Serrated lesions Workshop 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 implications Nat. 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 allow categorisation 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 lesions SSA/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)

1 0.92 (0.83-1.02)

0.10

Sex Male Female

17.298 10.581

3.996 (23.1) 2.663 (25.2)

1 1.24 (1.12-1.38)

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 reference lab (blue)

• 10 laboratories showed more 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 from conventional adenoma are sometimes present, and may represent SSL that has been overtaken by cytologically dysplastic cells and hence are not technically conventional adenomas” (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 year surveillance

• 5-year cumulative incidence of CRC: 1.5%

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

Serrated carcinoma: so what?

Questions ?

Serrated lesions Disclosure belangen spreker Serrated lesions Why should we discuss serrated lesions? Question 1 25% of CRC develop arise via the serrated route Dianummer 7 Dianummer 8 There are many serrated lesions in the population screening Hyperplastic polyps Hyperplastic polyps: subtypes Hyperplastic polyps: subtypes Hyperplastic polyp: subtypes Sessile serrated lesions “Complex sister” of the HP Dianummer 16 Dianummer 17 T and L shapes (anchors & hooks) Hyperplastic polyps versus SSL Dianummer 20 Variation per laboratory Influencing variation between pathologists Question 2 Effects of e-learning on SSL diagnosis Dianummer 25 Question 3 Dianummer 27 Dianummer 28 Dianummer 29 SSL: interaction with stroma… SSL and lipoma Dianummer 32 Dianummer 33 Issue with mixed polyps…… Traditional serrated adenoma Traditional serrated adenoma Ectopic crypt formation Serrated polyp: surveillance Surveillance Serrated polyposis Serrated polyposis (hyperplastic pp) Population screening: low prevalence CRC risk in serrated polyposis syndrome Question 4 Dianummer 45 Serrated carcinoma: so what? Dianummer 47