Endocrine Flashcards
What genes are associated with MEN1 syndrome
MEN1
CDKN1B
What genes are associated with MEN2 syndrome
RET genes
What tumours are associated with MEN1 syndrome and what are the approximate lifetime incidence (from eviq)
Mostly benign tumours
Parathyroid adenoma 90-95%
Pituitary adenoma 30-40%
GDP-NET 90% (gastroduodenopancreatic)
Adrenocortical adenoma 30-40%
Bronchopulmonary NET (indolent) 20%
Thymine NET (usually malignant) 2%
Meningioma 8%
What tumours are associated with MEN2 syndrome
Medullary thyroid carcinoma (90% by age 75)
Phaeochromocytoma
Primary hyperparathyroidism
What is a common term used to describe well differentiated neuroendocrine tumours
Carcinoid
What is the microscopic appearance of well differentiated neuroendocrine tumours (Kurt’s notes)
Uniform cells, round nuclei
Salt and pepper granular chromatin in nucleus
Granular cytoplasm
Organoid architecture (cells arranged into nests, cords, rosettes or ribbons)
No necrosis
What is detected using a DOTA scan
Somatostatin receptors expressed by well differentiated neuroendocrine tumours
68Ga-DOTA-somatostatin analog-PET/CT is best.
Scintigraphy is considered inferior
FDG PET is often negative in grade 1 NETs, but may be positive in grade 2 and 3
What is the usual behaviour of well differentiated neuroendocrine tumours
Malignant, but slow growing and indolent. Early NETs have low rates of metastasis.
How are well differentiated neuroendocrine tumours graded
Based on Ki67 and mitotic rate
G1: ki67 <3% mitotic index <2
G2: 3-20%, 2-20
G3: >20%, >20
How are poorly differentiated neuroendocrine tumours graded
They are not, but they can either be small cell or large cell types
What are the microscopic features of poorly differentiated small cell neuroendocrine tumours
Small size: <3 lymphocytes
Fusiform (elongated/tapering at both ends) nuclei
Cells appear bland/sheet like growth (as opposed to being pleomorphic like carcinomas)
Fine granular chromatin
Scanty cytoplasm
Extensive necrosis
Very high mitotic rate, ki67 nearly 100%
See Kurt’s notes “GI neuroendocrine tumours” and handbook for surgical pathologists pg 151
What are is the microscopic architecture and cytology associated with neuroendocrine tumours
Architecture: ie organoid architecture such as nests, cords, rosettes
Cytology: monotonous/uniform cells. contain secretory granules, secrete peptides and amines locally.
See handbook for surgical pathologists page 169
What are the microscopic features of large cell neuroendocrine tumours
Large cells, round nuclei, prominent nucleoli, moderate cytoplasm.
Sheet-like to nested growth
Ki67 usually 60-80%
What is the common pathway that a poorly differentiated neuroendocrine tumour develops
Arise from a non-neuroendocrine tumour and develop neuroendocrine differentiation
What syndrome is associated with Gastrinomas, and what are the common resulting pathology
Zollinger-Ellison syndrome
Acid hypersecretion causes extensive peptic ulcers. Most commonly tumour in proximal duodenum
What are the symptoms of carcinoid syndrome and what is the cause. How is it tested for
Flushing, diarrhoea, bronchoconstriction
Due to serotonin and kallikrein secretion from neuroendocrine tumours, usually only if they are metastatic to liver.
Test serum 5HT or urinary 5-HIAA
How do insulinomas usually present
Usually present when small/early due to hypoglycaemia
Which layer of the GI tract do neuroendocrine tumours usually grow in
Either the submucosa, or muscle with normal overlying mucosa
What are the common sites of neuroendocrine tumours in the GI tract
Small bowel most common: ileum
Appendix, rectum, stomach, pancreas
Are the majority of well differentiated neuroendocrine tumours functioning or non-functioning
Non-functioning
What percentage of adrenal adenomas are functional
15%
What are the two most common products of functional adrenal adenomas
Aldosterone: causes hypertension and low potassium
Cortisol: (independent of ACTH control) causes Cushing syndrome; central obesity, poor healing, striae, hirtuitism
What syndromes is adrenocortical carcinoma associated with
Mostly sporadic
Li Fraumeni
Lynch
What are microscopic features of adrenal cortical carcinoma
Thick fibrous capsule
Necrosis
Vascular or capsular invasion
Increased mitotic activity
Solid or nested growth
What tool is used to attempt to distinguish adrenal cortical adenoma from adrenal cortical carcinoma, what are it’s components
Modified Weiss criteria
Mitotic rate >6 per 50 HPF
Cytoplasm clear vs compact
Abnormal mitosis
Tumour necrosis
Invasion of capsule
Aside from the Weiss criteria, what two things can be used to distinguish adrenal cortical adenoma and carcinoma
Ki67: >5% associated with carcinoma
Loss of reticulum framework between clusters of cells + one of tumour necrosis, high mitotic rate, venous invasion
What is a myelolipoma
A benign mass, second most common adrenal neoplasm
Microscopically contains mature fat and bone marrow elements
Can be diagnosed on imaging due to high fat content
What part of the adrenal do phaeochromocytoma arise from
The adrenal medulla
What proportion of pheochromocytoma are considered malignant
All are. But rarely metastasize.
What can pheochromocytoma produce, and what are the resulting symptoms
Catecholamines
-hypertension, headache, tachycardia, palpitations, sweating
What are some typical microscopic features of pheochromocytoma
Nested architecture
Purple cytoplasm
Rich vascularity (frequently haemorrhage)
What is the typical IHC pattern of pheochromocytoma
Chromogranin, synaptophysin diffuse positivity
S100
SOX10
Negative: cytokeratins, SF1, Inhibin
What type of tumour are paragangliomas functionally and morphological related to
Pheochromocytoma
Where can paragangliomas arise
Arise from extra-adrenal paraganglia
Head and neck: arise from parasympathetic nerves. Generally non functional and good prognosis
Sympathetic paragangliomas: arise from pre sympathetic and parasympathetic chains. Frequently functional and same risks as pheochromocytoma
What is the IHC profile of angiosarcoma
cD31, CD34 positive (vascular markers)
MYC+ in radiation/lymphoedema associated tumours
HHV8- (kaposi is key differential)
