Morphological and genetic aspects of Spitz tumors

Abstract

Spitzoid melanocytic neoplasms (i.e. Spitz nevi, atypical Spitz tumors and spitzoid melanoma) are a clinical, histopathological and molecular genetic heterogeneous group of melanocytic skin tumors. Correlation of the histological features of spitzoid neoplasms with molecular genetic aberrations. A review and summary of the scientific literature. Several histopathological and molecular genetic distinct subtypes of spitzoid lesions have been defined. Epithelioid Spitz tumors commonly show a loss of the BAP1 gene and BRAF mutations and are associated with a hereditary tumor predisposition syndrome. Desmoplastic Spitz tumors frequently harbor HRAS mutations and gains of the chromosome arm 11p. Plexiform Spitz tumors often display ALK translocations. The morphology of Spitz tumors with ROS1, NTRK1, RET and BRAF fusion genes seems to be unspecific and is currently not well characterized. Morphological features offer valuable clues to the underlying genetic aberrations in spitzoid neoplasms. Genetic aberrations can be found in the entire biological spectrum of spitzoid neoplasms (i.e. Spitz nevi, atypical Spitz tumors and spitzoid melanoma) and are, therefore, probably not useful for distinguishing benign from malignant tumors; however, genetic aberrations represent important targets for therapeutic interventions and offer investigational treatment options for patients with metastatic disease. The appearance of multiple epithelioid melanocytic tumors with BAP1 loss indicates a hereditary tumor syndrome and warrants genetic counseling and preventive screening of affected individuals.