Serrated lesionsWorkshop Population Screening

Iris Nagtegaal

(potentiële) belangenverstrengeling Geen / Zie hieronder

Voor bijeenkomst mogelijk relevante relaties met bedrijven Bedrijfsnamen

• Sponsoring of onderzoeksgeld• Detachering

• Amgen, KWF, MLDS• FSB (screeningsorganisaties)

Disclosure belangen spreker

Serrated lesions• Hyperplastic polyps• Sessile serrated lesions with or without dysplasia• Traditional serrated adenoma• Serrated carcinoma

Why should we discuss serrated lesions?

Question 1• Serrated lesions are considered the precursor lesion of• A) less than 5% of CRC• B) 25% of CRC• C) 50% of CRC

25% of CRC develop arise via the serrated route

A global and simplified model of the serrated neoplasia pathway

IJspeert, J. E. G. et al. (2015) Serrated neoplasia—role in colorectal carcinogenesis and clinical implicationsNat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2015.73

There are many serrated lesions in the population screening

• In 2014 – 2015*: • 15,308 patients with at least one histologically confirmed serrated polyp• 27,879 serrated lesions

• Compare with data screening overall in 2014**:• 741,914 invited / 529,056 participated• Detection of 2,483 CRC and 12,030 advanced adenomas

*Ijspeerdt et al, in preparation , ** Toes-Zoutendijk, submitted

Hyperplastic polyps• New BSCP definition:

• Small serrated lesions showing no features that would allowcategorisation as SSL and no evidence of dysplasia

• WHO definition:• Elongation of straight crypts with variable degrees of serration;

serration developing in the more luminal aspects and proliferation is located in the lower third of the crypts

Hyperplastic polyps: subtypes• Microvesicular subtype, most common• Decreased number of goblet cells• Vesicular mucin containing• BRAF mutations

Hyperplastic polyps: subtypes• Goblet cell rich subtype, one-third of HP• Goblet cells• KRAS mutation

Hyperplastic polyp: subtypes• mucin-poor subtype, rare• Atrophic epithelium• Regenerative changes ?

Sessile serrated lesionsSSA/SSP/SSL

“Complex sister” of the HP• Irregular distribution of crypts• Dilatation of crypt bases• Serration present at crypt bases• Branched crypts• Horizontal extension of crypts• Herniation of crypts though the muscularis mucosa

Two or three adjacent characteristic crypts is minimum requirement (WHO)

T and L shapes (anchors & hooks)

Hyperplastic polyps versus SSL• In 2014 – 2015: 27,879 serrated polyps

• 76.1% hyperplastic polyps• 23.9% sessile serrated lesions• TSA: not included in this study• 3.4% dysplastic (n = 944)

Ijspeerdt et al, in preparation

N (total)N (%) of SSL Univariate OR (95% CI)† p-value

Age≤65 yr>65yr

12.159 15.720

2973 (24.5)3686 (23.4)

10.92 (0.83-1.02)

0.10

SexMaleFemale

17.298 10.581

3.996 (23.1)2.663 (25.2)

11.24 (1.12-1.38)

<0.001

Synchronous adenomaAbsentPresent

5.59522.284

1.227 (21.9)5.432 (24.4)

11.24 (1.09-1.41)

<0.001

Synchronous CRCAbsentPresent

26.7591120

6355 (23.7)304 (27.1)

11.28 (0.99-1.66)

0.06

Localization* Distal colonProximal colonMissing

17.733 8986 1160

2469 (13.9)3974 (44.2)216 (18.6)

18.70 (7.87-9.62)1.52 (1.20-1.92)

<0.001<0.001

Size<10mm≥10mmMissing

12.046214713.686

2730 (22.7)1284 (59.8)2645 (19.3)

111.79 (9.88-14.07)0.71 (0.65-0.79)

<0.001<0.001

Variation per laboratory• At least 50 polyps• Odds ratio of distribution SSL vs HP• Comparison to reference lab• Significant differences are red

Influencing variation between pathologists

More on the poster tomorrow:Ariana Madani

Question 2• Since the elearning, I diagnose SSL• A) more often• B) less often• C) as often as before

Effects of e-learning on SSL diagnosis• 23 laboratories showed less

deviation from the referencelab (blue)

• 10 laboratories showedmore deviation (red)

Question 3• What is your diagnosis?• A) SSL• B) postponed, need IHC• C) other

• SSL, n = 198• PLSP in 6.5% of SSL• EMA +• Then 92% pV600E BRAF

• Perineurioma, n = 18• 90% show serrated crypts• Then 100% pV600E BRAF

SSL: interaction with stroma…

SSL and lipoma• Own series: 6 out of 49 colorectal lipomas show serration• Most of SSL show lipocytes in submucosa

Issue with mixed polyps……• “lesions that are

indistinguishable fromconventional adenoma are sometimes present, and may represent SSL that has been overtaken bycytologically dysplastic cellsand hence are nottechnically conventionaladenomas” (WHO, p 165)

Traditional serrated adenoma

Traditional serrated adenoma• Often distal/rectum• Up to 2% of all colorectal polyps• 30-50% occur in HP/SSL (discussion!)• Villiform or filiform (tennis racket)• Dysplasia• Eosinophilic cytoplasm• Pencillate nuclei• Ectopic crypt formation• BRAF or KRAS mutation

Ectopic crypt formation

Serrated polyp: surveillance

Surveillance

Serrated polyposis

Serrated polyposis (hyperplastic pp)• At least 5 serrated polyps proximal of the sigmoid, at least 2 over 10 mm• Or: at least 1 serrated polyp in a first degree relative of a SPS patient• Or: over 20 serrated polyps throughout the whole colon

• NO known germ line mutation• Perhaps more than one syndrome (mixed polyposis ??)• Significant miss-rate!

Population screening: low prevalence

CRC risk in serrated polyposis syndrome• 260 patients• 1.9 events per

1000 persons yearsurveillance

• 5-year cumulativeincidence of CRC: 1.5%

Question 4• I believe in “Serrated colorectal carcinoma”• A)Yes• B) No

Serrated carcinoma: so what?

Questions ?