A 48-year-old man presents to his primary care physician with a sensation of fullness on the left side of his neck that he first noticed six weeks ago. He denies fever, night sweats, weight loss, or difficulty swallowing. Past medical history is negative. He is a non-smoker and drinks one glass of wine on weekends. Vital signs are within normal limits. On physical examination, a 2.5-cm, firm, non-tender, mobile lymph node is palpable in the left level II cervical chain. Oropharyngeal examination reveals slightly enlarged but symmetric palatine tonsils without visible mucosal lesions. Fine-needle aspiration (FNA) of the neck mass is performed, and pathology reveals metastatic squamous cell carcinoma. Immunohistochemical staining is positive for p16.
Which of the following is the most likely primary site of this patient's malignancy?
The correct answer is:
D) Palatine tonsil
This patient presents with a classic case of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). The presence of p16-positivity on immunohistochemistry is a highly sensitive and specific surrogate marker for high-risk human papillomavirus, primarily HPV-16. HPV-related cancers have a strong predilection for the lymphoid-rich tissues of the oropharynx, specifically the palatine tonsils and the lingual tonsils at the base of the tongue. Unlike traditional tobacco-related head and neck cancers, HPV-positive tumors often present in younger patients without traditional risk factors and frequently manifest as a cystic or firm neck mass with a very small, sometimes occult, primary tumor.
Answer choice A: Anterior two-thirds of the tongue, is incorrect. This is part of the oral cavity, and cancers of the oral cavity are more strongly associated with tobacco and alcohol use and are typically p16-negative.
Answer choice B: Glottic larynx, is incorrect. Laryngeal cancers are almost exclusively associated with smoking and present early with hoarseness. They are rarely associated with HPV.
Answer choice C: Nasopharynx, is incorrect. Nasopharyngeal carcinoma is strongly associated with the Epstein-Barr virus (EBV), not HPV. It typically presents with a neck mass, nasal obstruction, or epistaxis, and is more common in patients of East Asian or North African descent.
Answer choice E: Parotid gland, is incorrect. The most common malignancy of the parotid gland is mucoepidermoid carcinoma. While the parotid can be a site for metastatic skin cancer, it is not a primary site for p16-positive squamous cell carcinoma.
Key Learning Point
p16-positive squamous cell carcinoma in a cervical lymph node is hallmark for HPV-related oropharyngeal cancer. The most common primary sites are the palatine tonsils and the base of tongue. These patients have a significantly better prognosis and higher response to radiotherapy compared to p16-negative (tobacco-related) patients.
