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dysplasia in ulcerative colitis

Sunday 2 December 2012

There are 2 general patterns of growth of dysplasia in ulcerative colitis (UC), considered flat (endoscopically undetectable) or elevated (endoscopically detectable).

DALM (dysplasia-associated lesion or mass)

Elevated lesions are referred to by the acronym DALM (dysplasia-associated lesion or mass). Since the original description by Blackstone et al in 1991, it has been recognized that DALMs represent a heterogeneous group of lesions with different natural histories and risks of malignancy.

DALMs are further subclassified as "adenoma-like" or "non-adenoma like", depending on the gross characteristics of the lesion.

Grossly, "adenoma-like DALMs" represent well-circumscribed, smooth or papillary, nonnecrotic, sessile, or pedunculated polyps that are usually easily removed by routine endoscopic methods, similar to sporadic adenomas.

"Nonadenoma-like DALMs" include velvety patches, plaques, irregular bumps and nodules, wart-like thickenings, stricturing lesions, and broad-based masses. These lesions are not typically amenable to removal by colonoscopy.

It is well known that "nonadenoma-like DALMs" have a high risk (36%–85%) of either synchronous or metachronous cancer.

However, previous studies that evaluated the natural history and risk of malignancy in UC patients with a nonadenoma-like DALM included lesions in which biopsies were obtained from the surface of the mass and, despite the fact that the biopsy showed only dysplastic epithelium, the underlying carcinoma was either not sampled or not detected until a colonic resection was performed.

In contrast, adenoma-like DALMs possess a low risk of malignancy and, as a result, may be treated conservatively by polypectomy and continued surveillance (see below).

The adenoma-like DALMs in UC represent 2 types of lesions.

The first are sporadic adenomas that occur coincidentally in patients with UC, and, thus, are etiologically unrelated to the underlying inflammatory disease.

Sporadic adenomas may develop in both inflamed and noninflamed portions of the bowel.

Adenoma-like lesions that occur within noninflamed portions of the bowel (i.e., proximal to areas of chronic colitis) are easy to diagnose as sporadic adenomas since dysplasia and cancer in UC is believed to develop as a direct result of the underlying inflammatory condition.

Therefore, the risk of neoplasia is not increased in noninvolved portions of the colon. However, sporadic adenomas may also occur in areas involved by UC, in which case they are difficult to differentiate from UC-related adenoma-like polypoid dysplastic lesions, which may have a similar endoscopic and histologic appearance.

A recent study suggested that a large proportion of “DALMs” in patients with UC are, in fact, adenoma-like polyps rather than nonadenoma-like DALMs.

Differential Diagnosis of UC-related Adenoma-like Polypoid Dysplasia Versus Sporadic Adenomas

Several studies have been performed in an effort to identify features that may help differentiate UC-related adenoma-like polypoid dysplastic lesions from true sporadic adenomas in patients with UC.

These include morphology, immunohistochemistry, or molecular biology based-studies.

One study by Torres et al4 showed that UC-related polypoid dysplastic lesions have a higher degree of inflammation within the lamina propria, and often show a mixture of normal and dysplastic crypts at the surface of polyp in contrast to sporadic adenomas.

Stalk dysplasia, if present, should alert the pathologist that dysplasia may be present in the adjacent mucosa and that the lesion is more likely a UC-associated dysplastic lesion rather than a sporadic adenoma.

By immunohistochemistry, some studies have shown that UC-associated polypoid dysplastic lesions show a different pattern of genotypic abnormalities (p53, β-catenin, APC, p16, 3p) compared to sporadic adenomas.

For instance, by immunohistochemistry, Walsh et al7 showed a significantly higher degree of p53, and a lower degree of nuclear β-catenin, immunostaining in UC-associated adenoma-like polypoid dysplasia compared to sporadic adenomas.

However, the low sensitivity and specificity of these immunohistochemical stains render them of limited value in this differential diagnosis.

From a molecular point of view, Odze et al showed that adenoma-like polypoid dysplastic lesions in UC have a similar prevalence rate of loss of heterozygosity (LOH) of 3p, APC, and p16 compared to non-UC associated sporadic adenomas.

Several other studies have shown that nonadenoma-like DALMs in UC patients show a significantly higher prevalence rate of 3p and P16 mutations, indicating perhaps a different timing of molecular events in these latter lesions.

Natural History and Treatment of Adenoma-like DALMs

Despite pathobiologic differences between true sporadic adenomas and UC-related adenoma-like polypoid dysplastic lesions, there are compelling recent data to suggest that UC patients with an adenoma-like dysplastic lesion may be treated adequately by polypectomy and continued surveillance regardless of the underlying etiology, because of the low likelihood of development of either dysplasia or adenocarcinoma on follow-up.

For instance, in a recent long-term prospective follow-up study of 34 UC patients, all of whom had a polypectomy and continued surveillance for adenoma-like DALMs in UC, overall 58.8% developed at least 1 further adenoma-like DALM upon follow-up, but only 1 patient developed flat low-grade dysplasia, and only 1 other developed adenocarcinoma after his/her initial polypectomy.

Most important, there were no differences in the incidence rate of polyp formation between UC patients with an adenoma-like DALM compared to UC patients with a known sporadic adenoma (50%), or between either of these 2 UC patient groups and a non-UC control group with true sporadic adenomas (49%).

In another prospective cohort study by Rubin et al,13 the outcome of 30 UC patients and 18 CD patients with dysplastic polyps that resembled adenomas, all of which were treated by polypectomy and continued surveillance, were followed for an average of 4.1 years.

Similar to the results of Odze et al, 52% did not develop any further polyps, and none of the patients developed either flat dysplasia or adenocarcinoma. As a result of these studies, a recently proposed algorithm for UC patients with either an adenoma-like, or nonadenoma-like DALM has been proposed.

UC patients with a nonadenoma-like DALM, regardless of the grade of dysplasia detected on biopsy analysis, are recommended to receive a colectomy because of the high association with metachronous or synchronous carcinoma.

In contrast, adenoma-like DALMs located outside, or proximal to, areas of known colitis may be assumed to be sporadic in origin and, thus, treated conservatively by polypectomy and continued surveillance similar to patients with sporadic adenomas but without UC.

UC patients with an adenoma-like DALM located within an area of colitis may also be treated conservatively by polypectomy and continued surveillance if the lesion has been excised completely by endoscopy, shows an absence of dysplasia at the margins of the specimen, and there is no evidence of flat dysplasia elsewhere in the colon either adjacent to or distant from the polypoid lesion.

These recommendations apply to UC patients regardless of their age, duration, or extent of colitis, recognizing that adenoma-like lesions in patients with UC are more likely to represent true sporadic adenomas in patients older than 50 years, compared to those who are younger at the time of diagnosis.

The basis of this treatment algorithm relies heavily on the capacity of the endoscopist to adequately categorize elevated dysplastic in UC as either adenoma-like or nonadenoma-like.

Thus, regardless of the ability of the endoscopist to accurately classify a polypoid lesion in UC as adenoma-like or nonadenoma-like, the ability to remove the lesion completely by endoscopic methods is a more objective alternative method of determining whether a patient can be treated safely by polypectomy.

References

- What are the guidelines for treating adenoma-like DALMs in UC? Robert D. Odze MD, FRCP(c); 24 SEP 2008 http://onlinelibrary.wiley.com/doi/10.1002/ibd.20647/full