A 74-year-old woman presented with fatigue. Laboratory studies showed an 8.0 g/dL M spike and immunoglobulin G κ paraprotein. Wright-Giemsa–stained bone marrow aspirate revealed increased atypical plasma cells containing numerous, large, cytoplasmic azurophilic granules, in the shape of dots or commas (panels A1-A3), resembling intracellular microorganisms. They involved ∼30% of bone marrow cellularity on the core biopsy (hematoxylin and eosin [H&E]), exhibiting abundant finely vacuolated-appearing cytoplasm, and reminded us of the “storage-type” histiocytes in lysosomal storage diseases (panel B). They were positive for CD138 (panel C1). Although the cytoplasmic granules were colorless by H&E, they were positive for κ immunoglobulin light chain by immunostain (panel C2), consistent with the observed paraprotein. Grocott’s methenamine silver and periodic acid-Schiff stains were negative.

Various forms of cytoplasmic inclusions have been described in plasma cell neoplasms, including Russell bodies, crystals, Auer rod–like inclusions, and rarely azurophilic granules. Although some Auer rod–like inclusions are of lysosomal origin, most inclusions, including azurophilic granules, are the deposition of excess immunoglobulin. This abundancy of cytoplasmic azurophilic granules is extremely rare and has not been well documented. Morphologically, they can mimic microorganism infection or lysosomal storage diseases. Proper immunohistochemical and cytochemical studies play an important role in making the distinction.