Clinical, Morphological and Molecular Features of Spitz tumors

Abstract

Spitz tumors represent a heterogeneous group of challenging melanocytic neoplasms, displaying a range of biological behaviors, spanning from benign lesions, Spitz nevi (SN) to Spitz melanomas (SM), with intermediate lesions in between known as atypical Spitz tumors (AST). They are histologically characterized by large epithelioid and/or spindled melanocytes arranged in fascicles or nests, often associated with characteristic epidermal hyperplasia and fibrovascular stromal changes. In the last decade, the detection of mutually exclusive structural rearrangements involving receptor tyrosine kinases ROS1, ALK, NTRK1, NTRK2, NTRK3, RET, MET, serine threonine kinases BRAF and MAP3K8, or HRAS mutation, led to a clinical, morphological and molecular based classification of Spitz tumors. The recognition of some reproducible histological features can help dermatopathologist in assessing these lesions and can provide clues to predict the underlying molecular driver. In this review, we will focus on clinical and morphological findings in molecular Spitz tumor subgroups.

Keywords: ALK; Atypical Spitz tumor; BRAF –MAP3K8 fusion; HRAS mutation; MAP2K1 mutation; MET; NTRK1; NTRK2; NTRK3; RET; ROS1; Spitz melanoma; Spitz tumor; classification; dermoscopy-histopathology correlations; genetic alterations; histopathology; intermediate lesions; melanocytic lesions; melanocytomas; molecular driver; molecular morphological correlation; practical recommendations for diagnosis.