Cyclin D1 Positive Lymphoid Cells in the Proliferation Centers of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Are Not Due to CCND1 Translocations
JF Gradowski, R Sargent, FE Craig, SH Swerdlow. University of Pittsburgh School of Medicine, Pittsburgh, PA
Background: Cyclin D1 positive lymphoid cells in the proliferation centers have only rarely been reported in CLL/SLL. Little is known about their clinicopathologic associations or whether, like in mantle cell lymphoma, the cyclin D1 positivity is due to a CCND1 translocation.
Design: Lymph node biopsies in 6 cases of CLL/SLL with cyclin D1 positive proliferation centers (including one needle core biopsy) were reviewed as well as all available peripheral blood, flow cytometry (FC) and clinical data. ImmunoFISH analysis was performed using a cyclin D1 immunostain and a breakapart probe for the CCND1 gene. The proliferation centers were identified using the Bioview Duet System and the areas with previously identified proliferation centers were analyzed and photographed for FISH.
Results: The CLL/SLL occurred in adults (4 male, 2 female, age 54-84 years). The absolute lymphocyte counts in 2 cases were normal (no FC), 1 case had 4.3x109/L peripheral blood (PB) CLL cells, one 17x109/L PB CLL cells, one 250x109/L PB CLL cells and one case had a normal white blood cell count (no FC or differential). Imaging studies demonstrated extensive lymphadenopathy in all cases with adenopathy documented on both sides of the diaphragm in 5 of 6 cases and 2 cases with splenomegaly. Four of 5 evaluable cases had at least occasional residual germinal centers and all 6 cases had at least some patent sinuses. All cases had typical proliferation centers (PC) that were large and confluent in 1. Three cases had prominent paraimmunoblasts in the PC including 1 with increased large transformed cells. Five cases had a CD5+, CD10-, CD23+, FMC7-, CD20 dim+, dim surface light chain restricted phenotype with one case CD5 and surface immunoglobulin negative. 4/6 cases were CD38 negative on either the diagnostic lymph node specimen or subsequent bone marrow evaluation. There was bone marrow involvement in all 3/3 tested cases. CCND1 translocations were not identified in any of the cases.
Conclusions: Many but not all CLL/SLL with cyclin D1 positive lymphoid cells in the proliferation centers have features of "interfollicular SLL" with preservation of reactive germinal centers and patent sinuses. The cases all had significant adenopathy even though at least 3/6 cases had <5x109/L PB CLL cells. The explanation for Cyclin D1 positivity in this setting remains unknown, but it is not due to CCND1 translocation.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 196, Wednesday Morning