p16 expression: a marker of differentiation between childhood malignant melanomas and Spitz nevi

Abstract

Background: Childhood malignant melanomas frequently present as nodular melanomas with Spitzoid features. Spitz nevus and Spitzoid melanoma overlap clinically and histopathologically and there have been many attempts to differentiate between them. Spitz nevi differ from melanomas by their immunohistochemical pattern of expression of cell cycle and apoptosis regulators such as the p16 protein.

Objective: The aim of this study was to evaluate in a childhood population the expression of p16 in nodular malignant melanoma of Spitzoid type, Spitz nevi, and a control group of benign compound melanocytic nevi.

Methods: We performed immunohistochemical studies for expression of p16 in 6 Spitzoid malignant melanomas, 18 Spitz nevi, and 12 compound melanocytic nevi in children younger than 18 years. Statistical analysis was used to compare p16 expression, mitotic count/mm(2), and Ki-67 index of childhood nodular malignant melanomas and Spitz nevi.

Results: All the childhood melanoma cases were associated with loss of p16 without any correlation with their Breslow thickness whereas all the Spitz nevi and benign melanocytic nevi had strong positive nuclear and cytoplasmic expression of p16 staining. We found a statistically significant difference in p16 expression, mitotic counts, and Ki-67 index when comparing the Spitzoid melanomas with the Spitz nevi.

Limitations: This study is limited by the small number of malignant melanomas, which are known to be rare in childhood.

Conclusion: p16 Expression in childhood nodular Spitzoid malignant melanomas and Spitz nevi, in conjunction with clinical and histopathological evaluation, may be a useful tool in differentiating between these two entities.