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Metachronous/concomitant B-cell neoplasms with discordant light-chain or heavy-chain isotype restrictions: evidence of distinct B-cell neoplasms rather than clonal evolutions.

Abstract
Metachronous/concomitant B-cell neoplasms with distinct morphology are usually considered clonally related. We retrospectively analyzed 4 cases of metachronous/concomitant B-cell neoplasms with discordant light-chain/heavy-chain restrictions. The primary diagnoses included chronic lymphocytic leukemia (CLL; n = 2), lymphoplasmacytic lymphoma (n = 1), and pediatric follicular lymphoma (FL; n = 1). The respective secondary diagnoses included diffuse large B-cell lymphoma (DLBCL; n = 2), plasmablastic myeloma, and pediatric FL. The secondary B-cell neoplasm occurred after the primary diagnosis in 3 cases, with the median interval of 120 months (range, 21-216), whereas the remaining 1 case had the 2 neoplasms (CLL/DLBCL) diagnosed concurrently. Histology suggested aggressive transformation in 3 cases and recurrence in 1 case (FL). Nonetheless, 3 cases showed discordant light-chain restrictions between the 2 B-cell neoplasms, whereas in the remaining case (lymphoplasmacytic lymphoma/plasmablastic myeloma), the 2 neoplasms shared κ light-chain restriction but expressed different heavy-chain isotypes (IgM versus IgA). The 2 CLL/DLBCL cases had polymerase chain reaction-based IGH/K gene rearrangement study and amplicon sequence analysis performed, which demonstrated distinct clonal amplicons between the 2 B-cell neoplasms in each case. Concomitant/metachronous B-cell neoplasms may be clonally unrelated, which can be confirmed by immunoglobulin isotype analysis and/or genotypic studies. We advocate analysis of clonal identities in large cell transformation or recurrent disease compared with primary indolent B-cell neoplasm because of a potential difference in prognosis between clonally related and unrelated secondary B-cell neoplasms.
AuthorsQiang Wei, Siby Sebastian, Paulie Papavassiliou, Catherine Rehder, Endi Wang
JournalHuman pathology (Hum Pathol) Vol. 45 Issue 10 Pg. 2063-76 (Oct 2014) ISSN: 1532-8392 [Electronic] United States
PMID25179408 (Publication Type: Journal Article)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Isotypes
  • Immunoglobulin Light Chains
Topics
  • Aged
  • B-Lymphocytes (immunology, pathology)
  • Child
  • Clonal Evolution
  • Female
  • Flow Cytometry
  • Gene Rearrangement, B-Lymphocyte (genetics, immunology)
  • Humans
  • Immunoglobulin Heavy Chains (genetics, immunology)
  • Immunoglobulin Isotypes (genetics, immunology)
  • Immunoglobulin Light Chains
  • In Situ Hybridization, Fluorescence
  • Leukemia, Lymphocytic, Chronic, B-Cell (genetics, immunology, pathology)
  • Lymphoma, B-Cell (genetics, immunology, pathology)
  • Male
  • Neoplasms, Multiple Primary (genetics, immunology, pathology)
  • Neoplasms, Second Primary (genetics, immunology, pathology)
  • Polymorphism, Single Nucleotide

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