Elsevier

Human Pathology

Volume 33, Issue 5, May 2002, Pages 459-465
Human Pathology

GIST Symposium
Diagnosis of gastrointestinal stromal tumors: A consensus approach*,**

https://doi.org/10.1053/hupa.2002.123545Get rights and content

Abstract

As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GISTs), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and the development of novel and effective therapy for GISTs using the receptor tyrosine kinase inhibitor STI-571, these tumors have become the focus of considerable attention by pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a source of confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term “benign” for any GIST, at least at the present time. HUM PATHOL 33:459-465. Copyright 2002, Elsevier Science (USA). All rights reserved.

Section snippets

Historical overview

The way(s) in which spindle cell tumors, and subsequently epithelioid tumors, apparently arising from stromal/mesenchymal components of the GI tract have been perceived and classified over the past 50 to 60 years has been the subject of detailed reviews elsewhere,8, 9, 10, 11 and thus only a brief summary is provided here.

Following seminal descriptions in the 1940s by Stout and others, stromal tumors arising in the GI tract were generally regarded as smooth-muscle neoplasms (using the terms

Diagnosis of GIST

The question now arises as to whether this more rational basis for classifying stromal/mesenchymal neoplasms of the GI tract, which is underpinned and defined by the molecular genetic identification of the role of KIT should be adopted in routine daily practice. Stated simply, should the term “gastrointestinal stromal tumor” be limited specifically to that group of intra-abdominal mesenchymal lesions showing immunopositivity for KIT? As a corollary to the foregoing, should KIT immunostaining

Immunophenotype

Aside from consistent positivity for KIT (CD117), about 60% to 70% of GISTs show immunopositivity for CD34, 30% to 40% show immunopositivity for smooth-muscle actin (SMA), and around 5% show immunopositivity for S-100 protein. None of the latter antigens are specific for GIST (see Table 1). Desmin positivity in true KIT-positive GISTs is extremely uncommon (1% to 2% of cases) and is invariably focal, with positivity in only a small number of tumor cells. The immunophenotype of true KIT-positive

Anatomic location

GISTs may arise anywhere in the tubular GI tract, from the esophagus to the rectum. In addition, it has been appreciated in recent years that identical lesions also occur in extra-GI locations, principally mesentery, omentum, and retroperitoneum,23, 24, 25 and the demonstration of KIT expression in these lesions has helped validate their existence, particularly in exceptional sites such as the gallbladder26 or bladder.27 In terms of more detailed distribution,28 50% to 60% of lesions arise in

Prediction of behavior

Criteria for distinguishing benign from malignant GISTs, or at least to identify those lesions more likely to metastasize, have been sought, analyzed, and disputed for many years. Many parameters have been proposed—more than can usefully be reviewed herein—but the morphologic features that have gained greatest acceptance as being predictive of outcome are mitotic rate and tumor size.8, 9, 11, 35, 36, 37 The problem that has persisted (and that still remains unresolved) is that whereas these

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    *

    This proposal represents the consensus view of the authors and does not represent National Institutes of Health policy. The authors have all read and concur with the statements included in the manuscript.

    **

    Address correspondence and reprint requests to Christopher D.M. Fletcher, MD, FRCPATH, Department of Pathology, Brigham and Women's Hospital, 75 Francis Street Boston, MA 02115.

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