Primary pulmonary hyalinizing clear cell carcinoma harboring EWSR1::ATF1 fusion: a case report

Hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland-type tumor that occasionally arises in the lung. As it shows substantial morphological overlap with mucoepidermoid carcinoma (MEC), definitive diagnosis can be challenging. Therefore, molecular testing is essential, as MEC typically harbors CRTC1/3::MAML2 fusions, whereas HCCC is characterized by EWSR1 fusions.

A 60-year-old woman presented with persistent cough and hemoptysis. Imaging revealed a 3.0-cm solid nodule in the left lower lobe adjacent to the bronchus. She underwent robot-assisted left lower lobectomy with lymph node dissection. Histologically, the tumor consisted of uniform epithelioid cells with clear-to-pale eosinophilic cytoplasm arranged in nests and cords within prominent hyalinized stroma. Cytologic atypia was minimal. Immunohistochemically, tumor cells were positive for CK7, CK5/6, and p40 and negative for TTF-1. Venous invasion was present without lymph node metastasis. Break-apart fluorescence in situ hybridization revealed rearrangements of EWSR1 and ATF1, strongly supporting the presence of an EWSR1::ATF1 fusion, whereas MAML2 rearrangement was absent. The patient remains recurrence-free 1 year after surgery.

Accurately distinguishing primary pulmonary HCCC, which is rare and may mimic MEC, is essential for appropriate pathological classification and prognostic assessment. It is also important for thoracic surgeons to consider HCCC during the differential diagnosis of centrally located or endobronchial pulmonary tumors, particularly when a definitive preoperative diagnosis is challenging. Integrating histopathology with molecular testing for EWSR1 and MAML2 rearrangements is critical for accurate diagnosis.