Proliferative Nodules vs Melanoma Arising in Giant Congenital Melanocytic Nevi During Childhood

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The differential diagnosis between proliferative nodules (PNs) and melanoma arising in congenital melanocytic nevi (CMN) is crucial, as patients with PNs most often experience no increased risk of melanoma with metastases and death.


To analyze the utility of immunohistochemistry and fluorescence in situ hybridization (FISH) in distinguishing PNs from childhood and adult-onset melanoma arising in CMN.

Design, Setting, and Participants

A case series was conducted from June 29, 1989, to November 12, 2009, of 13 children with PNs arising in CMN in childhood and 5 children with melanomas arising in CMN in childhood. Five patients with giant CMN with no nodules were included as negative controls, and 6 patients with melanomas arising in CMN in adulthood were included as positive controls. Follow-up ranged from 3 to 21 years in all children (mean, 9.9 years) and from 3 months to 7 years in adults. Specimens were selected for immunohistochemistry and FISH. All histopathologic sections were reviewed by 2 dermatopathologists who examined all nodules arising at different ages in the same patient and, in the case of melanoma, all locations. Data analysis was performed from January 1, 2013, to January 31, 2015.

Main Outcomes and Measures

The ability to distinguish melanoma from PN using immunohistochemistry and/or FISH.


Of the 13 patients (5 boys and 8 girls) with PNs present at birth, all PNs were stable (mean follow-up, 9 years). Eight patients with PNs and 4 of 5 patients with childhood-onset melanoma showed homogeneous staining for HMB45, while heterogeneous staining for HMB45 was seen in 3 of 6 patients with adult-onset melanoma. Expression of p16 was strongly positive in most patients with childhood-onset PNs (10 of 11 patients) and melanoma (all patients) but negative in 4 patients with adult-onset melanoma. Patients with PNs and the 5 patients with childhood-onset melanoma had numerical chromosomal aberrations never observed in the adjacent CMN. The 2 children with FISH-positive PNs are melanoma free after 7 and 4 years. Only 1 patient with childhood-onset melanoma had a FISH aberration compared with 4 patients with adult-onset melanoma.

Conclusions and Relevance

Immunohistochemistry and the 4-probe FISH melanoma analysis are not useful for distinguishing PN from childhood-onset melanoma as opposed to adult-onset melanoma. Numerical anomalies seen in PNs but not in the adjacent CMN could be the result of a chromosomal segregation malfunction resulting in the development of nodules.

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