The Neck Lump with a Normal Panendoscopy

This is a carcinoma of unknown primary in the head and neck, presenting as a cystic level II squamous cell carcinoma node. In a patient with this smoking and alcohol history, the most likely occult primary is in the oropharynx (palatine tonsil or base of tongue), and the cystic nature of the node strongly suggests HPV-related oropharyngeal squamous cell carcinoma - cystic level II nodes are a recognised presentation of HPV+ disease.

Next step: PET-CT as the first-line investigation for an occult primary, combined with bilateral tonsillectomy and base-of-tongue biopsies (panendoscopy with directed biopsies). If PET-CT is negative, these directed biopsies are mandatory; they identify the primary in a substantial proportion of cases.

Why not simply excise the node:

• Excision of a metastatic node without addressing the primary risks spillage and extranodal spread, and compromises later neck dissection planes.
• It does not treat the primary, which may be small and curable with radiotherapy or surgery.
• It removes tissue needed for staging and for HPV/p16 testing, which determines prognosis and treatment.
• The diagnosis and staging must be complete before any definitive surgery, as treatment is planned by a multidisciplinary team.

With a confirmed squamous metastasis and no identified primary after PET-CT and tonsil/base-of-tongue biopsies, this is a true carcinoma of unknown primary. Management is by MDT and depends on nodal stage and resectability.

Neck management:

• Neck dissection (modified radical, levels I-V or selective II-IV depending on staging) followed by adjuvant radiotherapy to the neck and at-risk mucosal sites (bilateral neck and potential primary sites), or
• Primary chemoradiotherapy to the neck and mucosa, reserving surgery for salvage.

Either is acceptable; the choice depends on nodal burden, extranodal extension and patient preference. Bilateral neck treatment is usually advised because the primary site is unknown and may be midline.

HPV/p16 status:

• A p16-positive cystic level II node in a non-smoker or light smoker is very likely HPV-related oropharyngeal cancer even when the primary is not found; prognosis is substantially better, and treatment de-escalation trials are relevant.
• p16-negative disease in a heavy smoker carries a worse prognosis and a higher likelihood of a missed conventional primary; mucosal irradiation fields should be more generous.

I would test the nodal tissue for p16 and HPV, as it changes prognosis, follow-up intensity and eligibility for de-escalated regimens.

I would explain that:

• In many patients the primary never becomes apparent, and treating the neck plus at-risk mucosa gives outcomes comparable to known-primary disease of the same nodal stage.
• Follow-up should be regular (typically 2-3 monthly in year 1, then less frequently) with clinical examination and flexible nasendoscopy at each visit, and cross-sectional imaging at intervals. He should be taught to report hoarseness, dysphagia, otalgia or new lumps.
• Prognosis is driven by nodal stage, extranodal extension and HPV status; p16-positive disease has a markedly better prognosis than p16-negative disease.
• Late effects of neck dissection (shoulder stiffness, numbness) and radiotherapy (xerostomia, dysphagia, dental problems) should be discussed, with dental assessment before radiotherapy.
• Smoking and alcohol cessation reduces the risk of a second primary and improves treatment tolerance; this should be addressed explicitly.

The key judgement is that a negative work-up does not mean no treatment - the neck disease is real and must be treated, and follow-up is aimed at detecting the primary if it declares itself.