What is GIST (Gastrointestinal Stromal Tumor)?

What is a Gastrointestinal Stromal Tumor (GIST)?

A Gastrointestinal Stromal Tumor (GIST) is the most common type of mesenchymal tumor found in the digestive tract, originating from the interstitial cells of Cajal (the gut's pacemaker cells) or their precursors, and characterized by expression of the KIT (CD117) protein. 1

Key Characteristics of GISTs

• GISTs are rare tumors with an estimated incidence of approximately 1 per 100,000 people per year 1
• They occur most commonly in the stomach (60-70%) and small intestine (25-35%), with less frequent occurrence in the colon/rectum (5%), esophagus (<2%), and appendix 1
• Some GISTs can develop in the omentum, mesentery, or retroperitoneum without connection to the GI tract 2
• Most GISTs affect people over age 60, with a slight prevalence in males 1

How GISTs Are Identified

• GISTs are identified by their expression of specific proteins:
  • CD117 (c-KIT) - present in 95% of GISTs and is the major diagnostic marker 2, 3
  • CD34 - present in approximately 70% of cases 2
  • DOG-1 - another important diagnostic marker 3
• Most GISTs have mutations in either the KIT gene or the PDGFRA (platelet-derived growth factor receptor alpha) gene 1

Symptoms and Presentation

• Small GISTs (<2 cm) are often asymptomatic and found incidentally during procedures for other conditions 1
• Common symptoms of larger GISTs include:
  • Upper gastrointestinal bleeding and anemia 1
  • Abdominal pain or discomfort 1
  • Palpable abdominal mass 1
  • Small bowel GISTs may remain silent until presenting with acute hemorrhage or rupture 1
  • Rectal GISTs may cause pain, obstruction, and bleeding 1
  • Esophageal GISTs typically cause dysphagia (difficulty swallowing) 1
  • Some patients experience non-specific symptoms like weight loss, night sweats, and fever 1

Risk Assessment

• The risk of malignant behavior in GISTs is assessed based on:
  • Tumor size (larger tumors have higher risk) 1, 4
  • Mitotic rate (number of dividing cells seen under microscope) 4
  • Location (intestinal GISTs generally have worse prognosis than gastric GISTs) 4
  • Tumor rupture (significantly increases risk) 1

Associated Syndromes

• Some rare syndromes are associated with GISTs:
  • Carney triad: gastric GISTs, paraganglioma, and pulmonary chondromas 1
  • Carney-Stratakis syndrome: GISTs and paragangliomas 1
  • Neurofibromatosis type 1 (NF1): increased risk of GISTs, particularly in the small bowel 1
  • Familial GIST: extremely rare families with germline KIT or PDGFRA mutations that develop multiple GISTs at an early age 1

Diagnosis and Treatment

• Diagnosis typically involves:

  • Imaging studies (CT scan, MRI) 3
  • Endoscopic ultrasound (EUS) with biopsy for accessible tumors 1
  • Histological examination with immunohistochemistry testing for CD117 and other markers 1

• Treatment approaches include:

  • Surgical resection for localized disease 1, 3
  • Targeted therapy with tyrosine kinase inhibitors (like imatinib) for high-risk, metastatic, or unresectable tumors 1, 3
  • Regular follow-up with imaging for monitoring 5

Important Considerations

• GISTs differ from other GI tract tumors like leiomyomas (smooth muscle tumors) and schwannomas (nerve sheath tumors) in their molecular characteristics and treatment approach 2, 6
• Even small GISTs can sometimes behave aggressively, so proper risk assessment is crucial 4
• Advances in molecular testing have greatly improved diagnosis and treatment selection 1