Abstract:

Background and purpose: Hyalinizing clear cell carcinoma (HCCC) of salivary gland is a rare tumor with low-grade malignancy, which usually occurs in minor salivary glands. Due to its rarity, the tumor type is not well known to pathologists and misdiagnosis frequently occurred. The aim of this study was to investigate the histologic, immunophenotypic and molecular features of HCCC. Methods: Eight cases of salivary gland HCCC diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center from January 2015 to October 2019 were collected. Clinicopathologic characteristics were analyzed, and fluorescence in situ hybridization (FISH) assay was used to detect EWSR1 translocation in tumor tissue. Diagnostic criteria and differential diagnosis were summarized, with a review of the literature. Results: All patients were female, aged 26 to 68 years, and the tumor locations included the oral cavity, nasopharynx, parotid gland and other sites of head and neck. Microscopically, the tumors consisted mainly of clear cells and eosinophilic cells with variable proportions, arranged in nests, sheets and trabeculae. In 1 case, the tumor was composed almost entirely of eosinophilic cells; in 6 cases, obvious nuclear pseudo-inclusion bodies were seen; in 1 case, neoplastic cells were connected to the surface squamous epithelium; in 1 case, the glandular structure was seen in some areas of the tumor; in 3 cases, a sheath of lymphocyte was formed around the tumor nests; in 7 cases, there was a sclerosing or hyalinizing stromal reaction, showing desmoplastic changes; and 1 case featured stoma with myxoid changes. There was no definite keratinization or necrosis in all tumors, and mitotic figures were generally rare. Immunohistochemical staining showed that tumor cells of 8 cases were diffusely positive for AE1/AE3 protein, 7 cases expressed P63, and 7 cases focally expressed low molecular weight keratin CK7 or CAM5.2, however, S-100, calponin, PAX-8 and CD10 were all negative. All tumors showed low proliferative activity, with the Ki-67 proliferation index less than 5%. FISH test revealed EWSR1 translocation in all 8 cases. All patients demonstrated no recurrence or metastasis during the follow up ranging 4-50 months. Conclusions: HCCC of salivary gland is a low-grade malignancy occurring mainly in minor salivary glands, with characteristic histological and molecular features. This cancer type needs to be distinguished with many morphologic mimics of salivary gland. Most cases with salivary HCCC feature a good prognosis.

Key words: Salivary gland tumours, Hyalinizing clear cell carcinoma, Clinicopathologic features