Multiple Endocrine Neoplasia and Neuroendocrine Tumours Flashcards
How can a neuroendocrine tumour be differentiated from a metastatic tumour (stains)?
- Chromogranin-A= blood tests
- Synaptophysin= pathology use
=Grade / lymphovascular invasion etc etc
=Aka major synaptic vesicle protein p38 (SYP gene)
=Synaptic vesicle glycoprotein – present in neuroendocrine cells and brain and spinal cordalso present in the adrenal medulla (think phaeo etc)and pancreatic islet cells, small cell lung cancer and medullary thyroid carcinoma
=Hormone excess symptoms (flushing and diarrhoea)
= 24hr Urine 5-HIAA raised (downstream of serotonin pathway)
What does serotonin cause?
- Flushing
- Diarrhoea
- Bronchospasm (can be hypotensive)
- Right heart failure (serotonin to serotonin heart valves)
Why does right heart failure occur?
-Serotonin from neuroendocrine tumour cleared by enterohepatic circulation
-Too much= enterohepatic circulation overridden= hormones into IVC into right heart= heart valves
=Valve dysfunction (tricuspid regurgitation)
=Hepatic congestion (ascites)
=Peripheral oedema
=Elevated JVP
=Valve fibrosis
What are the clinical characteristics of NETs?
- Rare
- Significant majority arise in GI system (including pancreas)
- Usually slow growing= NETs or neuroendocrine carcinomas (G1-3)
- Wide spectrum of disease activity
- Often metastatic at presentation, late presentation
- Prolonged survival is possible
How can patients present?
- Enlargement of liver capsule= pain
- Indigestion
- Iron deficiency anaemia (GI cancer blood loss)
- Appendicitis
- Large tumour (terminal ileum common)= bowel obstruction, abdominal distention, vomiting and abdominal pain
- Rectal= tenesmus, rectal bleeding
- Pancreatic= CT imaging, abdominal pain, hormone presentation
- Lung= cough, incidental finding, maybe thoracic pain
What hormones are produced by neuroendocrine tumours and how to they present?
- Glucagon= diabetes, hyperglycaemia, rash
- Insulin= insulinoma= hypoglycaemia
- Gastrin= heartburn and multiple peptide ulcers
- Vasoactive intestinal polypeptide (VIP)= perfuse watery diarrhoea 10-15 times a day, hypokalaemia
What are the malignant neuroendocrine tumours?
-Small cell lung cancer (poor prognosis)
What are the benign neuroendocrine tumours?
- Appendiceal carcinoids
- Insulinomas (good prognosis)
- Gastric carcinoids
What are the neuroendocrine tumours that are in-between benign and malignant?
- Non-functioning pancreatic NETs
- Gastrinomas
- Glucagonomas
- Small bowel carcinoids
What are the functioning neuroendocrine tumours?
=produce hormones
- Carcinoids
- Gastrinomas
- Glucagonomas
- Insulinomas
What are the non-functioning tumours?
- Non-functioning NETS
- Bowel and pancreas
What are the primary sites for neuroendocrine tumours?
Mid-gut =appendix (17%) =ileum (16%) =ileo-caecal junction (11%) =caecum (3%)
Fore-gut
=stomach (7%)
=duodenum (4%)
=oesophagus (2%)
Hind-gut
=colorectal (7%)
Unknown (22%)- just finds metastases
How has the incidence of NETs changed?
-Much increased
=prevalence increased as people live longer
=more diagnosis as we are looking for them and are better at diagnosing
How is 5 year survival rates influenced by metastasis?
-Mets= 38%
-No nets= 85%
Overall 40%
What are the treatment options for NETs?
- Active surveillance (no symptoms- side effects of treatments worse)
- Surgery (bowel / pancreatic / hepatic)
- Somatostatin analogue therapy= Lanreotide, expensive drug, octreotide
What are the effects of somatostatin analogues?
- Hormonal levels down for excess serotonin
- Anti-tumour effect= anti-proliferative, slow down rate of change
Describe radionuclide therapy
-MIBG or radiolabelled somatostatin analogues (Lu)
-Must have positive uptake of relevant agent by neuroendocrine tumour
=periphery uptake + radiation crossfire
-Can target the relatively ischaemic central core of metastatic deposits
-Good for symptom control when SA no longer fully effective
-Potential toxicity to bone marrow and kidneys
Describe transarterial chemoemolisation
=localised liver metastasis, deprive of blood supply as molecules block off vessel
- Can be given in most large centres
- Only targets cancer deposits in the liver
- Destructive therapy so potential for rapid release of hormones from the dying cells= carcinoid crisis so lots of octreotide
- This can cause major swings in blood pressure – in both the patient AND the interventional radiologist
Describe multiple endocrine neoplasia
-Arises from tumour suppressor gene problem
=proliferation
-Relatively slow proliferation
=genetics, many screenings
Describe the genetics of multiple endocrine neoplasia
- 1:30,000
- Autosomal dominant inheritance, affects pretty much every generation
What are the genetic defects in MEN1?
- Defect in the MEN1 gene
- Gene product is menin
- Tumour suppressor gene
- Chromosome 11
What are the clinical features of MEN1?
3 Ps= pituitary, pancreas and parathyroid
- Primary hyperparathyroidism
- Pituitary adenomas
- Pancreatic tumours (functional or non-functional)
- Adrenal adenomas
- Bronchial / Thymic carcinoids
- (lipomas / angiofibroma)
How do we screen for MEN1?
-Annual calcium and PTH
-Annual fasting gut hormones
=Chromogrannin A, insulin-glucose, gastrin glucagon, pancreatic polypeptide
-3 yearly MRI of pituitary and now pancreas
-Consideration for CT / MRI of chest and thymus
What are the genetic defects in MEN2?
- Defect in the MEN2 gene
- Gene product is ret
- Proto-oncogene gene
- Chromosome 10
What are the clinical features of MEN2?
-2A (85%) =Hyperparathyroidism =Medullary thyroid cancer (prophylactic thyroidectomy) =Phaeochromocytoma -2B (5%) =Hyperparathyroidism =Medullary thyroid cancer =Phaeochromocytoma =neuromas, fibromas, musculoskeletal abnormalities =Marfanoid habitus -Familial medullary thyroid cancer (15%)
