The Adenoma/Carcinoma
Sequence in the Colon
A colon with an adenoma is
at increased risk to develop
a carcinoma
 The more adenomas there are,
the greater the risk

The Adenoma/Carcinoma
Sequence in the Colon
removing adenomas decreases
the incidence of colorectal
carcinoma
 big adenomas are at risk to
contain carcinomas and are
also markers of cancer risk for
the rest of the colon

The Sporadic Adenoma-Carcinoma
Sequence in the Colon
 Endoscopy with removal of adenomas
can prevent colorectal carcinoma.
 A ton of adenomas are removed every
year
 Few small cancers are picked up
during routine endoscopy
 The number of colorectal carcinomas
isn’t decreasing, but the deaths are!
Colorectal carcinoma (USA) American
Cancer Society Estimates
2004 2006
2009
New cases
145,290
148,610
146,920
Deaths
56,290
55,170
49,920
Males and females about equal
Why???
Cancers are stable while the population at
risk is increasing. Cancer deaths are down.
Data from
the CDC,
7/5/11
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
We know which adenomas are
at risk to contain invasive carcinoma
but
we have no idea which adenomas
are the precursors of most
ordinary colorectal carcinomas
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
a stalk
Stalk
Sure looks like carcinoma, but is it?
The key is the
lymphatics.
Normal colonic
mucosa has
very few
Metastatic carcinoma outlines lymphatics at the
very base of the mucosa and in the submucosa
Muscularis
mucosae
Recommendation: In the colon:
the diagnosis of “adenocarcinoma” is
limited to dysplastic epithelium that
invades into the submucosa.
The same epithelium confined to the
mucosa is called “high-grade dysplasia”
Therefore, “carcinoma-in-situ” and
“intramucosal carcinoma” do not exist in
the colon!
This is our approach at the U of M.
Summary of this adenoma
Endo:
2 cm pedunculated polyp
Proc:
Micro:
Polypectomy
Adenoma; it has
multifocal high-grade dysplasia
Dx:
Adenoma (at the U of M we do not
diagnose high-grade dysplasia)
Rx:
F-U:
None further
Surveillance
Same
polyp
Different
findings
Desmoplasia, with or without inflammation
The stroma of invasive colorectal
carcinoma
Risk of metastasis from invasive
carcinoma in pedunculated
adenomas
Depth of invasion
submucosa
muscularis
pericolic adipose
% mets
2
20
40
source: accumulated literature
Haggitt levels
submucosa
submucosa
Invasive carcinoma in a pedunculated
adenoma involves expanded submucosa
No carcinoma
in the
cauterized
tissue
Cautery marks the
resection margin
Summary of this adenoma
Endo:
Proc:
Micro:
Dx:
Rx:
F-U:
2 cm pedunculated polyp
Polypectomy
Superficial invasive carcinoma
in an adenoma, margin free
No adverse prognostic features
Same
None further
Surveillance
What are adverse prognostic
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 Carcinoma
Indications for Resection, 3 studies
St Marks* GIPS
Clev Clin
Margin
involved
<1mm
<2mm
CA Grade
high
high
high
Lymphatics
subjective yes
no
Blood vasc
no
no
yes
* both sessile and pedunc and must be removed in one piece.
Geraghty, Williams, Talbot . Gut, 32 :774 1991
Cooper, et al, Gastroenterol, 108:1657-1665, 1995
Volk, et al, Gastroenterol, 109:1801-1807, 1995
Invasive carcinoma in a pedunculated
adenoma: indications for colectomy
1. Invasive carcinoma at the margin
solid data
2. High-grade carcinoma: definition not clear;
data limited
3. Lymphatic invasion: data conflicting;
overlaps with other indications
The best indicator for colectomy:
Involvement of the margin
Tumor in the
cautery artifact at
the margin
Carcinoma in
the cautery
artifact: margin
involved
A bias cut of
the cauterized
margin
Invasive carcinoma in a pedunculated
adenoma: indications for colectomy
1. Invasive carcinoma at the margin
solid data
2. High-grade carcinoma:
definition not clear; data limited
3. Lymphatic invasion: data conflicting;
overlaps with other indications
This is a high-grade carcinoma
Invasive carcinoma in a pedunculated
adenoma: indications for colectomy
1. Invasive carcinoma at the margin
solid data
2. High-grade carcinoma: definition not clear;
data limited
3. Lymphatic invasion: data conflicting;
overlaps with other indications. This
is also a very subjective
determination
The least reproducible indicator:
lymphatic tumor thromboemboli
www.asge.org
Unfavorable histopathologic factors
associated with a high risk of node
metastasis or local recurrence after
endoscopic resection include
1. poorly differentiated histology,
2. vascular or lymphatic invasion,
3. cancer at the resection margin
4. incomplete endoscopic resection.
ASGE guideline: endoscopy for colorectal cancer
GASTROINTESTINAL ENDOSCOPY 61z:1-5. 2005
Pedunculated adenomas with
carcinoma confined to the
submucosa
can be considered to be
adequately treated by
endoscopic resection if
1. removed completely and
2. there are no unfavorable
histologic features.
Surveillance after the
endoscopic removal of a
malignant polyp should
consist of a follow-up
colonoscopy within 3 to 6
months after resection.
Next
scenario
Huge,
sessile
polyp
Biopsy before
polypectomy
Dysplasias
Low
Lots of
villous
surface
High
Adenomas at risk to contain
invasive carcinoma are
1. Large
2. Villous
and have
3. High-grade dysplasia
Big sessile
adenoma
Big carcinoma at the base
Summary of this adenoma
Endo:
Proc:
7 cm sessile polyp
Biopsy
Micro:
Adenoma with lots of villi,
high-grade dysplasia
Dx:
Rx:
Adenoma
It has to come out: possibilities:
If proximal: local resection
If rectal: ± mucosal resection
Treatment of GI Adenomas
Adenomas must be removed in toto
Endoscopic polypectomy, that is, gross
total resection, is definitive, regardless
if we see adenoma at a margin
After biopsy of a large adenoma, removal
is necessary, regardless of degree of
dysplasia
What you need to say about a colonic
adenoma in the pathology report
Architecture: tubular, villous,
tubulovillous, flat, serrated:
High-grade dysplasia:
Adenoma at the margin:
Maybe villi
Maybe
NO
NO
The word “adenoma”
YES!
Pseudoinvasion:
Invasive carcinoma:
YES!
This is when we mention the margin.
In the 2006 guidelines for patients with
adenomas, the most important determinants
of interval to the next colonoscopy are
1. Number of adenomas: 3 or more
2. Size: if any polyp containing adenoma is at
least 1 cm (polyp size, not adenoma size)
3. High grade dysplasia (no published criteria)
4. Villous features (no published criteria)
Winawer 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
the architecture, generally tubular,
villous, or tubulovillous, and/or
if high-grade dysplasia is present
There is no reason not to
tell them what they want.
After all, we pathologists are
a service organization!!!
They don’t know that there are no hard criteria as
to what is a villous component and what is HGD