Management of Carcinoma of Unknown Primary in the Neck
For squamous cell carcinoma involving cervical lymph nodes with unknown primary, the recommended management approach is neck dissection and/or irradiation of bilateral neck and head-neck axis, with induction chemotherapy using platinum-based combinations or chemoradiation for advanced stages. 1
Diagnostic Workup
Initial Assessment
- Thorough physical examination (head and neck, rectal, pelvic, breast)
- Basic blood and biochemistry analyses
- Urinalysis and fecal occult blood test
- CT scan of thorax, abdomen, and pelvis 2
Specialized Head and Neck Evaluation
- Head and neck CT scan or preferably CT/PET scan 2
- Flexible endoscopy followed by panendoscopy with biopsies of the nasopharynx, hypopharynx, and oropharynx
- Bilateral tonsillectomy 2
- Endoscopic examination under anesthesia with directed biopsies 1
Pathological Assessment
- Immunohistochemistry to exclude chemosensitive tumors (lymphomas, germ-cell tumors)
- Testing for p16 expression and, if positive, HPV status
- Epstein-Barr virus (EBV) status determination
- PD-L1 expression analysis for relapsed disease or distant metastases 2
Treatment Approach Based on Nodal Status
Early Stage Disease (N1)
- Neck dissection followed by post-operative radiotherapy to bilateral neck and head-neck axis 1
Advanced Stage Disease (N2/N3)
- Options include:
- Neck dissection followed by post-operative chemoradiotherapy
- Induction chemotherapy with platinum-based combination followed by definitive chemoradiation
- Definitive concurrent chemoradiotherapy 1
Chemotherapy Regimens
- For concurrent chemoradiotherapy: Platinum-based regimens (cisplatin or carboplatin)
- For induction chemotherapy: Cisplatin with 5-fluorouracil 1
Prognostic Factors to Consider
- Performance status and lactate dehydrogenase (LDH) levels 2
- Extracapsular extension (ECE)
- N3 disease
- Multiple levels of positive lymph nodes
- Positive lymph nodes in the lower neck
- HPV status (HPV-positive patients have superior survival) 1
Treatment Outcomes
- Complete response rates to combined chemotherapy-radiotherapy approach can reach 81% 3
- Patients with N3 disease who received chemotherapy have shown higher complete response rates and longer survival compared to those treated with surgery and/or radiotherapy alone 3
- Overall 5-year survival rates range from 10-21%, with better outcomes when primary tumors are identified 4
Important Considerations
- Referral to specialized centers is strongly encouraged 2
- Response evaluation is recommended after two to three chemotherapy cycles 2
- The diagnostic and therapeutic approach should be expedited to avoid delays in treatment initiation 5
- Multimodality therapy tailored to the specific presentation offers the best chance for disease control 6
The management of carcinoma of unknown primary in the neck has evolved significantly with improved diagnostic capabilities and therapeutic approaches. A systematic diagnostic workup followed by stage-appropriate treatment offers the best chance for long-term disease control and survival.