INTRODUCTION
‘The most important first step is to discuss the biopsy with an experienced pathologist. The pathologist may have an idea where the primary site might be, but because of lack of clinical information, has left the diagnosis open.’ [1]
Most cancer patients come to clinical attention with their primary tumour. However, around 10–15% of cancer patients present with distant metastases, and in a proportion of these, the primary site cannot be identified at the time of treatment. Metastatic cancer of unknown primary site (CUP) is a common clinical problem, representing one of the ten most frequent cancer diagnoses [2]. Its prognosis is poor: the median survival time is only four months [3].
Investigation of CUP patients is aimed at diagnosing the cancer type and likely primary site, in order to identify the known tumour subsets that may respond to treatment. Most CUPs are adenocarcinomas, for which the most commonly identified primary sites are the lung and pancreas. Nevertheless, the origin remains undiagnosed in most patients, even with modern imaging, and eventually at autopsy.
Pathological assessment is an important part of the clinical work-up of such patients. Biopsy is performed to confirm malignancy, to type the tumour, and thus identify the highly chemosensitive tumours, and, increasingly, where the tumour is an adenocarcinoma, to predict the likely primary site in order to provide prognostic information and guide therapy, as well as to inform the patient.