p16INK4A immunohistochemical staining may be helpful in distinguishing branchial cleft cysts from cystic squamous cell carcinomas originating in the oropharynx

• Published in: Cancer 2009-04, Vol.117 (2), p.108-119
• Main Authors: Pai, Reetesh K., Erickson, Julianna, Pourmand, Nader, Kong, Christina S.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Dermatology; fine‐needle aspiration; head and neck squamous cell carcinoma; human papillomavirus; Medical sciences; oropharynx; p16INK4A; Tumors; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 1934-662X; 0008-543X; 1934-6638; 1097-0142
• DOI: 10.1002/cncy.20001

BACKGROUND: We investigated p16INK4A expression in branchial cleft cysts and its utility in distinguishing branchial cleft cysts from metastatic head and neck squamous cell carcinomas (SCCs) in fine‐needle aspiration biopsies (FNABs). METHODS: A study set comprising 41 resections (15 SCC and 26 branchial cleft cysts) and a test set of 15 FNABs (11 SCC and 4 branchial cleft cysts) were analyzed with p16INK4A immunohistochemistry and human papillomavirus (HPV) polymerase chain reaction (PCR)/pyrosequencing. Cases with discrepant p16INK4A and PCR/pyrosequencing results were further evaluated with HPV in situ hybridization (ISH). SCCs were divided into keratinizing SCC and nonkeratinizing SCC groups and site of origin. RESULTS: Metastatic oropharyngeal nonkeratinizing SCC in the study set exhibited diffuse, strong p16INK4A (7 of 7) and HPV16 DNA positivity (6 of 6), while keratinizing SCC from the larynx and oral cavity was negative for p16INK4A. p16INK4A reactivity in the branchial cleft cyst study set was characterized by focal, strong staining (6 of 21) involving the superficial squamous epithelium. HPV DNA was identified in 7 of 19 branchial cleft cyst study set cases by PCR/pyrosequencing, but these cases were negative by HPV ISH. In the test set, oropharyngeal nonkeratinizing SCC exhibited diffuse, strong p16INK4A (3 of 3) and HPV16 DNA (2 of 2), while metastatic keratinizing SCC was negative for p16INK4A and HPV DNA. All 4 FNABs of branchial cleft cysts were negative for p16INK4A. Diffuse, strong p16INK4A correlated with oropharyngeal origin (P = .001) and nonkeratinizing morphology (P = .0001). CONCLUSIONS: Branchial cleft cysts can exhibit focal strong reactivity limited to the superficial squamous epithelium and glandular epithelium. Although p16INK4A immunohistochemistry may be helpful in distinguishing oropharyngeal nonkeratinizing SCC from branchial cleft cysts in FNAB specimens, it is not helpful in cases of keratinizing SCC because these cases are typically negative for p16INK4A. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society. p16INK4A immunohistochemistry may be helpful in localizing tumor origin of metastatic head and neck squamous cell carcinoma to the oropharynx, but it is not useful in differentiating between keratinizing squamous cell carcinoma and branchial cleft cysts.