Unknown Primary

Abstract

Ten percent to 15% of all cancer patients present with metastatic disease, of initially unknown origin. In one‐third, a primary site cannot be identified, which is called metastatic cancer of unknown primary ( CUP ). CUPs may present in solid organs, for example, liver, or in lymph nodes or serous cavities. CUP generally has a poor prognosis but there are so‐called “favourable” subsets of patients whose tumours are sensitive to therapy. To predict the patient's outcome and provide optimal treatment, it is therefore important to identify the type and subtype of the metastatic cancer, and, depending on the cancer type, to identify or predict its most likely site of origin. This can be achieved through clinical assessment, because different cancers tend to metastasize in characteristic patterns, and through investigations including radiology, serum tumour markers, and pathology. For the latter, microscopic examination of a biopsy of the metastasis itself enables tumour typing through morphology and immunohistochemistry. Lymphoma, melanoma, and sarcoma are first considered and excluded, because the diagnosis of CUP is usually limited to carcinomas; 90% of CUPs are adenocarcinomas, from lung, pancreas, stomach, colon, ovary, breast, prostate, and so on. Adenocarcinomas from different primary sites are sensitive to different chemotherapeutic agents and so it is important to identify or predict the site of origin and this can now be achieved through immunohistochemical profiling. The diagnostic and therapeutic nihilism of the past in CUP patients is thus disappearing; continued improvement in their outcome depends ultimately on the development of novel therapies.

Pulmonary metastases of the A549-derived lung adenocarcinoma tumors growing in nude mice. A multiple case study.

“…2 and Fig. 3C, red triangles), characteristic for well differentiated adenocarcinoma (Oien et al, 2007), and the areas of signet-ring morphology of trans-differentiated adenocarcinoma (Fig. 2, black triangles), were observed.…”

“…Lung cancer is a leading cause of malignancy-related death worldwide (Goto et al, 2002;Oien et al, 2007;Wei et al, 2011). Development of this malignancy is correlated with, for example, exposure of the pulmonary tissue to carcinogens such as nitrosoamines and peroxides, mainly found in tobacco smoke or air pollution (Coussens and Werb, 2002;Wei et al, 2011).…”