Plasmablastic myeloma transformation of light-chain multiple myeloma

Abstract

Plasmablastic myeloma (PBM) is an uncommon and aggressive morphologic variant of multiple myeloma (MM). The neoplastic immature cells exhibit diverse morphology, posing a diagnostic challenge. The diagnostic criteria for PBM include the identification of ≥ 2% plasmablasts in the bone marrow aspirate. This case describes the incidental finding of a light-chain multiple myeloma (LCMM) transformed into PBM, a phenomenon not previously reported.

INTRODUCTION

PBM represents a rare morphologic variant of MM associated with a poor prognosis, which may manifest de novo or rarely arise from an existing myeloma.^1,2 The diagnostic criteria for PBM, as proposed by Greipp et al., mandate the identification of ≥ 2% plasmablasts in the bone marrow aspirate.³ Plasmablastic morphology in MM independently predicts poor survival for multiple myeloma (MM) after autologous stem cell transplant.⁴ Neoplastic plasmablasts are typically characterized by basophilic cytoplasm, a large central nucleus (>10μm in diameter), high N:C ratio, variable prominent nucleoli, and lack perinuclear hof.⁵ Sometimes, distinguishing PBM from plasmablastic lymphoma (PBL) by morphology alone is impossible. Furthermore, neoplastic plasmablasts may display immature blast-like appearance resembling acute leukemia.⁶ It is imperative to distinguish PBM from acute leukemia and B-cell lymphoma with plasmablastic morphology to ensure an accurate diagnosis and proper management. This is the first case that describes PBM evolving from a LCMM.

CASE REPORT

A 78-year-old male, previously diagnosed with renal failure and lambda light chain restricted LCMM in March 2021 in Mexico. Despite undergoing various lines of therapy, the patient experienced weight loss and anemia, prompting him to seek further evaluation and management at our institution.

His complete blood count revealed a white blood cell count of 3.2 x10⁹/L (reference range (RR) 4.0–11.0 x10⁹/L), hemoglobin of 8.0 g/dL (RR 11.4–15.0 g/dL), platelet count of 115 x10⁹/L (RR 150–400 x10⁹/L), and an absolute neutrophil count of 1.86 x10⁹/L (RR 1.8–7.8 x10⁹/L). A serum free light chain assay showed a marked increase in the lambda light chain to 3703.96 mg/L (RR 5.71–26.3mg/L), while the kappa light chain was 5.39 mg/L (RR 3.3–19.4mg/L) with a kappa:lambda light chain ratio of 0.001. MRI and positron emission tomography-computed tomography (PET-CT) identified multifocal lytic lesions with increased metabolic activity within the skeletal system, but there was no evidence of metabolically active lymphadenopathy or soft tissue masses.

A subsequent BM examination was conducted, and the Wright-Giemsa-stained bone marrow aspirate revealed sheets of large, atypical cells exhibiting varying sizes and morphologies with occasional binucleated forms (Fig. 1A), and no recognizable mature plasma cells observed. The background trilineage hematopoiesis was markedly decteased. Some of these cells displayed basophilic cytoplasm, variable cytoplasmic vacuoles, a high nuclear-to-cytoplasmic (N:C) ratio, variable nucleoli, and an absence of perinuclear hof (Fig. 1B). Additionally, some cells displayed an immature morphology with open chromatin, reminiscent of acute monocytic leukemia, and rare cytoplasmic ‘needle-like’ inclusions resembling Auer rods (Fig. 1C). The bone marrow core biopsy (Fig. 1D) demonstrated diffuse malignant cells many with distinct nucleioli and ocassioanl binucleation, that are negative for EBV in situ hybridization (Fig. 1D, inset), ALK1 and HHV8 (not shown). Flow cytometry revealed lambda light chain-restricted plasma cells (Fig. 1E), which express dim CD45, CD138, and CD200, while being negative for CD34, CD19, CD20, CD56, CD13, CD33 and CD117. Serum immunofixation electrophoresis demonstrated free lambda light chains without a corresponding heavy chain component (Fig.1F). FISH studies demonstrated the loss of 1p, 13q, and 17p. The diagnosis of PBM was rendered.

Fig. 1.

A–C: Wright-Giemsa-stained marrow aspirate smears (original magnification x 1000) depict sheets of immature neoplastic cells, showing diversity in both size and morphology (A), with occasional binucleated forms (notched arrow). Some plasmablastic plasma cells exhibit basophilic vacuolated cytoplasm, a high N:C ratio, and variable nucleoli (B). Others display a moderate amount of light blue cytoplasm, resembling acute leukemia with monocytic differentiation. Infrequent cytoplasmic needle-like inclusions (black arrow) are also observed (C). In panel D, the bone marrow core biopsy (hematoxylin-eosin, original magnification x 400) demonstrates sheets of large neoplastic cells with prominent nucleoli, and they test negative for EBV in situ hybridization (inset). E. Flow cytometry demonstrated cytoplasmic lambda light chain restricted plasma cells. F. Serum immunofixation electrophoresis revealed LCMM through the presence of a lambda light-chain monoclonal band and the absence of heavy chains, including antisera to IgG, IgA, IgM, IgD, and IgE.

After one cycle of Idecabtagene vicleucel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy, the patient exhibited a robust response, leading to a significant reduction in the lambda light chain to 1.89 mg/L, and the absence of detectable monoclonal bands in serum and urine immunofixation electrophoresis. The patient returned to his home country for continued therapy and was lost to follow-up.

DISCUSSION

To the best of our knowledge, this represents the first reported case of PBM arising from previously treated LCMM, characterized by myeloma cells exclusively secreting either kappa or lambda light chain while exhibiting an inability to produce a heavy chain.⁷

PBM represents a rare aggressive morphologic variant of MM. Caution is advised when evaluating plasmablast morphology, as their immature appearance can occasionally be misleading and overlap with that of acute leukemia. Auer rod–like inclusions have been observed in plasma cell neoplasms,⁸ they might be misinterpreted as indicators of myeloid differentiation, especially in cases where there is suspicion of therapy-related acute myeloid leukemia.

Furthermore, the differentiation between PBM and PBL poses a challenge due to shared cytomorphological and immunophenotypic features.⁹ Both conditions express plasma cell markers (CD138, CD38, MUM-1) and exhibit high Ki67, while lacking B-cell markers (CD19, CD20, PAX5). PBL is characterized by positive EBV, C-MYC expression, and nodal involvement, whereas the presence of CRAB (hypercalcemia, renal failure, anemia, bone lesions), marrow involvement, absence of EBV, and a prior history of MM support the diagnosis of PBM.¹⁰ To effectively distinguish PBM from other B-cell lymphomas displaying plasmablastic features, it is essential to routinely perform HHV8 and ALK1 immunohistochemical stains. These lymphomas encompass primary effusion lymphoma, charaterized by positivity for HHV8 with frequent co-infection of EBV, ALK + large B-cell lymphoma (LBCL), which is ALK positive, and HHV8+ LBCL, identified by HHV8 positivity.

CONCLUSION

Our case underscores the importance of recognizing plasmablastic morphology in myeloma patients and distinguishing it from other entities, such as acute leukemia, PBL, and other lymphomas with plasmablastic features.

DATA AVAILABILITY STATEMENT

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FUNDING STATEMENT

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CONFLICT OF INTEREST

The authors declare no conflict of interest.

ETHICS APPROVAL STATEMENT

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