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

Hum Pathol. 2014 Oct;45(10):2063-76. doi: 10.1016/j.humpath.2014.06.021. Epub 2014 Jul 17.

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.

Keywords: B-cell neoplasms; Clonal identities; Concomitant/metachronous; Discordant heavy-chain isotype restrictions; Discordant light-chain isotype restrictions; Genotypic analysis.

MeSH terms

  • Aged
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Child
  • Clonal Evolution
  • Female
  • Flow Cytometry
  • Gene Rearrangement, B-Lymphocyte / genetics
  • Gene Rearrangement, B-Lymphocyte / immunology
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin Isotypes / genetics
  • Immunoglobulin Isotypes / immunology
  • Immunoglobulin Light Chains
  • In Situ Hybridization, Fluorescence
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / pathology
  • Male
  • Neoplasms, Multiple Primary / genetics
  • Neoplasms, Multiple Primary / immunology
  • Neoplasms, Multiple Primary / pathology
  • Neoplasms, Second Primary / genetics
  • Neoplasms, Second Primary / immunology*
  • Neoplasms, Second Primary / pathology
  • Polymorphism, Single Nucleotide

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin Isotypes
  • Immunoglobulin Light Chains