Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) & Carcinoid Tumors

Key Features

Essentials of Diagnosis

• GEP-NETs are neuroendocrine tumors that originate in the gastrointestinal tract

• About 60% GEP-NETs are nonsecretory or secretory without clinical manifestations; they may be detected incidentally or may present with weight loss, abdominal pain, or jaundice

• Carcinoid tumors arise from the intestines or lung, secrete serotonin, and may metastasize

General Considerations

• Pancreatic neuroendocrine tumors (pNETs) are of several types

  • A cells (20%) secrete glucagon

  • B cells (70%) secrete insulin

  • D cells (5%) secrete somatostatin or gastrin

  • F cells secrete pancreatic polypeptide

• GEP-NETs

  • Once regarded as rare

  • Incidence has increased to about 37 per million yearly in the United States, due to the incidental detection of small tumors on abdominal scans

  • About 40% are functional, producing hormones that are tumor markers

• Up to 25% of GEP-NETs are associated with one of four different inherited disorders

  • MEN-1

  • von Hippel-Lindau disease (VHL)

  • Neurofibromatosis 1 (NF-1)

  • Tuberous sclerosis complex (TSC)

• Insulinomas secrete excessive amounts of insulin (as well as proinsulin and C-peptide)

  • Usually benign (90% of cases)

  • Solitary in 95% of sporadic cases, but multiple in about 90% of cases arising in multiple endocrine neoplasia type 1 (MEN 1)

• Gastrinomas secrete excessive gastrin

  • About 50% are malignant and metastasize to liver

  • Typically found in duodenum (49%), pancreas (24%), or lymph nodes (11%)

  • Usually 5-year delay from symptom onset to diagnosis. Occur as part of MEN 1 in ~22%

• Glucagonomas are usually malignant and usually co-secrete other hormones, eg, gastrin

• Somatostatinomas and VIPomas (tumors secreting excessive somatostatin or vasoactive intestinal polypeptide) are very rare

• CCKomas are rare tumors of the endocrine pancreas that secrete cholecystokinin

• Carcinoid tumors

  • Can arise from the small bowel (53%, particularly terminal ileum), colon (12%), esophagus through duodenum (6%), or lung (bronchial carcinoid [5%])

  • Although usually indolent, metastases are common, particularly to liver, lymph nodes, and peritoneum

• Nonfunctional pNETs

  • Produce no significant hormones

  • Usually grow to large size prior to detection

  • May secrete chromogranin A (CgA) or pancreatic polypeptide, which can be used as tumor markers

Clinical Findings

Symptoms and Signs

• Nonfunctioning tumors typically present with mass effect and metastases, such as

  • Pancreatitis

  • Jaundice

  • Abdominal pain

  • Weight loss

• Insulinoma

  • Secrete insulin

  • Fasting hypoglycemic symptoms

• Gastrinoma

  • Abdominal pain (75%)

  • Heartburn (44%)

  • Bleeding (25%)

  • Weight loss (17%)

• Glucagonoma

  • Weight loss, diarrhea, nausea, peptic ulcer, hypoaminoacidemia

  • Necrolytic migratory erythema

  • Diabetes mellitus develops in 35%

• Somatostatinomas

  • Classic triad of symptoms

    • Diabetes mellitus because of its inhibition of insulin and glucagon secretion

    • Cholelithiasis because of its inhibition of gallbladder motility

    • Steatorrhea because of its inhibition of pancreatic exocrine function

  • Diarrhea, hypochlorhydria, and anemia

• VIPoma (so called "WDHA" [or Verner-Morrison syndrome])

  • Watery Diarrhea (profuse)

  • Hypokalemia

  • Acidosis

• CCKomas

  • May present with liver metastases and symptoms of diarrhea, peptic ulcer ...