Pancreatic Neuroendocrine Tumor (PNET)

Pancreatic neuroendocrine tumor (PNET) is defined as islet cell tumors of the pancreas that make islet cell type hormones. PNET can be functional or non-functional.

Functional: (means the tumor made hormones cause symptoms and show elevation)

• Insulinoma, Gastrinoma, Glucagnoma, VIPoma
• Most functional are more benign but still difficult to predict behavior and require close follow up.

Non-functional: (hormones released do not cause symptoms or no elevation of hormone at all)

• Does not see elevation of or hyperhormonal symptoms
• Most non-functional are more malignant (determined based on metastasis) because difficult to predict behavior.

Cause and risk factors/Association:

• MEN1 gene mutation has been associated with increased risk of endocrine tumors

Symptoms and Diagnosis of Pancreatic Neuroendocrine Tumors:

Non-functional:

• Indigestion, diarrhea, epigastric/abdomen pain, jaundice, palpable mass at right upper quadrant that is usually non-tender.

Functional

• Symptoms of excess hormones production depending on the type of hormones being excessively produced
• Insulinoma:
  • Usually benign solitary (arise from beta cells), elevated insulin levels
  • Hypoglycemia especially post fasting and relieved with glucose in take
  • Whipple Triad (Low sugar, Hypoglycemia Symptoms, Reversal of Symptoms with Glucose)
• Gastrinoma (ZES): see ZES section
  • Multiple ulcers (esophagus, stomach, duodenum, jejunum), elevated gastrin levels.
  • Can also arise from duodenum and peripancreatic tissues
  • Hypergastrenemia with ulcers refractory to conventional treatment.
  • Zollinger Ellison Syndrome (ZES): multiple duodenal ulcer, steatorrhea, prominent gastric rugal fold due to increase oxyntic gland mass
• VIPoma
  • Tumors cells that produce excess VIP (vasoactive intestinal peptide)
  • Achlorhydria (low acid secretion from VIP);
  • Vasodilation (flushing, hypotension), nausea vomiting, weakness.
  • Hyperglycemia (due to increased glycogenolysis), hypercalcemia (due to increased bone resorption)
  • Watery Diarrhea with hypokalemia (hence muscle weakness), hypotension (due to loss volume).
  • Increased potassium secretion
  • Labs: stool studies show Osmolar gap < 50mOsm/kg, increased potassium ( Na⁺)
  • Diagnosis: VIP > 75 pg/ml confirms and watery diarrhea). CT abdomen (pancreatic lesion usually found on the tail of pancreas)

Lab Markers and Morphological features

• See hormones for Functional PNET

Progression and Course of Disease

• Hard to predict and need close monitoring.

Treatment and Management

• Surgical resection for localized lesion (whipple procedure)
• Some patient can choose the wait and watch approach if the lesion does not show aggressive behavior.
• Chemotherapy if metastatic.