**1. Introduction**

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract (GIT) [1, 2]. All GISTs are considered to have some degree of malignant potential [3]. The most common site of GISTs is the stomach (60%) [4]. Other common sites are jejunum and ileum (30%), duodenum (5%), rectum (2–3%), colon (1–2%), and esophagus (<1%) [4].

It has been estimated that GISTs comprise about 18% of all sarcomas and 80% of mesenchymal tumors found in the GIT [5]. GIST's true incidence has been underestimated as they were usually misdiagnosed as leiomyomas, leiomyosarcomas, and leiomyoblastomas [6]. A study which used the Surveillance, Epidemiology and End Results (SEER) data from the National Cancer Institute, reported that the incidence of GIST has increased from 0.028 cases

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

per 100,000 in 1992 to 0.688 cases per 100,000 in 2002, which is a 25-fold increase in incidence. This increase occurred after the availability of diagnostic criteria, especially after the year 2000 [7]. In 1992, 93% of mesenchymal tumors of GIT were identified as smooth muscle neoplasm and 6% as GISTs. In 1995, Miettinen et al. [8] discovered that 70% of GIST are positive for CD34, a myeloid progenitor cell antigen. Furthermore, CD34 were also found in Schwann cell tumors and some smooth muscle tumors [6]. In the late 1990s, Hirota et al. [9] discovered that GIST expresses KIT (CD117), a receptor tyrosine kinase encoded by the proto-oncogene c-kit. Subsequent studies showed that mutations in c-KIT are present in 85–100% of GIST cases, but not in leiomyomas or leiomyosarcomas. These findings made a breakthrough in identifications and management of GISTs. In the SEER data published by Perez et al. [7], 82% of mesenchymal tumors of GIST were classified as GIST and 17% were classified as smooth muscle neoplasms in 2002, which shows how GISTs were poorly identified and were underdiagnosed [7]. GISTs appear to be more common in African Americans, Asians, and Pacific Islanders than in Caucasian patients, and men appear to have a slightly increased incidence [7, 10]. GISTs tend to be infrequent before the age of 30 and are most common after the age of 60 [7]. The median age of diagnosis is between 58 and 65 years [7, 10–13]. Two studies from Europe have shown that GIST incidence is about 1.1 cases/100,000/year [11, 14].

Neurofibromatosis type 1: patients with NF1 are more predisposed for multifocal GISTs that

Gastric GIST

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GISTs are characterized by mutations in KIT and PDGFRA genes that encode tyrosine kinase

Though 95% of GISTs are positive for KIT, only 60–85% have mutations in KIT. The most common mutations encountered are mutations of exon 11 (juxtamembrane domain) [4] which is found in about two-thirds of GISTs. Exon 9 (extracellular domain) is less common (9–20%) and is principally correlated with GIST of the small bowel and has a greater malignant poten-

About 5–10% of GISTs have PDGFRA mutations which have a tendency for localized gastric GIST and epithelioid type [4]. The most common type of mutation is the PDGFRA exon 18 mutation D842V, which is associated with imatinib resistance and has a lower risk of recur-

Approximately 12–15% of adult GIST and 90% of pediatric GIST do not have KIT and PDGFRA mutations [33]. Wild-type (WT) GISTs comprise GISTs that arise in NF1, Carney-Stratakis syndrome, and Carney triad [4]. WT GISTs may have other forms of mutations. BRAF V600E substitution has been described in 7–13% of WT GISTs [35, 36]. About 30% of WT GISTs are SDH deficient and occur solely in the stomach. They mainly affect children and young adults

The three main histopathologic subtypes of GIST are spindle cell, epithelioid, and mixed types, with spindle cell type being the most common constituting about 70% of GISTs, while the other two subtypes, epithelioid and mixed, are less common, accounting for 20 and 10% of all GISTS, respectively [6]. Epithelioid GIST is commonly observed in the stomach and omentum [6]. About 95% of GIST will be immunohistochemical positive for CD117(c-KIT) [4]. Epithelioid type has a weaker KIT positivity than spindle cell type [37]. In addition, 70–90% are positive for CD34, 20–30% for actin, 8–10% for S-100, and 2–4% for desmin [38]. DOG1 marker, also known as ANO1, has more than 95% sensitivity for GIST and is expressed in more than 35% of GISTs negative for c-kit [39, 40].

rence than GIST with KIT mutations as well as a more benign course 9 [34].

and have a variation in their nature from being indolent to progressive [4].

mainly affect the small intestine [31].

**3. Molecular biology**

receptor type III [32].

**3.1. KIT-mutant GIST**

**3.2. PDGFRA-mutant GIST**

**3.3. Wild-type GIST**

**4. Histopathology**

tial [4, 33].

Though rare, GISTs can also affect the pediatric population. A study carried out by Miettinen et al. which included 1782 patients with gastric GIST, reported 44 cases under the age of 21 (2.6%) [15] with an age range from 5 to 21 and a median age of 14.5 years [15]. Prakash et al. [16] reported six cases of gastric GIST with a mean age of 12.8 and an age range from 10 to 18. Pediatric GISTs are commonly of epithelioid type, occur more in females, and have a higher incidence of multifocal presentation and lymph node metastasis. Pediatric GISTs also tend to lack a KIT or a platelet-derived growth factor receptor-α (PDGFRA) mutation [17, 18].
