Clinical, Pathological, and Genomic profiles of Salivary Warthin tumor-like Mucoepidermoid Carcinoma

Abstract

Abstract Introduction/Objective Warthin tumor-like mucoepidermoid carcinoma(WTL- MEC) is one of the subvariant of mucoepidermoid carcinoma. It mimics the histological features of metaplastic Warthin tumors (mWTs). To investigate the clinicopathological, molecular features, and bio-behaviors of WTL-MEC, we retrospected a cohort of 29 WTL- MEC patients. Methods/Case Report The clinicopathological and microscopic data were collected. Dual-color FISH analysis was performed on paraffin-embedded sections of 29 WTL- MEC patients and 16 mWTs patients using a MAML2 break- apart probe. Whole-exome sequencing and whole transcription sequencing were performed on 3 WTL-MEC and 3 typical mucoepidermoid carcinomas (TMEC) patients. Genetic data were bioinformatically analyzed by software MuTect (v1.7), PINDEL (v0.2.5), SnpEff (v3.0), and etc. Results (if a Case Study enter NA) The cohort of WTL-MEC included 10 male and 19 female patients with a median age of 42.3 years (range, 8 to 68 years). Microscopically, the WTL-MEC lesion consisted of multi-cysts with variant shapes and sizes. The cystic spaces were lined by bi-layered and multilayered oncocytic cells. A transition zone between the bi-layered oncocytic epithelium to the multilayered oncocytic epithelium was observed in WTL-MEC. The cords of epidermoid cells and mucous cells could be found. The germinal center, extensive hyalinization, and mucus extravasation were observed. MAML2 rearrangement was identified in 29 (100%) WTL-MEC. No rearrangement was observed in mWTs by FISH. MET was the most commonly mutated gene in TMEC, and PRDM11 was the most commonly mutated gene in WTL-MEC. Twenty-nine patients were alive without recurrent at the end of the follow-up periods(5–128M). One Patient died due to the metastasis to the lung. Conclusion compared with mWTs, WTL- MEC usually presented in the young, non-smoking female. The histological feature of WTL-MEC depended mainly on the transition zone of the bi-layered oncocytic epithelium and the multilayered oncocytic epithelium. And MAML2 status can confirm the diagnosis. CRTC1-MAML2 and PRDM11 mutations appear to be the main driver event of WTL-MEC. Prognosis was usually favorable, but recurrence or metastasis may rarely occur.