Primary malignant melanoma of the lung with C-KIT mutation and SRD5A3-KIT fusion

Histopathological examination revealed tumor cells exhibiting epithelioid to spindle-shaped morphology, characterized by prominent nucleoli and intracytoplasmic melanin deposition (hematoxylin and eosin staining). Immunohistochemical analysis demonstrated diffuse and strong positivity for S-100, HMB-45, and Melan-A. Based on the histomorphological features and immunohistochemical profile, a diagnosis of malignant melanoma was established. NGS detected a somatic KIT exon 11 mutation (c.1727 T > C, p. Leu576Pro; variant allele frequency: 20.1%) and identified an SRD5A3-KIT gene fusion involving transcript variants NM_024592.4 (SRD5A3) and NM_000222.2 (KIT), with breakpoints in Exon 5 of SRD5A3 and Exon 6 of KIT. The fusion variant showed a somatic mutation frequency of 24.8%. These findings not only expand the molecular landscape of PMML but also suggest therapeutic opportunities through targeted kinase inhibition. This case underscores the critical role of integrated multimodal analysis (radiological-pathological-molecular) in characterizing rare malignancies.