ONCOLOGY

Question 1

Lynch:
- gene, assoc cancers, management

Answer 1

GENE
- HNPCC

CANCERS
- endometrial, ovarian, gastro, pancreatitis

TX
- scopes 1-2 years from age 25, 5 years younger than youngest fam member

Question 2

BRAF wild type in CrCa means

Answer 2

test for germline mutation

Question 3

CrCa MLH1 absence; what makes it suspicious for germline mutation?

Answer 3

If NON methylated

Question 4

FAP:

Answer 4

Loss of APC (adenomatous polyposis coli) gene
Can also be related to MUTYH-loss polyposis < 1%

	○ Autosomal dominant with high penetrance 
		§ Germaline APC mutation 
		§ 90%+ risk of developing CRC by age 45 

Associations with other cancers
§ Thyroid
§ Gatric
§ Ileal

Investigations
§ Thousands of adenomatous polyps in large bowel –> ‘carpet of adenomas’
§ Occurs throughout colon

Surveillance
Colonoscopy from 10-15 years, earlier if symptomatic

Question 5

FAP:
- gene, assoc cancers, management

Answer 5

GENE
- APC/ MUTYH-loss

CANCERS
- gastric, ill, thyroid

TX
- scopes from 10-15 years OR when symptomatic

Question 6

Highest risk factor for CrCa?

Answer 6

Fam Hx ESP if young
UC/Crohns

Question 7

Where does CrCa metastasise?

Answer 7

rectum distal: lungs
other: liver

Question 8

CrCa screening for:
- average risk
- moderate risk
- high risk

Answer 8

AVERAGE RISK
- iFOBT every 2 years from 50

MOD RISK
- iFOBT every 2 years 40
- colonoscopy every 5 years from 50

HIGH RISK
- iFOBT every 2 years from 35
- colonoscopy every 5 years from 45

Question 9

Colonoscopy FU?

Answer 9

1-2 adenomas + low risk: 5 years scope
3-4 adenomas OR high risk: 3 years scope
5-10 adenomas: yearly, if >10 then less than yearly

Question 10

Breast Cancer screening?

Answer 10

Every 2 years
50-75

MRI if fam hx/radiotherapy

Question 11

Cervical Cancer screening?

Answer 11

Every 5 years
25-75

Checks for high risk oncogenic types: 16,18

Question 12

When to suspect BRCA?

Answer 12

○ Ashkenazi Jewish heritage
○ First degree relative with breast cancer before 50
○ History of ovarian cancer at any age
- SEROUS HIGHEST RISK
○ 1st/2nd degree relative with ovarian cancer
○ Breast + ovarian cancer in same person
○ >=2 2nd degree relatives with breast cancer
○ Patient/relative bilateral breast cancer
○ Male breast cancer in relative

Question 13

Significance of BRCA 1 + BRCA2?

Answer 13

BOTH: bilateral cancers, earlier age, invasive ductal carcinomas

(1)
(ovarian, colon, prostate)

(2)
ovarian, colon, prostate, pncreatic, GB, bile duct, stomach, melanoma

Question 14

BRCA cancer prevention options?

Answer 14

Risk-reducing mastectomy and reconstruction
○ Still at risk because does not remove all vreast tissue
Risk-reducing salpingo-oophorectomy
Intensive surveillance for breast and ovarian cancer
Mammogram every 12 months
Breast exam every 6 months beginning at age 25

Question 15

Other causes of elevated Ca 19-9?

Answer 15

• Ovarian cyst
  
  • Heart failure
  • Hashimotos
  • RA
  • Diverticulitis
  • Cholidocholithiasis
  • Cholangiocarcinoma
    
    • GB cancer

Question 16

Tumour marker for SCLC?

Answer 16

Neuron specific enolase

Question 17

Tumour marker for neuroendo tumours

Answer 17

Chromogranin A

Question 18

Cell Cycle

Answer 18

IPMAT!

Interphase
- G1
- DNA synthesis
- G2

Protaphase/ pro metaphase
- Chromatin condenses into chromosomes
- nuclear membrane breaks down
- centromeres start moving apart

Metaphase
- Chromsomes lien up at centre

Anaphase
- break at centromere and move to app sides of cell

Telaphase
- Nuclear membrane reforms and cell splits into 2

Question 19

Mechanism of cell apoptosis?

Answer 19

increased nuclear kappa b –> IAP bcl2 oveexpressed –> antiapoptosis

E.g. BCL2 drugs reduce anti-apoptosis proteins
Bortezeimib anti proteasome reduces nuclear kappa b

Question 20

Mechanism of metastasis?

Answer 20

Tumour cell breaks off from main tumour and enters ECF
§ Secretes MMP –> ECM degraded –> bases through basement membrane
§ MMP also breaks ECM of blood vessel too
Tumour migrate through tight junctions of epithelial cells –> blood vessel –> other tissues

Question 21

Genetics for ALK mutation?

Answer 21

Chromosomal rearrangement

Question 22

Workup of cancer of unknown origin?

Answer 22

○ FBC, UEC
○ Urine
○ PSA
○ CTCAP
○ Mammography
○ IHC based on above
§ If still having difficulties
□ molecular cancer assay
Tumour markers

Question 23

To have a BRCA mutation cause breast cancer, you need to be
- heterozygous?
- homozygous

Answer 23

Homozygous

Question 24

Thymoma associations?

Answer 24

LEMS
MG
Pure cell aplasia
Combined immunodeficiency with hypogammaglobulinemia