HRAS-mutated Spitz tumor

It is often very difficult to confidently distinguish benign and malignant Spitz lesions, and a diagnosis of Spitz tumor of unknown malignant potential (STUMP) is rendered.

To address this problem, we performed molecular genetic analysis in a large group of Spitz tumors (93 Spitz nevi and 77 STUMPs) and identified a subgroup of 24 lesions harboring a HRAS mutation.

HRAS-mutated Spitz tumors lay predominantly in the dermis, havve a relatively low cellularity, show desmoplasia (with single cells interspersed between the collagen bundles), and have an infiltrating base.

In 29% of cases, melanoma had been the initial diagnosis, or an important differential diagnostic consideration, mainly based on the presence of multiple or deeply located mitotic figures, especially in adult patients.

In one series, none of the patients with the HRAS-mutated lesions developed recurrences or metastases (mean and median follow-up: 10.5 y).

This was in accordance with the literature: no HRAS mutations have so far been reported in Spitzoid melanomas.

HRAS mutation analysis may be a useful diagnostic tool to help differentiate between Spitz nevus and Spitzoid melanoma, thereby reducing the frequency of overdiagnosis of melanoma, and to help predict the biological behavior of a STUMP.

Moreover, this might be a first step toward a more reproducible classification of Spitz tumors combining histological and genetic data.

See also

 Spitz tumor

References

 HRAS-mutated Spitz tumors: A subtype of Spitz tumors with distinct features. van Engen-van Grunsven AC, van Dijk MC, Ruiter DJ, Klaasen A, Mooi WJ, Blokx WA. Am J Surg Pathol. 2010 Oct;34(10):1436-41. PMID: 20871217