Histologic characteristics and predictors of outcome in epithelial-myoepithelial carcinoma (EMC) of salivary gland: a multi-center study of 75 cases.

Epithelial-myoepithelial carcinoma (EMC) may occur de novo or ex pleomorphic adenoma (PA). We aimed to investigate the prognostic and clinicopathologic features and the utility of RAS Q61R immunohistochemistry in a multicenter retrospective cohort of 75 EMCs. Seven tumors (9%) were EMC ex PA, whereas 91% (n = 68) were EMC de novo. Compared with EMC de novo, EMC ex PA was associated with a significant higher percentage of hyalinized and myxoid stroma, larger tumor size, frequent perineural invasion (PNI), absence of nuclear enlargement, and lower frequency of pT1 disease. Seven out of 65 patients had adverse events (five local recurrence, two regional recurrences, two distant metastases, and two disease-related death). The 5-year and 10-year disease-specific survival were 100% and 91% respectively, and the 5-year and 10-year disease-free survival (DFS) were 90% and 85% respectively. Adverse pathologic features that were associated with RFS on univariate survival analysis included PNI, atypical mitosis, mitotic count, and tumor size ≥ 4 cm. Among them, PNI and atypical mitosis remained as independent prognostic factors on multivariate survival analysis. The frequency of RAS Q61R immunopositivity was 31% (12/39) in EMC de novo, 0% (0/5) in EMC ex PA, and 0% (0/32) in non-EMC salivary neoplasms. In conclusion, although most of the EMCs are de novo, 9% are EMCs ex PA. PNI, mitotic index, atypical mitosis, and large tumor size predict shortened RFS in EMC. RAS Q61R immunopositivity is highly specific for EMC de novo and is absent in EMC ex PA.