GISTs and Neuroendocrine Tumors: Key Concepts

GISTs (Gastrointestinal Stromal Tumors)

  • Most common type of sarcoma, arising from interstitial cells of Cajal (ICC).
  • Commonly found in the stomach (60%), ileum, and jejunum (30%).
  • Minute growths (1-10mm) are termed micro/mini/subclinical GISTs.
  • M:F ratio is approximately 1.1.
  • Mean age at diagnosis: 60-65 years.
  • Associated with mutations in tyrosine kinase C-KIT (75-80%) and PDGFRA (5%).
  • ICC express c-KIT.
  • Symptoms include gastrointestinal bleeding or abdominal pain.
  • CT scans show solid, heterogeneous masses.
  • Endoscopy reveals subepithelial lesions.
  • Endoscopic ultrasound reveals hypoechoic solid masses.
  • Diagnosis confirmed through histologic examination and immunohistochemistry.
  • Most specific marker: DOG1.
  • Most useful marker: c-KIT (CD117).
  • Treatment involves surgical resection and tyrosine kinase inhibitors like Imatinib mesylate (Gleevec).
  • Prognosis depends on tumor size, mitotic rate, and site of origin.
  • Complete surgical resection improves outcomes.

Neuroendocrine Tumors (NETs)

  • Heterogeneous group derived from neuro-endocrine cells in various organs.
  • Associated with genetic cancer syndromes like von Hippel–Lindau (VHL) syndrome and Multiple endocrine tumour (MEN).
  • Can be functioning (symptomatic) or nonfunctioning (silent).
  • Histopathology shows positive staining for chromogranin A and specific hormones.
  • May be benign or malignant.
  • Investigations include biochemical tests, specific imaging (ultrasound, CT, MRI, PET), and endoscopy with biopsy.

Specific Neuroendocrine Tumors & Their Markers

  • Gastrinoma:
    • Mediator: Gastrin.
    • Effects: Zollinger-Ellison syndrome, peptic ulcer, steatorrhea, diarrhea.
  • Insulinoma:
    • Mediator: Insulin.
    • Effects: Recurrent hypoglycemia.
  • VIPoma:
    • Mediator: Vasoactive intestinal peptide (VIP).
    • Effects: Verner-Morrison syndrome, watery diarrhea, hypokalemia, achlorhydria, flushing.
  • Glucagonoma:
    • Mediator: Glucagon.
    • Effects: Skin rash, diabetes.
  • Somatostatinoma:
    • Mediator: Somatostatin.
    • Effects: Non-ketotic diabetes mellitus, steatorrhea, gallstones
  • Carcinoid:
    • Mediators: Serotonin, kinins.
    • Effects: Flushing, wheezing, right-sided cardiac valvular disease.

Gut Hormone Panel

  • Patient should fast overnight.
  • Stop PPIs for 2 weeks and H2 antagonists for 72 hours before.
  • Samples must be collected and sent to the lab immediately on ice.
  • Separate within 30 minutes of collection.
  • Transported to referral lab by courier on dry ice.

Case Studies

  • Gastrinoma (Zollinger-Ellison syndrome): Multiple, recurrent, or giant ulcers; GERD, diarrhea. Diagnose with fasting hypergastrinemia. Treat with PPIs or H2 receptor blockers; possible surgical care.
  • Carcinoid Syndrome: Flushing, palpitations, ventricular failure. Confirm with liver scan for metastasis and urine 5-HIAA test.
  • VIPoma: Watery diarrhea despite fasting, muscle cramps, elevated VIP levels. Treat by addressing fluid and electrolyte loss; confirm with radioimmunoassay for VIP levels.
  • Insulinoma: Increased hunger, confusion, and fainting, relieved by food intake. Supervised fasting with monitoring of blood glucose, insulin and C-peptide.
  • Glucagonoma: persistent subacute eczema, diabetes mellitus and recurrent episodes of deep-vein thrombosis. Serum glucagon :2340 pg/mL
  • Somatostatinoma Pentad of diabetes mellitus, cholelithiasis, weight loss, steatorrhea and diarrhea and Hypochlorhydria /achlorhydria