Myeloma with BRAF p.V600E mutation and atypical plasma cells

Abstract

About 5% of myelomas have mutations in the BRAF gene [1], only 14% of which have the p.V600E variant [2]. The detection of BRAF p.V600E mutations in the marrow may raise concerns for metastatic malignancy (such as melanoma) or hairy cell leukemia. Morphological features of myeloma with BRAF p.V600E have not yet been described in the literature.

This was a 55-year-old male with IgA Lambda M protein (1.3 g/dL) and multiple bone lesions. His blood count was unremarkable other than mild anemia (hemoglobin 11.1 g/dL). The bone marrow showed diffuse infiltration of neoplastic plasma cells (60%–70%) with eccentrically located large round nuclei, vesicular chromatin, centrally located single prominent nucleolus, abundant basophilic cytoplasm, and a frequent perinuclear hof (Figure 1 A, Wright Giemsa, 1000x; B, hematoxylin and eosin [H&E], 1000x). The abnormal cells had a typical myeloma immunophenotype, expressing CD38, CD138 (Figure 1 C, red, 600x), MUM-1/IRF4 (Figure 1 D, 600x), normal/dim CD45, aberrant bright CD56, partial CD20 and no CD19, CD81, CD27, Cyclin D1, and S100. By in-situ hybridization stains, they were positive for Lambda (Figure 1 E, 600x) but negative for Kappa (Figure 1 F, 600x) expression. Although these plasma cells showed marked atypical features, the proliferation index based on simultaneous labeling of CD138 and Ki-67 (Figure 1 C, brown, 600x) was very low (< 5%). BRAF p.V600E mutation was demonstrated by next-generation sequencing and immunohistochemical staining (Figure 1 G, 600x). A fluorescence in situ hybridization panel showed a hyperdiploid karyotype without high-risk abnormalities.

The BRAF p.V600E mutation is uncommon in myeloma. It is unknown if plasma cells in these cases exhibit atypical morphologic features like those in our case. The BRAF p.V600E mutation may raise potential alternative diagnoses such as metastatic melanoma, which may sometimes demonstrate cells mimicking atypical plasma cells.

The authors declare no conflict of interest.

The study samples were from a protocol approved by the Institutional Review Board.

A written informed consent was obtained from the participant.