Pancreatic neuroendocrine neoplasms- causes, symptoms, diagnosis, treatment, pathology

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. Now, 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, 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 (δ) cells which secrete
somatostatin, which decreases the release of other hormones, including insulin, glucagon,
and serotonin. There are also gamma (γ) cells, also called
pancreatic polypeptide cells, which secrete pancreatic polypeptide, which stimulates the
release of digestive enzymes from the stomach and small intestine, as well as slow down
intestinal movement. Finally, there are a few rare cell types called
enterochromaffin cells, as well as 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 hormones. 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. Functional panNETs are less common and depend
on the type of cell they arise from and the hormone they produce. The most common functional panNET is an insulinoma
which arises from β cells that make insulin. Insulinomas are usually benign solitary tumors
that cause hypoglycemia, or low blood glucose, and in severe cases can lead to confusion
and loss of consciousness. The second most common type is a gastrinoma
that arises from the G cells that make gastrin. Gastrinomas secrete large amounts of gastrin,
which results in excess hydrochloric acid secretion, which produces a syndrome called
Zollinger-Ellison syndrome. Excess hydrochloric acid erodes the mucosa,
which results in peptic ulcers. A unique feature of Zollinger-Ellison syndrome
is that the peptic ulcers are formed not only in the stomach, and duodenum, but there’s
so much acid that ulcers are also formed in more distant parts of the small intestine
like the jejunum. The acid also inactivates the pancreatic digestive
enzymes, which allows food, especially fat to pass right through the intestines undigested,
leading to greasy and smelly stools—called steatorrhea. The third most common type of panNETs is a
VIPoma which arises from the D1 cells that make vasoactive intestinal peptide. VIPomas result in WDHA syndrome, where WD
stands for watery diarrhea, which is due to increased fluid secreted by the small and
large intestine, H stands for hypokalemia, or low potassium levels in the blood due to
potassium losses in the intestinal fluid, and A stands for achlorhydria, the absence
of hydrochloric acid secretion. The fourth type is the glucagonoma which arises
from the α cells that make glucagon. Excess glucagon leads to increased blood glucose,
resulting in diabetes mellitus. Glucagonomas also result in a loss of lipids
and proteins that are used to form glucose, and they typically cause a necrolytic migratory
erythema, which is a red blistering rash that mostly affects the mouth and limbs. The fifth type is a somatostatinoma that arises
from δ cells which secrete somatostatin. The excess somatostatin inhibits release of
other pancreatic hormones, like insulin, gastrin and VIP; which leads to diabetes mellitus,
steatorrhea, and hypochlorhydria, or decreased hydrochloric acid secretion. Finally, there are also panNETs that develop
from pancreatic polypeptide cells and enterochromaffin cells, but these are very rare. Diagnosis of functional panNETs is based on
measuring pancreatic hormone levels. Non-functional tumors are usually hard to
detect since no increase hormone levels can be found in the blood. In addition, MRI or CT imaging of the pancreas
can help identify a tumor and estimate its size. The treatment for a panNETs depends on the
type and size. When dealing with a functional tumor, with
the exception of somatostatinomas, somatostatin-like medications are given to reduce hormone production. In addition, gastrinomas can be treated with
medications that block gastric acid secretion. When dealing with nonfunctional panNETs, large
tumor that cause compression can be managed with surgery. All right, as a quick recap, pancreatic neuroendocrine
neoplasms, or panNETs, are tumors of hormone producing cells of the pancreas, and their
symptoms depend on their size and cellular origin. PanNETs can be non-functional tumors, meaning
they don’t produce any hormones, or they can be functional tumors, meaning they produce
hormones. The most common types of functional tumors
include insulinomas that make insulin, gastrinomas that make gastrin, glucagonomas that make
glucagon, VIPomas that make vasoactive intestinal peptide, and somatostatinomas that make somatostatin.


  1. You guys got me through pharmacy school i still watch your videos. So informative so simple.
    – mike the pharmacist

  2. Hi, im interested in buying the Osmosis package however i live in the UK so i was wondering if i would be able to purchase it and how much it would cost in £? Thanks!

  3. random thought… if we develop cryostasis technology would you be able to go into a cryo pod at night to sleep and double your life?

  4. Oh my there are faces on each of the exocrine and endocrine cells 🙂 so cute! I wonder how long that took to draw

  5. Hi Osmosis! The playlist of gastrointestinal pathology is not in order, could you make it in order for us not to get confused. Thanks 😀

  6. I think gastrin stimulates pancreatic enzymes secretion.. and in that case reason given for steatorrhea doesn't work out for me:(

  7. guys you mentioned that gamma cells produce pancreatic polypeptide … which i think is not right those cells called F cells or PP cells. From where is this gamma cells ??

  8. seriously>this channel is amazing and very useful to me i hope you will make videos that cover all other medical topics thank you for your effort and keep going:)

Leave a Reply

(*) Required, Your email will not be published