MEN syndrome Flashcards
Define hyperplasia
Increase in the number of cells in tissue or organ in response to a stimulujs
How many parathyroid glands are mostly affected by hyperplasia?
The 4 glands
What is the microscopic picture of hyperplasia of parathyroid?
-Microscopically, the most common pattern seen is that of chief cell hyperplasia, which may involve the glands in a diffuse or multinodular pattern
-Less commonly, the constituent cells contain abundant water-clear cells (‘water-clear cell hyperplasia)
-In many instances there are islands of oxyphils, and poorly developed, delicate fibrous strands may envelop the nodules
The patient developed stupor, confusion and hypoglycaemia, why do you think that happened?
Scenario: man with parathyroidectomy, pancreatic mass
Insulinoma
What cells are insulinomas derived from?
Beta cell of islets of langerhans
What other causes of unresponsive hypoglycaemia do you know?
-Abnormal insulin sensitivity
-Diffuse liver disease
-Inherited glycogenoses
-Ectopic production of insulin by certain retroperitoneal fibromas and fibrosarcomas
What is the clinical picture of insulinoma?
-Confusion
-Stupor
-Loss of consciousness (blood glucose 2.5mmol/L or less)
–> these episodes are precipitated by fasting or excercise
–> promptly relieved by feeding or parentaral administration of glucose
Biochemical diagnosis of insulinoma
-High circulating levels of insulin
-High insulin to glucose ratio
What do you suspect as another pathology in this patinet?
Scenario: man with parathyroidectomy, pancreatic mass
MEN 1
What gene mutations occur in insulinoma?
-MEN 1 (also implicated in a number of sporadic neuroendocrine tumours)
-Loss of function mutations in tumour suppressor genes which result in activation of oncogenic mammalian TOR (mTOR) signalling pathway (PTEN)
-Inactivation in genes involved in telomere maintenance e.g. death-domain associated protein (DAXX)
What is the two hit hypothesis?
-Like all genes, tumour suppressor genes may undergo a variety of mutations: however, most loss of function mutations that occur in tumour suppressor genes are recessive in nature. Thus, in order for a particular cell to become cancerous, both of the cell’s tumour suppressor genes must be mutated. This idea is known as the ‘two hit’ hypothesis.
What is a telomere?
-A telomere is a region of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighbouring chromosomes.
What is apoptosis?
Programmed cell death.
Scenario: female with thyroid nodule, elevated calcitonin levels
What is the single best test to diagnose?
FNAC
Pathology report: FNAC showed malignant cell features, amyloid deposits, immunohistochemistry stains positive with calcitonin, stains negative for thyroxine
What type of cancer is this and why?
-Medullary thyroid cancer
-Amyloid deposits, calcitonin positive on IHC
What cells are present in medullary thyroid carcinoma?
-Parafollicualr C cells
What is IHC in simple words
-Method of localising specific antigens in tissues or cells based on antigen-antibody recognition
How does IHC work?
-Antibodies are linked to an enzyme or fluorescene dye. When the antibodies bind to the antigen in the tissue sample, the enzyme or dye is activated, and the antigen can then be seen under a microscope.
What is the type of antigen-antibody reaction in IHC?
-Complement fixation
What is TNM thyroid
-Tx: cannot be assessed
-T0: no evidence f primary
-T1: limited to thyroid, 1cm or less
-T2: limited to thyroid >1cm but <4cm
-T3: limited to thyroid >4cm
-T4: extending beyond capsule, any size
If patient developed hypertension, what do you think they might have?
Phaeochromocytoma
How do you diagnose phaeochromocytoma?
Plasma:
-Gold standard: free metanephrine
-Chromogranin A can be raised but is non specific
Urine
-24 hr urinary metanephrine if plasma metanephrine unavailable
Imaging:
Localisation
–> CT
–> MRI
Functional imaging
–> PET
–> MIBG scintigraphy
If phaeochromocytoma was familial (MEN 2a) what other condition would you suspect?
-Hyperparathyroidism secondary to parathyroid hyperplasia
Describe MEN 1/causative gene
Three P;s
-Parthyroid (95%): parathyroid adenoma
-Pituitary (70%): prolactinoma/ACTH/Growth hormone secreting adenoma
-Pancreas (50%): islet cell tumours/zollinger ellison syndorme
Most common presentaiton = hypercalcaemia
MENIN gene (chromosome 11)
Autosomal dominant
Describe MEN 2
2a
-Hyperparathyroidism (usually hyperplasia)
-Phaeochromocytoma
-Medullary thyroid cancer
RET oncogene (chromosome 10)
Autosomal dominant
2b:
Same as 2a with addition of:
–> marfanoid body habitus
–> mucosal neuromas
RET oncogene (chromosome 10
Autosomal dominant
How would you treat medullary thyroid cancer?
-Total thyroidectomy with block neck dissection
