Lynch -- HNPCC Flashcards
If a person has lynch syndrome, what does this greatly increase the risk of developing?
Colorectal cancer
Endometrial cancer
Brain cancers (gliomas)
Other malignancies
T/F Lynch syndrome is the most common familial cause of colorectal cancer
T
What percentage of CRCa cases does Lynch syndrome account for?
3%
What is the genetic basis for lynch syndrome?
Germline mutation in one of several DNA mismatch repair genes, or loss of expression of MSH2 due to deletion in the EPCAM gene
What mismatch repair genes are associated with lynch syndrome?
MLH1, MSH2, MSH6, PMS2
What malignancies are more common in Lynch syndrome patients?
Colorectal cancer
Endometrial cancer
Ovarian, gastric, small bowel, hepatobiliary, TCC of renal pelvis and ureter, and brain
What is the Muir-Torre variant of Lynch syndrome associated with?
The normal malignancies of Lynch, plus sebaceous tumours and cutaneous keratoacanthomas
What does Turcot syndrome describe?
Historical term describing the link between familial CRC and brain tumours
What is the modern understanding of the link described by Turcot syndrome?
That the link between CRC and medulloblastomas is familial adenomatous polyposis
And the link between CRC and gliomas is Lynch syndrome
What is the main thing that will make a clinician suspicious of Lynch?
Familial CRC
+/- multiple malignancies
What are the two risk factor criteria for determining who is at risk of developing Lynch?
Amsterdam II and Bethesda
What is a good way to remember the Amsterdam II criteria?
3-2-1 rule
3 affected family members, 2 generations, 1 diagnosed under 50 years
T/F The Amsterdam criteria is more sensitive, Bethesda more specific
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
What is the sensitivity and specificity of MSI testing for Lynch syndrome?
85% and 90%
In what clinical scenario should one consider Lynch syndrome?
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
What are some key DDx’s for Lynch syndrome?
Attenuated familial adenomatous polyposis (AFAP)
Constitutional mismatch repair deficiency syndrome (occurs much earlier in life)
What is the average lifetime risk of developing CRC in Lynch syndrome patients?
70%
Which side of the colon is CRC development more common in Lynch syndrome patients?
The right hand side (ie, ascending colon)
Morphologically, how are the adenomas that CRCs in Lynch arise from different from sporadic adenomas?
They tend to be larger, flatter, more proximal
Higher grade of dysplasia
Faster adenoma-carcinoma sequence (ie 35 months, vs 10 to 15 years)
How do patients with Lynch syndrome typically first present?
With symptoms of CRC such as GIT bleeding, abdo pain, change in bowel habits
What percentage of patients with Lynch syndrome have other malignancies at the time of first diagnosis?
7-10%
T/F because of higher adenoma-carcinoma sequence, CRCs from Lynch syndrome are more fatal at 5 years than sporadic CRC
F
Overall 5 year survival from CRC in Lynch syndrome is higher as compared with sporadic CRC
Who should receive screening for extra-colonic cancers when considering Lynch syndrome?
h
