Cancer of Unknown Primary Site

This review summarizes how sophisticated imaging, immunohistochemical testing, and molecular-profiling tools are changing the approach to cancer of unknown primary site. Increasingly, treatment decisions are personalized on the basis of the mutational status of a patient's tumor. Cancer of unknown primary site is a heterogeneous group of cancers for which the anatomical site of origin remains occult after detailed investigations. 1 , 2 The emergence of sophisticated imaging, immunohistochemical testing, and molecular-profiling tools has influenced our approach to unknown primary cancer, although it has also increased the ambiguity of designations for this disorder. In the era of tailored therapeutic strategies, this situation presents both an opportunity and a challenge. The past four decades have seen a shift in our understanding of unknown primary cancer (Figure 1). First, improved imaging techniques increased our confidence in the classification of some cancers . . .