[1363] Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma with Transformation to Histiocytic/Dendritic Cell Sarcoma: Alterations of 17p as a Potential Risk Factor.

Haipeng Shao, Liqiang Xi, Mark Raffeld, Andrew L Feldman, Rhett P Ketterling, Ryan Knudson, Jaime Rodriguez-Canales, Jeffrey Hanson, Stefania Pittaluga, Elaine S Jaffe. Center for Cancer Research, National Cancer Institute, Bethesda, MD; H Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Mayo Clinic, Rochester, MN

Background: The concurrent occurrence of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and histiocytic/dendritic cell (H/DC) sarcoma is extremely rare. Recent studies have demonstrated clonal identity between follicular lymphoma and H/DC sarcoma in the same patient, indicative of transdifferentiation of the B-cell neoplasm.
Design: The consultation files of the Hematopathology section of the National Cancer Institute, National Institutes of Health were searched to identify concurrent CLL/SLL and H/DC sarcoma. The clinical, morphologic, immunophenotypic, and cytogenetic (FISH) features of both CLL/SLL and H/DC sarcomas were evaluated. Laser capture microdissection and subsequent IG gene PCR analysis were performed to determine the clonal relationship between CLL/SLL and the H/DC sarcomas.
Results: 7 cases of CLL/SLL and metachronous or synchronous H/DC sarcoma were identified. All seven patients were elderly man (median age, 71 years). The CLL/SLL preceded the development of H/DC sarcomas in 6 of 7 patients, and one patient had both tumors diagnosed concurrently The H/DC sarcomas included 1 histiocytic sarcoma, 3 interdigitating dendritic cell sarcomas, 1 Langerhans cell sarcoma, 1 histiocytic/dendritic cell sarcoma, and 1 immature histiocytic/monocytic sarcoma. Laser-capture microdissection (LCM) and PCR analysis showed identical clonal immunoglobulin V-D-J or V-J gene rearrangements in CLL/SLL and H/DC neoplastic cells in all cases. There was a preferential usage of IGHV4-39 in the V-D-J gene rearrangement. By FISH analysis, Chromosome 17p abnormalities were disproportionately present in the H/DC sarcomas in 5 of 6 cases studied. Of the 5 cases, concurrent 17p deletion was identified in 2 cases. H/DC neoplastic cells were mostly negative for PAX5 and showed strong expression of PU.1 but variable and weak expression of CEBPb.
Conclusions: CLL/SLL and concurrent H/DC sarcoma are very rare. The clonal relationship between CLL/SLL and H/DC sarcoma suggests direct transdifferentiation of CLL/SLL to H/DC sarcomas. Down-regulation of PAX5 and upregulation of PU.1 appear critical for this transdifferentiation. The disproportionate presence of chromosome 17 abnormalities suggests an important role of genes in this region (such as p53) in this high grade transformation.
Category: Hematopathology

Monday, February 28, 2011 9:15 AM

Platform Session: Section B, Monday Morning


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