title: 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.
authors.affiliation: Department of Pathology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People's Republic of China 530021; Department of Pathology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Siby
authors.initials: S
authors.lastname: Sebastian
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Paulie
authors.initials: P
authors.lastname: Papavassiliou
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Catherine
authors.initials: C
authors.lastname: Rehder
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710. Electronic address: endi.wang@duke.edu.
authors.forename: Endi
authors.initials: E
authors.lastname: Wang
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002648:Child; D060965:Clonal Evolution; D005260:Female; D005434:Flow Cytometry; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide
chemical_list: D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D007147:Immunoglobulin Light Chains
keywords: B-cell neoplasms; Clonal identities; Concomitant/metachronous; Discordant heavy-chain isotype restrictions; Discordant light-chain isotype restrictions; Genotypic analysis