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Case Reports

Abstract

We report the case of a 77-year-old man with a history of invasive melanoma of the left frontal scalp diagnosed in 2016 with a local recurrence in 2021. He underwent wide local excision with negative margins. In 2024, he presented with a new 1.2 cm nodule with central crust on the left temple. Shave biopsy revealed a nodular dermal proliferation of multinucleated giant cells exhibiting occasional emperipolesis and mononuclear cells with relatively uniform, round-to-oval nuclei and prominent nucleoli. Frequent mitotic figures were noted. Immunohistochemistry showed CD68 positivity in multinucleated cells and a subset of mononuclear cells, patchy cytokeratin (AE1/AE3/PCK26) expression, and CD163 positivity in some mononuclear cells; SOX10, S100, Melan-A and ER were negative. The differential diagnosis included dedifferentiated melanoma with osteoclast-like giant cells, poorly differentiated carcinoma with osteoclast-like giant cells, giant cell-rich atypical fibroxanthoma, keratin-positive giant cell tumor, and giant cell tumor of soft tissue. Molecular studies identified pathogenic or likely pathogenic variants in NRAS Q61R, RAC1 P29S, TP53 V147D, and TP53 V173G suggestive but not diagnostic of dedifferentiated melanoma. Given the patient’s history, along with the lesion’s morphology and mutational profile suggestive of dedifferentiated melanoma, molecular analysis on the 2021 melanoma specimen was performed, which showed a BRAF K601E mutation, arguing against recurrence. The patient underwent local excision with negative margins and favorable clinical evolution. This case illustrates a rare giant cell–rich tumor mimicking melanoma recurrence, in which integrated morphologic, immunophenotypic, and molecular analyses were critical for accurate diagnosis and management.