectively. Fluorescence in situ hybridization (FISH) for C-MYC and BCL2 gene rearrangements were also performed. The Kaplan-Meier method was used to estimate overall survival (OS).
Results: Among the 39 patients, 21 (54%) were male and 18 (46%) were female, with a median age of 69 years. The median OS was only 9 months and the 5-year OS was only 30%. The majority of patients presented with advanced stage (III/IV) disease (62%), high LDH levels (63%), and high (3-5) International Prognostic Index scores (54%). Treatment regimens were aggressive, but only 41% of the patients had a complete remission. Morphologically, the tumors were composed predominantly of medium-sized, centroblast-like cells with high proliferation and numerous tingible-body macrophages. Seventy percent of the cases had Ki67 expression ≥80%. Twenty-nine cases (74%) had a GBC phenotype. The majority of cases (77%) expressed BCL2 protein, but only 44% of these had a BCL2 gene rearrangement. High C-MYC protein expression was seen in 41% of the cases, and 85% of these had C-MYC rearrangement. Seven cases were “double hit” lymphomas with rearrangement of both C-MYC and BCL2. However, none of the immunohistochemical or FISH markers were predictive of survival.
Conclusions: High-grade B-cell lymphoma with features intermediate between BL and DLBCL is a morphologically recognizable entity with an extremely poor prognosis. Most cases fall into the GCB category, with high proliferation, and high BCL2 and C-MYC expression. However, only a subset of cases with BCL2 and C-MYC expression have rearrangement of these genes, suggesting other mechanisms of gene deregulation in this entity.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 176, Tuesday Afternoon