Dermatopathology
p16 Expression: A marker of differentiation between childhood malignant melanomas and Spitz nevi

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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/mm2, 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.

Section snippets

Patients

Six pathological formalin-fixed, paraffin-embedded skin biopsy specimens of patients with a diagnosis of Spitzoid nodular malignant melanoma made between 1998 and 2010 were obtained from the archives of the department of pathology of our tertiary care pediatric hospital. The childhood melanoma cases were all examined and confirmed by a minimum of two dermatopathologists. Spitzoid melanoma characteristically has higher degree of cytologic atypia than Spitz nevus.5 The most useful

Spitzoid nodular malignant melanoma

Patient age ranged between 3 and 14 years with a mean value of 8.67 years (SD = 4.18). Breslow thickness ranged between 1.22 and 5.58 mm with a mean value of 3.36 mm (SD = 1.75). Follow-up time ranged between 3 and 60 months with a mean value of 19.8 months (SD = 21.27). Ki-67 index ranged between 18% and 75% with a mean value of 48.5% (SD = 21.98). Mitotic count/mm2 ranged between 2 and 12 mitoses/mm2 with a mean value of 6.17 mitoses/mm2 (SD = 3.60).

All our childhood Spitzoid nodular

Discussion

p16 Has been shown to be essential for melanocyte senescence and found to be expressed in Spitz nevus and other types of benign melanocytic nevi.14, 15 This finding was corroborated in our series because all Spitz nevi and melanocytic nevi were positive for p16 staining. An analysis of cell cycle inhibitory proteins including p16, p21, and p27 showed that the majority of Spitz nevus cells expressed high levels of p16. Maldonado et al14 speculate that Spitz nevi and melanocytic nevi in general

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    Funding sources: None.

    Conflicts of interest: None declared.

    Reprints not available from the authors.

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