The Adenoma/Carcinoma Sequence in the Colon

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 200420062009 New cases145,290 148,610146,920 Deaths56,290 55,170 49,920 Males and females about equal Why??? Cancers are stable while the population at risk is increasing. Cancer deaths are down.

5. 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

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 lymphaticsat 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 invasivecarcinoma in pedunculated adenomas Depth of invasion% mets submucosa 2 muscularis20 pericolic adipose 40 source: accumulated literature

19. Haggitt levels submucosa submucosa Invasive carcinoma in a pedunculatedadenoma 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 freeNo 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 CarcinomaIndications for Resection, 3 studies St Marks*GIPSClevClin Margin involved<1mm <2mm CA Gradehigh high high Lymphaticssubjective yes no Blood vascnoyesno * 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

24. Invasive carcinoma in a pedunculatedadenoma: 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. 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. Invasive carcinoma in a pedunculatedadenoma: 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. Invasive carcinoma in a pedunculatedadenoma: 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. 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

32. 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.

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. Dysplasias LowHigh Lots of villous surface

37. 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. Some gastroenterologists want to know the architecture, generallytubular, 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