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