Metastatic malignant melanoma with neuroendocrine differenti
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The distinction between a neuroendocrine tumor (NET) and various epithelial and non-epithelial tumors with focal neuroendocrine differentiation is an established clinical dilemma. The diagnosis relies on the identification of clear-cut immunoreactivity towards neuroendocrine markers such as chromogranin A (CgA), synaptophysin (SYP), and CD56, but the expression of one or several of these markers might also be found in subsets of non-NETs.

As these tumors are biologically distinct from NETs, the associated treatment options vary; therefore, proper recognition is imperative for the patient’s overall prognosis. The distinction between a metastatic NET and non-NET tumor with focal neuroendocrine differentiation could be particularly difficult when assessing biopsy material of metastatic deposits from a cancer of unknown primary (CUP), given the general privation of tissue material for immunohistochemical purposes.

This patient was a 74-year-old man of Middle Eastern ethnicity. An initial biopsy of a soft tissue metastasis displayed a neuroendocrine profile indicative of a metastatic neuroendocrine carcinoma, positive for CD56 and synaptophysin, and focally for ISL LIM homeobox 1 and insulinoma-associated protein 1. The Ki-67 index was 50%. Chemotherapy was initiated, but the patient progressed. Scrapings from a pathological hip fracture 3 months later revealed focal synaptophysin immunoreactivity and widespread melanoma antigen, human melanoma black 45, and SOX10 positivity, which are indicative of metastatic malignant melanoma with focal neuroendocrine differentiation.

Conclusively, Malignant melanoma may display neuroendocrine differentiation, and the entity should be considered a rare differential diagnosis when assessing biopsies of suspected neuroendocrine carcinomas.