Clinical, morphological, and genomic features of FGFR fusion Spitz neoplasms

Spitz neoplasms are defined as melanocytic tumours with characteristic spitzoid morphology and a Spitz-associated genomic driver such as activating mutations in HRAS or a Spitz-associated genomic fusion involving BRAF, RET, ROS1, NTRK1, NTRK2, NTRK3, ALK, or MAP3K8. The current literature suggests differences in clinical behaviour among distinct genomic subtypes of Spitz, and in malignant cases, treatment options may be influenced by the fusion. We present the first series of FGFR1 fusion Spitz tumours and compare their clinical, histological, and genomic findings to a cohort of non-FGFR1 fusion Spitz tumours. FGFR1 fusion Spitz tumours were more likely to involve the head and neck. No recurrences were seen among six patients with follow-up (mean of 24 months). Histologically, the lesions typically had a nodular silhouette (6/7 cases) and a plexiform arrangement of nests (5/7 cases). Within larger nested aggregates, there was often either a lobulated nesting pattern (6/7 cases) or sweeping fascicles of spindled melanocytes in a storiform pattern (6/7 cases) mimicking a dermatofibroma. Melanin pigmentation was frequent (5/7 cases), mostly at the lateral edges. In isolation, this pigmentation along with a predominance of intraepidermal spindle cells laterally gave this region of the tumours a pigmented spindle cell naevus of Reed-like appearance. The most common FGFR1 fusion partner was MYO5A, and one case involved FN1. None of the cases had genomic variants in TERT or CDKN2A. We believe FGFR1 fusions constitute a distinct subtype of Spitz neoplasm and FGFR1 should be added to the list of Spitz-associated genomic fusions.