HPV-positive cystic neck mass with no visible primary
A 56-year-old man presents with a 3 cm painless right level II neck mass that has grown over 3 months. He has a 30 pack-year smoking history but quit 5 years ago. He has no sore throat, hoarseness, dysphagia, or weight loss. Flexible nasendoscopy shows no mucosal lesion; tonsils are symmetric and small. Fine-needle aspiration of the mass shows squamous cell carcinoma, p16-positive. Contrast CT of the neck shows a 3.2 cm cystic right level II node with no other suspicious nodes; PET-CT shows FDG avidity only in that node. He asks whether he needs 'the full neck dissection and radiation' and whether the tonsils should be removed. He is worried about swallowing and voice outcomes because he is a high school teacher.
1. What is the appropriate diagnostic and staging workup to identify the primary, and why is PET-CT alone insufficient?
Read the worked answer
A p16-positive cystic level II neck node in a 56-year-old smoker is highly suspicious for an oropharyngeal squamous cell carcinoma, most often tonsillar or base of tongue. PET-CT can miss small mucosal primaries, especially when the primary is buried in lymphoid tissue or is cystic; it also cannot distinguish HPV-related lymphoid tissue from normal. Therefore, the next step is examination under anaesthesia with panendoscopy, directed biopsies of the nasopharynx, base of tongue, and hypopharynx, and bilateral tonsillectomy (or at least ipsilateral tonsillectomy if the contralateral tonsil is normal). Bilateral tonsillectomy increases the detection rate of occult tonsillar primaries. If no primary is found, random biopsies of the base of tongue and nasopharynx are taken. The neck node should be re-biopsied or excised if FNA is inconclusive, but here FNA is diagnostic. HPV testing is already positive. I would also check EBV (for nasopharyngeal carcinoma) and HIV risk factors. Staging includes PET-CT (already done) and MRI of the neck for soft tissue detail. The goal is to find the primary so that treatment can be targeted and de-escalated.
2. Assuming no primary is found after panendoscopy and bilateral tonsillectomy, what are the treatment options, and how do you weigh them for a patient concerned about function?
Read the worked answer
If no primary is identified, this is an HPV-positive unknown primary of the head and neck. Treatment options are (1) primary radiotherapy to the bilateral neck and potential mucosal sites (whole pharynx) with concurrent cisplatin, or (2) neck dissection followed by adjuvant radiotherapy based on pathology, or (3) transoral robotic surgery (TORS) with ipsilateral neck dissection and adjuvant therapy, although TORS cannot target an unknown primary. The patient is a high school teacher concerned about voice and swallowing, so I would favour a de-escalation approach if eligible. However, his 30 pack-year smoking history lowers the favourable risk profile and may exclude him from some de-escalation trials. I would discuss that radiation to the bilateral neck and pharynx causes xerostomia and dysphagia, while surgery may spare some radiation but carries risks of nerve injury and shoulder dysfunction. I would recommend multidisciplinary tumour board review and shared decision-making, including the option of enrolling in a clinical trial. If he chooses radiation, I would use intensity-modulated radiotherapy and consider sparing the contralateral parotid. If he chooses surgery, I would perform a comprehensive neck dissection and use pathology to guide adjuvant therapy.