Primary pulmonary malignant melanoma (PPMM) is extremely rare. Diagnosis requires rigorous exclusion of metastatic melanoma by a thorough history and extensive physical examination. Metastatic melanoma is often multiple and bilateral, and involves lung parenchyma and/or pleura. PPMM often arises in the bronchus and is detected as a pigmented lesion on bronchoscopy. In contrast, peripheral nodular melanoma is almost always metastatic.

The histology of PPMM, similar to melanoma from other sites, generally shows large polygonal discohesive cells with abundant eosinophilic cytoplasm containing variable amounts of melanin pigment. Tumor cell nuclei are generally moderately enlarged with dense chromatin, prominent nucleoli, and occasional intranuclear cytoplasmic inclusions. Scattered mitotic figures are often present. Differential diagnosis includes poorly differentiated neoplasms, both primary and metastatic. Carcinoid tumors (see Chapter 10, Part 6) may contain melanin pigment but are generally synaptophysin and chromogranin positive, unlike melanoma. Clear-cell “sugar” tumors or PEComas (see Chapter 25, Part 2) are generally positive for S-100 and HMB-45 and are usually peripheral lesions, not endobronchial, that are strongly positive for glycogen on periodic acid-Schiff (PAS) stain.