P16-positive cystic squamous cell carcinoma in midline neck: metastasis from oropharynx or primary carcinoma arising from thyroglossal duct cyst?

Cystic squamous cell carcinoma (SCC) of the lateral neck is considered metastatic human papilloma-virus (HPV)-related oropharyngeal SCC (HPV-OPSCC) until proven otherwise. P16 immunohistochemistry is diffusely positive in those carcinomas and is used as a surrogate marker of active human papillomavirus (HPV) infection. Thyroglossal duct cysts (TDC) are one of the differential diagnoses for cystic neck lesions. SCC arising from TDC is extremely rare. In this study, we report a p16-positive cystic SCC located in the midline neck. Radiologic features and the presence of thyroid tissue in the cyst wall indicated that it was a TDC. The morphologic features of the lesion raised the question: is the carcinoma metastatic HPV-OPSCC? The HPV confirmative test, high-risk HPV RNA in situ hybridization, was negative. We then studied p16 immunohistochemistry in the squamous epithelium of benign TDC and found that rare benign TDC can show diffuse and strong p16 positivity.