[Unknown primary cancer]

Unknown primary cancers (UPCs) are heterogeneous group of tumors with widely varying clinical features. Majority of patients with UPC do not respond to systemic therapy and show an unfavorable median survival duration. However, some subgroups are responsive to treatment. The definition of these subgroups is based on the organ sites involved at the time of presentation and/or on the histologic findings. These subgroups include patients with squamous cell carcinoma involving the high- or mid-cervical lymph node, female patients with adenocarcinoma involving the axillary lymph nodes, selected female patients with peritoneal carcinomatosis, patients with histology of poorly differentiated or undifferentiated carcinomas, and patients with poorly differentiated neuroendocrine carcinomas. Identification of these specific patients who may have clinical and pathological features of highly treatable unknown primary carcinoma is required. However, for most responsive UPCs, the tumor origin, biology and precise lineage are not yet fully clarified. On the other hand, a large group of patients with insensitive tumor remains. Research into the molecular characterization of UPC cells will improve our understanding of metastases from UPC and will resolve eventually this important clinical problem.