Myeloid Neoplasms Secondary to Plasma Cell Myeloma: An Intrinsic Predisposition or Therapy-Related Phenomenon? A Clinicopathologic Study of 41 Cases and Correlation of Cytogenetic Features With Treatment Regimens
ABSTRACT We describe 41 cases of myeloid neoplasms (MNs) secondary to plasma cell myeloma (PCM). The types of MN included myelodysplastic syndrome (MDS) in 34 (82.9%), acute myeloid leukemia (AML) in 4 (9.8%), and myeloproliferative neoplasm (MPN) or MDS/MPN in 3 (7.3%) cases. The latency from treatment to diagnosis of MN ranged from 9 to 384 months, with a median of 60 months. Of 37 cases with cytogenetic studies, complex abnormalities were detected in 22 (59.5%), -5(q)/-7(q) in 4 (10.8%), other abnormalities in 8 (21.6%), and normal karyotype in 3 (8.1%) cases. Complex abnormalities and -5(q)/-7(q) correlated directly with multiple chemotherapeutic regimens, particularly with combined melphalan/cyclophosphamide. Moreover, the features of cytogenetic abnormalities in our series were significantly different from those with concomitant PCM/MN who had significantly lower complex abnormalities. The latency, skewed proportion of MDS, and bias toward complex cytogenetic abnormalities/unbalanced aberrations of chromosomes 5/7 suggested an alkylating mutagenic effect on pathogenesis of secondary MN. Kaplan-Meier survival analysis demonstrated a median survival of 19 months, which was better than that for therapy-related (t)-MDS/AML. In contrast to t-MDS, the survival in our patients appeared to depend on subtypes of MDS as seen in de novo diseases.
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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 (LPL) (n=1) and pediatric follicular lymphoma (FL) (n=1). The respective secondary diagnoses included diffuse large B-cell lymphoma (DLBCL) (n=2), plasmablastic myeloma (PM) 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), while 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, while in the remaining case (LPL/PM), the 2 neoplasms shared κ-light-chain restriction but expressed different heavy-chain isotypes (IgM versus IgA). The two CLL/DLBCL cases had PCR-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.Human pathology 10/2014; 45(10). DOI:10.1016/j.humpath.2014.06.021 · 2.81 Impact Factor
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