Contemporary Pathology of Gastrointestinal Stromal Tumors
Section snippets
Epidemiology
The incidence of GIST in the United States and Europe is difficult to determine because GISTs have been recognized and uniformly diagnosed as a discrete entity only since the late 1990s. Recent population-based studies in some European countries found an incidence between 11 and 14.5 cases per million.14, 15, 16 These findings would translate into an annual incidence in the United States of 4,000 to 5,000 cases. However, the prevalence of GIST may be even higher, as many patients live with the
Clinical Features
The majority of patients diagnosed with GISTs are between 40 and 80 years of age (median age approximately 60 years).22 There is no clear sex predilection. Rarely, GISTs occur in children; pediatric GISTs are considered a separate clinicopathologic entity, occurring predominantly in the second decade.23, 24 Most GISTs are sporadic, but familial GISTs associated with inherited germline mutations have been identified.25, 26, 27, 28, 29, 30, 31 GISTs have also been demonstrated in association with
Immunohistochemical markers and PCR-based assays in the diagnosis of Gastrointestinal Stromal Tumors
KIT has been demonstrated as a very specific and sensitive marker in the differential diagnosis of mesenchymal tumors in the GI tract;48 around 95% of GISTs express KIT.5, 6, 49, 50 Different KIT staining patterns can be seen. Most GISTs show strong and diffuse cytoplasmic staining, whereas nearly half show concurrent dot-like (Golgi-pattern) staining (Fig. 5 A and B). In a minority of cases, a purely dot-like (see Fig. 2B) or even a membranous staining pattern can be observed. The extent and
Risk assessment in Gastrointestinal Stromal Tumors
Morphologic risk assessment in GISTs provides the basis for clinical management and optimal patient care. The vast majority of studies of GISTs suggest that the two most important prognostic features to assess the risk of aggressive behavior in a primary GIST are mitotic activity and tumor size. These two features were the foundation of the consensus approach for risk assessment in GISTs published by Fletcher and colleagues1, 68 in 2002 (Table 1). Subsequent data collected by Miettinen and
Proposed prognostically valuable immunohistochemical markers in Gastrointestinal Stromal Tumors
The tumor suppressor gene CDKN2A (p16) on chromosome 9p21 is an important cell cycle inhibitor that has been shown to be inactivated in a significant proportion of malignancies.72, 73, 74, 75, 76, 77 Immunohistochemistry has been used to assess p16 status, and the down-regulation of p16 correlates with aggressive behavior in GISTs, apparently even in tumors that are classified as low risk according to standard morphologic parameters.73, 74, 76
Another cell cycle inhibitor, p27, has been shown to
Differential diagnosis
The main differential diagnostic considerations for spindle cell GISTs are smooth muscle tumors, desmoid fibromatosis, schwannoma, inflammatory myofibroblastic tumor, inflammatory fibroid polyp, solitary fibrous tumor, and synovial sarcoma (Fig. 8). Importantly, all of these tumor types are consistently negative for KIT. Mural leiomyomas occur most commonly in the esophagus, and at this location are more common than GISTs, with a 3-to-1 ratio.83 In contrast to the syncytial appearance of
Molecular classification of Gastrointestinal Stromal Tumors
Objective clinical response to imatinib has been shown to depend on the type of RTK mutation, and a molecular classification of GISTs has been proposed.95, 96 Based on the results of clinical trials (phase I–III)12 investigating over 700 genotyped GISTs,11, 97, 98 the objective response rate for KIT exon 11 mutant GISTs is 72% to 86%, compared with 38% to 48% for KIT exon 9 mutations, and up to 28% for wild-type GISTs.11, 97, 98, 99 Primary resistance to imatinib has been likewise demonstrated
Summary
There is a wide morphologic spectrum of GISTs, but virtually all cases are amenable to the proposed primary parameters for risk assessment (size, mitotic index, and anatomic site). In addition to the common morphologic subgroups of GIST (spindle cell, epithelioid, and mixed), unusual morphologic variants, morphologic changes after TKI treatment, and treatment effects on GISTs are encountered. Promising new immunohistochemical markers (such as DOG1.1) will likely be diagnostically valuable,
Acknowledgments
The authors thank Kim Vu for expert assistance in figure production and Lindsey P. Lyle for gross photography. The authors also thank Dr. Chris Corless of Oregon Health and Science University, Portland, Oregon for the adapted and corrected 2007 NCCN risk assessment chart.
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Assessment of metastatic risk of gastric GIST based on treatment-naïve CT features
2016, European Journal of Surgical OncologyCitation Excerpt :Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of the gastrointestinal tract.1,2 Within the gastrointestinal tract, GIST occurs most frequently in the stomach (40–60%) followed by the small intestine (25–35%), colorectum (5–15%) and esophagus (<1%).3–6 Risk stratification of GIST is currently based on size, mitotic count and tumor location.
Resistance to treatment in gastrointestinal stromal tumours: What radiologists should know
2013, Clinical RadiologyCitation Excerpt :Gastrointestinal stromal tumours (GISTs) constitute less than 1% of all GI tumours, but with an annual incidence of 15 cases per million in the UK, GISTs are still the most common mesenchymal tumours of the GI tract.1 Considered to be smooth muscle tumours until the 1990s, GISTs are now known to be derived from interstitial cells of Cajal (the pacemaker cells of the GI tract) or their precursors.2 The characteristic feature in the pathogenesis of GISTs is the presence of activating mutations of the gene encoding the receptor tyrosine kinase (RTK) KIT.
Exon 11 mutations, Ki67, and p16<sup>INK4A</sup> as predictors of prognosis in patients with GIST
2011, Pathology Research and PracticeCitation Excerpt :Macroscopically, GISTs are non-encapsulated, well-defined, intra-abdominal nodular lesions, which can cause a bulging in the lumen of the gastrointestinal tract [22,35]. On histology, about 70% of GISTs are composed of spindle-cells, 20% of epithelioid cells, and the remaining 10% of mixed cell types [10,22,27]. The tyrosine-kinase receptor CD117 (KIT) is present in 90–95% of GISTs, usually with diffuse cytoplasmic expression [16,28].
Gastrointestinal stromal tumor as a cause of cancer-associated thrombosis
2019, Revista de Gastroenterologia de MexicoGastrointestinal stromal tumors of the small intestine: the challenge of diagnosis and the outcome of management
2023, World Journal of Surgical Oncology
This work supported in part by the University of Texas M.D. Anderson Cancer Center Physician Scientist Program (A.J.L.). B.L. was supported by the FWF Austrian Science Fund.