Clinical and Histopathologic Analyses of Nasopharyngeal Hyalinizing Clear Cell Carcinoma

Abstract

The aim of this study was to evaluate the clinicopathologic features, molecular characteristics, treatment strategy, and prognosis of nasopharyngeal hyalinizing clear cell carcinoma (HCCC). Retrospective observational case series. Institutional pathology records between 2006 and 2022 were searched for all cases of nasopharyngeal HCCC. We included 10 male and 16 female patients aged 30 to 82 years (median: 60.5 y, mean: 54.6 y). The most common symptoms were blood-stained rhinorrhea and nasal obstruction. Tumors most often involved the lateral wall of the nasopharynx, followed by the superior posterior wall. Microscopically, all tumor cells were arranged in sheets, nests, cords, and single cells in a hyaline/myxoid/fibrous stroma. The tumor cells were polygonal, with or without distinct cell borders, and displayed abundant clear-to-eosinophilic cytoplasm. All 26 cases were positive for pancytokeratin, CK7, p40, and p63 but negative for myoepithelial differentiation markers. Ki-67 labeling was low and ranged from 1% to 10%. All 26 cases demonstrated EWSR1 and EWSR1-ATF1 rearrangements, and no case demonstrated MAML2 rearrangement. Complete follow-up data were available for 23 patients: 14 patients underwent endoscopic surgery alone, 5 underwent radiation therapy followed by endoscopic surgery, 3 underwent radiation therapy followed by biopsy, and 1 underwent cisplatin chemotherapy before endoscopic surgery. Clinical follow-up ranged from 6 to 195 months; 13 patients (56.5%) were alive without tumor, 5 patients (21.7%) died of disease, 5 patients (21.7%) survived with tumor. HCCCs of the nasopharynx are rare tumors. The definitive diagnosis depends on histopathology, immunohistochemistry, and molecular studies. The optimal treatment for patients with nasopharyngeal HCCC is wide local excision. Radiation and chemotherapy might be good options for managing locally advanced cases. Nasopharyngeal HCCC is less indolent than previously thought. Tumor stage and the choice of treatment are key factors affecting the prognosis of nasopharyngeal HCCC patients.

The Role of Gene Fusions in Thymic Epithelial Tumors

“…Hyalinizing clear cell carcinomas (HCCC) with EWSR1 rearrangement can occur in the thymus and have been included in the 2021 WHO classification [10,20]. These tumors were first reported in the head and neck [11,[56][57][58] and later also in the lung [13,15,[59][60][61]. For primary thymic HCCC the 2021 WHO classification indicates that clear cell carcinomas without EWSR1 rearrangement may or may not represent true thymic clear cell carcinoma [20].…”

“…While CRCT1 was found to be fused with MAML2 in mucoepidermoid carcinomas, as in mucoepidermoid carcinomas elsewhere in the body, YAP1 was identified as the fusion partner of MAML2 in metaplastic thymomas and KMT2A in type B2 and B3 thymomas. EWSR1 gene rearrangements are present in hyalinizing clear cell carcinomas [10], similar to hyalinizing clear cell carcinomas in the head and neck [11,12] and lung [13][14][15]. Gene fusions involving the NUTM1 gene are also found in thymic tumors, specifically in NUT carcinomas, which are considered a subtype of thymic carcinomas [16,17].…”

Case report: Successful management of primary hyalinizing clear cell carcinoma in nasopharynx: a report of 2 cases and system analysis

“…Hyalinizing clear cell carcinoma (HCCC), also referred to as clear cell carcinoma (CCC) by the World Health Organization (WHO), is a rare tumor believed to originate from salivary glands, often presenting as an oral submucosal lesion in individuals of middle to advanced age (1). Although its primary occurrence is in the oral cavity, it can also uncommonly manifest in locations such as the trachea (2), bronchi (3) and nasopharynx (4). Initially described by Milchgrub et al in 1994, this unique carcinoma exhibits distinctive histomorphology, characterized by infiltrating cords and nests of tumor cells featuring clear cytoplasm, all set within a hyalinized stroma (5).…”

“…The occurrence of local or distant metastases at the time of presentation is infrequent, with no instances (0 out of 10) of nasopharyngeal HCCC presenting with distant metastases reported (6,8). Symptoms associated with nasopharyngeal HCCC include otorrhea, nasal congestion, epistaxis, and tinnitus (4,7). Standard treatment approaches involve surgical resection and neck dissection in the presence of lymphadenopathy during the initial evaluation.…”