Endoscopy, Morphology, Morphometry and Molecular Markers: Predicting Cancer Risk in Colorectal Adenoma

Kjetil Søreide; Bjørn S Nedrebø; Andreas Reite; Kenneth Thorsen; Hartwig Kørner


Expert Rev Mol Diagn. 2009;9(2):125-137. 

In This Article


In 1985, Haggitt introduced a classification for protruding tumors (Figure 1) in the colon and rectum.[17] The level of invasion into the polyp was shown to correlate well with prognosis, and, thus, is considered to be an important guide for treatment of colorectal neoplasia. Nonprotruding lesions are divided into flush/slightly elevated lesions, laterally spreading and depressed lesions.[4] It is important to note that the various nonprotruding lesions have varying potential with regard to invasion into the submucosa. While flat adenomas have mostly benign features, depressed-type lesions are considered more aggressive.[18] There is a sharp transition from malignant cells in the depressed lesion to the normal surrounding mucosa without adenomatous components.[6] This is considered as important evidence supporting the de novo carcinogenesis model in colorectal neoplasia. Furthermore, the size of the neoplasia is of great prognostic importance; Kudo and coworkers showed in a large number of colorectal neoplasia that depressed-type lesions of 6-10 mm diameter showed submucosal invasion in approximately 24%, as compared with 1.3% in protruding lesions, and 0.5% in flush or slightly elevated lesions, and increased with the size of the lesion.[4]

Figure 1.

The Haggitt classification. Histological classification of the extent of invasion of pedunculated malignant colorectal polyps. Level 0: Carcinoma in situ or intramucosal carcinoma. Not invasive. Level 1: Carcinoma invading through muscularis mucosa into submucosa, but limited to the head of the polyp. Level 2: Carcinoma invading the level of the neck of the adenoma. Level 3: Carcinoma invading any part of the stalk. Level 4: Carcinoma invading into the submucosa of the bowel wall below the stalk of the polyp, but above the muscularis propria.

Submucosal Invasion

Submucosal invasion is central in the understanding of early colorectal neoplasia. Classification of submucosal invasion is based on the division of the submucosa (Sm) into three layers, from sm1 to sm3 (Figure 1). Sm1 characterizes lesions that are limited to the upper third of the sumucosal layer; Sm2 the middle third; and Sm3 the lower third of the submucosal layer. Sm1 lesions are further subdivided into three categories (a, b and c) with regard to the degree of horizontal involvement of the upper submucosal layer (ratio of involving part and non-involving part). While Sm1a + b lesions have a very low risk for metastasis, the malignant potential increases with depth of submucosal invasion.[18] Beside the depth of invasion, affection of submucosal vessels is also important. A strong relationship between submucosal invasion and potential of spread to regional lymph nodes and distant organs has been demonstrated.[4]

Protruding lesions are usually removed by endoscopic polypectomy. According to the Haggitt classification (Figure 1), up to type III microinvasive cancer can be treated safely with polypectomy alone. Type IV lesions, however, should be treated by surgical resection due to increased risk of lymph node metastases. In sessile rectal adenomas (and even T1 rectal cancers), transanal endoscopic microsurgery is a suitable method in selected patients.[19,20,21,22]

Nonprotruding lesions can be removed by the endoscopic mucosal resection (EMR) technique (sm1a + b), while sm1c lesions and beyond should be treated surgically because of increased risk of regional lymph node involvement.[7] The EMR technique is based on elevation of the lesion by injection of 0.9% saline into the Sm, followed by resection with a snare through the colonoscope, and retrieval of the tissue with endoscopic forceps. While this technique usually allows removal of lesions up to 20 mm in size, larger polyps can be removed by endoscopic piece-meal resection. Improvements in endoscopy techniques and imaging will certainly allow for better detection and minimal-invasive treatment of early colorectal neoplasia and precancers. However, the fundamental aim in reducing mortality from CRC is prevention of the lesions from developing in the first place.


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