[ALK rearranged Spitz melanocytoma: a clinicopathological and molecular genetic analysis of two cases].

Abstract

Objective: To investigate the clinicopathological, immunohistochemical and molecular characteristics of cutaneous ALK-rearranged Spitz melanocytoma. Methods: Two cases of cutaneous ALK-rearranged Spitz melanocytoma from outside hospital consultations in Department of Pathology, Affiliated Cancer Hospital of Fudan University in August 2020 and in Shanghai Ackermann Medical Laboratory in June 2022 were collected. The clinicopathological features, immunophenotypes and molecular profiles of two patients with cutaneous Spitzoid melanocytic tumor harboring ALK-rearrangement were analyzed. The literatures were reviewed. Results: The study included an 8-year-old boy and an 11-year-old girl, who presented with a polypoid lesion in the skin of right thigh and left auricle measuring 1.0 cm and 1.2 cm, respectively. Histologically, they were composed of medium to large-sized epithelioid to plump spindle cells, arranged in nested, plexiform or fascicular patterns in the superficial dermis. The neoplastic cells had abundant eosinophilic cytoplasm with round to ovoid vesicular nuclei containing prominent eosinophilic nucleoli. One case showed mild to moderate nuclear pleomorphism and mitotic activity (average, 2/mm²). Immunohistochemically, the epithelioid and plump spindle cells showed diffuse and strong staining of S-100 protein, SOX10, and ALK (D5F3 and 1A4), but did not express HMB45, PNL2 and MiTF. ALK-rearrangement was detected by fuorescence in situ hybridization in both cases. Subsequent next generation sequence (NGS) analysis identified KANK1::ALK and TPM3:ALK fusions. At 34 and 14 months after surgical resection, both patients remained well with no signs of recurrence or metastasis. Conclusions: ALK-rearranged Spitz melanocytoma represents a morphologically and genetically distinct subset of Spitz melanocytoma, characterized clinically by predilection in children and adolescents, with Spitzoid morphology in plexiform pattern, positive immunohistochemical stains, and rearrangement of ALK. As some cases show atypical features and high mitotic activity, a distinction from Spitz melanoma is warranted.