„Cancer of unknown primary“ – histologische und molekularpathologische Grundlagen in der Diagnostik

Cancer of unknown primary (CUP) requires multimodal diagnostics that include all specialist disciplines involved. Given the challenging diagnosis, a high level of technical expertise is warranted for each case. Conceptually, the CUP diagnostics used today aim to confirm malignancy and to trace the tumor to the tissue of origin (identification of the “actual” tumor type) whenever possible. In order to achieve a high level of diagnostic specificity, this approach requires the integration of various diagnostic methods like imaging, morphologic and immunohistochemical assessment of the histologic specimen as well as molecular methods. Here, the molecular profile might provide hints towards a likely primary and is particularly helpful in patients with prior malignancies to clarify the clonal relationship of both cancers. Molecular analysis is also becoming increasingly important for the identification of predictive biomarkers and therapeutic target structures. This constellation influences the diagnostic workflow and requires the use of complementary procedures. Here, liquid biopsies are increasingly used in clinical practice. From a biological and clinical perspective, it is unclear whether the concept of tracing the neoplasm back to the tissue of origin and to tailor therapy accordingly makes sense for all tumors in the heterogenous CUP group or whether the focus should be on new concepts to improve the generally dismal prognosis in CUP.