Neuroendocrine Tumors (NET)

What Are Neuroendocrine Tumors?

NETs arise from neuroendocrine cells scattered throughout the body (lungs, GI tract, pancreas, adrenal glands). These cells secrete hormones and bioactive substances. When neoplastic, they can produce excessive hormones causing carcinoid syndrome or hormone-related symptoms.

Key fact: Many NETs are incidental findings on imaging for unrelated reasons. Grade (Ki-67 proliferation index) determines aggressiveness and treatment approach.

Types & Sites

• GI NETs: Foregut (stomach, duodenum), midgut (small bowel, appendix), hindgut (colon, rectum). Different sites have different behavior.
• Pancreatic NETs (pNETs): Insulinomas, gastrinomas, VIPomas. Can be functional (hormone-secreting) or non-functional.
• Lung NETs: Typical carcinoid (low-grade) or atypical carcinoid (higher-grade).
• Other sites: Thyroid, adrenal, pituitary.

Risk Factors

• Genetic syndromes: MEN-1, NF-1, VHL, SDHX mutations increase risk.
• Age: Can occur at any age; typical presentation 50-70 years.
• Chronic inflammation: Achlorhydria (no stomach acid), chronic atrophic gastritis.

Symptoms

• Carcinoid syndrome: Flushing, diarrhea, wheezing, heart problems (from serotonin secretion). Typically indicates metastatic disease.
• Functional symptoms: Depends on hormone: hypoglycemia (insulinoma), severe diarrhea (gastrinoma), hypokalemia (VIPoma).
• Mass effect: Obstruction, bleeding, abdominal pain.
• Incidental: Many discovered on imaging for unrelated reasons.

Diagnosis

Diagnostic approach:

• Biochemical markers: 24-hour urine 5-HIAA (serotonin metabolite), chromogranin A, gastrin, insulin levels depending on symptoms.
• Imaging: CT, MRI, endoscopy (for GI NETs).
• Functional imaging: Somatostatin receptor scintigraphy, PET imaging to detect neuroendocrine uptake.
• Biopsy: Confirms diagnosis and allows immunohistochemistry (synaptophysin, chromogranin).
• Grade: Ki-67 index and mitotic count determine low (G1), intermediate (G2), or high-grade (G3).

Staging & Prognosis

Uses TNM system with grade. Grade is prognostic:

• G1 (low-grade): Ki-67 <2%. Often indolent; 5-year survival 80-90%+.
• G2 (intermediate): Ki-67 3-20%. More aggressive; 5-year survival 40-80%.
• G3 (high-grade): Ki-67 >20%. Very aggressive; 5-year survival <40%.

Treatment Options

Surgery

Often first-line for localized disease. Curative if complete resection achievable. Even with metastases, debulking can improve quality of life.

Somatostatin Analogs

Octreotide, lanreotide. Reduce hormone secretion and slow tumor growth in some patients. Used for carcinoid syndrome symptom relief and as maintenance therapy.

Targeted Therapy

mTOR inhibitors: Everolimus improves progression-free survival in pNETs. Tyrosine kinase inhibitors (sunitinib) also used for pNETs.

Chemotherapy

For high-grade NETs or advanced disease. Platinum-based chemotherapy used for high-grade NETs; less effective in low-grade tumors.

Peptide Receptor Radionuclide Therapy (PRRT)

Using radiolabeled somatostatin analogs (Lu-177 dotatate, Y-90 dotatate). Targets NET cells expressing somatostatin receptors. Emerging standard for advanced NETs.

Hepatic-Directed Therapy

For metastases to liver: embolization, chemoembolization, or radioembolization.

Carcinoid Syndrome Management

• Somatostatin analogs (mainstay)
• Dietary management (avoid triggers: alcohol, spicy foods)
• Antihistamines and 5-HT3 antagonists for symptom relief
• Echocardiogram screening (carcinoid can affect heart valves)

Prognosis & Follow-Up

Highly variable based on grade and site. Low-grade NETs often have excellent long-term survival even with metastases. Regular monitoring with biochemical markers and imaging guides treatment decisions.

Key Questions for Your Doctor

• What grade and stage is my NET?
• Is my tumor functional? What hormone is it secreting?
• Is surgery an option?
• Do I need somatostatin analog therapy?
• Am I a candidate for PRRT or other targeted therapies?
• What surveillance plan should I follow?