Neoplasms of Unknown Primary Site

Abstract

OverviewCancer of unknown primary site (CUP) is a clinical syndrome accounting for 2–3% of all cancer diagnoses. This heterogeneous group is comprised of patients who have no anatomic primary site identified after a standard clinical evaluation. Complete pathologic evaluation is essential. Accurate prediction of the tissue of origin, based on examination of a biopsy from a metastatic lesion, is now possible in most patients using improved immunoperoxidase stains and molecular gene expression profiling. After completion of clinical and pathologic diagnostic evaluation, approximately 20% of patients with carcinoma of unknown primary site are included in favorable prognosis subsets and require specific treatment as detailed in this chapter. Until recently, the remaining 80% of patients have been treated with empiric combination chemotherapy. However, as therapy for various solid tumors improves and becomes more site specific, empiric chemotherapy is less likely to provide optimal treatment. Site‐specific therapy directed by the tissue of origin predicted by molecular profiling or immunoperoxidase staining is now appropriate for these patients. New data supporting the use of site‐specific therapy are reviewed.