CUP syndrome-diagnostics from the perspective of pathology

Abstract

Histologic and immunohistologic workup of tumor material from metastases of apreviously unknown primary tumor is important for identifying their origin, but is often insufficient for this purpose without clinical oncologic and radiologic evaluation. In the initial cancer of unknown primary (CUP) situation, histologic and immunohistochemical workup together with clinicoradiologic correlations contribute significantly to the identification of the primary tumor. There are now accepted guidelines to follow when there is an initial CUP situation. Molecular diagnostic tools can be used to investigate changes at the nucleic acid level, which can provide clues about the primary tumor, including potential targets for therapy. If, despite broad and interdisciplinary diagnostics, it is not possible to identify the primary tumor, the diagnosis is CUP syndrome. If atrue CUP situation is present, it is important to assign the tumor to atumor class or aspecific therapy-sensitive subgroup as best as possible so that the best possible treatment can be given. However, for afinal assignment to aprimary tumor or afinal classification as CUP, acomparison with medical oncological and imaging findings is indispensable. When CUP is suspected, close interdisciplinary collaboration between pathology, medical oncology, and imaging is essential to achieve aviable classification as CUP or identification of apresumptive primary tumor, in the interest of providing the most specific and effective therapy for affected individuals.