A 20 minute presentation in Question and Answer format on Serrated Polyposis Syndrome and Lynch Syndrome.

1. HIGH RISK CANCER SYNDROMES
- A PRACTICALAPPROACH
20 MINUTES,
ANSWER 20 QUESTIONS,
TWO SYNDROMES: SERRATED P. SYN.
AND LYNCH SYNDROME
Douglas Riegert-Johnson, MD
Gastroenterology
Medical Genomics
Hyperlinks to references Additional slides attached as
addendum.

2. NO CONFLICTS OF
INTEREST.
NO OFF LABEL DRUG
INDICATIONS DISCUSSED.

3. 3 Questions for a Medical Geneticist
• Usefulness of direct to consumer genetic testing (23andme)?
• Limited value in the general GI practice. Useful, and
usually accurate, for ancestry testing, connecting relatives,
and carrier testing for a few diseases (HFE).
• Is gene therapy available for GI disease?
• No. Two non GI inherited diseases have an approved gene
therapy – Leber’s hereditary optic neuropathy (RPE65
mutations) (US) and Lipoprotein Lipase Deficiency
(Europe).
• Can I have my genome sequenced and the results given to
me in accessible format?
• Closest easily accessible commercially available product is
testing of 1,691 of 22,000 genes ($9,500 cash up front,
Illumnia).
3

4. Serrated Polyposis Syndrome
and Lynch Syndrome are the most
commonly seen syndromes in GI practice
Prevalence of both about 1 in 200.
For comparison, prevalence of Familial Adenomatous
Polyposis (FAP) is less than 1/1000.
If you have FAP, PJS, JP cases or other cases you would
like to discuss, please ask at the Q and A session or see
me after.

5. TAKE AWAYS: What are the shared
features of both Serrated Polyposis
Syndrome and Lynch Syndrome?
• Prevalence about 1 in 200.
• As a general rule, surveillance colonoscopy
recommended every year, but still there is a residual
colorectal cancer risk.
• About 1/200 CRC per year for SPS with yearly colonoscopy, about
1/100 for LS.
• Risk is cumulative, so LS 10 years f/u 10% chance of colorectal
cancer.
• Surgery for polyps not usually needed.
Serrated polyposis syndrome cancer risk Gut 2016.
Lynch syndrome colon cancer risk with interval colon cancer.

6. SPS LS
Similarities
✔ ✔ Prevalence about 1/200
✔ ✔ As a general rule, colonoscopy
every year, cumulative ½ to 1%
colorectal cancer risk.
✔ ✔ Polyps usually controlled
without surgery
Differences
✖ ✔ Referral to a genetic counselor
✖ ✔ Extra colonic cancers (especially
endometrial) with a high enough
risk to require surveillance

7. Serrated Polyposis Syndrome
Recurrent growth of a mucus covered serrated polyp at site
of previous EMR scar.

8. Serrated Polyposis Syndrome.
Who has it?
Part 1: What is a serrated polyp?
Slide with Serrated Polyp Histology in Addendum.
Any of the three types of serrated polyps
qualify for WHO SPS criteria,
sessile serrated polyp
hyperplastic
traditional serrated adenoma.

9. Serrated Polyposis Syndrome
Who has it?
Part 2: Tips to remember WHO criteria.
5 ✕ 2 = 10
5 serrated
polyps
proximal to
sigmoid
2 are
> than 10
mm
Patients close to meeting criteria on
initial colonoscopy, usually do meet
criteria on follow up.
>20
More
than
>20
serrated
polyps
through
the
colon
1 serrated
polyp in an
individual
with 1 st
degree
relative
with SPS
1/ 1st

10. Does Serrated Polyposis Syndrome
mimic Lynch Syndrome? Do SPS patients
need to be tested for Lynch syndrome?
No.
Lynch syndrome does not commonly present as
serrated polyposis syndrome.
LS patient do not have serrated polyps more often than
the general population. LS serrated polyps.

11. What causes SPS?
1. Unknown.
It is not caused by heritable traits with
a strong effect. Unlike Lynch syndrome and FAP,
which are caused by mutations in single genes.
2. Smoking.
Typically hyperplastic polyp predominant (not sessile
serrated polyp). If smoking is stopped, polyps regress.
3. Genetic traits, very rare. Commercial genetic testing not available
for most. Genetic testing not recommended.

12. Can SPS polyps be controlled with
colonoscopy? Or is surgery needed?
• Usually 3 colonoscopies needed to remove all polyps in
SPS patients.
• Surgery is not often needed, but is an option.
• In patients where all polyps appear to have been
removed, follow up cancers are rare with colonoscopy
every year, 1/200 chance per year.
• One study, 260 SPS patients under surveillance with 2
colorectal cancers dx, 1 CRC for about every 500 years of
screening.
Clinical risk factors for cancer in SPS. Dutch 2015.26603485.

13. Serrated Polyposis Syndrome
Only one patient I have had with
SPS has gone to surgery.
After 13 colonoscopies b/t 43yo to 61
yo, there were still 10 polyps > 20 mm.
Patient concerned about eventually
not being healthy enough for
colonoscopy or surgery. He elected to
have a subtotal colectomy (IRA).
Surgery was without complications.

14. Can you ever increase the interval
between colonoscopies for SPS?
Do I have to have a colonoscopy
every 12 months?
It has been proposed, but not written in guidelines,
The interval can be increased to 2 years, if there are 2
successive colonoscopies where,
• Less then 10 polyps
• No polyps > 10 mm
• No polyps with HGD
Gut commentary on SPS 2016

15. What are the colonoscopy recommendations for
family members of SPS patients?
• Only 1 in 7 first degree relatives of SPS patients will have
SPS. Most SPS patients will not have a relative with SPS.
• First degree relatives of SPS patients should have
colonoscopy at age 40 or 10 years prior to index patient’s
diagnosis of SPS.
Serrated polyposis family member reference.

16. LYNCH SYNDROME
COLON CA, ENDOMETRIAL CA.
Caused by mutations in 1 of 5 genes
involved in DNA mismatch repair-
MMR Genes (MLH1, MSH2 > MSH6, PMS2, EPCAM).
Term HNPCC no longer used.

17. What is the gastroenterologist’s role in the
diagnosis of Lynch Syndrome?
• 2018
Patients with a diagnosis of colorectal cancer –
NOT MUCH.
• Almost all colorectal cancer patients should have a
screening test for Lynch syndrome initiated by the
pathologist completed on their tumor slides.
• This test is immunohistochemistry for the Lynch syndrome
gene. This same test predicts response to
immunotherapies.
• Positive tumor screening testing > Genetic counselor, or
testing by oncologist.

18. ? No personal history of colon or
endometrial cancer, but a family history of
cancer
Consider evaluating for Lynch syndrome if
• Two colon or endometrial cancers in first and/or second
degree relatives. (EG sister with colon CA, mother with
endometrial CA)
• A colon cancer under 50 in a first degree relative
If relative’s colon cancer diagnosed in 2018, then the
relatives were likely already screened.

19. What is the GIs role in caring for patients
with Lynch syndrome?
• Stress compliance with colonoscopy.
• Provide quality colonoscopy.
• Referral to genetic counselors, GYN, patient support
groups.

20. Compliance is Key.
Link to Canadian study of colonoscopy in patients with Lynch syndrome (MSH2)
68 Women with Lynch syndrome (MSH2)
Colonoscopy recommended every 1-2 years
28 Colonoscopy on
schedule
14% Colon CA
Age at colon cancer
diagnosis 79 years
Median survival 80 years
40 Colonoscopy not on
schedule
17% Colon CA
Age at colon cancer
diagnosis 57 years
Median survival 63 years

21. > 2 Year Interval – 5 cancers
1-2 Year Interval – 4 cancers
< than 1 year – 2 cancers
0
1
2
3
4
5
6
7
A B C D E F G H I J K
Interval between last colonoscopy and 11 colon cancer
diagnoses (years) (LS MSH2 XX)

22. How to perform colonoscopy for Lynch
syndrome patients.
• Carefully, as always.
• Pay attention to the right colon.
• Chromoendoscopy is optional.
• 4 of 5 studies show increase in adenoma detection for Lynch
syndrome. ? If the degree is clinically significant.
• Is the benefit of the dye or the time the dye forces you to take?
• My practice> Chromoendoscopy.

23. Can you ever increase the interval
between colonoscopies for Lynch
syndrome ?
Do I have to have a colonoscopy every 12
months?
• Guideline recommendations are for colonoscopy initiation
to begin at 20(-25) then every 1-2 years.
• One versus Two Year interval?
• My practice> One year, or about one year.
• NEW: Personalized risk estimates at lscarisk.org.

24. Coming soon!
Personalized recommendations for
Lynch syndrome patients.
• These will be based on an ongoing prospective 1900
patient study in Europe.
• Not in guidelines at this time.

25. Male MSH6

26. What is the current recommendation for
upper endoscopy in Lynch Syndrome
patients?
• Guidelines do not recommend routine EGD.
• My practice: I perform an EGD for all new patients.
• Routine EGD is indicated for
• Asians.
• Those with a family history of upper GI cancer.
• Begin EGD 30(-35) yo, q 3(-5) years with colonoscopy.
National Comprehensive Cancer Network
3.2017

27. SPS LS
Similarities
✔ ✔ Prevalence about 1/200
✔ ✔ As a general rule, colonoscopy
every year, cumulative ½ to 1%
colorectal cancer risk.
✔ ✔ Polyps usually controlled
without surgery
Differences
✖ ✔ Referral to a genetic counselor
✖ ✔ Extra colonic cancers (especially
endometrial) with a high enough
risk to require surveillance

28. Serrated Polyposis Syndrome
Who has it?
Part 2: Tips to remember WHO criteria.
5 ✕ 2 = 10
5 serrated
polyps
proximal to
sigmoid
2 are
> than 10
mm
Patients close to meeting criteria on
initial colonoscopy, usually do on
follow up.
>20
More
than
>20
serrated
polyps
through
the
colon
1 serrated
polyp in an
individual
with 1 st
degree
Relative
with SPS
1/ 1st

29. 29

30. END

31. ADDENDUM

32. What are the differences between
Serrated Polyposis S. and Lynch
Syndrome?• Lynch syndrome mutations are inheritable and if you have
one you are likely to be affected.
• LS has extra colonic cancer risks requiring surveillance.
• If possible, suspected Lynch syndrome patients should be
referred for genetic counseling. Directory at
www.nsgc.org. Why?
• Reproductive counseling.
• Testing for Lynch syndrome becoming more and more complex,
NOT less complex.

33. Pre implantation
genetic diagnosis:
Screening embryos for
genetic disease, and
only used if not
affected > risk brought
close to 0.
Other topics reviewed
by the GCs including
genetic discrimination.

34. Why refer to a genetic counselor?
What is the inheritance risk for Lynch
Syndrome?
A: ½ or 50% for each child.

35. Hyperplastic
polyp
Sessile Serrated
Polyp
“The boot”
Traditional serrated
adenoma
“The red fern”

36. Relevance of SSPs
Risk Stratification for Colorectal Cancer in the future
Patients with serrated polyps had higher 10 year colon cancer risk than
patients with adenomas (3.7% @ 10 years)
A population-
based
randomized trial,
12 955
individuals aged
50-64 years
were screened
with flexible
sigmoidoscopy.
Norway Gut 2014