Critical Appraisal of Histologic Grading for Mucoepidermoid Carcinoma of Salivary Gland

Abstract

Multiple 3-tiered grading systems exist for mucoepidermoid carcinoma (MEC), leading to controversial results on the frequency and prognostic values of each grade. We aimed to identify prognostic histologic factors and to evaluate grading schemes in this retrospective study of 262 resected primary head and neck MECs. The rate of nodal metastasis was 8.4%. Large tumor size, tumor fibrosis, infiltrative border, lymphovascular invasion, perineural invasion, atypical mitosis, mitotic index (MI) ≥4/2 mm2 (4/10 HPFs), necrosis, and pT4 stage were associated with increased risk of nodal metastasis. The 5-year recurrence-free survival (RFS) was 95%. Significant prognostic factors for RFS included infiltrative border, tumor-associated lymphoid stroma, architectural patterns (macrocystic, microcystic, and noncystic), anaplasia, atypical mitosis, MI, necrosis, lymphovascular invasion, margin, pT stage, and tumor size. Nuclear anaplasia, high mitotic rate, and ≥25% microcystic component were significant independent prognostic factors on multivariate survival analysis. There was no significant difference between low-grade (LG) and intermediate-grade (IG) MECs in terms of risk of nodal metastasis and outcomes using all 4 known grading systems. Rather, high-grade MEC was consistently associated with an increased risk of nodal metastasis at presentation and decreased RFS and distant metastasis–free survival (DMFS) compared with the LG/IG MECs. We therefore recommend simplifying MEC grading to a 2-tiered grading scheme using MI and/or tumor necrosis. Using a 2-tiered grading, high-grade histology independently predict RFS, and is associated with a 25% risk of nodal metastasis, a 5-year RFS of 76%, and a 5-year DMFS of 76%, whereas LG MEC has a nodal metastasis rate of 7.0%, 5-year RFS of 97% and 5-year DMFS of 99%.

Immunohistochemical Expression of XIAP in Mucoepidermoid Carcinoma

“…MEC's biological behavior varies from being comparatively indolent (low grade) to being clinically aggressive (high grade). The prognosis for MEC varies significantly and is mostly based on the tumor's pathological grade [5,6].…”

“…Salivary gland carcinomas' (SGCs) histologic grading has been demonstrated to be a reliable indicator of the tumors' behavior and to be important in therapy optimization. It is not advisable to apply universal grading standards to SGCs because they typically exhibit intrinsic biological behavior [5,7]. New tools for immunohistochemical (IHC) diagnosis and prognostication, such as cell-proliferation markers, anti-apoptotic proteins, myoepithelial antigens, matrix metalloproteinases, steroid receptors, growth factors, and their receptors, have been combined with recent developments in histopathological classification.…”