Secretory carcinoma of the salivary gland: a multi-institutional clinicopathologic study of 90 cases with emphasis on grading and prognostic factors

• Authors: Bin Xu, Memorial Sloan Kettering Cancer Center; Kartik Viswanathan, Emory University; Kavita Umrau, Memorial Sloan Kettering Cancer Center; Thair A.D. Al-Ameri, National Institute of Health; Snjezana Dogan, Memorial Sloan Kettering Cancer Center; Kelly R. Magliocca, Emory University; Ronald A. Ghossein, Memorial Sloan Kettering Cancer Center; Nicole A. Cipriani, University of Chicago; Nora Katabi, Memorial Sloan Kettering Cancer Center
• Journal Title: Histopathology
• Volume: Volume 81, Number 5
• Publisher: John Wiley and Sons | 2022-09-05, Pages 670-679
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1111/his.14772
• Subjects: Health Sciences, Oncology
• Keywords: Secretory carcinoma; salivary gland carcinoma; ETV6::NTRK3 fusion; grading; prognosis

Abstract

Background: Secretory carcinoma (SC) is a rare form of salivary carcinoma that was first described in 2010 and is characterized by ETV6::NTRK3 fusion in most cases. In this large retrospective study, we aimed to identify adverse clinicopathologic factors and propose a prognostically relevant grading scheme for SC. Methods: A detailed clinicopathologic review was conducted on 90 SCs from the major and minor salivary glands. Results: The median age at presentation was 50 years (range: 7-93). Sixty-nine (77%) tumors originated from major salivary glands, whereas the remaining 21 involved minor salivary glands. Six cases (7%) had cervical nodal metastasis. Only lymphovascular invasion (LVI) was associated with risk of nodal metastasis (p<0.05). The 5-year disease specific survival and disease-free survival (DFS) were 98% and 87% respectively. On univariate survival analysis, adverse prognostic factors associated with decreased DFS included minor salivary gland origin, atypical mitosis, high mitotic index, high-grade transformation (HGT), necrosis, nuclear pleomorphism, infiltrative tumor border, fibrosis at the invasive front, LVI, positive margin, and advanced pT stage (p<0.05). When adjusted for pT stage and margin status: mitotic index, LVI, nuclear pleomorphism, and HGT remained as independent prognostic factors. Conclusion: We therefore propose a two-tiered grading system for SC. The low-grade SC is defined as those with <5 mitoses/10 high power fields and no tumor necrosis, and high-grade SC as those with ≥5 mitoses/10 high power fields and/or necrosis. This proposed grading system can be useful to risk stratify patients with SC for appropriate clinical management.