Flashcards in Cancer predisposition syndromes Deck (24)
- Molecular defects
- Associated tumors
- Surveillance protocol
1) Loss of imprinting (paternal uniparental disomy) at chr 11q15
2) Most commonly: Wilms tumor, hepatoblastoma
3) Until 4 years of age: abdo US q 3 months, AFP q 3 months
Until 8 years of age: renal US q 3 months
Name 6 associated tumors
- Pleuro-pulmonary blastoma
- Cystic nephroma
- Pineoblastoma, CNS PNET, pituitary blastoma
- Sertoli-Leydig neoplasms
- Thyroid cysts
- Wilms tumor
(- Intra-ocular medulloepithelioma)
Name cancer predisposition syndromes linked to a DNA repair defect
- Fanconi anemia
- Bloom syndrome
- Ataxia telangiectasia
- Nijmegen breakage
Neuro-cardio-facio-cutaneous syndrome: what pathway is mutated?
Name 4 examples of neuro-cardio-facio-cutaneous syndromes
List 7 malignancies encountered in Li-Fraumeni syndrome
- Choroid plexus carcinoma
- Adrenocortical carcinoma
- Bone sarcomas
- Soft tissue sarcomas
- Leukemia (especially hypodiploid ALL)
- Breast cancer of early onset
- Lung cancer
Outline surveillance protocol for Li-Fraumeni syndrome
- Bloodwork q 3-4 months: CBC, ESR, LDH, hormonal levels
- Whole body MRI q 1 year
- Brain MRI q 1 year
- Abdo-pelvic US q3-4 months
Outline surveillance protocol for DICER1 syndrome
Chest CT @ 3-6 months of age, and @ 2.5-3 yrs
Chest X-R q 6 months until age 8
Abdo and renal U/S + Neck and thyroid U/S q 6 months (at SickKids)
Brain MRI if Sx
List 6 tumors associated with Von Hippel Linday
- Hemangioblastoma (retina, cerebellum)
- Pancreatic and renal cysts
- Renal cell carcinoma
- Pheochromocytoma, paraganglioma
- Endolymphatic sac tumors
Outline the surveillance protocol in Von Hippel Lindau syndrome
- Whole-body MRI q 1y
- Ophtalmology exam q 1y
- Plasma fractionated metanephrines q 1y(starting age 2)
- Audiology q 2y (starting age 5)
- Brain MRI q 2y (starting age 8)
- Abdominal MRI q 1y (starting age 10)
What are the genes implicated in Gorlin syndrome?
- PTCH1 (chr 9); most common
- SUFU (chr 10); strongly associated with medulloblastoma
What physical abnormalities are seen in Gorlin syndrome?
Palmar and plantar pits
What tumors are associated with Gorlin syndrome (4)?
- Basal cell carcinoma
- Odontogenic keratocysts
- Cardiac and ovarian fibromas
What surveillance protocol is suggested for patients with Gorlin syndrome?
- Skin exam q 1y
- Echocardiography *1 in infancy
- Dental exam, jaw X-R 12-18 months (starting age 8)
- Ovarian US *1 @ 18 y.o.
- If SUFU: brain MRI 4-6 months
What genes are implicated in bMMRD?
MLH1, MSH2, MSH6, PMS2
Autosomal recessive inheritance
What is the most prevalent phenotypic features in bMMRD?
- Cafe au lait spots
- High grade gliomas
- Colorectal cancer
Outline the suggested surveillance protocol in bMMRD?
- Brain MRI q 6m
- CBC q 6m (starting age 1)
- Abdominal US q6m (starting age 1)
- Colonoscopy q 1y (starting age 4-6)
- Whole body MRI q 1y (starting age 6)
What is the tumor spectrum in familial adenomatous polyposis?
- Colorectal adenomas and carcinomas
- Desmoid tumors
Management in familial adenomatous polyposis?
- AFP, abdominal US q3months starting age 5
- Colonoscopy q1y starting age 10
- Colectomy usually recommended in adolescence
What causes familial adenomatous polyposis?
APC gene mutation (chr 5)
= tumor suppressor gene
When a genetic origine should be suspected in the setting of Wilms tumor? (5)
- Nephrogenic rests
- Bilateral tumors
- Young age at presentation
- Histology: stromal predominant
- Associated GU abnormalities, cryptorchidism, hypospadias
When should one suspect a cancer predisposition syndrome in the setting of osteosarcoma?
- Young age at presentation
- Short stature
- Dysmorphisms: facial, poikiloderma
- Sun sensitivity
When should one suspect a cancer predisposition syndrome in the setting of hematological malignancy?
- Cafe-au-lait macules, or other NF1 features
- Low hypodiploidy
- High toxicity of treatment