Cervical lymph node metastases of squamous cell carcinoma from an unknown primary site: a favourable prognosis subset of patients with CUP.

Squamous cervical cancer of unknown primary site (SQCCUP) presents in patients as neck lymph nodes involved by squamous carcinoma in the absence of identifiable primary in the head, neck or lung. This CUP subset affects male patients previously exposed to alcohol and tobacco, though a proportion of cases may be related to chronic infection of the oropharynx by human papilloma virus. A standardised diagnostic work-up consisting of panendoscopy of the upper aerodigestive tract, CT of the chest/abdomen and histology supplemented by immunohistochemistry is warranted for the diagnosis. The scant available evidence on the molecular biology of the disease is reviewed. The cornerstones of management are excisional biopsy or surgical extirpation of the disease followed by bilateral neck external beam radiotherapy and chemotherapy. The necessity for complete surgical resection of involved neck nodes, irradiation of all head/neck mucosal sites and administration of concurrent chemotherapy is currently being debated. Aggressive multimodal therapy results in longterm disease control in 50-60% of patients, though data are mainly based on retrospective cohorts. Factors predicting for superior patient outcome are radical management with surgery or radiotherapy, low stage and volume of disease, absence of extracapsular spread and good performance status. Recently introduced molecular profiling platforms may provide biological classification to a primary tissue of origin as well as insights into the pathophysiology of this clinical entity.