[1177] High Frequency of Clonal Immunoglobulin Receptor Gene Rearrangements in Sporadic Histiocytic/Dendritic Sarcomas

W Chen, SK Lau, D Fong, J Wang, E Wang, DA Arber, LM Weiss, Q Huang. City of Hope National Medical Center, Duarte; Stanford University, Stanford; Loma Linda University, Loma Linda; Duke University, Durham

Background: True histiocytic/dendritic cell (H/DC) sarcomas are extremely rare but aggressive hematopoietic neoplasms. The diagnosis of H/DC sarcomas is based on morphology and the presence of immunophenotypic features of D/DC differentiation. The current WHO definition of H/DC sarcoma requires the absence of clonal B/T cell receptor gene rearrangements. Nonetheless, rare case of H/DC sarcoma with detectable IGH gene rearrangements have been described. Recently, Feldman et al provided compelling evidence that patients with follicular lymphoma and concurrent H/DC sarcoma share identical genotypic features, suggesting the trans- or de-differentiation of two otherwise morphologically and immunophenotypically distinctive neoplasms. Here, we investigate the molecular characteristics of 23 patients with sporadic H/DC sarcomas.
Design: PCR on genomic DNA from formalin-fixed, paraffin-embedded tumor tissues with primer sets designed to detect IGH and IGK gene rearrangements was performed. Q-PCR for major and minor break points of IGH/BCL2 fusion was also measured. All positive cases were verified by direct DNA sequencing. Furthermore, a t(14;18) positive histocytic sarcoma case was confirmed by targeted FISH analysis.
Results: Twenty-five specimens from 23 patients with a confirmed diagnosis of H/DC sarcoma (14 H and 9 DC) were included. None had a history of or concurrent diagnosis of lymphoma. All cases were negative for CD20. Nine of 23 cases showed clonal IGH (with or without IGK) gene rearrangements, while 2 cases demonstrated only clonal IGK gene rearrangements. All 11 (48%) cases with gene rearrangements were further sequenced to determine immunoglobulin gene VDJ or VJ assemblies and segment usage. Among those, one histiocytic sarcoma case showed IGH/BCL2 by PCR, which was further confirmed by FISH analysis. Notably, all IGH and/or IGK positive H/DC sarcomas were negative for B-cell associated transcription factors PAX-5 and Bob-1, while 4/7 histiocytic sarcoma cases were positive for OCT-2.
Conclusions: This study provides evidence that clonal IG receptor gene rearrangements may be detected at a high frequency in sporadic H/DC sarcomas, challenging the current definition of H/DC sarcoma by the WHO. The finding of one de novo histiocytic sarcoma with a IGH/BCL2 fusion in neoplastic histiocytes is intriguing and requires further investigation.
Category: Hematopathology

Monday, March 9, 2009 9:15 AM

Platform Session: Section D, Monday Morning