Is the Approach to Patients with Unknown Primary Tumor any Different in 2018?

Abstract

Cancer of unknown primary site (CUP) is defined as the presence of cervical lymph node metastasis with no conclusive evidence of a primary tumor despite full clinical work-up. Squamous cell carcinoma is the most frequent histology, accounting for 53–77% of CUP to neck nodes. However, less frequent histologic types are present in a non-negligible number of patients (e.g., adenocarcinoma, melanoma, papillary thyroid cancer). In recent years, human papillomavirus (HPV)-infection is playing a progressively stronger role in the pathogenesis of this disease. To date, 36% of CUPs are positive for both p16 and HPV-DNA. Office-based endoscopic evaluation of the upper aerodigestive tract plays an essential role as the initial clinical evaluation. Ideally, this should be performed using high-definition endoscopes and biologic endoscopy techniques such as the Narrow Band Imaging. Radiologic assessment should comprise both cross-sectional (MRI, CT scan) and metabolic (PET) imaging techniques. When all examinations are negative, the patient should undergo an endoscopic examination under anesthesia, that can be accompanied by bilateral tonsillectomy and (in selected cases) base of tongue mucosectomy. Therapeutic approach may be composed by a combination of surgical and non-surgical treatments. Neck dissection and radiotherapy/chemo-radiotherapy showed similar results as first-line procedures. However, there is still no adequate data to obtain clear indications on this matter. Prognostic outcomes are generally favorable and HPV-related tumors demonstrated significantly better results.