Hyalinizing clear cell carcinoma of the head and neck: A multicenter retrospective study of 87 cases focusing on prognostic pathologic features and grading scheme Journal Article
| Authors: | Xu, B.; Viswanathan, K.; Barbesier, M.; Ladenheim, A.; Antonescu, C. R.; Ghossein, R.; Lubin, D.; Magliocca, K.; Matar, S.; Mikula, M. W.; Resta, I. T.; Roy, D.; Sohn, S. Y.; Verma, A.; Prasad, M. L.; Rooper, L.; Brandwein-Weber, M.; Baloch, Z.; Katabi, N. |
| Article Title: | Hyalinizing clear cell carcinoma of the head and neck: A multicenter retrospective study of 87 cases focusing on prognostic pathologic features and grading scheme |
| Abstract: | 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. © 2025 United States & Canadian Academy of Pathology |
| Keywords: | immunohistochemistry; adult; cancer survival; controlled study; human tissue; aged; middle aged; primary tumor; survival rate; major clinical study; overall survival; clinical feature; histopathology; cancer recurrence; cancer patient; cancer radiotherapy; disease free survival; postoperative care; follow up; lymph node metastasis; antineoplastic agent; cancer grading; mitosis; disease association; smad protein; cohort analysis; retrospective study; cancer mortality; distant metastasis; adjuvant chemotherapy; recurrent disease; clear cell carcinoma; disease specific survival; salivary gland carcinoma; regional metastasis; perineural invasion; head and neck carcinoma; cytokeratin ae1; cytokeratin ae3; smooth muscle actin; tumor necrosis; mitosis index; clinical outcome; eosinophil; hyalinizing clear cell carcinoma; mortality rate; cancer prognosis; lymph vessel metastasis; distant metastasis free survival; transcription factor sox10; prognosis; human; male; female; article; tertiary care center; patient risk; involved margin; ewsr1 translocation; hyalinizing clear cell carcinoma of the head and neck |
| Journal Title: | Modern Pathology |
| Volume: | 38 |
| Issue: | 11 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2025-11-01 |
| Start Page: | 100834 |
| Language: | English |
| DOI: | 10.1016/j.modpat.2025.100834 |
| PUBMED: | 40617532 |
| PROVIDER: | scopus |
| PMCID: | PMC12323664 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Nora Katabi -- Source: Scopus |
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