AssessmentsPancreatic neuroendocrine neoplasms
Pancreatic neuroendocrine neoplasms
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 39-year-old woman comes to the clinic because of stomach pain and weight loss for the past two months. Her stomach pain is periodic and located in the right upper quadrant, and it is made worse by eating. She has also experienced multiple episodes of malodorous fatty diarrhea per day. Her medical history includes surgical removal of a pituitary prolactinoma and a parathyroid adenoma. Family history is significant for a pituitary mass in her mother at age 28. Her temperature is 37.0°C (98.6°F), pulse is 88/min, respirations are 10/min, and blood pressure is 132/84 mm Hg. Physical examination shows a thin woman with mild tenderness to palpation of the right upper quadrant. Laboratory studies show a serum glucose level of 210mg/dL. Abdominal computed tomography (shown below) shows the presence of a pancreatic mass and cholelithiasis. Which of the following is the most likely diagnosis?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Tanner Marshall, MS, Evan Debevec-McKenney, Jahnavi Narayanan, MBBS, Brittany Norton, MFA
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.
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.
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