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. This heterogeneity has made the design and interpretation of clinical studies difficult. (See "Overview of the classification and management of cancers of unknown primary site".)
Adenocarcinomas of unknown primary site comprise approximately 70 percent of CUPs. In these patients, the focus is on identifying specific subsets in which disease-oriented therapy may be more effective than empiric therapy; this is based upon a combination of clinical features, immunohistochemistry (IHC), and molecular tumor profiling.
The diagnosis and management of patients with adenocarcinoma of unknown primary are reviewed here. The diagnosis and management of the other CUPs are discussed separately. (See "Overview of the classification and management of cancers of unknown primary site".)
The incidence of adenocarcinoma of unknown primary site increases with age. The clinical presentation is determined by the sites of metastatic tumor involvement, which are frequently multiple and often include the liver, lungs, lymph nodes, and bones.
In autopsy series, the most frequently identified primary sites are lung, pancreas, hepatobiliary tree, and kidney, together accounting for approximately two-thirds of cases . However, tumors may arise from a wide variety of other primary sites. Adenocarcinomas of the breast and prostate are identified infrequently at autopsy, despite being the most common cancers in women and men, respectively. In 20 to 30 percent of patients, no primary site can be identified.