title: High frequency of clonal immunoglobulin receptor gene rearrangements in sporadic histiocytic/dendritic cell sarcomas.
abstract: The diagnosis of histiocytic/dendritic cell (H/DC) sarcomas is currently based on morphology and the presence of immunophenotypic features of H/DC differentiation. The issue whether clonal immunoglobulin receptor gene rearrangements are present in H/DC sarcomas has been debated over decades until the recent data by Feldman et al, which provided compelling evidence that patients with follicular lymphoma and concurrent/synchronous H/DC sarcoma share identical genotypic features, suggested the possibility of transdifferentiation or dedifferentiation of 2 otherwise morphologically and immunophenotypically distinctive neoplasms. Here we investigated the molecular characteristics of 23 patients with sporadic H/DC sarcoma. Nine of the 23 cases (39%) showed clonal IGH (+/-IGK) gene rearrangements, whereas 2 (9%) cases showed only clonal IGK gene rearrangements, which were further validated and confirmed by direct DNA sequencing. One histiocytic sarcoma showed t(14;18) by quantitative-polymerase chain reaction, which was confirmed by fluorescence in situ hybridization analysis showing IGH/BCL2 fusions in neoplastic histiocytes. Notably, all IGH/IGK-positive H/DC sarcomas were negative for B-cell-associated transcription factors PAX5 and BOB.1, whereas 4 of 7 IGH/IGK-positive histiocytic sarcoma cases were positive for Oct2. In addition, no evidence of Epstein-Barr virus infection was detected in 8 of 11 IGH/IGK-positive H/DC sarcoma cases by in situ hybridization, suggesting that Epstein-Barr virus infection may not play an important role in the pathogenesis of these tumors. This study provides evidence that clonal immunoglobulin receptor gene rearrangements may be detected at a high frequency in sporadic H/DC sarcomas. The findings suggest that a large subset of H/DC sarcomas have inherited B-cell genotypes, thus providing new insights for the pathogenesis of these rare but aggressive neoplasms.
authors.affiliation: Department of Pathology, City of Hope National Medical Center, Duarte, CA 91010, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Sean K
authors.initials: SK
authors.lastname: Lau
authors.forename: Dean
authors.initials: D
authors.lastname: Fong
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Endi
authors.initials: E
authors.lastname: Wang
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Arber
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Weiss
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D054740:Dendritic Cell Sarcoma, Follicular / Q000235:genetics*; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D054747:Histiocytic Sarcoma / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains