Learning Objectives After completing this course, the reader will be able to: Compare the diagnostic performances of 18F‐FDG PET/CT and conventional CT with respect to their ability to detect primary tumor sites in carcinoma of unknown primary patients with extracervical metastases. Describe the rate of identification of primary tumor sites using 18F‐FDG PET/CT and conventional CT. This article is available for continuing medical education credit at http://CME.TheOncologist.com Background. The aim of the present study was to evaluate prospectively the diagnostic value of 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) and conventional CT regarding the ability to detect the primary tumor site in patients with extracervical metastases from carcinoma of unknown primary (CUP) site. Patients and Methods. From January 2006 to December 2010, 136 newly diagnosed CUP patients with extracervical metastases underwent 18F‐FDG PET/CT. A standard of reference (SR) was established by a multidisciplinary team to ensure that the same set of criteria were used for classification of patients, that is, either as CUP patients or patients with a suggested primary tumor site. The independently obtained suggestions of primary tumor sites using PET/CT and CT were correlated with the SR to reach a consensus regarding true‐positive (TP), true‐negative, false‐negative, and false‐positive results. Results. SR identified a primary tumor site in 66 CUP patients (48.9%). PET/CT identified 38 TP primary tumor sites and CT identified 43 TP primary tumor sites. No statistically significant differences were observed between 18F‐FDG PET/CT and CT alone in regard to sensitivity, specificity, and accuracy. Conclusion. In the general CUP population with multiple extracervical metastases 18F‐FDG PET/CT does not represent a clear diagnostic advantage over CT alone regarding the ability to detect the primary tumor site.

BackgroundCancers of unknown primary (CUPs) constitute ~5% of all cancers. The tumors have an aggressive biological and clinical behavior. The aim of the present study has been to uncover whether CUPs exhibit distinct molecular features compared to metastases of known origin.MethodsEmploying genome wide transcriptome analysis, Linear Discriminant Analysis (LDA) and Quadratic Discriminant Analysis (QDA), we defined the putative origins of a large series of CUP and how closely related a particular CUP was to corresponding metastases of known origin. LDA predictions were subsequently used to define a universal CUP core set of differentially expressed genes, that by means of gene set enrichment analysis was exploited to depict molecular pathways characterizing CUP.ResultsThe analyses show that CUPs are distinct from metastases of known origin. CUPs exhibit inconsistent expression of conventional cancer biomarkers and QDA derived outlier scores show that CUPs are more distantly related to their primary tumor class than corresponding metastases of known origin. Gene set enrichment analysis showed that CUPs display increased expression of genes involved in DNA damage repair and mRNA signatures of chromosome instability (CIN), indicating that CUPs are chromosome unstable compared to metastases of known origin.ConclusionsCIN may account for the uncommon clinical presentation, chemoresistance and poor outcome in patients with CUP and warrant selective diagnostic strategies and treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1128-x) contains supplementary material, which is available to authorized users.

Background. Carcinoma of unknown primary (CUP) represents a heterogeneous group of metastatic malignancies for which no primary tumor site can be identified after extensive diagnostic workup. Failure to identify the primary site may negatively influence patient management. The aim of this review was to evaluate