Anaplastic Multiple Myeloma Mimicking High-Grade Lymphoma or Acute Leukemia: A Case Report

This case report describes a 66-year-old man with a 2-year history of multiple myeloma (MM) harboring t(4;14) who presented with severe pancytopenia and biochemical evidence of disease progression. The purpose is to highlight the anaplastic morphology of plasma cells that can mimic high-grade lymphoma or acute leukemia, the diagnostic utility of flow cytometry and immunohistochemistry for confirming plasma cell origin and light chain restriction, and the association of such morphology with unfavorable genetics and poor clinical outcome.

Anaplastic MM is reported to feature pleomorphic, markedly enlarged plasma cells and is associated with poor prognosis. The abnormal cytology can be confused with acute leukemia or aggressive lymphoma at presentation, necessitating ancillary studies for correct classification. t(4;14) translocation with FGFR3 overexpression has recognized adverse prognostic implications in MM. Prior case reports and reviews document aggressive clinical courses and diagnostic challenges in anaplastic variants of MM.

• Clinical course: Patient with known MM and t(4;14) previously treated with bortezomib-cyclophosphamide-dexamethasone followed by autologous stem cell transplantation; relapsed early on lenalidomide maintenance; subsequently received bortezomib-lenalidomide-dexamethasone without response.
• Laboratory assessment at admission: Complete blood count showing pancytopenia; free light chain assay showing markedly elevated serum lambda light chains.
• Bone marrow studies: Trephine biopsy and aspirate performed. • Histomorphology (H&E, Giemsa): Interstitial infiltration by large pleomorphic atypical cells with prominent, irregular and multilobate nuclei, visible nucleoli, thin granular chromatin, and vacuolated cytoplasm, initially suggesting high-grade lymphoma or acute leukemia with monoblastic differentiation.
• Flow cytometry: Assessment of plasma cell markers demonstrating CD38, CD138, and CD56 expression consistent with plasma cell lineage.
• Immunohistochemistry: Strong CD138 expression confirming plasma cell nature; kappa immunoglobulin light chain negative; lambda light chain restriction; CD138-Ki-67 double IHC to assess proliferative index.
• Cytogenetics/molecular: Prior identification of t(4;14) translocation (bone marrow analysis).

• Severe pancytopenia at presentation: hemoglobin 5.9 g/dL, white blood cell count 1.47×10^9/L, platelet count 44×10^9/L.
• Biochemical progression: serum lambda free light chain 2152.5 mg/dL.
• Morphology: Bone marrow infiltrated by large pleomorphic atypical cells with monocytoid features, irregular/multilobate nuclei, visible nucleoli, and vacuolated cytoplasm, mimicking high-grade lymphoma or acute leukemia.
• Immunophenotype: Flow cytometry positive for CD38, CD138, and CD56 indicating plasma cell origin.
• Immunohistochemistry: Strong CD138 positivity; kappa light chain negative; lambda light chain restriction; Ki-67 proliferative index increased at 12% among atypical plasma cells.
• Genetics: Known t(4;14) translocation, an adverse prognostic abnormality.
• Treatment response: Refractory to bortezomib-lenalidomide-dexamethasone following early relapse post-autologous transplant, consistent with aggressive disease biology.
• Diagnostic implication: Despite leukemia/lymphoma-like morphology, integration of clinical history with flow cytometry and IHC confirmed anaplastic plasma cell myeloma.

This case demonstrates that anaplastic MM can closely mimic acute leukemia or aggressive lymphoma on morphology alone. The patient’s refractory disease course and anaplastic cytology align with the presence of the adverse t(4;14) translocation. Ancillary studies—flow cytometry showing plasma cell markers (CD38, CD138, CD56) and IHC confirming CD138 positivity with lambda light chain restriction and increased Ki-67—were essential for correct classification as plasma cell myeloma rather than a myeloid or lymphoid neoplasm. The markedly elevated lambda free light chains supported active plasma cell dyscrasia. Recognizing this phenotype is clinically important due to its association with poor outcomes and resistance to conventional therapies.

Anaplastic morphology in plasma cell myeloma can lead to diagnostic confusion with acute leukemia or high-grade lymphoma. Correlation of clinical history with flow cytometry, immunohistochemistry, and known cytogenetic abnormalities such as t(4;14) is crucial for accurate diagnosis. This case underscores the aggressive clinical behavior and therapeutic resistance of anaplastic MM and highlights the need for heightened diagnostic vigilance and consideration of alternative/novel treatment strategies in such high-risk presentations.

This is a single-patient case report without long-term follow-up or comprehensive genomic profiling beyond the known t(4;14) abnormality, limiting generalizability and precluding conclusions about treatment efficacy or broader outcome measures.