Expression of p16 in benign and malignant cystic squamous lesions of the neck

SummaryMetastatic cystic squamous cell carcinomas of the neck often harbor human papillomavirus 16 and, in turn, overexpress p16. P16 immunohistochemistry could be useful in the evaluation of patients who present with cystic squamous lesions of the neck, particularly when the distinction between a benign lymphoepithelial cyst and a metastatic squamous cell carcinoma cannot be easily resolved on clinical or pathologic grounds. Implementation of this strategy, however, awaits a description of p16 expression in benign lymphoepithelial cysts. The purpose of this study was to evaluate p16 staining in cystic squamous lesions of the neck with an emphasis on benign lymphoepithelial cysts. P16 immunohistochemistry was performed on tissue sections and fine needle aspirates of benign (n = 49) and malignant (n = 16) squamous lesions of the neck. P16-positive cases were further evaluated by human papillomavirus 16 in situ hybridization. P16 staining was seen in the tissue sections of 16 of 37 (43%) benign lymphoepithelial cysts. P16 staining tended to localize to regions of the squamous epithelium penetrated by interdigitating lymphocytes. In the aspirates, p16 staining was noted in 5 of 12 (42%) benign lymphoepithelial cysts and in 3 of 16 (19%) cystic squamous cell carcinomas. Human papillomavirus 16 was detected in the 3 p16-positive cystic squamous cell carcinomas but in none of the p16-positive benign lymphoepithelial cysts. P16 overexpression is not always linked to high-risk human papillomavirus integration, but may be intrinsic to the reticulated epithelium that lines benign lymphoepithelial cysts. This observation limits the role of p16 staining as a surrogate marker of human papillomavirus 16 infection and as a diagnostic tool in separating benign from malignant cystic squamous lesions of the neck.