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 resemble Spitz tumors morphologically but have conventional initiating mutations (eg, BRAF and NRAS). The current World Health Organization 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. The author reviewed the logic of the World Health Organization definition of Spitz tumors, the spectrum of tumors produced by initiating mutations, and problems with the definition of Spitz melanoma and provides an example of this rare entity in the context of related tumors.