1. 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

2. 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

3. 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!

4. Colorectal carcinoma (USA) American Cancer Society Estimates
New cases , , ,920
Deaths 56, , ,920
Males and females about equal
Why???
Cancers are stable while the population at risk is increasing. Cancer deaths are down.

5. Data from the CDC, 7/5/11
From , the age adjusted colorectal cancer incidence decreased by 13% and the mortality decreased by 12%. Screening increased by 13% from

6. 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

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

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

9. Polyp with a stalk

10. Head
Stalk

11. Sure looks like carcinoma, but is it?

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

13. Metastatic carcinoma outlines lymphatics at the very base of the mucosa and in the submucosa
Muscularis mucosae

14. 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.

15. Summary of this adenoma
Endo: 2 cm pedunculated polyp
Proc: Polypectomy
Micro: Adenoma; it has
multifocal high-grade dysplasia
Dx: Adenoma (at the U of M we do not diagnose high-grade dysplasia)
Rx: None further
F-U: Surveillance

16. Same polyp
Different findings

17. Desmoplasia, with or without inflammation
The stroma of invasive colorectal carcinoma

18. Risk of metastasis from invasive carcinoma in pedunculated adenomas
Depth of invasion % mets
submucosa 2
muscularis 20
pericolic adipose
source: accumulated literature

19. Haggitt levels
submucosa
submucosa
Invasive carcinoma in a pedunculated adenoma involves expanded submucosa

20. Cautery marks the resection margin
No carcinoma in the cauterized tissue

21. Summary of this adenoma
Endo: 2 cm pedunculated polyp
Proc: Polypectomy
Micro: Superficial invasive carcinoma in an adenoma, margin free No adverse prognostic features
Dx: Same
Rx: None further
F-U: Surveillance

22. 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

23. 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 yes no
* both sessile and pedunc and must be removed in one piece.
Geraghty, Williams, Talbot . Gut, 32 :
Cooper, et al, Gastroenterol, 108: , 1995
Volk, et al, Gastroenterol, 109: , 1995

24. 1. Invasive carcinoma at the margin solid data
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

25. The best indicator for colectomy: Involvement of the margin
Tumor in the
cautery artifact at the margin
The best indicator for colectomy:
Involvement of the margin

26. Carcinoma in the cautery artifact: margin involved
A bias cut of the cauterized margin

27. 2. High-grade carcinoma: definition not clear; data limited
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

28. This is a high-grade carcinoma

29. 3. Lymphatic invasion: data conflicting;
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

30. The least reproducible indicator: lymphatic tumor thromboemboli

31.
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:

32. Pedunculated adenomas with carcinoma confined to the submucosa
can be considered to be adequately treated by
endoscopic resection if removed completely and
2. there are no unfavorable histologic features.

33. Surveillance after the endoscopic removal of a malignant polyp should
consist of a follow-up colonoscopy within 3 to 6 months after resection.

34. Next scenario
Huge, sessile polyp

35. Biopsy before polypectomy

36. Lots of villous surface
Dysplasias
Low High
Lots of villous surface

37. 1. Large 2. Villous and have 3. High-grade dysplasia
Adenomas at risk to contain
invasive carcinoma are
1. Large
2. Villous
and have
3. High-grade dysplasia

38. Big sessile adenoma
Big carcinoma at the base

39. Summary of this adenoma
Endo: 7 cm sessile polyp
Proc: Biopsy
Micro: Adenoma with lots of villi,
high-grade dysplasia
Dx: Adenoma
Rx: It has to come out: possibilities:
If proximal: local resection
If rectal: ± mucosal resection

40. 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

41. What you need to say about a colonic adenoma in the pathology report
Architecture: tubular, villous, tubulovillous, flat, serrated: Maybe villi
High-grade dysplasia: Maybe
Pseudoinvasion: NO
Adenoma at the margin: NO
The word “adenoma” YES!
Invasive carcinoma: YES!
This is when we mention the margin.

42. In the 2006 guidelines for patients with adenomas, the most important determinants of interval to the next colonoscopy are
Number of adenomas: 3 or more
Size: if any polyp containing adenoma is at least 1 cm (polyp size, not adenoma size)
High grade dysplasia (no published criteria)
Villous features (no published criteria)
Winawer et al: Gastroenterol, 130:1872, 2006

43. 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.

44. There is no reason not to tell them what they want.
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