DP01 Verocay or nay? An unusual Spitz naevus

Abstract

Spitz tumours are defined by molecular alterations, which include HRAS activating mutations, activating fusions of receptor tyrosine kinases (e.g. ROS1, ALK, NTRK3) and activating fusions of kinases (BRAF, RAF1, MAP3K8) (de la Fouchardière A, Tee MK, Peternel S et al. Fusion partners of NTRK3 affect subcellular localization of the fusion kinase and cytomorphology of melanocytes. Mod Pathol 2021; 34: 735–47). These mutations confer distinctive morphological features to the lesion, recognition of which can direct ancillary investigations and distinction from melanoma. In NTRK-driven tumours, the fusion partner can affect the subcellular localization of the fusion kinase and cytomorphology of the cell. We present a case of NTRK:MYO5A-fused Spitz naevus with characteristic spindled morphology and pseudo-Verocay bodies. A 9-year-old patient presented with a supraumbilical lesion that histologically comprised a dome-shaped dermal melanocytic proliferation with biphenotypic appearance and deep extension. It contained fascicles of spindled cells with ‘pseudo-Verocay bodies’ and superficial dermal nests containing banal naevus cells. Initial low-power impression of NTRK immunohistochemistry appeared negative; however, higher-power examination revealed weak, granular staining along dendritic processes. BRAF, ALK, ROS1 and PRAME were negative. Molecular analysis revealed presence of a MYO5A:NTRK3 fusion consistent with a MYO5A:NTRK3-fused Spitz naevus. A subset of NTRK3-fused tumours is diagnostically challenging as their Spitz classification may be missed due to absence of typical epithelioid morphology and glassy cytoplasm [Addo AK, Beydoun HM, Jeyakumar JE et al. Clinical, morphologic, and molecular findings in neurotrophic tyrosine receptor kinase 3 (NTRK3) fusion Spitz neoplasms. Mod Pathol 2025; 38:100888]. MYO5A:NTRK3-fused Spitz naevi in particular present with spindled melanocytes, fascicular architecture and nuclear palisading resembling Verocay bodies, raising differential diagnoses of soft-tissue neoplasms. MYO5A:NTRK3-fused Spitz naevi show a linear pattern of NTRK immunohistochemistry due to localization of the MYO5A:NTRK3 fusion protein within dendritic processes. This feature may be disregarded on low-power examination and poses a risk of false negative interpretation. Five morphological patterns of NRTK3-driven Spitz tumours are documented, which range from conventional Spitz to spindle cell variants. Recognizing the specific features of NTRK3:MYO5A-fused Spitz naevi facilitates accurate histological interpretation, prompting pathologists to request the relevant investigations and avoid misdiagnoses.