Diagnosing therapy-related acute myeloid leukemia with 8% blasts in bone marrow with concomitant plasma cell myeloma

A 75-year-old woman with immunoglobulin A lambda plasma cell (PC) myeloma (PCM), status post multiple chemotherapies and autologous stem cell transplant (×3), presented with sudden-onset pancytopenia. Bone marrow (BM) core biopsy was hypercellular (80%) with 70% CD138⁺ PCs with few Dutcher bodies (→ [PC]; panels A-B) (panel A, hematoxylin and eosin stain; panel B, CD138 immunostain) and dysplastic hypolobated megakaryocytes. BM aspirate smears showed 70% atypical PCs, 8% blasts (★; panels A-C) (panel C, Wright-Giemsa stain), and 40% ring sideroblasts (panel D, Perl stain). Plasmablastic transformation of PCM was considered; however, flow cytometry identified an aberrant lambda monotypic PC (panels E-F [FITC, fluorescein isothiocyanate; PE, phycoerythrin]) and myeloblast populations (panels G-I [APC, allophycocyanin]). Cytogenetics revealed a complex karyotype: 48∼51,XX,+add(5)(q13),add(5)(q13),del(7)(q11.2),+8,15,+18,+21,+1∼2mar[cp20]. Next-generation sequencing showed TP53 p.R273H, TP53 p.C176F, and TET2 p.H514fs mutations with variant allele frequencies of 34%, 31%, and 12%, respectively.

Per World Health Organization classification, in the presence of a concomitant nonmyeloid neoplasm such as PCM, the percentage of neoplastic PCs should be excluded from the differential count to classify the myeloid neoplasm appropriately. On excluding 70% neoplastic PCs, 8% myeloid blasts represented 24% (of nonmyeloma cells), thus meeting criteria for acute myeloid leukemia (AML). A diagnosis of therapy-related AML and PCM was rendered and the patient received combination chemotherapy. This case illustrates the importance of proper calculation of the percentage of myeloblasts of nonmyeloma cells in aspirate smears and avoiding misclassifying an AML as myelodysplastic syndrome.