The clinical outcome, pathologic spectrum, and genomic landscape of 454 cases of salivary mucoepidermoid carcinoma

Abstract Objectives To investigate the clinicopathological and molecular features of salivary mucoepidermoid carcinoma (MEC).Design The clinical features, treatment outcomes, and pathological parameters of 454 MECs were evaluated, and their genomic features were analyzed using whole-exome sequencing and whole-transcriptome sequencing.Results 414 patients were alive without relapse at follow-up, after an average period of 62 months (1–116 months). The disease progressed after initial treatment in 40 patients. The lungs were the most common site of distant metastasis. For classical MECs, histologic gradings of the AFIP, modified Healey, and MSK systems were significantly associated with recurrence and lymph nodal metastasis; these gradings were significantly related to lymph nodal metastasis for the subtypes. Older age, minor salivary gland involvement, clinical symptoms, high TNM stage, high-grade tumor, and improper surgical modality were the main prognostic factors. BAP1 was the most frequently mutated gene in MEC. Mutations in CDKN2A, MET, and TP53 were more frequently found in aggressive tumor phenotypes. MAML2 rearrangement was observed in 42% of patients, and EWSR1 rearrangement in 8%. Specific genetic events (in TP53 and FBXW7) associated with CRTC1–MAML2 fusion might cause MEC progression and might be associated with unfavorable prognosis.Conclusions A complete understanding of the high heterogeneity of MEC in histology and genetics would help in accurate diagnosis and treatment.