Morphologic clues and utility of fluorescence in situ hybridization for the diagnosis of nevoid melanoma

Background: Nevoid melanomas include melanomas with a low power silhouette similar to melanocytic nevi. However, at higher power magnification, nevoid melanoma may have severe nuclear atypia and dermal mitoses. Methods: We performed a clinical, pathological and molecular study on a series of 58 examples of nevoid melanoma, excluding cases with spitzoid morphology. Results: We identified distinct morphologic patterns: 'classic' nevoid melanoma, superficial spreading melanomas with nevoid invasive melanoma, lentigo maligna with nevoid invasive melanoma and deep penetrating nevus-like nevoid melanoma. Fluorescence in situ hybridization (FISH) was positive in 74% of cases. Copy number gains in 8q24 were common in amelanotic nevoid melanoma. The median follow-up was 28 months (range 140). At last follow-up, 37 patients had no evidence of disease, 3 were alive with metastases and 6 died from metastatic melanoma. Of these six patients who died, four had a sentinel lymph node biopsy (SLNB) performed, which was negative in all four. Conclusions: We describe distinct clues to the diagnosis of nevoid melanoma including occult intraepidermal atypia, and expansile nesting resulting in asymmetric silhouette or dermal papillae expansion. We also describe that nevoid melanoma have infrequent SLNB involvement in aggressive cases, and have frequent 8q24 gains rather than 9p21 deletions. Our results suggest that nevoid melanoma are distinct from spitzoid melanomas and should be distinguished.