Neoplasia Of The Endocrine Pancreas Flashcards
What are the two rare cell types in the exocrine pancreas?
D1 cells
- produces vaoactive interstinal polypeptide (VIP) which induces glycogenolysis and hyperglycemia and induces increased GI fluid excretion which causes diarrhea
Enterochromaffin cells
- produces serotonin and are the source of the carcinoid syndrome produces by pancreatic tumors
Pancreatic neuro endocrine tumors (PanNETs or islet cell tumors)
This encompasses endocrine pancreas neoplasms that arise in islets in pancreas
- these are super rare compared to exocrine pancreas (only account for 2%)
What are the metastasis rates for endocrine pancreas (PanNET) tumors
90% of insulin producing tumors are benign
60-90% of all others are malignant
Sporadic PanNETs show what three major gene mutations or pathways
1) presence of MEN1 gene
- MEN1 often shows insulin producing neuro endocrine tumors
2) loss of function mutations in tumor suppressor genes PTEN/TSC2
- activates oncogenes mTOR signaling pathway
3) inactivating mutations in either X-linked, alpha-thalassemia syndrome gene(ATRX) or death-domain assocaited protein (DAXX)
3 most common clinical syndrome in functional pancreatic endocrine tumors
1) hyperinsulinemia
2) hypergastrinemia and Zollinger-Ellison syndrome
3) MEN
B-cell tumors (insulinomas)
Most common PanNET
Produces hyperinsulinemia and hypoglycemia
- often blood glucose levels will fall below 50 mg/dL during symptomatic moments
Lab values show high levels of insulin and a high insulin:glucose ratio
Hypoglycemic episodes are often precipitated by fasting or extreme exercise
Clincial manifestations
- confusion/AMS
- loss of conciousness
- stupor
Treatment = surgical removal
Insulinoma morphology
Most often found in the pancreas tissues and are benign
- 10% = carcinomas that can be metastasis
Usually small <2 cm in diameter and are encapsulated pale-red brown nodules that are anywhere in the pancreas
less than 1% = ectopic pancreatic tissues
Gastrinomas (zollinger -Ellison syndrome)
Are found in the “gastrinoma triangle”
- triangle that encompasses the head of the pancreas and the descending duodenum
About a 50% chance are locally invasive or metastasis at time of diagnosis
25% of patients with gastrinomas arise in conjunction with other endocrine tumors as part of the MEN1 syndrome
- if this is the case, the gastrinomas are often multi focal and NOT singular
Other symptoms of Zollinger-Ellison syndrome and treatment
Shows hypergastrinemia show one would expect
- peptic ulcers
- GERD
- jejunum ulcers
- *all of the above are refractive to general therapies alone**
50% shows diarrhea
Treatment = excision of the gastrinomas and PPIs (NEED BOTH)
Glucagonomas (a-cell tumors)
Show excessive serum levels of glucagon
Always shows the following 3 things
1) symptoms of mild DM
2) necroilytic migratory erythema
3) anemia
most common symptoms arise first in perimeopasusal and post menopausal women
Somatostatinomas (d-cell tumors)
Super rare and are difficult to localize
Require high somatostatin levels to diagnosis (however its also a diagnosis of exclusion or if somatostatin levels are elevated with the following symptoms)
Associated symptoms
- diabetes mellitus
- steatorrhea
- Cholelithiasis
- hypochlorhydria
VIPoma (D1-cell tumors)
Super rare and are often locality invasive and metastatic
Classically presents with:
- severe watery diarrhea
- hypokalmeia
- achlorhydria
- *also obviously high VIP levels in blood**
should always perform a VIP assay on patients with severe watery diarrhea
often associated with other neural crest tumors (neuroblastoma, ganglioneuromas and pheochromocytoma
Pancreatic carcinoid and polypeptide secreting endocrine tumors
Carcinoid
- produces atypical carotid syndrome due to excess serotonin release
Polypeptide
- produces no symptoms except mass effect when it gets large enough
