Understanding spitzoid tumours: new insights from molecular pathology

Spitzoid tumours are a morphologically diverse group of lesions that share histological similarity to the Spitz naevus, a benign melanocytic skin tumour. Distinguishing classic Spitz naevi from cutaneous malignant melanoma is usually achievable on standard histology sections, but occasionally equivocal lesions are encountered that show features intermediate between these two entities and consequently generate considerable clinical and histopathological concern. The nomenclature and diagnostic criteria for spitzoid lesions are not standardized and this article begins by considering the adverse effect this has on our understanding of spitzoid tumour biology. Investigations of some of the hallmark features of cancer and neoplasia in spitzoid tumours are described, and the contribution of these studies to our understanding of spitzoid tumour biology is considered, along with their potential diagnostic utility. These studies compare spitzoid tumours with better-characterized melanocytic lesions, and from such comparisons assumptions concerning the biological nature of different spitzoid tumours can be made. In contrast, investigations of the mitogen-activated protein kinase (MAPK) pathway and DNA gains and losses have suggested that Spitz naevi may be genetically distinct from other melanocytic tumours. The studies that led to this conclusion are reviewed, as well as subsequent work examining whether the same applies to all spitzoid tumours. Possible explanations for the considerable inconsistencies within some of these data are explored. Finally, potential pathways of tumour progression within spitzoid lesions are considered, with an emphasis placed upon insights gained from investigations of MAPK genes and DNA gains and losses.