Primary melanoma of the lung: a clinicopathologic and immunohistochemical study of eight cases

Abstract

Primary malignant melanoma of the lung (PMML) is an uncommon neoplasm that may be confused with more conventional types of lung cancer. Although the previously proposed criteria for diagnosis, including the presence of an in situ component, are often difficult to satisfy, this lesion is characterized by a poor prognosis, ultimately leading to patient death. We report eight cases of PMML that presented as solitary, central endobronchial neoplasms, resulting in a picture that closely resembled carcinoid tumor or poorly differentiated non-small-cell carcinoma of the lung. The mean age at diagnosis was 51 years (range 45-71). The patients included one woman and seven men. The histologic growth pattern varied from organoid to fascicular and included epithelioid to spindled cells with hyperchromatic to vesicular nuclei, prominent eosinophilic nucleoli, and abundant eosinophilic to clear cytoplasm with occasional intranuclear cytoplasmic inclusions. A bronchial in situ component was present in four cases. Initial interpretations included carcinoid tumor, non-small-cell carcinoma, and malignant melanoma. Melanin was present in all neoplasms on hematoxylin and eosin staining, although very focally in one case, and was Fontana-Masson positive in all cases. Immunohistochemically, diffuse strong positivity for S-100, HMB-45, and vimentin was present in all seven tumors tested. All seven tumors were negative for cytokeratin, CAM 5.2, and chromogranin. Ultrastructural examination of the eighth case showed dysmorphic premelanosomes but no neurosecretory granules. None of the patients had disseminated disease at presentation, and all patients underwent surgical resection (seven lobectomies and one excision). In this series, primary malignant melanoma of the lung was characterized by an aggressive postoperative course, with five patients dying of metastatic disease from 4 to 32 months after resection (median 14 months). Two patients are alive with metastatic disease at 4 and 30 months after surgery, and the eighth patient is alive with no evidence of disease 108 months after surgery at last follow-up. Metastatic melanoma was identified in various sites, including the lungs, adrenal glands, liver, mesentery, brain, and bone. The cases herein presented indicate that PMML should be included in the differential diagnosis of primary bronchial tumors.