Lynch -- HNPCC

Question 1

If a person has lynch syndrome, what does this greatly increase the risk of developing?

Answer 1

Colorectal cancer

Endometrial cancer

Brain cancers (gliomas)

Other malignancies

Question 2

T/F Lynch syndrome is the most common familial cause of colorectal cancer

Answer 2

T

Question 3

What percentage of CRCa cases does Lynch syndrome account for?

Answer 3

3%

Question 4

What is the genetic basis for lynch syndrome?

Answer 4

Germline mutation in one of several DNA mismatch repair genes, or loss of expression of MSH2 due to deletion in the EPCAM gene

Question 5

What mismatch repair genes are associated with lynch syndrome?

Answer 5

MLH1, MSH2, MSH6, PMS2

Question 6

What malignancies are more common in Lynch syndrome patients?

Answer 6

Colorectal cancer

Endometrial cancer

Ovarian, gastric, small bowel, hepatobiliary, TCC of renal pelvis and ureter, and brain

Question 7

What is the Muir-Torre variant of Lynch syndrome associated with?

Answer 7

The normal malignancies of Lynch, plus sebaceous tumours and cutaneous keratoacanthomas

Question 8

What does Turcot syndrome describe?

Answer 8

Historical term describing the link between familial CRC and brain tumours

Question 9

What is the modern understanding of the link described by Turcot syndrome?

Answer 9

That the link between CRC and medulloblastomas is familial adenomatous polyposis

And the link between CRC and gliomas is Lynch syndrome

Question 10

What is the main thing that will make a clinician suspicious of Lynch?

Answer 10

Familial CRC

+/- multiple malignancies

Question 11

What are the two risk factor criteria for determining who is at risk of developing Lynch?

Answer 11

Amsterdam II and Bethesda

Question 12

What is a good way to remember the Amsterdam II criteria?

Answer 12

3-2-1 rule

3 affected family members, 2 generations, 1 diagnosed under 50 years

Question 13

T/F The Amsterdam criteria is more sensitive, Bethesda more specific

Answer 13

F

Amsterdam has specificity of 98% but only sensitive for 22%, meaning it can rule people out

Bethesda only has specificity of 77%, but sensitive at 82% meaning it’s more powerful at ruling people in

Question 14

What is the sensitivity and specificity of MSI testing for Lynch syndrome?

Answer 14

85% and 90%

Question 15

In what clinical scenario should one consider Lynch syndrome?

Answer 15

In a patient with synchronous or metochronous CRC

CRC prior to 50 years of age

Multiple Lynch associated malignancies

In cases with familial clustering of Lynch syndrome associated malignancies

Question 16

What are some key DDx’s for Lynch syndrome?

Answer 16

Attenuated familial adenomatous polyposis (AFAP)

Constitutional mismatch repair deficiency syndrome (occurs much earlier in life)

Question 17

What is the average lifetime risk of developing CRC in Lynch syndrome patients?

Answer 17

70%

Question 18

Which side of the colon is CRC development more common in Lynch syndrome patients?

Answer 18

The right hand side (ie, ascending colon)

Question 19

Morphologically, how are the adenomas that CRCs in Lynch arise from different from sporadic adenomas?

Answer 19

They tend to be larger, flatter, more proximal

Higher grade of dysplasia

Faster adenoma-carcinoma sequence (ie 35 months, vs 10 to 15 years)

Question 20

How do patients with Lynch syndrome typically first present?

Answer 20

With symptoms of CRC such as GIT bleeding, abdo pain, change in bowel habits

Question 21

What percentage of patients with Lynch syndrome have other malignancies at the time of first diagnosis?

Answer 21

7-10%

Question 22

T/F because of higher adenoma-carcinoma sequence, CRCs from Lynch syndrome are more fatal at 5 years than sporadic CRC

Answer 22

F

Overall 5 year survival from CRC in Lynch syndrome is higher as compared with sporadic CRC

Question 23

Who should receive screening for extra-colonic cancers when considering Lynch syndrome?

Answer 23

h