A 66-year-old man presented with normocytic anemia and thrombocytopenia as well as pulmonary metastatic melanoma, stable on encorafenib/binimetinib therapy. After an extensive, unrevealing evaluation, including imaging studies with no evidence of skeletal metastasis, an iliac crest bone marrow biopsy was performed. A hemodilute aspirate smear (panels A-B; Wright-Giemsa stain; ×50 objective, original magnification ×500) showed trilineage hematopoiesis, including megakaryocytes (yellow arrow) as well as rare large, atypical cells (red arrow), frequently with vacuolated cytoplasm, rarely with retained cytoplasmic pigment (panel B). The core biopsy (panels C-D; hematoxylin and eosin stain; ×20 objective, original magnification ×200 [C] and ×40 objective, original magnification ×400 [D]) showed cellular marrow focally involved by scattered and occasionally clustered pleomorphic, atypical cells, including many large, bizarre forms closely resembling megakaryocytes. These large, atypical cells demonstrated between 1 and multiple irregular nuclei, vesicular chromatin, prominent “cherry-red” nucleoli, abundant pale, granular cytoplasm, many mitotic figures, and very rare cells with retained pigment. S100 and SOX-10 stains highlighted these atypical cells, supporting a diagnosis of metastatic melanoma (panels E-F; ×40 objective, original magnification ×400).

Known as “the great masquerader,” melanoma can demonstrate a broad range of cytological features, in this case mimicking megakaryocytes, a diagnostic dilemma when evaluating marrow for cytopenias of uncertain etiology. Careful morphologic examination and immunohistochemical staining for melanoma markers can aid in avoiding this pitfall.

A 66-year-old man presented with normocytic anemia and thrombocytopenia as well as pulmonary metastatic melanoma, stable on encorafenib/binimetinib therapy. After an extensive, unrevealing evaluation, including imaging studies with no evidence of skeletal metastasis, an iliac crest bone marrow biopsy was performed. A hemodilute aspirate smear (panels A-B; Wright-Giemsa stain; ×50 objective, original magnification ×500) showed trilineage hematopoiesis, including megakaryocytes (yellow arrow) as well as rare large, atypical cells (red arrow), frequently with vacuolated cytoplasm, rarely with retained cytoplasmic pigment (panel B). The core biopsy (panels C-D; hematoxylin and eosin stain; ×20 objective, original magnification ×200 [C] and ×40 objective, original magnification ×400 [D]) showed cellular marrow focally involved by scattered and occasionally clustered pleomorphic, atypical cells, including many large, bizarre forms closely resembling megakaryocytes. These large, atypical cells demonstrated between 1 and multiple irregular nuclei, vesicular chromatin, prominent “cherry-red” nucleoli, abundant pale, granular cytoplasm, many mitotic figures, and very rare cells with retained pigment. S100 and SOX-10 stains highlighted these atypical cells, supporting a diagnosis of metastatic melanoma (panels E-F; ×40 objective, original magnification ×400).

Known as “the great masquerader,” melanoma can demonstrate a broad range of cytological features, in this case mimicking megakaryocytes, a diagnostic dilemma when evaluating marrow for cytopenias of uncertain etiology. Careful morphologic examination and immunohistochemical staining for melanoma markers can aid in avoiding this pitfall.

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