6. Familial tumour syndromes

Question 1

Definition of familial tumour syndromes

Answer 1

Also known as neurocutaneous syndromes; tumours/hamartomas found in skin & nervous system; often autosomal dominant inheritance

Question 2

Types of familial tumour syndromes

Answer 2

1. Neurofibromatosis-1
2. Neurofibromatosis-2
3. Tuberous sclerosis
4. Von hippel-lindau syndrome

Question 3

Features of neurofibromatosis-1

Answer 3

1. Neural tumours: neurofibroma (skin, VII nerve, spinal cord nerve roots), meningioma, optic nerve glioma, pheochromocytoma
2. Cutaneous, musculoskeletal & renal abnormalities
3. Risk of sarcomatous transformation of
   neurofibromas → malignant nerve sheath tumours

Question 4

Molecular pathogenesis of neurofibromatosis-1

Answer 4

Loss of 17q (NF-1 gene) which encodes neurofibromin (tumour suppressor regulating signal transduction)

Question 5

Features of neurofibromatosis-2

Answer 5

Neural tumours: VIII nerve Schwannoma, meningioma, ependymomas of spinal cord

Question 6

Molecular pathogenesis of neurofibromatosis-2

Answer 6

Loss of 22q (NF-2 gene) which encodes merlin

tumour suppressor regulating membrane receptor signaling, including contact inhibition

Question 7

Features of tuberous sclerosis

Answer 7

1. Brain: cortical tubers & hamartomas
2. Renal angiomyolipomas
3. Skin lesions: adenoma sebaceum, shagreen patch, ungula fibromas
4. Lung lesions

Question 8

Molecular pathogenesis of tuberous sclerosis

Answer 8

TSC 1 (encodes hamartin) & TSC 2 (encodes tuberin)
genes, whose protein products combine to form a complex which inhibits the kinase mTOR (responsible for controlling protein synthesis & cell size)

Question 9

Features of von-hippel-lindau syndrome

Answer 9

1. Hemangioblastomas affecting cerebellum & retina
2. Renal cell carcinoma
3. Pheochromocytoma
4. Endolymphatic sac tumour (inner ear)
5. Cysts involving pancreas, liver, kidneys, adrenals

Question 10

Molecular pathogenesis of von-hippel-lindau syndrome

Answer 10

VHL gene (3p25-p26) which encodes pVHL, a
tumour suppressor that is a component of a ubiquitin ligase complex responsible for the downregulation of hypoxia-induced factor 1

Question 11

Morphology of von-hippel-lindau syndrome

Answer 11

1. Grossly: tumour stuck onto meninges

2. Histologically: psammoma bodies