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Pancreatic neuroendocrine neoplasms

Gastrointestinal System - REVIEWED CLINICAL

Gastrointestinal System - REVIEWED CLINICAL

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USMLE® Step 1 questions

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High Yield Notes

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Pancreatic neuroendocrine neoplasms

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Questions

USMLE® Step 1 style questions USMLE

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A 47-year-old woman comes to the physician due to midline abdominal pain that has been ongoing for several months. The pain is described as a burning sensation and worsens after meals. As a result, the patient has been eating less and has experienced a 5 kg (11 lb) weight loss. She has a history of peptic ulcer disease, which was diagnosed last year. She was prescribed omeprazole but has not noticed an improvement in symptoms after initiating therapy. Medical history is also notable for low back pain. Vitals are within normal limits. Physical examination reveals mild tenderness to palpation of the epigastric region. An endoscopy is performed and shows multiple ulcers in the stomach and duodenum. A urea breath test is negative. Administration of intravenous secretin is followed by an increase in serum gastrin levels by 200 pg/mL. Which of the following is the most likely cause of this patient’s symptoms?  

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With pancreatic neuroendocrine neoplasms, neuroendocrine refers to pancreatic cells which release hormones in response to signals from the nerves, and neoplasm refers to a cancer.

So, pancreatic neuroendocrine neoplasm is a cancer of neuroendocrine cells that are within the pancreas.

They can also be called pancreatic neuroendocrine tumors, or just panNETs for short.

In addition to endocrine cells, the pancreas also has exocrine cells, which make up a majority of the gland.

Most pancreatic cancers arise from exocrine cells and they’re called adenocarcinomas, whereas only a minority arise from panNETs.

The pancreas is a long, skinny gland the length of a dollar bill which sits to the left of the duodenum and behind the stomach, in the upper abdomen, or the epigastric region.

It plays two main roles - there’s the exocrine part of the pancreas which has acinar cells that make digestive enzymes that are secreted into the duodenum to help digest food.

There’s also the endocrine part of the pancreas which has a few different types of islet cells, or neuroendocrine cells, each of which make different hormones.

These neuroendocrine cells are present in clusters, or islands, called islets of Langerhans.

The largest group of cells are the beta (β) cells which secrete insulin.

Insulin mainly lowers the blood glucose levels by transporting glucose into the cells, and also pushes potassium into cells, which decreases potassium in the blood.

Another group are the alpha (α) cells which secrete glucagon, a hormone that does exactly the opposite of insulin, it raises the blood glucose levels by getting the liver to generate glucose from amino acids and lipids, and to break down glycogen into glucose.

There are also Delta cells which secrete somatostatin, which decreases the release of other hormones, including insulin, glucagon, and serotonin.

There are also pancreatic polypeptide cells, which secrete pancreatic polypeptide, which stimulates the release of digestive enzymes from the stomach and small intestine, and slows down intestinal movement.

Finally, there are a few rare cell types called enterochromaffin cells, D1 cells, and G cells, which are scattered in the islets of Langerhans.

Enterochromaffin cells secrete serotonin, which helps with motility of the gastrointestinal tract.

D1 cells release a hormone, vasoactive intestinal polypeptide or VIP, which relaxes the small intestine and stimulates the release of intestinal digestive enzymes, but inhibits hydrochloric acid release from the stomach.

G cells are found in the pancreas and stomach, and the secrete gastrin.

Gastrin stimulates the parietal cells in the stomach mucosa to secrete hydrochloric acid, and also stimulates the glands in the epithelial layer.

In pancreatic neuroendocrine neoplasms, one of the many types of neuroendocrine cells mutates and starts dividing uncontrollably, forming a tumor over time.

Sometimes the mutation is in a tumor suppressor gene like PTEN and MEN1.

Tumor suppressor genes usually regulate cell growth, so when they mutate, the result is uncontrolled cell growth.

Mutation of the MEN1 gene results in an inherited condition known as multiple endocrine neoplasia, or MEN, type I, where adenomas or malignant tumors form in the parathyroid gland, pituitary gland, and pancreas.

Some PanNETs are benign tumors which means that they don’t invade nearby tissues, whereas others are malignant tumors meaning that they do invade surrounding tissues and even metastasize or spread through the lymph to distant ones.

PanNETs are classified into functional tumors, which secrete hormones, and non-functional tumors, which don’t secrete any hormone.

Non-functional panNETs are more common, and they’re usually asymptomatic until they grow to a large size and metastasize to other organs like the liver.

Large tumors can compress surrounding structures, for example, a tumor might compress the common bile duct, leading to a backup bile and causing obstructive jaundice, which is when the skin turns yellow from the buildup of bilirubin in the tissues.

Summary

Pancreatic neuroendocrine Tumors (PNETs) are a type of tumor that arises in the endocrine tissue of the pancreas. These tumors include insulinomas, gastrinoma, glucagonoma, and VIPomas, and secrete hormones including insulin, gastrin, glucagon, and vasoactive intestinal peptide respectively. Symptoms of PNETs may include abdominal pain, weight loss, and changes in bowel habits. Treatment options may involve drugs like somatostatin and surgery.

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "The Pathologic Classification of Neuroendocrine Tumors" Pancreas (2010)
  6. "Update on pancreatic neuroendocrine tumors" PubMed (2014)