Imaging–Endoscopy Discordance in Occult Tonsillar Tumors: Diagnostic Challenges of Submucosal Mucoepidermoid Carcinoma—A Case Report and Literature Review

Background and Clinical Significance: Cervical lymphadenopathy with an occult primary tumor represents a common yet diagnostically challenging clinical scenario in head and neck oncology. While endoscopic evaluation is typically relied upon for tumor localization, submucosal lesions may remain undetected. Case Presentation: We report a 41-year-old woman presenting with an isolated right level II neck mass without constitutional symptoms. Initial fiberscopic examination revealed no mucosal abnormalities; however, contrast-enhanced computed tomography demonstrated asymmetric enlargement of the right palatine tonsil with effacement of the adjacent parapharyngeal fat plane, alongside multiple enlarged cervical lymph nodes. Subsequent positron emission tomography supported focal metabolic activity in the tonsillar region. Histopathological examination confirmed a low-grade mucoepidermoid carcinoma arising from the minor salivary glands of the palatine tonsil. Immunohistochemistry showed strong p16 positivity (70%), while MAML2 rearrangement was not detected. Conclusions: This case highlights a critical pitfall where imaging–endoscopy discordance signals a submucosal malignancy. Furthermore, strong p16 expression should be interpreted in conjunction with tumor morphology and clinical context, as p16 positivity is not entirely specific for HPV-related squamous cell carcinoma. Through integration of the current case with a focused literature review, we propose a structured diagnostic framework emphasizing imaging prioritization and morphology-based interpretation to improve recognition of occult submucosal tonsillar malignancies.