M/C mesenchymal tumour of the gastrointestinal tract (80%)
M/C malignant subepithelial lesions (SELs) of the gastrointestinal tract
What is now known as GIST, used to be called gastrointestinal (GI) smooth muscle tumour: leiomyoma if benign, leiomyosarcoma if malignant, and leiomyoblastoma if with epithelioid histology. Tumours previously classified as gastrointestinal autonomic nerve tumours have also turned out to be GISTs, as have many tumours historically classified as gastrointestinal schwannomas or other nerve sheath tumours.
Electron microscopic studies from the late 1960s and on demonstrated that most of the “GI smooth muscle tumours” differed from typical smooth muscle tumours by their lack of smooth muscle-specific ultrastructure. Immunohistochemically they lacked smooth muscle antigens, especially desmin. As they also lacked Schwann cell features, gastrointestinal stromal tumour was then proposed as a histogenetically non-committal term for these tumours. Kindblom and associates in 1998 found that these tumours actually originate from the interstitial cells of Cajal. Hirota and colleagues discovered that these tumours express CD117 antigen (C-Kit), a gain of function mutation responsible for activating the growth of these tumours. Although GISTs are considered rare tumours, most GISTs are discovered incidentally so the true prevalence is unknown. Traditional chemotherapy and radiation are not effective on GISTs, therefore surgical resection has always been the mainstay of treatment. With the discovery of mutations associated with these tumours, the treatment has changed dramatically. Imatinib mesylate, a selective tyrosine kinase receptor inhibitor (TKI), is used as an adjuvant or neoadjuvant therapy to improve the morbidity and mortality associated with GISTs. Due to growing resistance, sunitinib and regorafenib are effective second-line TKIs.
Originate from the interstitial cells of Cajal located within the muscle layer and are characterized by over-expression of the tyrosine kinase receptor KIT.
Carney triad (CT), named for J Aidan Carney, is considered to be a specific type of multiple endocrine neoplasia (MEN). The three classically associated tumors are a subset of gastric epithelioid leiomyosarcoma (it is now known that this subset is actually gastrointestinal stromal tumor arising from the interstitial cells of Cajal), pulmonary chondroma, and extra-adrenal paraganglioma. The condition manifests more commonly in females. Multiple tumors in multiple organs in young patients, with occasional sibling involvement, suggested an inherited disorder, but the underlying genetic basis has not been identified.
Gastric gastrointestinal stromal tumor (GIST)
Asymptomatic (15-30%): Incidental finding
Gastrointestinal bleeding (M/C): Acute melena and hematemesis
Subsequent anemia, weakness
Tumour-induced mass effect: Abdominal pain, distension, and discomfort
Subclinical microscopic or mini (< 1 cm) GISTs (35%)
M/C IHC marker: KIT (CD117) (DIAGNOSTIC)
M/specific marker: Discovered on gastrointestinal stromal tumor 1 (DOG1)
Endoscopic ultrasonography (EUS):
Nonspecific smooth bulge covered with normal mucosa
GISTs are usually hard and the cushion sign is negative
EUS-guided fine needle aspiration (EUS-FNA):
Typical finding of KIT- or CD34-positive spindle-shaped cells or epithelial cells