1) Hematology, 2) Research Center for Functional Genomics and Translational Medicine, 4) Surgery, 7) Radiotherapy/Oncology, 9) Genetics, and 10) Animal Facility; Iuliu Hatieganu University of Medicine and Pharmacy;
3) Hematology, 6) Surgery, 8) Radiotherapy and 11) Chemotherapy, Ion Chiricuta Oncology Institute;
5) Department of Surgery, Octavian Fodor Regional Institute of Gastroenterology and Hepatology,
Cluj Napoca, Romania.
Almost one in every three patients with advanced tumors have distant metastasis at the time of clinical diagnosis. In most cases, the primary tumor site is identified immediately, within a few days. But for some patients, the primary lesion cannot be found after the initial clinical assessment. These cases are called cancers of unknown primary origin (CUPs), a clinical diagnosis very difficult to manage by physicians due to the absence of a standard-of-care for the initial therapeutic regimen, as well as due to the impossibility to include these cases in randomized clinical trials. A cancer of unknown primary site is often associated with a poor prognosis as patients are usually treated with a non-selective empirical therapy. In the current paper, we summarize both the diagnostic challenges for patients with a cancer of unknown primary site as well as the current available therapeutic options, with emphasis on the management of this unique disease entity. Key words: cancers of unknown primary site – differential diagnosis – clinical management.
Abbreviations: AFP: α-fetoprotein; AR: androgen receptor; Bcl 2: B-cell chronic lymphocytic leukemia/lymphoma 2; BM: basement membrane; HPV: human papilloma virus; CD: cluster of differentiation; CEA: carcinoembryonic antigen; CK: cytokeratin; CTC: circulating tumor cell; DTC: disseminated tumor cell; FISH: fluorescence in situ hybridization; GI: gastrointestinal; IHC: immunohistochemistry; MPO: myeloperoxidase; MSA: muscle-specific actin; OCT4: octamer-binding transcription factor 4; p504S: α-methylacyl-CoA racemase; PS: performance status; PSA: prostate-specific antigen; S100P: placental S100 protein; WT1: Wilms tumor 1.