[Carcinoma of unknown primary site (CUP syndrome)]

Despite the growing array of sophisticated diagnostic tools for establishing a diagnosis of human neoplasia, 2-6% of all cancer patients still present metastatic cancer of which detailed investigations fail to identify the primary anatomic site. The site is found in less than 25% of patients before death and frequently goes undiscovered at post-mortem examination. At the time of first diagnosis with carcinoma of unknown primary site, usually more than 80% of patients present with dissemination. Prognosis depends on the site(s) involved and is unaffected by whether the primary site is ever found. Node dissection may be curative for patients with metastases to peripheral lymph nodes. Objective long-term response is possible in combination with chemotherapy in patients with small-cell malignancies, peritoneal carcinomatosis (in women), or poorly differentiated carcinomas involving external lymph nodes, mediastinum, or retroperitoneum but without metastases to viscera or bone. Toxic therapies are recommended only for palliation of symptoms and maintaining quality of life support in patients with good functional status. Patients should be encouraged to participate in clinical trials for novel therapies.