Mucoepidermoid carcinoma: a five-decade journey

Several decades after a comprehensive description of mucoepidermoid carcinoma (MEC), there is no uniformly accepted grading system. The most recent debate regarding the histologic grading of MECs, centers on the wide range of reported prevalence of cyclic AMP response element-binding protein (CREB)-regulated transcription coactivator (CRTC1-MAML2) rearrangement in high-grade (HG) MECs. We hypothesize that difficulties in morphologic classification may partially explain problems in grading MECs. We believe that HG MECs, as diagnosed over the last several decades, represent a blend of true MECs with unrelated clinicopathologic entities. To examine the historic aspects of this problem, and to identify neoplasms that most commonly mimic “high-grade” MEC, we reviewed 46 cases of alleged MEC diagnosed in our department from 1956 to 1974. The diagnosis of MEC was confirmed in 22 cases and was changed in 24 cases. Compared to cases of confirmed MEC, cases with changed diagnoses had higher incidence of lymph node metastases, perineural invasion, and shorter overall survival. Adenosquamous carcinoma, squamous cell carcinoma, and salivary duct carcinoma emerged as the most common mimics of HG MEC. The single most common diagnostic issue in these cases is the level of keratinization acceptable for MEC. Twenty cases of confirmed MEC were tested for CRTC1-MAML2 rearrangement and 5 low-grade MECs, 7 intermediate grade MECs, and 2 cases of HG MEC were translocation-positive.