Endocrine tumors Flashcards
(50 cards)
What is Multiple Endocrine Neoplasia type 1 (MEN1)
MEN1 gene inactivated= loss of menin tumor suppressor protein function
-Tumors manifest in parathyroid, anterior pituitary, and enteropancreatic endocrine cells
What causes MEN1
MCC is familial: germline mutation passed on from zygote, is in each nucleus, and each target tissue
In MEN1, when do tumors actually occur
as a result of two hit loss of function of the MEN1 gene
First hit is a small, silent mutation
Second hit is loss of heterozygosity
Where do MEN1 tumors manifest
Hormonal: parathyroid, pancreatic endocrine tumor (gastrinoma, glucagon/VIP/SS), and pituitary tumors (prolactinoma)
Non-hormonal: foregut carcinoid (thymic, bronchial)
An example of MEN1 dispersed tumors in one organ is
manifestation of cushing’s syndrome (Cortisol secreting microadenoma)
What are ways you can specifically treat some MEN1 tumors
Thymus: cervical thymectomy
PT: subtotal parathyroidectomy
Gastrin: No surgery! PPI
Non-classic MEN1 tumors include
dermal lesions (facial angiofibroma, collagenoma) cutaneous and visceral lipomas smooth muscle (esophageal, uterine)
What is MEN2
autosomal dominant mutation of RET proto-oncogene
-Mutation= RET does not need ligand bind to activate!
What is RET proto-oncogene
a receptor tyrosine kinase that activates intracellular pathways
is activated by ligand receptor binding
What are the different areas MEN2 tumors manifest
Type 2a: medullary thyroid, pheochromocytoma*, hyperPTH
Type 2b: medullary thyroid, pheo, multiple neuromas, marfanoid habitus
Explain a MEN2a pheochromocytoma
MC in adrenal gland
50% are bilateral
Produce Epi, or Epi&NE
What is hyperparathyroid-Jaw tumor syndrome
germline inactivation of CDC73/HRPT2 tumor suppressor gene= loss of parafibromin tumor suppressor fxn
Dx difficult 2/2 incomplete and variable penetrance
What are target tissues for hyperparathyroid-jaw tumor syndrome
parathyroid (hyper PTH**) (parathyroid cancer)
jaw (ossifying tumors)
kidney (b/l renal cysts)
uterus
What is parathyroid carcinoma
rare, highly morbid endocrine neoplasm (hard to tell from benign tumor)
Death MC 2/2 intractable hypercalcemia, dehydration, coma
How can you attempt to treat parathyroid carcinoma
remove en bloc at 1st operation
if resection incomplete, high rate of recurrence from local or distant mets (lung, cervical nodes, liver)
What is Von Hippel-lindau syndrome
autosomal dominant d/o of VHL tumor suppressor gene
-defective pVHL cells overproduce HIF= overproduction of vascular endothelial growth factor (HIF target)
(usually, pVHL degrades hypoxia inducible factors)
Tumors associated with VHL syndrome include
CNS hemangioblastoma retinal hemangioblastoma pancreatic cysts kidney cancer/cysts pheo (MC in adrenal medulla) endolymphatic sac tumor **All produce NE!
What is Neurofibromatosis type 1
Mutation of NF1 tumor suppressor gene, leading to truncated neurofibromin (does NOT inhibit ras)
What is ras
a G protein involved in tumorigenesis
neurofibromin usually turns it off. but when NF1 is mutated, it can not turn it off
What tumors are associated with NF type 1
Pheo (Epi&NE producing) Neurofibromas (2+) optic glioma lisch nodule (2+) cafe au-lait macules (6+)
What are succinate dehydrogenase related PHEO’s
pheos usually in younger ages, extra-adrenal, multiple, and metastatic
Can secrete only dopamine
What is the difference between the two SDH pheos
SDHB: MC extra-adrenal, secrete NE and Dop, malignant either at dx or follow up. 10% FHx
SDHD: Most are head/neck PGLs, do not secrete catecholamines, and >99% benign
What are neuroendocrine tumors (NET) / rare endocrine tumors
heterogenous neoplasms from amine and peptide producing cells of neuroendocrine system
functional or non-functional
arise sporadically or along w/ hereditary syndrome
Where do NET/rare endocrine tumors arise
respiratory tract, pancreas, anywhere along GI (including appendix)
