Some patients are found to have evidence of metastatic disease at their initial presentation prior to diagnosis of a primary site. In many cases, a subsequent biopsy reveals adenocarcinoma but the primary site is not always clear.
In this situation, there is a temptation to investigate the patient endlessly in order to determine the original primary site. However, there is a compromise between exhaustive investigation and obtaining sufficient information to plan appropriate management. For all patients, histological examination of an accessible site of metastasis is required. The architecture of the tissue can assist the pathologist in determining the likely primary site, and therefore it is better to perform a biopsy rather than fine needle aspiration. The greater volume of tissue also permits the use of immunohistochemistry. Extensive imaging to search for the primary is rarely indicated; a careful history to identify symptoms and risk factors (including familial) will often permit a judicious choice of imaging.
Management of the patient will depend on that person’s circumstances, as well as on the site(s) involved and the likely primary sites. The overriding principle is to ensure that a curable diagnosis has not been overlooked. For example, lung metastases from a testicular teratoma do not preclude cure; nor do one or two liver metastases from a colorectal cancer. Early discussion with an oncologist within a multidisciplinary team is essential and avoids unnecessary investigation; for example, a single hCG-based pregnancy test in a young man with lung metastases might confirm the presence of a teratoma and allow rapid administration of potentially curative chemotherapy. Treatment should not necessarily wait for a definitive diagnosis; appropriate analgesia, radiotherapy and surgical palliation can all be helpful. Some patients remain free of cancer for some years after resection of a single metastasis of an adenocarcinoma of unknown primary, justifying this approach in selected patients.
In those with no obvious primary, systemic chemotherapy may achieve some reduction in tumour burden and alleviation of symptoms, but long-term survival is rare.
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