Clinicopathologic correlations in gastrointestinal stromal tumors.

The study of a large series of gastrointestinal stromal tumors (GISTs) from Dr. Hasegawa and colleagues in Tokyo, published in this issue, is very timely in light of the series of overview papers and a consensus approach to GIST diagnosis that also appears in this issue. This large new study has the important benefits of being confined to cases diagnosed and treated at a single institution, and using CD117 (c-kit) immunopositivity as an essential diagnostic criterion, in line with recent recommendations. Owing to the relatively recent appreciation of the central role of KIT mutations and CD117 expression in GISTs, most of the previously published large series that focused on clinicopathologic correlation and outcome analyses did not use CD117 immunopositivity as a diagnostic requirement, and hence there has been at least some heterogeneity in the cases included. The study of Hasegawa et al confirms that even small lesions (5 cm) with a low mitotic rate may metastasize, and these authors have concluded independently that it is best to use risk assessment in predicting GIST behavior, as promulgated by Franquemont 1 and in the recent consensus document, rather than seeking to draw a sharp line between benign and malignant lesions. The key parameters in their prognostic system are tumor size, proliferative activity (measured by MIB-1 immunostaining), and necrosis. The prognostic importance of tumor size and proliferative activity (however measured) in GISTs has been widely established. The study of Hasegawa et al also raises important issues that are not addressed often enough when large case studies are published from around the world. Readers will note that in most cases (62.6%), tumors were identified incidentally through endoscopic screening in the absence of symptoms. Endoscopic screening of the gastrointestinal tract is commonplace in Japan, due in part to concerns about the comparatively high incidence of gastric carcinoma, whereas this practice is significantly less common in Western countries. Thus most GISTs in patients in the United States and Europe are diagnosed after the development of symptoms. Accrual of so many cases through endoscopic screening leads to very significant biases in the results—specifically, the median tumor size is noticeably smaller than in major studies from the United States, 2 there is a substantial overrepresentation of gastric lesions (84.8%) in comparison to other large series of unselected cases, and the overall survival figures for GIST of 81.7% at 5 years and 67.4% at 10 years are significantly better than those for patients diagnosed because of symptomatic lesions. There are other, more minor biases in the data of Hasegawa et al; for example, the high overall proportion of cases immunopositive for CD34 and the low overall number of cases with skeinoid fibers are both artifacts of the marked predominance of gastric lesions in this study. These observations do not detract in the least from the value and importance of Hasegawa et al’s thorough study. However, they do point to additional potential sources of major bias in published data. As both physicians and scientists, we need to take note of discrepancies such as these before developing (or sharing) misleading impressions or confusing differences of opinion with regard to GISTs and other tumor types.