Lymphoepithelial Carcinoma of Oral Cavity: A Systematic Review

Abstract

Introduction: Lymphoepithelial Carcinoma is a subtype of Oral Squamous Cell Carcinoma, morphologically similar to non-keratinizing Nasopharyngeal Carcinoma, un-differentiated subtype. Oral Lymphoepithelial Carcinoma is extremely rare and its characteristics differs from those at other sites of head and neck region. Awareness of the occurence of this lesion in oral cavity is important to promote differentiation from other oral neoplasms. Objectives: To explore the demographics, clinical and histopathological features, differential diagnosis, treatment and patient outcomes in Lymphoepithelial Carcinoma of oral cavity. Methods: Case reports and case series of Lymphoepithelial Carcinoma of Oral cavity were searched from the year 2002- 2024 by a systematic search of scientific databases, including PubMed Central (National Library of Medicine), Google Scholar (Google, Mountain View, USA), COCHRANE CENTRAL. Results: Total of 14 Case reports and 2 Case series that is 16 articles which were satisfying our inclusion-exclusion criteria were considered in the review. The mean age of the study participants across the studies were 50.23 in the middle-aged population with most common affected site was tongue and oral mucosa of the posterior teeth. Histopathological features showing nests and cohesive sheets of undifferentiated carcinoma mixed with a lymphoid stroma. IHC for cytokeratin AE1/AE3, p40, and p53 are positive. Conclusion: Oral lymphoepithelial-like carcinoma (LELC) is a rare variant of head and neck squamous cell carcinoma, histologically resembling nasopharyngeal carcinoma (NPC). While NPC is strongly associated with Epstein-Barr Virus (EBV), oral LELC typically lacks EBV involvement. Some oropharyngeal cases may be linked to high-risk HPV, highlighting the need for p16 and HPV testing.