A 55-year-old male with a history of relapsed/refractory multiple myeloma and widespread osseous and extramedullary involvement, presented with acute encephalopathy and altered mental status. Brain MRI demonstrated extensive leptomeningeal enhancement without evidence of infarction or hemorrhage. Cerebrospinal fluid cytology showed markedly increased cellularity comprised of sheets of atypical plasma cells with plasmablastic morphology.  The neoplastic cells were positive for VSCD38 and CD56 with kappa light chain restriction.

These findings confirmed central nervous system involvement by multiple myeloma.

Learning points:

1. Leptomeningeal involvement by multiple myeloma is rare but clinically significant and often presents with acute neurologic symptoms such as encephalopathy or altered mental status.
2.  Cytologic evaluation of CSF can reveal highly pleomorphic plasma cells with mitotic activity; flow cytometry is essential for confirming clonal plasma cell infiltration.

Diagnostic pitfall

• Plasmablastic myeloma involving the CSF can closely mimic acute leukemia or high-grade lymphoma due to marked cellularity, blast-like morphology, and high mitotic activity. Correlation with clinical history, morphology, and immunophenotyping is essential to avoid misdiagnosis.