5. Neuroendocrine Tumors

 

 

1. Gastrointestinal Neuroendocrine Tumors (GI NETs)

Overview

  • GI NETs are neoplasms derived from neuroendocrine cells and classified by location and clinical context.

1.1 Gastric NETs

Subtypes of Gastric NETs

  1. Type 1 (70–80%):
    • Associated Conditions: Chronic atrophic gastritis, pernicious anemia.
    • Pathophysiology:
      • Gastric achlorhydria → elevated serum gastrin → neuroendocrine cell hyperplasia → multifocal polypoid NETs.
    • Clinical Features:
      • Indolent course, low metastatic potential.
      • Grade 1, Stage I tumors.
    • Management:
      • Endoscopic resection (ER) for tumors <2 cm.
      • Endoscopic surveillance every 6–12 months.
  2. Type 2 (5%):
    • Associated Conditions: Zollinger-Ellison Syndrome (ZES) from gastrinoma.
    • Pathophysiology: Hypergastrinemia leads to NET formation.
    • Clinical Features:
      • Intermediate malignant potential.
      • Often multifocal but less aggressive than sporadic NETs.
    • Management:
      • Endoscopic resection for tumors <2 cm.
      • Surveillance every 6–12 months.
  3. Type 3 (Sporadic, 15–20%):
    • Associated Conditions: None.
    • Pathophysiology: Not related to elevated gastrin.
    • Clinical Features:
      • Aggressive with high metastatic potential (local and hepatic metastases in up to 65%).
    • Management:
      • Partial or total gastrectomy with lymphadenectomy.
      • Systemic therapy for metastatic disease.

Diagnostic Approach

  • Endoscopy with Biopsy: Diagnostic gold standard.
  • Serum Markers:
    • Chromogranin A (elevated in most NETs).
    • Serum gastrin (especially elevated in Type 1 and 2).
  • Imaging:
    • CT/MRI for staging.
    • Ga68-PET/CT for somatostatin receptor imaging.

Prognosis

  • Type 1 NETs: Excellent prognosis.
  • Type 3 NETs: Poor prognosis due to aggressive nature.

1.2 Colorectal Neuroendocrine Tumors (NETs)

Overview

  • Colon NETs: Rare but aggressive.
  • Rectal NETs: More common and generally indolent.

Incidence

  • Colorectal NETs constitute ~1% of all colorectal tumors.
  • Rectal NETs: Often detected due to increased colonoscopy screening.

Clinical Features

  • Rectal NETs:
    • Small (<1 cm), low-grade, and often asymptomatic.
    • Larger tumors may present with rectal bleeding or pain.
  • Colon NETs:
    • Frequently present with bowel obstruction or distant metastases.

Risk of Metastases

  • Rectal NETs:
    • Tumors <1 cm: <5% risk.
    • Tumors 1–2 cm: Intermediate risk (~10–15%).
    • Tumors >2 cm: High risk (>60%).
  • Colon NETs: Higher metastatic potential regardless of size.

Management

  • Rectal NETs:
    • <1 cm: Endoscopic mucosal resection (EMR).
    • 1–2 cm: Endoscopic submucosal dissection (ESD) or transanal excision.
    • >2 cm or invasive features: Surgical resection with lymphadenectomy.
  • Colon NETs:
    • Segmental colectomy with lymph node dissection.

Follow-Up Recommendations

  • Low-risk rectal NETs (<1 cm): Endoscopic surveillance at 12 months.
  • Higher-risk tumors: Surveillance every 6–12 months with imaging and colonoscopy.

1.3 Pancreatic Neuroendocrine Tumors (PanNETs)

Overview

  • Incidence: ~1 case per 100,000 annually.
  • Types:
    • Functional: Hormone-producing (e.g., insulinomas, gastrinomas).
    • Non-functional: No hormone secretion (more common).

Clinical Features

  • Symptoms depend on hormonal secretion:
    • Insulinoma: Hypoglycemia.
    • Gastrinoma (ZES): Peptic ulcers, diarrhea.

Indications for Surgical Resection

  • Tumor Size:
    • 2 cm: Surgery recommended.
    • <2 cm: Consider observation or surgery based on functional status, symptoms, and growth.
  • Other Criteria:
    • Presence of metastases.
    • Functional tumors with significant hormone secretion.
    • Tumors causing symptoms due to local invasion.

Management

  1. Localized Disease:
    • Surgical resection (e.g., enucleation for small tumors, distal pancreatectomy for larger tumors).
  2. Hormonal Therapy:
    • Somatostatin analogs (e.g., octreotide) for hormone-related symptoms.
    • Considered in metastatic or inoperable cases to control symptoms.
  3. Metastatic Disease:
    • Targeted therapies (e.g., everolimus, sunitinib).
    • Peptide receptor radionuclide therapy (PRRT) for advanced cases.

2. Gastrointestinal Stromal Tumors (GISTs)

Overview

  • GISTs are mesenchymal tumors originating from interstitial cells of Cajal.
  • Incidence: 7–15 cases per million annually.
  • Most Common Location: Stomach (~60%).

Pathophysiology

  • Caused by activating mutations in KIT (CD117) or PDGFRA genes.
  • Familial GISTs (5%): Associated with conditions such as:
    • Neurofibromatosis.
    • Carney-Stratakis syndrome (paraganglioma + GIST).

Histological and Diagnostic Features

  • Histology:
    • Spindle cell, epithelioid, or mixed morphology.
    • CD117 (KIT) and DOG-1 positive.
  • Imaging:
    • CT: Large, smooth submucosal mass.
    • EUS: Subepithelial lesion arising from the muscularis propria.
    • PET-CT: Useful for metastatic assessment.

Prognostic Factors

  • Tumor size (>5 cm) and high mitotic rate correlate with worse outcomes.
  • Poor prognosis associated with mesenteric fat infiltration, ulceration, and lymphadenopathy.

Clinical Presentation

  • Symptoms:
    • GI bleeding (28% for small intestine, 50% for gastric).
    • Abdominal pain: 8–17%.
    • Incidental asymptomatic mass: 13–18%.
    • Acute abdomen: 2–14%.

Management

  1. Surgical Resection:
    • Indicated for tumors >2 cm.
    • Goal: R0 resection (negative margins).
  2. Adjuvant and Neoadjuvant Therapy:
    • Imatinib (Tyrosine Kinase Inhibitor): For high-risk or large tumors.
    • Sunitinib or regorafenib: For imatinib-resistant cases.
  3. Metastatic Disease:
    • Systemic therapy with TKIs.
    • Consider surgery for isolated metastases.

Prognosis

  • 5-year survival: ~70–80% for localized gastric GISTs post-resection.
  • Poorer prognosis for tumors >10 cm or metastatic disease.

References

  1. European Society for Medical Oncology (ESMO) Guidelines.
  2. British Society of Gastroenterology (BSG) Guidelines.
  3. National Comprehensive Cancer Network (NCCN) Guidelines.


Figure 1: GIST.