Pancreatic Neuroendocrine Tumor - Causes, Types, Symptoms, Diagnosis, and Treatment

Introduction:

Pancreatic neuroendocrine tumors arise in the hormone-producing cells in the pancreas. It generally does not cause any symptoms, but a few symptoms like heartburn, muscle cramps, indigestion, and weight loss appear in some patients. It is found using certain laboratory tests and imaging studies like the computed tomography (CT) scan, magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS). It is treated with chemotherapy, radiation therapy, and surgery.

What Is a Pancreas?

The pancreas is in the middle of the stomach, spleen, duodenum (first part of the small intestine), and colon (part of the large intestine). It is a gland with two types of cells, exocrine and endocrine cells. Exocrine cells secrete enzymes that are transferred to the intestines to help digestion. Endocrine cells contain hormone-secreting cells called the alpha cells and the beta cells. These hormone-secreting cells club together to form the islet of Langerhans on the pancreas. They secrete hormones vital to many body functions and channel into blood circulation.

What Is a Pancreatic Neuroendocrine Tumor?

The abnormal tissue growth in the islets of Langerhans of the pancreas is called a pancreatic neuroendocrine disorder. Neoplasms (abnormal tissue growth that occurs when cells multiply abnormally) developing from the endocrine cells also secrete hormones leading to excessive accumulation of hormones in the body, creating various symptoms. They can be cancerous (malignant) or non-cancerous (benign), and they cause serious health issues.

What Causes Pancreatic Neuroendocrine Tumors?

The causes of pancreatic neuroendocrine tumors are unclear. However, mutations (changes in the DNA-deoxyribonucleic acid sequence) in specific genes of the hormone-secreting cells of the pancreas causes pancreatic neuroendocrine tumor. It causes abnormal tissue growth (tumor), or the cancer cells split and spread to various organs.

What Are the Types of Pancreatic Neuroendocrine Tumors?

• Functioning Pancreatic Neuroendocrine Tumors: They secrete hormones and are streamed into the blood circulation. They cause various symptoms depending on the type of hormone they secrete.

• Non-functioning Pancreatic Neuroendocrine Tumors: They also produce hormones but do not cause symptoms.

The pancreatic neuroendocrine tumors are classified based on the type of hormones they secrete.

• Gastrinomas: These tumors secrete gastrin, a hormone that stimulates stomach acid production and helps digestion. The symptoms of gastrinomas are associated with Zollinger-Ellison syndrome. Most of these tumors turn into cancer.

• Insulinomas: This is the most common type of pancreatic neuroendocrine tumor and is 90 % benign. They produce the hormone insulin that maintains blood glucose levels. They channel the glucose (blood sugar) into the fat cells and the liver for storage or the production of energy needed by the body. These tumors grow slowly and are not cancerous.

• Glucagonomas: This tumor produces the hormone glucagon, elevating the glucose levels in the blood. They cause mild diabetes. These tumors grow into larger sizes and have around a 70 % chance of becoming malignant and spreading to other organs.

• VIPomas: These tumors secrete the hormone (VIP) vasoactive intestinal polypeptide, which increases intestinal secretions, relaxes certain gastrointestinal muscles, and controls the water balance in the body. Most VIPomas are malignant and are spread to other organs by the time they are diagnosed. VIPomas and their symptoms are also known as pancreatic cholera or Verner-Morrison syndrome.

• Somatostatinomas: These tumors secrete the hormone somatostatin, which suppresses the secretion of other hormones. They lead to an abnormal increase in blood glucose levels. These tumors become cancerous.

• ACTHomas: These tumors secrete the adrenocorticotropic hormone (ACTH), which leads to the overproduction of cortisol by stimulating the adrenal glands. Cortisols are released in response to stressful events.

• GRFomas: The growth hormone-release factor (GRF) induces the secretion of growth hormones. They result in acromegaly, a condition where there is an abnormal bony expansion of the arms, legs, and head.

• PPHrPomas: It is an extremely rare neoplasm that stimulates the parathyroid hormone-related protein (PPHrP) secretion, resulting in hyperparathyroidism.

• Calcitoninomas: This tumor secretes calcitonin.

What Are the Symptoms of Pancreatic Neuroendocrine Tumors?

Pancreatic tumors generally do not cause any symptoms. However, depending on the type of neoplasm, a few symptoms develop.

• Non-functioning Neuroendocrine Tumors: Non-functioning neoplasms do not have specific symptoms. However, they exhibit large size and spread to other body parts when diagnosed. Due to the massive size and compression of the tumor on the neighboring structures, a few symptoms develop.

  • Jaundice (skin and eyes become yellow).

  • Indigestion.

  • Diarrhea.

  • Lump in the stomach or the back.

  • Pain in the stomach and the back.

  • Nausea.

  • Loss of appetite.

• Gastrinoma:

  • Diarrhea.

  • Pain in the stomach or the back.

  • Esophageal reflux.

  • Burping.

  • Ulcers in the stomach.

  • Bleeding ulcers.

  • Abnormal fat in the feces.

• Insulinoma:

  • Low blood sugar levels.

  • Slow and progressive weight gain.

  • Extreme hunger.

  • Visual disturbances.

  • Headaches.

  • Seizures.

  • Feeling weak and tired.

  • Rapid heartbeat.

  • Irritability.

  • Coma in severe cases.

• Glucagonoma:

  • Diarrhea.

  • Weight loss.

  • Dizziness.

  • Feeling weak and tired.

  • Headache.

  • Sores in the mouth.

  • Frequent urination.

  • Blood clot formation in the lungs.

  • Dry skin.

  • Rashes in the skin, especially on the face, belly, and legs.

  • Painful and swollen legs due to blood clot formation in the lower body.

• VIPoma (VIP - Vasoactive Intestinal Polypeptide):

  • Thirst.

  • Abdominal pain.

  • Unexplained weight loss.

  • Watery diarrhea.

  • Dehydration.

  • Cramps.

  • Lethargy.

  • Nausea.

  • Confusion.

  • Frequent urination.

  • Numbness.

  • Tingling sensation.

  • Rapid heartbeat.

• Somatostatinoma:

  • Diarrhea.

  • Gallstones (calcified deposits or stone formation in the gallbladder).

  • Unexplained weight loss.

  • The skin and the eyes turn a yellow color.

  • Frequent urination.

  • Dry skin.

  • Hunger.

  • Confusion.

  • Headache.

• ACHTomas (ACTH - Adrenocorticotropic Hormone):

  • Elevated blood pressure levels.

  • Inhibits the actions of the immune system.

  • Cushing's syndrome (moon-like face, thin and flimsy skin)

  • Weak and brittle bones (easily breakable).

  • Muscle weakness.

  • Behavioral changes.

  • Flushing (becoming red).

• GRFomas (GFR - Growth Hormone-Releasing Factor):

  • Acromegaly (expansion of the bones of the arm, legs, and head).

What Tests Are Performed to Find Pancreatic Neuroendocrine Tumors?

• Physical Examination: The doctor checks the stomach region for lumps and rules out any pain while touching.

• Complete Blood Count: The complete blood analysis is done to screen the blood parameters like the red blood cells, white blood cells, platelets, hemoglobin, eosinophils, basophils, and neutrophils. The changes in the normal values of these parameters help the doctor rule out the disease or condition.

• Ultrasound: In ultrasound, a high-frequency sound wave is used to obtain images of the internal organs.

• Computerized Tomography (CT) Scan: Computerized tomography uses high-frequency radio waves to get pictures of the internal organs at multiple angles on a computer screen. It gives a detailed view of the internal organs, neighboring structures, tissues, and other bony structures.

• Magnetic Resonance Imaging (MRI): In magnetic resonance imaging, a high-frequency sound wave in a magnetic field is used to take pictures of the internal organs. It helps find abnormal tissues in the internal organs.

• Somatostatin Receptor Scintigraphy (SRS): This test detects neuroendocrine tumors and other cancer types. Radioactive octreotide is a drug that is similar to somatostatin. It is injected into the veins of the patient. The drug reaches the target area through blood circulation and attaches to the somatostatin receptors on the surface of the neuroendocrine tumors.

How Are Pancreatic Neuroendocrine Tumors Treated?

The treatment depends on the type of neuroendocrine tumor. However, any of the following mentioned treatments are performed.

• Surgery: Surgical removal of the tumors is the first choice of treatment.

• Surgical Enucleation: Surgical enucleation is the removal of the tumor as a whole without cutting or splitting the lesion.

• Chemotherapy: In chemotherapy, a medication that kills and destroys cancer cells is recommended for patients where surgery is not advisable.

• Peptide Receptor Radionuclide Therapy: This treatment uses a radioactive drug, like Lutetium Lu 177 dotatate, to target and kill the tumor cells. The radioactive drug is injected into the patient through the vein, and the drug reaches the target tumor. It stays there for several weeks and starts killing the tumor cells.

• Targeted Therapy: In targeted therapy, certain drugs are used to find and target the particular type of cancer cells and destroy them.

• Radiofrequency Ablation: In radiofrequency ablation, an electrical conduction system generates energy waves, which heat and kill cancer cells.

• Hepatic Artery Obstruction: Hepatic artery supplies blood to the liver, pancreas, and the duodenum (first part of the small intestine). The blood supply to the tumor is stopped by injecting a gelatin sponge or beads.

Who Is at Risk of Getting Pancreatic Neuroendocrine Tumors?

Males are at a higher risk of developing these lesions than females. In addition, a few genetic disorders also increase the risk of pancreatic neuroendocrine tumors.

• Multiple Endocrine Neoplasias, TYPE 1 (MEN 1) Syndrome: It is an uncommon disorder causing abnormal lesions in the endocrine glands, the small intestine, and the stomach.

• Von Hippel-Lindau Disease: It is a genetic condition that causes tumor growth in multiple organs in the body.

• Von Recklinghausen’s Disease: It is an inherited condition leading to the development of cancerous and non-cancerous tumors in the nerves. It also affects the skin and the bones.

• Tuberous Sclerosis: A rare genetic disorder that leads to the development of non-cancerous tumors in multiple body parts and organs.

What Is the Prognosis of Pancreatic Neuroendocrine Tumors?

The prognosis is good if the tumor is detected early and surgical removal is done. However, most pancreatic neuroendocrine tumors are found when they are already spread to other organs. In that case, the five-year survival rate of these patients is around 39.4 %.

Conclusion:

Pancreatic neuroendocrine tumors are cancerous lesions that develop from the islet cells of the pancreas. These cells secrete certain hormones for body functions. Unfortunately, the lesions that arise from these cells also secrete hormones. As a result, they cause certain symptoms like headaches, unintended weight loss, abdominal cramps, diarrhea, behavioral changes, tiredness, etc. Also, certain laboratory tests and imaging studies exist to find and locate the tumors. They are then treated surgically depending on the location and size of the tumor. Chemotherapy, radio ablation, and targeted therapies are performed if surgery is impossible. However, most of these tumors are found when spread to other organs in the body. So, to prevent complications and life-threatening situations, it is better to consult a doctor if any associated symptoms appear. It helps the doctor plan the treatment, prevent complications, and expand the patient’s lifespan.