The absence of CD56 on malignant plasma cells in the cerebrospinal fluid is the hallmark of multiple myeloma involving central nervous system.

By immunohistochemistry, the CD56-positive myeloma cells were detected in three (38%) bone marrow (BM) and one (13%) cerebrospinal fluid (CSF) samples from eight patients with multiple myeloma involving the central nervous system (CNS MM). Of the three patients with CD56-positive BM myeloma cells, two had CSF myeloma cells negative for CD56. In a control cohort of 84 MM patients without CNS involvement, the BM myeloma cells were CD56-positive in 68 (80%) cases (P < 0.0001). The prevalence of CD56-negative myeloma cells in the BM and CSF of our patients suggests that CD56 downregulation may play a role in the pathogenesis of CNS MM.