Clinicopathological Analysis of Salivary Glands Warthin-like Mucoepidermoid Carcinoma: A Systematic Review.

PURPOSE

This systematic review summarizes the current literature on Warthin-like mucoepidermoid carcinoma (WL-MEC), highlighting its clinicopathological, immunohistochemical and molecular characteristics.

METHODS

This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered by PROSPERO (protocol CRD42024523598). Case reports and case series published in English on WL-MEC of major and minor salivary glands were included. The search was conducted in MEDLINE/PubMed, Scopus, Web of Science, and Embase databases in November 2024, along with a search in grey literature. Twenty-one articles met the eligibility criteria. The extracted information included clinicopathological data, immunohistochemical and molecular tests, treatment, recurrence, metastasis, follow-up, and status. The data analysis was performed descriptively, and presented as absolute and relative frequencies, and means or median for numerical variables.

RESULTS

78 WL-MEC cases were analyzed, with a female predominance observed and a wide age range, peaking in the sixth decade of life. Most cases involved the parotid gland and presented as indolent nodular masses, often asymptomatic. Histologically, the majority were low-grade tumors, with multicystic growth patterns and a lymphocytic infiltrate. Immunohistochemical analysis revealed consistent expression of p63, p40, CK5/6, and exhibited low Ki67 proliferation index (< 5%). MAML2 rearrangement was identified in all molecularly analyzed cases (n = 72/ 100%). Surgical treatment was the most common approach, which typically resulted in low recurrence rates, no distant metastasis, and favorable overall outcomes.

CONCLUSION

WL-MEC cases typically present as indolent, asymptomatic nodules in the parotid gland, often with a female predominance and a wide age range, peaking in the sixth decade of life. Surgery is the primary treatment and is associated with a favorable prognosis, characterized by low rates of recurrence and metastasis. These tumors commonly exhibit low-grade histopathological features, a multicystic pattern, and lymphocytic inflammatory infiltrate. The detection of MAML2 rearrangement, typically via FISH, is an essential diagnostic tool, emphasizing the molecular similarities between WL-MEC and conventional MEC.