Spitz melanoma.

It has long been recognized that the histopathologic differential diagnosis between Spitz nevus and melanoma is sometimes extraordinarily difficult. Both can be composed of large oval to spindled melanocytes with abundant cytoplasm and large nuclei. Genomic studies over the last decade have clarified that Spitz tumors have diverse genetic initiating events, and that for each of these, there are benign, intermediate grade, and malignant lesions. Another discovery is that some melanomas can morphologically resemble Spitz tumors but have conventional initiating mutations (e.g., BRAF, NRAS). The current WHO definition of Spitz tumors restricts the spectrum to neoplasms with an activating mutation affecting the MAP kinase pathway, mostly fusions involving kinase genes. Whether splitting off Spitz tumors from other neoplasms that are only morphologically spitzoid will stand the test of time is uncertain, but for now, it does bring order to what has been a complex area. The recognition of Spitz melanoma will enable classification, follow-up, and the delineation of rational treatment guidelines for this important group of tumors, most of which are in young people. I have reviewed the logic of the WHO definition of Spitz tumors, the spectrum of tumors produced by initiating mutations, problems with the definition of Spitz melanoma, and have provided an example of this rare entity in the context of related tumors.