Salivary gland-like low-grade clear cell carcinomas of the thoracic cavity: A clinical, immunohistochemical, and molecular analysis of three cases

Three cases of an unusual neoplasm with striking clear cell features resembling salivary gland origin of the thoracic cavity are presented. The patients were three men between the ages of 52 and 69 years (average: 60.5 years), who presented with non-specific symptoms, such as chest pain, cough, and dyspnea. Diagnostic imaging showed that two tumors were intrapulmonary neoplasms, one in right lower lobe and one in the left upper lobe, while the third tumor was located in the anterior mediastinum. Surgical resection was accomplished in all cases. Grossly, the tumors were described as light tan, soft and well-delineated. Necrosis and hemorrhage were not present. Histologically, the three tumors showed similar morphological features consisting of a neoplastic cellular proliferation arranged in small lobules and round glandular structures, some of which contained amorphous eosinophilic secretions. Individual tumor cells had abundant clear cytoplasm, round nuclei, and inconspicuous nucleoli. Cellular atypia was minimal and only scattered mitotic figures were present. Immunohistochemical studies showed that the tumor cells were positive for pancytokeratin and GATA-3, focally and weakly positive for DOG1 and TRPS1 while negative for numerous other epithelial and neuroendocrine markers. Molecular analysis showed negative results for EGFR, ROS1, or ALK mutation, MAML2 and EWSR1 rearrangement and ETV6::NTRK3 fusion, respectively. Clinical follow up showed that all patients were alive without tumor recurrence or metastasis. We believe that the histological features, immunohistochemical profile, and the results of the molecular analysis are supportive of a yet undescribed tumor entity, provisionally designated as salivary gland-like low-grade clear cell carcinomas.