The Who and When of Molecular Testing for Tumors of Unknown Primaries: One Resident’s Perspective

Abstract

To the Editor It was with great interest that I read the article by Dumur and colleagues1 on their clinical verification of the only US Food and Drug Administration–approved microarray-based test for the diagnosis of poorly and undifferentiated tumors, the Pathwork Tissue of Origin (TOO) Test (Pathwork Diagnostics, Sunnyvale, CA). Briefly, the Pathwork TOO Test is one of several tests currently on the market (CancerTYPE ID, Biotheranostics, San Diego, CA, and miRview mets, Rosetta Genomics, Rehovot, Israel, being others) that attempt to correlate the RNA profile of a given undifferentiated tumor with its suspected tissue of origin (hence, the clever names) through complementary DNA microarray analysis and predetermined algorithms. Based on the findings in the study by Dumur et al,1 the Pathwork TOO test seems to perform glowingly, with a reported 97% concordance rate between the TOO result and final diagnosis, when immunohistochemical and radiologic studies are included. Yet, while most of the available data for these assays are and have been promising with regard to their ability to retrospectively correlate diagnoses with standard analytic methods, several important questions remain, including “When is it appropriate to use one of these tests?” and “Who decides when these tests should be ordered?” As these tests are relatively new to the market and the field of pathology in general, some basic questions are, of course, warranted, especially because they are rather costly, and, as yet, there have been no published prospective studies comparing ultimate outcomes of cases diagnosed with these new techniques vs cases undergoing standard immunohistochemical workups. A recent case seen in our group raises some of these questions and provides a real-life example of when requests for these assays could be made. The patient was a 69-year-old man who had an abdominal computed tomography (CT) scan following a 1-month …