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Cancer. 2004 Dec 1;101(11):2636-40.

Genetic similarities between Spitz nevus and Spitzoid melanoma in children.

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Department of Pathology, Columbia University Medical Center, New York, New York, USA.



Melanoma in children is rare. Diagnosis of the subtype of melanoma known as Spitzoid melanoma can be extremely challenging in this age group. Spitzoid melanoma clinically and histopathologically resembles a benign melanocytic proliferation referred to as Spitz nevus. In some cases, distinction between the two is impossible. Initial misdiagnoses of Spitzoid melanomas as Spitz nevi, thus leading to fatal outcomes, have occurred. The genetic basis and biologic behavior of Spitzoid melanoma is unknown. Although melanoma specimens exhibit high rates of mutation in the B-RAF and N-RAS genes, the Spitzoid melanoma subtype has not been evaluated. Spitz nevi have been found to be associated with a low percentage of mutations in the H-RAS gene; however, the mutational profile of H-RAS in Spitzoid melanoma is unknown.


The authors evaluated a unique series of melanomas occurring in prepubescent children that showed Spitz nevus-like histopathology (Spitzoid melanoma). All of the melanomas in the current series have metastasized to lymph nodes, confirming the diagnosis of melanoma. The authors examined these tumors, as well as age-matched Spitz nevi, for mutations in the B-RAF, N-RAS, and H-RAS genes.


Activating hotspot mutations in the B-RAF, N-RAS, and H-RAS genes were not identified in Spitzoid melanoma or Spitz nevus specimens.


There are genetic similarities with respect to the B-RAF, N-RAS, and H-RAS genes between Spitzoid melanoma and Spitz nevi. Such similarities further differentiate these two tumor types from other melanoma subtypes and from melanocytic nevi, respectively. However, mutation analysis of B-RAF, N-RAS, and H-RAS was not useful in differentiating between Spitzoid melanoma and Spitz nevus in children.

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