title: Transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma to interdigitating dendritic cell sarcoma: evidence for transdifferentiation of the lymphoma clone.
abstract: Interdigitating dendritic cell sarcoma (IDCS) is a rare tumor derived from interdigitating dendritic cells. Three cases of IDCS associated with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) have been described, but no clonal relationship between the 2 neoplasms was demonstrated. We present a detailed case analysis of a CLL/SLL with metachronous IDCS and demonstrate that these 2 neoplasms are clonally related. The IDCS and CLL cells had trisomy 12 and identical monoclonal immunoglobulin heavy chain gene rearrangements. Analysis of transcription factors with a role in myeloid differentiation demonstrated PU.1 up-regulation and C/EBPalpha down-regulation in IDCS compared with CLL. High-density array comparative genomic hybridization also identified gains in part of chromosome 16q in IDCS. Our study demonstrates for the first time clonal transformation of CLL/SLL into IDCS. This phenomenon may be triggered by alterations in lineage-determining transcription programs, which result in transdifferentiation, coupled with additional oncogenic stimuli caused by chromosomal imbalances.
authors.affiliation: Division of Hematopathology, Department of Pathology & Laboratory Medicine, Weill Cornell Medical College, New York, NY 10021, USA.
authors.forename: Cory R
authors.initials: CR
authors.lastname: Fraser
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Mario
authors.initials: M
authors.lastname: Gomez
authors.forename: Taotao
authors.initials: T
authors.lastname: Zhang
authors.forename: Susan
authors.initials: S
authors.lastname: Mathew
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Knowles
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.forename: Wayne
authors.initials: W
authors.lastname: Tam
mesh_terms: D000368:Aged; D001854:Bone Marrow Cells / Q000737:chemistry / Q000473:pathology; D054338:Cell Transdifferentiation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D002881:Chromosomes, Human, Pair 12; D002999:Clone Cells; D054739:Dendritic Cell Sarcoma, Interdigitating / Q000235:genetics / Q000473:pathology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000473:pathology*; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology; D008297:Male; D009378:Neoplasms, Multiple Primary; D012334:RNA, Neoplasm / Q000032:analysis; D014314:Trisomy
chemical_list: D012334:RNA, Neoplasm