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First page of Primary Melanoma of the Lung – A Vanishing Entity

Background Primary melanoma of the lung has been considered an extremely rare and highly aggressive malignancy that accounts for 0.01% of all primary lung tumors. Molecular studies, as well as pertinent clinical history, have since brought into question whether these tumors truly represent primary lesions of the lung. The current study evaluates a series of four melanomas of the lung to assess whether primary melanoma of the lung is truly a diagnostic consideration, or if these cases represent metastases of other primary sites. Methods The pathology archives at the University of Chicago Medical Center were searched for patients who underwent robotic or endobronchial ultrasound-guided fine needle aspiration from 2018 to 2024. Clinicopathologic data, including demographics, fine needle aspiration results, and follow-up information including molecular studies and surgical resections, was collected from patients’ electronic medical record. Results In total 15959 robotic-guided/endobronchial ultrasound-guided FNAs were reviewed, with two cases (0.0001%) being metastatic melanoma with no known cutaneous primary after immunohistochemical and molecular studies. Both patients had molecular studies performed. Notable mutations included BRAF, TERT, NRAS, CDKN2A, and NF1, which are frequently seen in cutaneous melanomas. High tumor mutational burden (UV signature with >98 mutations per megabase) was also detected by next generation sequencing. Conclusion Based upon molecular signatures, clinical history, and presumed lack of precursor cell type within the bronchial epithelium, melanomas arising within the lung are most likely metastatic tumors.

S. Karger AG, Basel
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2025
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