Cancer of unknown primary site (CUP) is a relatively common clinical entity, accounting for 4 to 5 percent of all invasive cancers . Within this category, tumors from many primary sites with varying biology are represented. Squamous cell carcinomas (SCCs) comprise approximately 5 percent of CUPs. (See "Overview of the classification and management of cancers of unknown primary site".)
Effective treatment is available for some patients with SCC of unknown primary site who fit certain clinical syndromes, particularly those with involvement of the cervical or inguinal lymph nodes. For this reason, appropriate evaluation of these patients is essential prior to embarking on treatment.
●Cervical lymph nodes are the most common metastatic site for SCCs. Patients with tumor involving upper or mid level cervical nodes are likely to have a primary cancer of the head and neck. In contrast, a lung primary should be suspected in those with lower cervical lymph nodes.
●SCCs of unknown primary site involving inguinal lymph nodes usually arise from a primary anogenital malignancy. Some of these patients may be curable with locoregional therapy directed against their primary tumor.
The diagnosis and management of patients with SCC of unknown primary site other than those presumed to be of head and neck origin is reviewed here. The evaluation and treatment of head and neck squamous carcinoma of unknown primary is discussed separately. (See "Head and neck squamous cell carcinoma of unknown primary".)