Polyps – Where do they come from and what do you do with them?! Ron G. Landmann, MD Grand Rounds Department of Surgery St. Luke’s-Roosevelt Hospital Center.

Polyps – Where do they Polyps – Where do they come from and what do come from and what do youyou

do with them?!do with them?!

Ron G. Landmann, MDRon G. Landmann, MDGrand RoundsGrand Rounds

Department of SurgeryDepartment of SurgerySt. Luke’s-Roosevelt Hospital CenterSt. Luke’s-Roosevelt Hospital Center

March 21, 2007March 21, 2007

PolypsPolyps Cancer epidemiologyCancer epidemiology Definition of the malignant polypDefinition of the malignant polyp Natural history of adenomatous polypsNatural history of adenomatous polyps Biology of polypsBiology of polyps The anatomy of the polypThe anatomy of the polyp Correlations with MalignancyCorrelations with Malignancy Endoscopic polypectomy alone???Endoscopic polypectomy alone??? Special considerationsSpecial considerations

* No discussion of technique* No discussion of technique

Colorectal Cancer – Colorectal Cancer – EpidemiologyEpidemiology

Incidence: Approx. 150,000 cases/yearIncidence: Approx. 150,000 cases/year Deaths: Approx. 50,000 deaths/yearDeaths: Approx. 50,000 deaths/year

At diagnosisAt diagnosis 10% in situ disease10% in situ disease 30% local disease30% local disease 30% regional disease30% regional disease 30% distant disease30% distant disease

5 year survival, all patients: 50%5 year survival, all patients: 50% local - 90%local - 90% regional - 60%regional - 60% distant - 5%distant - 5%

U.S. Cancer Statistics Working Group. United States Cancer Statistics: 2003 Incidence and Mortality (preliminary data). Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2006.

Incidence/Prevalence of Incidence/Prevalence of PolypsPolyps

Adenomatous polypsAdenomatous polyps 30% of Western population30% of Western population

Most cancers arise from polypsMost cancers arise from polyps

*excludes syndromes*excludes syndromes

Carcinoma in situ vs. Carcinoma in situ vs. cancercancer

ThinkThink Carcinoma Carcinoma in situ = in situ = high grade dysplasiahigh grade dysplasia Carcinoma Carcinoma in situin situ ≠ ≠ cancercancer

HistologyColorectal cancer is defined

by invasion of/through muscularis mucosa

Genetic model of colorectal tumorigenesis

Histology1. Colorectal cancer is

defined by invasion of muscularis mucosa

2. Lymphatics are located in submucosa

Colon Cancer StagingColon Cancer StagingT-stageT-stage

TisTis Intraepithelial or invasion of lamina Intraepithelial or invasion of lamina propriapropria

T1T1 Invades submucosaInvades submucosa

T2T2 Invades muscularis propriaInvades muscularis propria

T3T3 Invades subserosa or pericolic/rectal Invades subserosa or pericolic/rectal tissuestissues

T4T4 Into other organs/perforates visceral Into other organs/perforates visceral peritoneumperitoneum

N-N-stagestage

00 0 LN0 LN

11 1-3 positive LNs1-3 positive LNs

22 > 3 positive LNs> 3 positive LNs

Colon Cancer StagingColon Cancer StagingAJCC 5AJCC 5

StageStageTT NN MM 5 year DSS 5 year DSS

(%)(%)

ColoColonn

RectuRectumm

00 TisTis 00 00

II 1-21-2 00 00 7575 7070

IIII 3-43-4 00 00 6565 5555

IIIIII AnAnyy

1-21-2 00 4545 4040

IVIV AnAnyy

AnAnyy

11 55 55

Relationship Between TNM Stage and Survival in Colorectal Carcinoma

CA Cancer J Clin 2004;54;295-308

Treatment of CRCTreatment of CRC

PolypectomyPolypectomy Colonic ResectionColonic Resection

Treatment depends on the risk of Treatment depends on the risk of lymph node metastasis.lymph node metastasis.

Pathology is key!1. Colorectal cancer is defined by

invasion of muscularis mucosa2. Lymphatics are located in

submucosa

Incidence of malignant Incidence of malignant polypspolyps

DefinitionDefinition Malignant polyps or T1 lesions (limited Malignant polyps or T1 lesions (limited

to the submucosa)to the submucosa) Represent 5% of all adenomasRepresent 5% of all adenomas

Colonoscopy polypectomy series: 2 – Colonoscopy polypectomy series: 2 – 12%12%

Colorectal resection series: 4 – 9%Colorectal resection series: 4 – 9%

Haggitt Level (1985)Haggitt Level (1985)Classification of polyps with Classification of polyps with

invasive cancerinvasive cancer

Haggitt RC, Glotzbach RE, Soffer EE, Wruble LD. Prognostic factors in colorectal carcinoma arising in adenomas: Implications for lesions removed by endoscopic polypectomy. Gastroenterology 89:328-36, 1985, p 330.

LevelLevel DefinitionDefinition Resected Resected (N)(N)

+ LN (N)+ LN (N)

00 Carcinoma Carcinoma in situin situ

11 Invasion of Invasion of headhead

66 0 (< 1%)0 (< 1%)

22 Invasion of Invasion of neckneck

33 0 (< 1%)0 (< 1%)

33 Invasion of Invasion of stalkstalk

44 0 (< 1%)0 (< 1%)

44 Invasion of Invasion of submucosa submucosa of bowel wall of bowel wall below polypbelow polyp

1313 4 (31%, 4 (31%, 12-25%)12-25%)

Villuous/sessile (flat) polyps with invasive cancer are by definition Haggitt 4.

Sessile PolypsSessile PolypsKudo, 1993Kudo, 1993

Risk of lymph node metastasis in each sessile Risk of lymph node metastasis in each sessile lesion is not the samelesion is not the same

Haggitt’s: no detail for sessile lesionsHaggitt’s: no detail for sessile lesions Classification of submucosal invasion:Classification of submucosal invasion:

Sm1—Invasion into the upper third of the submucosaSm1—Invasion into the upper third of the submucosa Sm2—Invasion into the middle third of the submucosaSm2—Invasion into the middle third of the submucosa Sm3—Invasion into the lower third of the submucosaSm3—Invasion into the lower third of the submucosa

High rate of LN metastasis: 12-25%High rate of LN metastasis: 12-25%

Sm systemSm system

Able to determine Sm1, Sm2, Sm3 in Able to determine Sm1, Sm2, Sm3 in 97% of cases97% of cases

Haggitt Level 1, 2, 3 = Sm1Haggitt Level 1, 2, 3 = Sm1 Haggitt Level 4 = Sm1, Sm2, or Sm3Haggitt Level 4 = Sm1, Sm2, or Sm3

Endoscopist must properly resect Endoscopist must properly resect and prepare specimenand prepare specimen

Pathologist must properly section Pathologist must properly section and examine all layersand examine all layers

Correlations with Correlations with MalignancyMalignancyMorphologyMorphology

MorphologMorphologyy

IncidenceIncidence % % MalignantMalignant

TubularTubular 7575 55

TubulovillouTubulovillouss

1515 2020

VillousVillous 1010 4040

Correlations with Correlations with MalignancyMalignancy

GradeGrade

DysplasiDysplasiaa

% % malignantmalignant

MildMild 55

ModeratModeratee

2020

SevereSevere 3030

Correlations with Correlations with MalignancyMalignancy

SizeSizeSize Size (cm)(cm)

% % malignantmalignant

< 1< 1 11

1 – 21 – 2 1010

≥ ≥ 22 5050Muto, 1975

Correlations with Correlations with MalignancyMalignancy

SizeSize

Muto, 1975

Size Size (cm)(cm)

% % malignantmalignant

≤≤ 0.50.5 NegligibleNegligible

0.6 – 1.50.6 – 1.5 22

1.6 – 2.51.6 – 2.5 1919

2.6-3.52.6-3.5 4343

≥≥ 3.53.5 7676Nusco, 1997

Size Size (cm)(cm)

% % malignantmalignant

< 1< 1 11

1 – 21 – 2 1010

≥ ≥ 22 5050

Relationship betweenRelationship betweenSize and Morphology Size and Morphology

TubularTubular TubulovillTubulovillousous

VillousVillous

< 1 < 1 cmcm

76%76% 25%25% 14%14%

1-1-2cm2cm

20%20% 47%47% 26%26%

> 2 > 2 cmcm

4%4% 28%28% 60%60%

St. Mark’s Hospital Data

Increased risk of LN Increased risk of LN MetastasisMetastasis

Unfavorable pathologic features of Unfavorable pathologic features of malignant CR polypsmalignant CR polyps Poor differentiation (only on univariate)Poor differentiation (only on univariate) Lymphovascular invasion (P < 0.009)Lymphovascular invasion (P < 0.009) Invasion below submucosa (Haggitt Level 4)Invasion below submucosa (Haggitt Level 4) Depth of invasion in Sm3 (P < 0.001)Depth of invasion in Sm3 (P < 0.001) Site in lower 1/3 of the rectum (P < 0.001)Site in lower 1/3 of the rectum (P < 0.001)

Positive resection margin (< 1 mm or 1 HPF)Positive resection margin (< 1 mm or 1 HPF) Not really – this is inadequate treatment, not an Not really – this is inadequate treatment, not an

adverse risk factor!adverse risk factor!

P-values from Nascimbeni et al. N = 353 T1 colorectal sessile lesions

Management of Management of Pedunculated Malignant Pedunculated Malignant

PolypsPolyps Haggitt Level 1, 2, 3Haggitt Level 1, 2, 3

Complete excision or snaringComplete excision or snaring Risk of LN metastasis < 1%Risk of LN metastasis < 1%

Haggitt Level 4Haggitt Level 4 Treat as sessile lesionsTreat as sessile lesions

Management of Sessile Management of Sessile Malignant PolypsMalignant Polyps

< 2cm in diameter< 2cm in diameter Adequate snare in one piece via colonoscopyAdequate snare in one piece via colonoscopy Requires microscopic free margin of at least Requires microscopic free margin of at least

2mm2mm

Piecemeal removalPiecemeal removal Requires further excision/follow-up or resectionRequires further excision/follow-up or resection

High risk factors (LVI, Sm3, distal 1/3 High risk factors (LVI, Sm3, distal 1/3 rectum)rectum) Oncologic resectionOncologic resection Full thickness transanal excisionFull thickness transanal excision

Lesions amenable to Lesions amenable to colonoscopic polypectomycolonoscopic polypectomy

Pedunculated or sessile < 2cmPedunculated or sessile < 2cm Well/moderately differentiatedWell/moderately differentiated No lymphovascular invasionNo lymphovascular invasion Haggitt Level 1-3 or Sm1Haggitt Level 1-3 or Sm1 Close follow-up availableClose follow-up available

Endoscopically Endoscopically complete excisioncomplete excision Negative resection margins (2mm)Negative resection margins (2mm)

Criteria for Treatment of Criteria for Treatment of Malignant CR Polyps by Malignant CR Polyps by

Polypectomy AlonePolypectomy Alone Determined by risk of metastasisDetermined by risk of metastasis

Low risk of Lymph Node MetastasisLow risk of Lymph Node Metastasis PedunculatedPedunculated

Haggitt Level 1, 2, 3Haggitt Level 1, 2, 3 Level 4 Sm1, Sm2Level 4 Sm1, Sm2

SessileSessile Sm1, Sm2Sm1, Sm2

High risk of Lymph Node MetastasisHigh risk of Lymph Node Metastasis Lower 1/3 of the submucosa (Sm3)Lower 1/3 of the submucosa (Sm3) LVILVI Distal 1/3 of rectumDistal 1/3 of rectum

Malignant Colorectal Malignant Colorectal Polyps that Should have an Polyps that Should have an Oncologic Bowel ResectionOncologic Bowel Resection

Lesions in colonLesions in colon Pedunculated Haggitt Level 4 with invasion into distal Pedunculated Haggitt Level 4 with invasion into distal

third of submucosa (Sm3) or LVIthird of submucosa (Sm3) or LVI Sessile lesions removed with margin < 2mmSessile lesions removed with margin < 2mm Sessile lesions removed piecemealSessile lesions removed piecemeal Sessile lesions with depth of invasion into distal third of Sessile lesions with depth of invasion into distal third of

submucosa (Sm3)submucosa (Sm3) Sessile lesions with LVISessile lesions with LVI

Lesions in middle third and upper third rectumLesions in middle third and upper third rectum Same as lesions in colonSame as lesions in colon

Lesions in distal third rectumLesions in distal third rectum Pedunculated Haggitt Level 4 with invasion into distal Pedunculated Haggitt Level 4 with invasion into distal

third of submucosa (Sm3) or pedunculated lesions with third of submucosa (Sm3) or pedunculated lesions with LVILVI

All sessile lesionsAll sessile lesions

Why not just resect Why not just resect anyway?!anyway?!

What if ???What if ??? What if it’s clipped in ½?What if it’s clipped in ½?

PedunculatedPedunculated Repeat endoscopy.Repeat endoscopy. Require good resection with margin (2mm)Require good resection with margin (2mm)

SessileSessile Requires operative oncologic resection (even if Sm1, Sm2)Requires operative oncologic resection (even if Sm1, Sm2)

Unable to determine exact pathologic depthUnable to determine exact pathologic depth What if it’s shredded by forceps?What if it’s shredded by forceps?

Requires operative oncologic resectionRequires operative oncologic resection What if it’s a very small lesion?What if it’s a very small lesion?

Requires marking/tattoo CIRCUMFERENTIALLYRequires marking/tattoo CIRCUMFERENTIALLY What if it’s carcinoma in situ?What if it’s carcinoma in situ?

It’s not cancer. This is high grade dysplasia. Requires close It’s not cancer. This is high grade dysplasia. Requires close follow-up.follow-up.

Unless,Unless, poor margins: repeat endoscopy with good marginspoor margins: repeat endoscopy with good margins Piecemeal resection: discussion with pathologist and patientPiecemeal resection: discussion with pathologist and patient

What if it’s a large, non-endoscopically resectable polyp?What if it’s a large, non-endoscopically resectable polyp? Repeat endoscopy (2Repeat endoscopy (2ndnd MD?) MD?) Oncologic resectionOncologic resection

Other considerations…Other considerations…

When in doubtWhen in doubt Repeat colonoscopy Repeat colonoscopy

(endoscopy)(endoscopy) Personally review Personally review

pathologypathology Get a second opinionGet a second opinion Have a frank Have a frank

discussion with discussion with patientpatient

PolypsPolyps Natural history of adenomatous polypsNatural history of adenomatous polyps Biology of polypsBiology of polyps Cancer epidemiologyCancer epidemiology The anatomy of the polypThe anatomy of the polyp Correlations with MalignancyCorrelations with Malignancy Endoscopic polypectomy alone???Endoscopic polypectomy alone??? Special considerationsSpecial considerations Indications for PolypectomyIndications for Polypectomy

What if it’s clipped in ½What if it’s clipped in ½ What if it’s shredded by forceps?What if it’s shredded by forceps?

Pathology…Pathology… Marking/tattooMarking/tattoo Chances of Malignancy by histopath and size/morphologyChances of Malignancy by histopath and size/morphology * NO technique *** NO technique **