Serrated lesions Workshop Population Screening · • Sessile serrated lesions with or without...
Transcript of Serrated lesions Workshop Population Screening · • Sessile serrated lesions with or without...
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 ?