Serrated lesions

Prof. Luigi TornilloPathoBasic

5.5.2015

• Introduction• Serrated lesions

– Morphology– Molecular pathology

• Clinical meaning

„Initial presumptions ... were that thediagnostic pathology associated withbowel cancer screening would berelatively straightforward . Nevertheless , this has shown not to be the case“

Shepherd NA, Griggs RKL, Mod Pathol, 2015

Serrated Polyps : Classification(s )

• WHO– Hyperplastic Polyps

• Microvesicular (MVHP)• Goblet cell rich (GCHP)• Mucin poor (MPHP)

– Sessile serratedadenoma/polyp (SSA/P)

• Without dysplasia• With dysplasia

– Traditional serratedadenoma (TSA)

• Riddell– Hyperplastic Polyps

• Microvesicular (MVHP)• Goblet cell rich (GCHP)• Mucin poor (MPHP)

– Sessile serrated polyp(aka SSA/P)

– Serrated polyp withdysplasia

• Sessile serrated polypswith dysplasia

– Serrated dysplasia– Adenomatous dysplasia

• Traditional serratedadenoma (TSA)

– Serrated polyp, unclassified

„It is recommended that... serrated adenoma (without a modifier) should not be used “

WHO, 2010

Bateman, AC, JCP 2014

Serrated polyps : risk factors

Haque et al., Dig Dis Sci, 2014

Hyperplastic polyps

• Small, < 5mm, very rare >10mm

• Distal colon , rectum (90%)

• 25-30% all polyps• 3 variants

– MVHP– GCHP– MPHP

Microvesicular hyperplasticpolyps

• Straight crypts , carrot shaped• Serration at the top• Immature/neuroendocrine cells base• Stellate crypts• Microvesicular mucin droplets

Goblet cell hyperplastic polyps

• Smaller• Least serrated• Wider crypts• Goblet cells• Probably what we call „hyperplastic

aspect“

Mucin poor hyperplastic polyps

• Very rare• Degenerated

MVHP?• Goblet cell and

mucin lacking• Regenerative

atypia

HP: molecular pathology

• MVHP– BRAFV600E (75%)

– KRASwt (90%)

– CIMP+

• GCHP– BRAFwt (all)

– KRASG12X (50%)

– CIMP-

„There is evidence that the reproducibilityof diagnosis of SSLs is poor, that is , thatsignificant inter-observer variability existsin the differentiation of these lesions fromother polyps “

Bateman JCP, 2014

Sessile serrated adenoma/polyp(SSA/P, SSL)

• 9% (15%?) of all polyps

• More frequent on theright (75%)

• Larger (15-20% > 10 mm)

• Mucus

SSA: endoscopic appearance

Bordaçar et al., Dig Liv Dis 2015

Sessile serrated adenoma/polyp(SSA/P, SSL): histology

• Serrated appearance at the bottom• Disordered growth of the crypts• T-shaped , boot-shaped

– WHO: at least 3 crypts; prob. 1 crypt

• Inverted maturation• Crypt dilatation

O‘Brien et al et al, Histopathology, 2015

SSA: Dysplasia ?

• „Serrated “ dysplasia– Often focal– Vesicular nuclei, small nucleoli– Often low -grade– Grading not needed– Progression

• Conventional dysplasia

SSA/P: Molecular pathology

• Without dysplasia– BRAFV600E (up to 80%)– CIMP-H 50%– KRASG12X rare (1%)

• With dysplasia (advanced )– Inactivation - Methylation

• MLH1• CTNBB1• MGMT

Bettington M, et al., Histopathology, 2013O‘Brien M, Histopathology, 2015

SSA: progression

• SSA do have preneoplastic potential

• SSA progression to CRC: more rapid than „conventional“ adenomas ? Probably methylation

• Large studies missing and datacontroversial

Traditional serrated adenoma (TSA)

• Least frequent serrated polyp (1% of all polyps)

• Distal colon, rectum

• Tubulovillous or villous architecture

• Dysplasia (serrated and conventional)

• Often (50%) mixed with SSL or conventionaladenoma

O‘ Brien M, Histopathology, 2015Chetty R, JCP 2015

„The proportion of a lesion that is requiredto show the characteristic features of a TSA - in contrast to areas showing theappearances of a ‘classical’ adenoma - in order to make a diagnosis of TSA is notclearly defined “

Bateman JCP, 2014

TSA: molecular pathology

• Inhomogeneous– KRASG12X (30%) (adenomatous

dysplasia)– BRAFV600E (50%) (serrated dysplasia)– MGMTmet (50%)– CIMP-H frequent– Progression

O‘ Brien, Histopathology, 2015Chetty, JCP 2015

Serrated polyps : DD

• SSP vs HP– Architectural

features (one crypt)

• TSA vs SSL– Architectural

changes– Villiform architecture– Ectopic crypts

• SSP vs prolapse– Erosions– Ischemic changes– Fibrosis– Fibromuscular

hyperplasia

• SP vs carcinoma– Pseudoinvasion

Serrated polyps : progression

O‘ Brien, Histopathology, 2015

O‘ Brien, Histopathology, 2014

Bettington M, et al., Histopathology, 2013

Interval CRC (6 mo – 5ys)

• 5-7% of all cases• Serrated polyps ?

– More frequent right– Sessile difficult resection– MSI rapid growth– BRAFV600E aggressive

Samadder et al, Gastroenterology, 2014

Serrated polyposis

• At least five histologically diagnosedserrated polyps proximal to the sigmoidcolon , of which two are >10 mm in diameter

• Any number of serrated polyps occurringproximal to the sigmoid colon in an individual who has a first degree relative with serrated polyposis

• More than 20 hyperplastic polyps of anysize but distributed throughout the colon

Snover et al., WHO, 2010

SSA: surveillance

Bordaçar et al., Dig Liv Dis 2015

Literature• Snover et al., Serrated polyps of the colon and rectum and serrated

polyposis , in Tumors of the Digestive System , Lyon, IARC, 2010, 160-65• Lewin, Weinstein and Riddell‘s Gastrointestinal Pathology and its Clinical

Implications , 1352-75• O‘Brien M et al., Colorectal serrated pathway cancers and precursors ,

Histopathology, 2015; 66:49–65.• Bettington M et al, The serrated pathway to colorectal carcinoma: current

concepts and challenges, Histopathology, 2013; 62:367–386• Batts, V, The pathology of serrated colorectal neoplasia: practic al answers

for common questions. Mod Pathol, 2015;28:S80-S87• Bettington M et al, Critical Appraisal of the Diagnosis of the Sessile

Serrated Adenoma , Am J Surg Pathol, 2014;38:158-66• Chetty R , Traditional serrated adenomas (TSAs) admixed with oth er

serrated (so-called precursor) polyps and conventional a denomas: a frequent occurrence, J Clin Pathol 2015;68:270–273.

• Haque TR et al., Risk Factors for Serrated Polyps of the Colorectum, DigDis Scie 59:2874–2889

• Rau TT et al., Defined morphological criteria allow reliable diagnosis o f colorectal serrated polyps and predict polyp genetics. Virchows Arch2014:464:663–672