The Adenoma/Carcinoma The Adenoma/Carcinoma Sequence in the ColonSequence in the Colon

A colon with an adenoma isA colon with an adenoma is at increased risk to developat increased risk to develop a carcinomaa carcinoma The more adenomas there are,The more adenomas there are, the greater the riskthe greater the risk

The Adenoma/Carcinoma The Adenoma/Carcinoma Sequence in the ColonSequence in the Colon

removing adenomas decreases removing adenomas decreases the incidence of colorectal the incidence of colorectal carcinomacarcinoma big adenomas are at risk to big adenomas are at risk to contain carcinomas and are contain carcinomas and are also markers of cancer risk for also markers of cancer risk for the rest of the colonthe rest of the colon

The Sporadic Adenoma-Carcinoma The Sporadic Adenoma-Carcinoma Sequence in the ColonSequence in the Colon

Endoscopy with removal of adenomas Endoscopy with removal of adenomas can prevent colorectal carcinoma.can prevent colorectal carcinoma. A ton of adenomas are removed every A ton of adenomas are removed every yearyear Few small cancers are picked up Few small cancers are picked up during routine endoscopyduring routine endoscopy The number of colorectal carcinomas The number of colorectal carcinomas isn’t decreasing, isn’t decreasing, but the deaths are!but the deaths are!

Colorectal carcinoma (USA) American Colorectal carcinoma (USA) American Cancer Society EstimatesCancer Society Estimates

20042004 20062006 20092009

New cases New cases 145,290145,290 148,610148,610 146,920146,920

Deaths Deaths 56,29056,290 55,170 55,170 49,92049,920

Males and females about equalMales and females about equal

Cancers are stable while Cancers are stable while the population at the population at risk is increasingrisk is increasing. Cancer deaths are down. . Cancer deaths are down.

Why???Why???

From 2003-2007, the age adjusted colorectal cancer incidence decreased by 13% and the mortality decreased by 12%. Screening increased by 13% from 2002-2010

Data from the CDC, 7/5/11

We know which adenomas areWe know which adenomas are

at risk to contain invasive carcinomaat risk to contain invasive carcinoma

we have no idea which adenomas we have no idea which adenomas

are the precursors of most are the precursors of most

ordinary colorectal carcinomasordinary colorectal carcinomas

but but

Small Adenoma with Highest-GD: the real cancer precursor?Small Adenoma with Highest-GD: the real cancer precursor?

Case based practical approaches to adenomas using the information taken from the adenoma-carcinoma sequence to make clinical decisions

Polyp with Polyp with a stalk a stalk

StalkStalk HeadHead

Sure looks like carcinoma, but is it?Sure looks like carcinoma, but is it?

The key is the The key is the lymphatics. lymphatics. Normal colonic Normal colonic mucosa has mucosa has very fewvery few

Metastatic carcinoma outlines lymphatics at the Metastatic carcinoma outlines lymphatics at the very base of the mucosa and in the submucosavery base of the mucosa and in the submucosa

Muscularis Muscularis mucosaemucosae

the diagnosis of the diagnosis of “adenocarcinoma” “adenocarcinoma” is is limited to dysplastic epithelium that limited to dysplastic epithelium that invades into the submucosainvades into the submucosa. . The same epithelium confined to the The same epithelium confined to the mucosa is called mucosa is called “high-grade dysplasia“high-grade dysplasia””

Therefore, Therefore, “carcinoma-in-situ” “carcinoma-in-situ” andand ““intramucosal carcinoma” intramucosal carcinoma” do not exist in do not exist in the colon!the colon!This is our approach at the U of M.This is our approach at the U of M.

Recommendation: In the colon: Recommendation: In the colon:

EndoEndo:: 2 cm pedunculated polyp2 cm pedunculated polyp

Proc:Proc: PolypectomyPolypectomy

Micro:Micro: Adenoma; it hasAdenoma; it has

multifocal high-grade dysplasiamultifocal high-grade dysplasia

Dx:Dx: Adenoma (at the U of M we do not Adenoma (at the U of M we do not diagnose high-grade dysplasia)diagnose high-grade dysplasia)

Rx:Rx: None furtherNone further

F-U:F-U: SurveillanceSurveillance

Summary of this adenoma

Same Same polyppolyp

Different Different findingsfindings

DesmoplasiaDesmoplasia, with or without inflammation, with or without inflammation

The stroma of The stroma of invasiveinvasive colorectal colorectal carcinomacarcinoma

Risk of metastasis from invasiveRisk of metastasis from invasivecarcinoma in carcinoma in pedunculatedpedunculated

adenomasadenomas

Depth of invasionDepth of invasion % mets% metssubmucosasubmucosa 22muscularismuscularis 2020pericolic adiposepericolic adipose 4040

source: accumulated literaturesource: accumulated literature

Haggitt levelsHaggitt levels

Invasive carcinoma in a Invasive carcinoma in a pedunculated pedunculated adenoma involves adenoma involves expandedexpanded submucosa submucosa

submucosasubmucosasubmucosasubmucosa

Cautery marks the Cautery marks the resection marginresection marginCautery marks the Cautery marks the resection marginresection margin

No carcinoma in the cauterized tissue

Endo:Endo: 2 cm 2 cm pedunculatedpedunculated polyp polyp

Proc:Proc: PolypectomyPolypectomy

Micro:Micro: Superficial invasive carcinoma Superficial invasive carcinoma in an adenoma, in an adenoma, margin freemargin free No adverse prognostic featuresNo adverse prognostic features

Dx:Dx: Same Same

Rx:Rx: None furtherNone further

F-U:F-U: SurveillanceSurveillance

Summary of this adenoma

What are adverse prognostic adverse prognostic features?features?Those features that have been associated with an adverse outcome after polypectomy, such as residual carcinoma at the polypectomy site and nodal metastases. These are likely to be indications for resection after the polypectomy

Adenomas with CarcinomaAdenomas with CarcinomaIndications for Resection, 3 studiesIndications for Resection, 3 studies

St Marks*St Marks* GIPSGIPS Clev ClinClev Clin

MarginMargin involvedinvolved <<1mm 1mm <2mm <2mm

CA GradeCA Grade highhigh high high highhigh

LymphaticsLymphatics subjectivesubjective yes yes nono

Blood vascBlood vasc nono yesyes nono

* both sessile and pedunc and must be removed in * both sessile and pedunc and must be removed in one piece.one piece.Geraghty, Williams, Talbot . Gut, 32 :774 1991Geraghty, Williams, Talbot . Gut, 32 :774 1991Cooper, et al, Gastroenterol, 108:1657-1665, 1995Cooper, et al, Gastroenterol, 108:1657-1665, 1995Volk, et al, Gastroenterol, 109:1801-1807, 1995Volk, et al, Gastroenterol, 109:1801-1807, 1995

Invasive carcinoma in a Invasive carcinoma in a pedunculatedpedunculatedadenoma: indications for colectomyadenoma: indications for colectomy

1. Invasive carcinoma at the margin 1. Invasive carcinoma at the margin

solid datasolid data2. High-grade carcinoma: definition not clear;2. High-grade carcinoma: definition not clear;

data limiteddata limited

3. Lymphatic invasion: data conflicting;3. Lymphatic invasion: data conflicting;

overlaps with other indicationsoverlaps with other indications

The best indicator for colectomy: The best indicator for colectomy: Involvement of the marginInvolvement of the margin

Tumor in theTumor in thecautery artifact at cautery artifact at

the marginthe margin

A bias cut of A bias cut of the cauterized the cauterized marginmargin

Carcinoma in Carcinoma in the cautery the cautery artifact: margin artifact: margin involvedinvolved

Invasive carcinoma in a pedunculatedInvasive carcinoma in a pedunculatedadenoma: indications for colectomyadenoma: indications for colectomy

1. Invasive carcinoma at the margin 1. Invasive carcinoma at the margin

solid datasolid data

2. High-grade carcinoma: 2. High-grade carcinoma:

definition not clear; data limiteddefinition not clear; data limited3. Lymphatic invasion: data conflicting;3. Lymphatic invasion: data conflicting;

overlaps with other indicationsoverlaps with other indications

This is a high-grade carcinomaThis is a high-grade carcinomaThis is a high-grade carcinomaThis is a high-grade carcinoma

Invasive carcinoma in a pedunculatedInvasive carcinoma in a pedunculatedadenoma: indications for colectomyadenoma: indications for colectomy

1. Invasive carcinoma at the margin 1. Invasive carcinoma at the margin

solid datasolid data

2. High-grade carcinoma: definition not clear;2. High-grade carcinoma: definition not clear;

data limiteddata limited

3. Lymphatic invasion: data conflicting;3. Lymphatic invasion: data conflicting;

overlaps with other indications. This overlaps with other indications. This is also a is also a very subjective very subjective determinationdetermination

The least reproducible indicator: The least reproducible indicator: lymphatic tumor thromboembolilymphatic tumor thromboemboli

Unfavorable histopathologic factors Unfavorable histopathologic factors associated with a high risk of node associated with a high risk of node metastasis or local recurrence after metastasis or local recurrence after endoscopic resection include endoscopic resection include 1. poorly differentiated histology, 1. poorly differentiated histology, 2. vascular or lymphatic invasion, 2. vascular or lymphatic invasion, 3. cancer at the resection margin3. cancer at the resection margin4. incomplete endoscopic resection4. incomplete endoscopic resection. .

ASGE guideline: endoscopy for colorectal cancerASGE guideline: endoscopy for colorectal cancerGASTROINTESTINAL ENDOSCOPY 61z:1-5. 2005 GASTROINTESTINAL ENDOSCOPY 61z:1-5. 2005

www.asge.orgwww.asge.org

PPedunculatededunculated adenomas with adenomas with carcinoma confined to the carcinoma confined to the submucosasubmucosacan be considered to be can be considered to be adequately treated byadequately treated byendoscopic resection if endoscopic resection if 1. removed completely 1. removed completely and and 2. there are no unfavorable 2. there are no unfavorable histologic features. histologic features.

SurveillanceSurveillance after the after the endoscopic removal of a endoscopic removal of a malignant polyp shouldmalignant polyp shouldconsist of a follow-up consist of a follow-up colonoscopy within 3 to 6 colonoscopy within 3 to 6 months after resection.months after resection.

Next Next scenarioscenario

Huge, Huge, sessile sessile polyppolyp

Biopsy before Biopsy before polypectomy polypectomy

Lots of Lots of villous villous surfacesurface

DysplasiasDysplasias

LowLow HighHigh

Adenomas at risk to containAdenomas at risk to contain

invasive carcinoma areinvasive carcinoma are

1. Large1. Large

2. Villous2. Villous

and haveand have

3. High-grade dysplasia3. High-grade dysplasia

Big sessile adenoma

Big carcinoma at the base

Endo:Endo: 7 cm sessile polyp7 cm sessile polyp

Proc:Proc: BiopsyBiopsy

MicroMicro:: Adenoma with lots of villi,Adenoma with lots of villi,

high-grade dysplasiahigh-grade dysplasia

Dx:Dx: Adenoma Adenoma

Rx:Rx: It has to come out: possibilities:It has to come out: possibilities:

If proximal: local resectionIf proximal: local resection

If rectal: ± mucosal resectionIf rectal: ± mucosal resection

Summary of this adenoma

Treatment of GI AdenomasTreatment of GI AdenomasAdenomas must be removed in totoAdenomas must be removed in toto

Endoscopic polypectomy, that is, gross Endoscopic polypectomy, that is, gross total resection, is definitive, total resection, is definitive, regardless regardless if if we see adenoma at a marginwe see adenoma at a margin

After After biopsybiopsy of a large adenoma, removal of a large adenoma, removal is necessary, is necessary, regardless of degree of regardless of degree of

dysplasiadysplasia

What you need to say about a colonic What you need to say about a colonic adenoma in the pathology reportadenoma in the pathology report

Architecture:Architecture: tubular, villous, tubular, villous, tubulovillous, flat, serrated:tubulovillous, flat, serrated: Maybe villiMaybe villiHigh-grade dysplasia:High-grade dysplasia: MaybeMaybe

Pseudoinvasion:Pseudoinvasion: NONO

Adenoma at the margin:Adenoma at the margin: NONO

The wordThe word ““adenomaadenoma”” YES!YES!

Invasive carcinoma:Invasive carcinoma: YES!YES!

This is when we mention the margin.This is when we mention the margin.

In the 2006 guidelines for patients with In the 2006 guidelines for patients with adenomas, the most important adenomas, the most important determinants determinants of interval to the next colonoscopyof interval to the next colonoscopy are are

1.1. Number of adenomas: 3 or moreNumber of adenomas: 3 or more

2.2. Size: if any polyp containing adenoma is at Size: if any polyp containing adenoma is at least 1 cm (polyp size, not adenoma size)least 1 cm (polyp size, not adenoma size)

3.3. High grade dysplasia (no published criteria)High grade dysplasia (no published criteria)

4.4. Villous features (no published criteria)Villous features (no published criteria)

Winawer et al: Gastroenterol, 130:1872, 2006Winawer et al: Gastroenterol, 130:1872, 2006

At the U of M, the gastroenterologists with whom we work do not find either high-grade dysplasia or villous features to be useful for determining surveillance intervals. They use size of the initial adenoma and the number of adenomas at the initial colonoscopy to make that decision.

Some gastroenterologists want to know Some gastroenterologists want to know the the architecturearchitecture, generally, generally tubular, tubular, villous, or tubulovillous, villous, or tubulovillous, and/or and/or if if high-high-grade dysplasiagrade dysplasia is present is present

There is no reason not to There is no reason not to tell them what they want. tell them what they want. After all, we pathologists are After all, we pathologists are a service organization!!!a service organization!!! They don’t know that there are no hard criteria as They don’t know that there are no hard criteria as to what is a villous component and what is HGDto what is a villous component and what is HGD