Association Between the Histological Subtypes, Anatomical Locations, and MAML2 Rearrangement of Head and Neck Mucoepidermoid Carcinoma

Abstract

Purpose: Mucoepidermoid carcinoma is the most common malignant tumor of the salivary gland. MEC harboring MAML2 rearrangement has a favorable prognosis. This study investigated the histologic and locational diversity of head and neck mucoepidermoid carcinoma, clinicopathologic characteristics, and associations with CRTC1/3::MAML2 fusion. Methods: Patients with head and neck mucoepidermoid carcinoma (n = 128) treated from February 2004 to December 2016 were included. Retrospective analysis encompassed clinical data, pathologic findings, and prognoses, with concurrent performance of fluorescence in situ hybridization to detect MAML2 rearrangement. Results: The 128 head and neck mucoepidermoid carcinomas comprised 76 parotid gland, 29 oral cavity, 10 submandibular/sublingual, 8 pharynx, 2 lip, 2 sinonasal cavity, and 1 larynx MEC. The parotid gland was the most common site (59%), and the classic subtype was predominant (69%). MAML2 fusion was detected in 84% of analyzed cases and was strongly associated with low-grade tumors (P < 0.001). MAML2-negative cases exhibited higher rates of lymphovascular invasion, nodal metastasis, and poorer outcomes. Tumors in the parotid, submandibular gland, sublingual gland, oral cavity, and oropharynx, showed more frequent MAML2 rearrangement, than nasopharynx, larynx, lip, and paranasal sinus origin (P < 0.001). The classic and Warthin-like subtypes showed higher MAML2 rearrangement than other subtypes (P = 0.001). MAML2 fusion status was a statistically significant predictor of overall survival by univariate (P = 0.039) and multivariate (P = 0.048) analyses. Conclusion: The presence MAML2 fusion is a favorable prognostic marker in mucoepidermoid carcinoma, with its prevalence varying by location and subtype. Its varying prevalence across locations and subtypes highlights its significant prognostic relevance. These findings underscore the importance of molecular testing and histopathologic evaluation in predicting clinical outcomes. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.