Extremely rare primary tracheal hyalinizing clear cell carcinoma: two case reports.

Abstract

Background: Primary tracheal hyalinizing clear cell carcinoma (HCCC) is an exceptionally rare, low-grade malignant epithelial tumor. Its nonspecific respiratory manifestations and overlapping histopathological features with other clear cell neoplasms can delay diagnosis. Molecular alterations involving the Ewing sarcoma breakpoint region 1 (EWSR1) gene are diagnostically valuable; however, the clinicopathological features, optimal management, and long-term outcomes of tracheal HCCC remain insufficiently characterized. We present two cases to expand the limited evidence regarding its diagnosis and surgical treatment.

Case description: Two women presented with respiratory symptoms caused by primary tracheal tumors. The first patient underwent segmental tracheal resection with end-to-end reconstruction. Histopathological and immunohistochemical findings supported HCCC, and molecular testing identified an EWSR1::ATF1 fusion. The second patient also underwent segmental tracheal resection and reconstruction. Histopathological examination revealed tumor cells with clear cytoplasm arranged in nests and cords within a hyalinized stroma, and fluorescence in situ hybridization demonstrated EWSR1 rearrangement, confirming the diagnosis of HCCC. R0 resection was achieved in both patients. Postoperative recovery was satisfactory, and no recurrence or metastasis was identified during the available follow-up.

Conclusions: Primary tracheal HCCC should be considered in the differential diagnosis of tracheal clear cell tumors. Accurate diagnosis requires integration of histomorphology, immunohistochemistry, and molecular testing for EWSR1 alterations. Complete surgical resection with negative margins appears to be an effective treatment for localized disease. Because late recurrence or metastasis may occur and evidence remains limited, prolonged postoperative surveillance and further accumulation of molecularly confirmed cases are warranted.