[Malignant melanoma with anaplastic lymphoma kinase positivity: a clinicopathological analysis of three cases]

Objective: To investigate the expression of anaplastic lymphoma kinase (ALK) in malignant melanoma and analyze its clinicopathological and molecular features. Methods: Eighty-seven malignant melanomas that were surgically resected at the First Affiliated Hospital, Zhejiang University School of Medicine between January 2015 and December 2019 were collected. Immunohistochemical staining was performed to evaluate ALK expression. Positive cases were further analyzed using clinical, pathological, and molecular testing data. Relevant literature was systematically reviewed, and follow-up was conducted. Results: Three cases showed ALK-positive expression. They were all in male patients, aged 52, 79, and 51 years, with tumors located in the left temporooccipital skin, maxillary gingiva, and left plantar skin, respectively. Cases 1 and 3 had a history of smoking and diabetes; case 2 had a history of alcohol use. Histologically, case 1 exhibited pagetoid spread with prominent lymphocytic infiltration; case 2 showed nodular growth with ulceration; while case 3, a recurrent lesion, was surrounded by abundant lymphocytes. All three cases displayed sheet-like proliferation of epithelioid or short spindle-shaped tumor cells, conspicuous nucleoli, and frequent mitoses. Marked pigmentation was observed in cases 1 and 3, but not in case 2. Fluorescence in situ hybridization (FISH) revealed ALK gene rearrangement in case 2, but not in cases 1 and 3. The nCounter analysis showed high expression of ALK exons 20-29 and intron 19 with low expression of exons 1-19 in cases 1 and 3, consistent with an alternative transcription initiation (ATI)-driven ALK expression pattern. In contrast, case 2 exhibited high expression of exons 20-29 but low expression of both exons 1-19 and intron 19, supporting an ALK fusion subtype. No mutations of KRAS, NRAS, BRAF, or PIK3CA were detected in any of the cases. Conclusions: Both ALK fusion and ATI-driven ALK expression patterns can present in malignant melanomas. Aberrant ALK activation suggests its potential role in molecular pathogenesis of malignant melanoma. Further investigation of ALK as a therapeutic target seems necessary.