title: Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma: a study of seven cases.
abstract: Histiocytic and interdigitating dendritic cell sarcomas are rare tumors originating from bone marrow-derived myeloid stem cells. Recent studies have shown evidence of cross-lineage transdifferentiation of B cells in follicular lymphoma to histiocytic and dendritic cell sarcomas. In this study, we report the morphologic, molecular and cytogenetic analysis of seven cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) associated with histiocytic and dendritic cell sarcomas. All seven patients were elderly males (median age 71 years). The B-cell neoplasms preceded the development of the histiocytic and dendritic cell sarcomas in six of seven patients, and one patient had both tumors diagnosed at the same time. The tumors included four interdigitating dendritic cell sarcomas: one Langerhans cell sarcoma, one histiocytic sarcoma and one immature neoplasm with evidence of histiocytic origin. Laser-capture microdissection and PCR analysis showed identical clonal immunoglobulin gene rearrangements in the two phenotypically distinct components in all cases. There was a preferential usage of IGHV4-39 by the V-D-J gene rearrangement. By fluorescence in situ hybridization (FISH) analysis, two cases showed deletion 17p in both components, whereas four cases had normal cytogenetic findings by FISH in the CLL/SLL cells, but acquired cytogenetic abnormalities in the corresponding histiocytic and dendritic tumors. Chromosome 17p abnormalities were the most common cytogenetic abnormality detected in the sarcomas, seen in five of six cases studied. Compared with the CLL/SLL cells, the histiocytic/dendritic cells were largely negative for PAX5, but showed strong expression of PU.1 and variable and weak expression of CEBPβ. Our study provides evidence for transdifferentiation of CLL/SLL B cells to tumors of dendritic and less often histiocytic lineage, and suggests that secondary genetic events may play a role in this phenomenon.
authors.affiliation: Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Shao
authors.forename: Liqiang
authors.initials: L
authors.lastname: Xi
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Feldman
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: Ryan
authors.initials: R
authors.lastname: Knudson
authors.forename: Jaime
authors.initials: J
authors.lastname: Rodriguez-Canales
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hanson
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000032:analysis; D054338:Cell Transdifferentiation; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D054739:Dendritic Cell Sarcoma, Interdigitating / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015322:Gene Rearrangement, B-Lymphocyte; D054747:Histiocytic Sarcoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D054752:Langerhans Cell Sarcoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D061346:Laser Capture Microdissection; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D008396:Maryland; D008875:Middle Aged; D008969:Molecular Sequence Data; D051757:PAX5 Transcription Factor / Q000032:analysis; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000032:analysis; D015534:Trans-Activators / Q000032:analysis; D060152:V(D)J Recombination; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D014408:Biomarkers, Tumor; D022782:CCAAT-Enhancer-Binding Protein-beta; D051757:PAX5 Transcription Factor; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C545012:CEBPB protein, human; C497281:PAX5 protein, human