Hyalinizing Clear Cell Carcinoma of the Head and Neck: A Multicenter Retrospective Study of 87 Cases Focusing on Prognostic Pathologic Features and Grading Scheme.

Hyalinizing clear cell carcinoma (HCCC) is a salivary gland carcinoma characterized by the presence of clear and eosinophilic cells within a hyalinized stroma and the EWSR1 rearrangement. Aiming to identify prognostic factors and establish a grading system, we herein conducted a detailed clinicopathology review of a large retrospective cohort of 87 HCCCs from 7 tertiary centers. Most HCCCs (91%) originated from minor salivary glands, although major salivary glands were affected in 8%. The most common sites were base of tongue, palate, nasopharynx, and maxilla. Eosinophilic cells were more prevalent than clear cells. Histologic features included intraosseous component (19%), perineural invasion (48%), lymphovascular invasion (LVI, 16%), nuclear pleomorphism (14%), tumor necrosis (26%), and a mitotic index (MI) ≥ 5/2 mm2 (9%). Factors associated with increased risk of nodal metastasis at presentation included LVI, high MI, and tumor necrosis. The 10-year disease-specific survival (DSS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) rates were 80%, 51%, and 87%, respectively. Significant prognostic factors identified on univariate survival analysis included MI ≥ 5/2 mm2, tumor necrosis, atypical mitosis, and nuclear pleomorphism for DSS; LVI, MI ≥ 5/2 mm2, and percentage of clear cells for DFS; and nodal metastasis, LVI, MI ≥ 5/2 mm2, tumor necrosis, and atypical mitosis for DMFS. The only independent prognostic factor for DFS identified on multivariate survival analysis was MI ≥ 5/2 mm2. High-grade HCCCs, defined as tumors with MI ≥ 5/2 mm2 and/or tumor necrosis, were associated with an increased risk of nodal metastasis at presentation and shortened DSS and DMFS. Among 67 HCCCs examined for EWSR1 rearrangement, 65 (97%) harbored EWSR1 translocation. In conclusion, we identified multiple prognostic factors in HCCC, including MI, necrosis, atypical mitosis, nuclear pleomorphism, LVI, and percentage of clear cells. We herein proposed a prognostically relevant 2-tiered grading system, classifying HCCC with a MI ≥ 5/10 2 mm2 and/or tumor necrosis as high grade.