The diagnostic challenges of patients with carcinoma of unknown primary.

CUP classifiers were expected to gradually replace the classical multistep approach in identifying the culprit tumors to guide site-specific therapy. Immunohistochemistry staining led to the prediction of a single tissue of origin in 10.8-51%. CUP classifiers identified the primary site in 61-89% of these cases and were concordant with immunohistochemistry in 57.1-100%. Immunohistochemistry is cheap, fast and broadly available whereas CUP classifiers are less widely available and have not been validated in randomized control trials. The diagnostic recommendations consist of a standard pathology evaluation based on morphology and algorithmic immunohistochemistry assessment. Physicians should weigh in the input of the CUP classifier to the clinical picture and pathology investigations before performing additional investigations.