GIST SymposiumDiagnosis of gastrointestinal stromal tumors: A consensus approach*,**
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
References (38)
- et al.
KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors
Am J Pathol
(2000) - et al.
Gastrointestinal stromal tumor workshop
Hum Pathol
(2001) - et al.
Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT)
Mod Pathol
(2000) - et al.
Extragastrointestinal (soft tissue) stromal tumors: An analysis of 48 cases with emphasis on histologic predictors of outcome
Mod Pathol
(2000) - et al.
Gastrointestinal cancer incidence and prognosis by histologic type, SEER population-based data 1973–1987
Cancer
(1995) - et al.
Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors
Science
(1998) - et al.
Molecular insights into the histogenesis and pathogenesis of gastrointestinal stromal tumors
Int J Surg Pathol
(2000) - et al.
Gastrointestinal pacemaker cell tumor (GIPACT): Gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal
Am J Pathol
(1998) - et al.
CD117: A sensitive marker for gastrointestinal stromal tumors that is more specific than CD34
Mod Pathol
(1998) Mesenchymal tumors of the gut: Historical perspectives, new approaches, new results and does it make any difference?
Monogr Pathol
(1990)
Gastrointestinal stromal tumours: An update
Sarcoma
Gastrointestinal stromal tumors: Recent advances in understanding of their biology
Hum Pathol
Gastrointestinal stromal tumors—Definition, clinical, histological, immunohistochemical and molecular genetic features and differential diagnosis
Virchows Arch
Gastric stromal tumors: Reappraisal of histogenesis
Am J Surg Pathol
Malignant small bowel neoplasm of enteric plexus derivation (plexosarcoma). Light and electron microscopic study confirming the origin of the neoplasm
Dig Dis Sci
Gastrointestinal autonomic nerve tumors: A clinicopathologic, immunohistochemical and ultrastructural study of 12 cases
Am J Surg Pathol
Gastrointestinal stromal tumours: Correlation of immunophenotype with clinicopathologic features
J Pathol
CD34 expression in stromal tumors of the gastrointestinal tract
Appl Immunohistochem
Gastrointestinal stromal tumors: Value of CD34 antigen in their identification and separation from true leiomyomas and schwannomas
Am J Surg Pathol
Cited by (0)
- *
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.