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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
IgVH mutational status and clonality analysis of Richter's transformation: Diffuse large B-cell lymphoma and Hodgkin lymphoma in association with B-cell chronic lymphocytic leukemia (B-CLL) represent 2 different pathways of disease evolution.
Am. J. Surg. Pathol. 31, 1605-1614 (2007)
Approximately 5% of B-cell chronic lymphocytic leukemia (B-CLL) patients develop a secondary aggressive lymphoma, usually of diffuse large B-cell type (DLBCL), termed Richter's transformation (RT). Rarely, classic Hodgkin lymphoma (HL) is observed. Published small series suggest that tumor cells in DLBCL and HL can be clonally identical to the B-CLL clone or arise as an independent, secondary lymphoma. We describe the morphology, immunophenotype, and clinical features of 34 classic RT patients with DLBCL, 6 cases of B-CLL with HL, and 8 cases with scattered CD30-positive Hodgkin and Reed-Sternberg (HRS)-like cells. The clonal relationship of the 2 components was analyzed using sequencing analysis of immunoglobulin heavy chain variable region (IgVH) genes. In classic RT, 18/23 B-CLL cases (78%) showed clonal progression to DLBCL with identical IgVH sequences in both lymphoma components, whereas in 5 cases (22%) the DLBCL was clonally unrelated. Among clonally related RT samples, 73% carried unmutated IgVH genes, whereas 4/5 unrelated cases were mutated. Immunophenotypically, most cases of DLBCL irrespective of clonal relatedness showed significant differences in phenotype compared with the B-CLL, with common loss of CD5 and CD23. Using immuno-laser capture microdissection, sequencing of the IgVH CDR3 region of isolated HRS cells showed that 2/2 cases with HL were clonally unrelated, whereas they were clonally identical in 1/2 cases of B-CLL with scattered HRS-like cells. HRS or HRS-like cells in all 3 unrelated cases showed evidence of Epstein-Barr virus infection. Of interest, 5/6 cases of B-CLL with HL, and 5/6 cases of B-CLL with HRS cells showed mutated IgVH genes.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Richter's transformation; clonality analysis; IgH mutational analysis; B-cell chronic lymphocyte leukemia; Hodgkin lymphoma; microdissection
Language
english
Publication Year
2007
HGF-reported in Year
2007
ISSN (print) / ISBN
0147-5185
e-ISSN
1532-0979
Quellenangaben
Volume: 31,
Issue: 10,
Pages: 1605-1614
Publisher
Lippincott Williams & Wilkins
Reviewing status
Peer reviewed
Institute(s)
Institute of Pathology (PATH)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-500300-001
Scopus ID
34748861564
Erfassungsdatum
2007-10-22