Beyond the Skin: A Rare Case of Primary Malignant Melanoma of the Lung.

Primary malignant melanoma of the lung (PMML) is an exceedingly rare neoplasm. Due to its rarity and the high prevalence of metastatic melanoma to the lungs, PMML presents a significant diagnostic challenge and requires rigorous exclusion of extrapulmonary primary sites. We report the case of an 84-year-old lady who presented with a two-month history of fever, non-productive cough, and unintentional weight loss. Imaging revealed a solitary hypermetabolic mass in the superior segment of the left lower lobe. Histopathological examination of a transbronchial biopsy demonstrated immunohistochemical positivity for S100 and SOX10, consistent with a diagnosis of melanoma. A comprehensive dermatologic, mucosal, ophthalmologic, and systemic evaluation revealed no evidence of a primary lesion elsewhere, thereby fulfilling the criteria for PMML. Molecular testing revealed no actionable mutations (BRAF, NRAS, c-KIT), precluding targeted therapy. Given the tumour's unresectable nature due to proximity to critical mediastinal structures and the patient's comorbidities, she was initiated on a modified combination immune checkpoint inhibitor regimen with nivolumab and ipilimumab. PMML is a rare clinical entity with a limited number of reported cases. Diagnosis relies on histopathology, immunoprofiling, and thorough exclusion of extrapulmonary primaries. Treatment strategies are extrapolated from studies in cutaneous and unknown primary melanoma, with immune checkpoint inhibitors serving as the cornerstone of therapy in BRAF-wild-type, unresectable cases. This case highlights the importance of a meticulous diagnostic approach to solitary pulmonary lesions and underscores the evolving role of immunotherapy in managing rare malignancies such as PMML. Reporting such cases enhances the clinical understanding and guides future management of this rare disease.