ALK⁺ anaplastic large cell lymphoma expressing CD33 and myeloid nuclear differentiation antigen

An 83-year-old man with a history of prostate cancer treated with androgen deprivation therapy presented with an enlarging 7-cm left neck mass. Fine-needle aspiration revealed neoplastic cells with “bean-shaped” nuclei, condensed chromatin, and moderate amounts of lightly basophilic cytoplasm (panel A: Wright-Giemsa, 60× objective, total magnification ×600). Flow cytometry results revealed neoplastic cells within the “monocyte-gate” expressing CD45, CD4, and CD33 (subset) and not expressing CD38, CD11b, CD56, CD34, or any other myeloid or lymphoid antigen (panel B and data not shown). The neoplastic cells expressed CD30 and anaplastic lymphoma kinase (ALK), with a subset also expressing cytoplasmic myeloid nuclear differentiation antigen (MNDA) (panels C-E, immunostains; 60× objective, total magnification ×600).

MNDA is typically expressed in the nuclei of myelomonocytic cells and a subset of B cells but can be expressed in the cytoplasm of these cells during states of genotoxic stress, likely due to cleavage of its nuclear localization signal. Aberrant cross-lineage antigen expression occurs in anaplastic large cell lymphoma (ALCL), in particular expression of CD20, CD19, PAX5, CD13, and CD33 and very rarely myeloperoxidase. This is the first case, to our knowledge, of ALK⁺ ALCL expressing cytoplasmic MNDA and CD33. It is important not to misclassify ALK⁺ ALCL as a monocytic neoplasm due to cytomorphologic and immunophenotypic overlap.

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