Gastrointestinal stromal tumor

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract, which are rare overall. All GISTs have malignant potential, and they most commonly occur in the stomach or small intestine. Clinical presentation includes GI bleeding, abdominal pain, and/or ileus. Initial evaluation typically involves imaging studies (e.g., abdominal ultrasound or CT with contrast). Definitive diagnosis is made by a multidisciplinary team at specialized GIST centers and includes core biopsy. Management is based on tumor size, location, and risk stratification and includes endoscopic surveillance, surgical resection, and tyrosine kinase inhibitors. Factors associated with a poor prognosis include large tumors, high mitotic count, and rectal location.

• Incidence: 10–15 cases per million worldwide; ∼ 5000 cases per year in the US ^[1]
• Age of onset: ∼ 60 years of age ^[2]

Epidemiological data refers to the US, unless otherwise specified.

GISTs are malignant mesenchymal neoplasms of the GI tract. ^[3]

• Origin: interstitial cells of Cajal or related precursor cells
• Mutations in c-KIT or PDGFRA → constitutive activation of receptor tyrosine kinases due to ligand-independent autophosphorylation → activation of downstream effectors → decreased apoptosis and uncontrolled cellular proliferation

Clinical features of GISTs depend on the size and anatomical location of tumors. ^[3][4]

• Small tumors (< 2 cm): often asymptomatic
• Large tumors (> 2 cm): variable clinical features
  • Stomach (∼ 60% of GISTs), small intestine (∼ 35% of GISTs): may manifest with GI bleeding ^[3]
  • Colon and rectum: may manifest with abdominal pain, bowel obstruction

• Initial studies ^[3][4]
  • Ultrasound: hypoechogenic lesions that may displace surrounding structures and/or intra-abdominal metastases
  • CT abdomen (with contrast): mass with clearly defined borders, possibly heterogeneous contrast enhancement
• Specialized studies ^[2][3]
  • Endoscopy or endoscopic ultrasound: esophageal, gastric, or duodenal GISTs < 2 cm
  • Core biopsy: molecular genetic testing for CD117 (c-KIT) or PDGFRA mutations and immunohistochemistry
  • MRI: assessment of rectal GISTs
  • CT chest, abdomen, and pelvis with contrast: staging

Refer all patients with suspected GIST to a multidisciplinary team at a specialized reference center for GISTs. ^[2]

Management should be provided by a multidisciplinary team at a specialized reference center for GISTs and may include: ^[2][3]

• Surgical resection: for localized disease
• Chemotherapy with tyrosine kinase inhibitors (e.g., imatinib, dasatinib)
  • May be considered as adjuvant or neoadjuvant therapy
  • Indications: high risk of recurrence (e.g., c-KIT and/or PDGFRA mutations, nonresectable or metastatic GIST)
• Conservative treatment (endoscopic monitoring): may be considered for gastric GISTs < 2 cm with low mitotic count

The prognosis depends on the size, mitotic count, and location of the tumor.

• Factors associated with low risk of progression, metastases, and recurrence (2%) ^[5]
  • Small tumors (> 2 cm but ≤ 5 cm)
  • Gastric location
• Factors associated with a high risk of progression (90%) ^[5]
  • Large tumors (> 10 cm)
  • Tumors > 5 cm with a mitotic count > 5 per 50 high-power field
  • Jejunal or ileal location

Metastases (e.g., to the liver or abdominal cavity) are present in 15% of patients with GISTs at the time of diagnosis. ^[4]