TY - JOUR
T1 - Clonally related histiocytic/dendritic cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma
T2 - A study of seven cases
AU - Shao, Haipeng
AU - Xi, Liqiang
AU - Raffeld, Mark
AU - Feldman, Andrew L.
AU - Ketterling, Rhett P.
AU - Knudson, Ryan
AU - Rodriguez-Canales, Jaime
AU - Hanson, Jeffrey
AU - Pittaluga, Stefania
AU - Jaffe, Elaine S.
N1 - Funding Information:
This study was supported by the intramural research program of the Center for Cancer Research, National Cancer Institute. We thank Dr Anne Vandersteenhoven of Palmetto Richland Memorial Hospital (Columbia, SC), Dr Fan Zhou of Southwest Washington Medical Center (Vancouver, WA), Dr Stephen C Groo of Western Regional Medical Command and Madigan Army Medical Center (Tacoma, WA), Dr Wayne Tam of New York Presbyterian Hospital (New York, NY), Dr Yu Wang of St Luke’s Cornwall Hospital (Newburgh, NY) and Dr Nathan A Dunsmore of Greater Baltimore Medical Center (Baltimore, MD) for their contribution of cases in this study. We also thank Thu Anh Pham and Trinh Pham in our molecular laboratory for their assistance with the molecular studies and Cynthia Harris and Hong Jin in our immunohistology lab for their help with the immunostains.
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
KW - CLL
KW - dendritic cells
KW - histiocytic sarcoma
KW - laser capture microdissection
KW - p53
KW - transdifferentiation
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U2 - 10.1038/modpathol.2011.102
DO - 10.1038/modpathol.2011.102
M3 - Article
C2 - 21666687
AN - SCOPUS:80455155161
SN - 0893-3952
VL - 24
SP - 1421
EP - 1432
JO - Modern Pathology
JF - Modern Pathology
IS - 11
ER -