Metastases of unknown origin: Principles of diagnosis and treatment

DEFINITION Cancer of unknown primary (CUP) origin refers to patients who present with histologically confirmed metastatic cancer in whom a detailed medical history, complete physical examination, including pelvic and rectal examination, full blood count and biochemistry, urinalysis and stool occult blood testing, histopathological review of biopsy speimens with the use of immunohistochemistry, chest radiography, computed tomography of the abdomen and pelvis, and in certain cases mammography, fail to identify the primary site. EPIDEMIOLOGY of CUP The cancer of unknown primary accounts for 3%-5% of all human cancers. DIAGNOSIS of CUP The standard diagnostic procedure for the majority of patients includes histopathologic review of biopsy specimens with the use of immunohistochemistry, full blood count, routine biochemistry, fecal occult blood testing, urine testing, chest radiography, and computed tomography of the abdomen and pelvis. The four common histologic diagnoses are: adenocarcinoma (70%), poorly differentiated carcinoma (20%), squamous carcinoma (10%), and poorly differentiated neoplasms (5%). PROGNOSIS of CUP The prognosis for most patients with unknown primary tumors is poor, with survival often less than 6 months from diagnosis. THERAPY of CUP Based on clinical and pathologic features, approximately 40% of patients can be categorized within subsets for which specific treatment has been defined. Empiric therapy is an option for the remaining 60% of patients. CONCLUSION Metastatic tumors of unknown origin have a unique clinical presentation due to a specific biology. Insight into the molecular biology of unknown primary tumors will be essential for the development of more effective treatments.