Dysplasia-associated Lesion Or Mass Research Articles

Pseudopolyps, adenomatous Polyps, and DALMs (dysplasia-associated lesion or mass)

Pseudopolyps, adenomatous Polyps, and DALMs (dysplasia-associated lesion or mass)

Longest Follow-Up of Patients with Ulcerative Colitis After Adenoma Removal

Dysplasia-associated lesion or mass (DALM) in ulcerative colitis (UC) and Crohn colitis is uncommon, sessile, and often irregularly shaped; it arises

Adenoma-Like Dysplastic Polyps in Inflammatory Bowel Disease

Patients with extensive, longstanding inflammatory bowel disease (IBD) are at substantial risk of developing colorectal cancer. Regular colonoscopic surveillance to detect mucosal dysplasia is a widely advocated, although unproven, means of reducing mortality in this group. Once diagnosed, dysplasia indicates a state of heightened cancer risk throughout the large bowel, warranting either total colectomy or close observation to detect any progression. The precise clinical and pathologic parameters calling for 1 option or the other are a subject of ongoing debate. However, there is broad consensus that when dysplasia presents as an endoscopically visible raised lesion, or DALM (dysplasia associated lesion or mass), immediate colectomy is indicated, because such lesions frequently harbor occult invasive carcinoma and could be a marker of neoplasia elsewhere in the bowel. Nevertheless, clinicians are sometimes confronted by dysplastic polyps that are endoscopically indistinguishable from ordinary adenomatous polyps and can be removed locally for pathologic examination. Given the high prevalence of adenomatous polyps in Western societies, clinicians could be understandably reluctant to recommend colectomy to patients for what could be a fortuitous and innocuous lesion unrelated to colitis. The close histologic similarities between colitis-associated dysplasia and the dysplasia of ordinary adenomatous polyps have thus far resisted pathologists’ efforts to distinguish between them. Nonetheless, clinical experience has shown that conservative management of patients with adenoma-like dysplastic polyps results in favorable outcomes. This case illustrates the importance of the endoscopic–pathologic correlation in classifying IBD-associated dysplastic lesions and highlights some of the unresolved issues pertaining to the management of patients in whom they are encountered.

Dysplasia in ulcerative colitis?clinical consequences?

The overall absolute risk of colorectal cancer (CRC) in longstanding extensive or total ulcerative colitis (UC) is estimated to be 10%-15%. The size of this risk is 6- to 10-times that expected in the background population. By performing complete colonoscopies with multiple biopsies from the entire colon and rectum at regular intervals, surveillance programmes for high-risk UC patients aim at detecting mucosal dysplasia in order to select CRC-prone individuals for prophylactic colectomy. In many of the hitherto reported surveillance programmes, the UC patients surveyed have a much lesser risk of dying from CRC than do non-surveyed patients, although randomized studies are lacking. The inter- and intra-observer variability of dysplasia among pathologists is a major pitfall in the surveillance of these patients, as well as the influence of active inflammation, making dysplasia assessment difficult. The practical issues discussed here are, to a large extent, based on the recommendations from the Swedish Gastroenterological Association. Screening colonoscopy should be performed approximately 8-10 years after onset of disease. After negative results for screening or surveillance colonoscopy, the intervals between colonoscopies should not exceed 2 years. Biannual investigations of between 8 and 20 years' duration have been adopted in the Swedish studies, with annual colonoscopies from that point. Findings of CRC, a dysplasia-associated lesion or mass (DALM) with high-grade dysplasia (HGD) or low-grade dysplasia (LGD), or HGD in flat mucosa, are considered as indications for proctocolectomy, as well as repeated, confirmed findings of multifocal LGD. The management of unifocal LGD in flat mucosa is controversial (e.g. proctocolectomy or increased surveillance). Polyps may be handled with snare polypectomy. The safest way of handling UC patients at high risk of developing CRC is by performing regular colonoscopic surveillance. Dysplasia is a useful prognostic marker for subsequent cancer development but has its limitations. A combination of enhanced colonoscopic surveillance using markers that are more sensitive than dysplasia might be the optimal way to manage the increased CRC risk in these patients.

A novel mouse model for colitis-associated colon carcinogenesis induced by 1,2-dimethylhydrazine and dextran sulfate sodium.

To develop an efficient animal colitis-associated carcinogenesis model and to detect the expression of beta-catenin and p53 in this new model. Dysplasia and cancer were investigated in mice pretreated with a single intraperitoneal injection of 20 mg/kg body mass of 1,2-dimethylhydrazine prior to three repetitive oral administrations of 30 g/L dextran sulfate sodium to give conditions similar to the clinically observed active and remission phases. Immunohistochemical staining of beta-catenin and p53 was performed on paraffin-imbedded specimens of animals with cancer and/or dysplasia, those without dysplasia and the normal control animals. At wk 11, four early-invasive adenocarcinomas and 36 dysplasia were found in 10 (90.9%) of the 11 mice that underwent 1,2-dimethylhydrazine-pretreatment with 3 cycles of 30 g/L dextran sulfate sodium-exposure. Dysplasia and/or cancer occurred as flat lesions or as dysplasia-associated lesion or mass (DALM) as observed in humans. Colorectal carcinogenesis occurred primarily on the distal portion of the large intestine. No dysplasia and/or cancer lesion was observed in the control groups with 1,2-dimethylhydrazine pretreatment or 3 cycles of 30 g/L dextran sulfate sodium exposure alone. Immunohistochemical investigation revealed that beta-catenin was translocated from cell membrane to cytoplasm and/or nucleus in 100% of cases with dysplasia and neoplasm, while normal membrane staining was observed in cases without dysplasia and the normal control animals. Nuclear expression of p53 was not detected in specimens. A single dose of procarcinogen followed by induction of chronic ulcerative colitis results in a high incidence of colorectal dysplasia and cancer. Abnormal expression of beta-catenin occurs frequently in dysplasia and cancer. This novel mouse model may provide an excellent vehicle for studying colitis-related colon carcinogenesis.

The color of dysplasia in ulcerative colitis

The color of dysplasia in ulcerative colitis

Evaluation of polypoid lesions in inflammatory bowel disease.

This article discusses patients with inflammatory bowel disease (IBD), a group which is at increased risk for colorectal carcinoma based on extent and duration of their disease. Patients with chronic IBD (at least 8-10 years duration) should be screened with colonoscopy every 1 to 2 years with multiple jumbo biopsies every 10 cm through the entire colon. Patients with sporadic adenomas can be followed after complete polypectomy, whereas patients with adenoma-like dysplasia-associated lesion or mass (DALMs) need increased surveillance. Patients with flat dysplasia or non adenoma-like DALMs are at high risk for progression and should undergo colectomy. The patients who have indeterminate lesions can be differentiated based on the endoscopic, histologic, and molecular features of the lesion. Long-term follow-up is necessary to determine the natural history of these lesions.

P53 protein overexpression in low grade dysplasia (LGD) in barrett’s esophagus: Immunohistochemical marker predictive of progression

OBJECTIVES: The presence of low grade dysplasia (LGD) within Barrett’s esophagus (BE) has a multitude of ramifications. Identification of markers that could risk stratify LGD would be of great clinical benefit. We aimed to prospectively evaluate the prognosis of the immunohistochemical overexpression of p53 protein in BE colocalized to LGD. METHODS: Consecutive BE patients in whom LGD was found had a repeat esophagogastroduodenoscopy within 8–12 wk per an ongoing prospective study. At each esophagogastroduodenoscopy, a therapeutic scope was used in conjunction with the Seattle Biopsy Protocol. Patients were observed until development of multifocal high grade dysplasia (mHGD), presence of an HGD dysplasia-associated lesion or mass (DALM) lesion, or frank adenocarcinoma. p53 protein overexpression was determined by computerized immunoquantitation using image analysis software on step serial-sectioned specimens of BE segment(s) harboring LGD. Kaplan-Meier survival curves were made on the ability of p53 staining colocalized to areas of LGD to predict progression to mHGD, HGD DALM, or cancer during prospective follow-up. RESULTS: Forty-eight BE patients with LGD were observed for a mean of 41.2 ± 22.5 months. During this period, five of 48 patients progressed to mHGD with a focus in which intramucosal cancer could not be excluded (one), mHGD/DALM with one or more foci in which intramucosal cancer could not be excluded (two), cancer (one), or mHGD (one). Twelve had persistent LGD and 31 had regressed to no dysplasia. p53 staining was positive and colocalized to areas of LGD in 4/31 of patients that regressed, 3/12 that persisted, and 3/5 that progressed. Kaplan-Meier curves differed significantly between p53 positive and negative patients for outcome defined as progression of LGD. CONCLUSIONS: p53 colocalization with LGD at index LGD diagnosis is a risk factor for progression of LGD. This can potentially be used to risk stratify BE LGD patients in terms of surveillance intervals or enrollment into secondary prevention studies.

Long-term follow-up of Barrett’s high-grade dysplasia

OBJECTIVE: The management of Barrett’s high-grade dysplasia (HGD) remains controversial. The aims of this study were to evaluate prospectively the outcome of unifocal HGD (uHGD) in patients with Barrett’s esophagus, and to determine demographic and endoscopic features predictive of progression to multifocal HGD (mHGD) and/or adenocarcinoma. METHODS: Consecutive Barrett’s patients in whom uHGD was found at initial endoscopy or during surveillance underwent intensification of medical treatment and repeat endoscopy. The study endpoint was progression to mHGD or adenocarcinoma or HGD in conjunction with a dysplasia-associated lesion or mass (DALM). HGD diagnosis was confirmed by a second, blinded pathologist. RESULTS: A total of 15 Barrett’s patients with uHGD met inclusion criteria and have been prospectively followed for a mean ± SD of 36.8 ± 23.2 months. All were white and male, with a mean age ± SD of 61.4 ± 14.9 yr. Barrett’s length varied from 1 to 13 cm (mean, ± SD, 6.8 ± 4 cm). Overall, eight (53.3%) uHGD progressed: four of 15 (26.7%) to frank cancer between 17 and 35 months of follow-up, two of 15 (13.3%) to mHGD with DALM in conjunction with one or more foci of possible intramucosal cancer after 12–91 months of follow-up, one of 15 (6.7%) to mHGD with a focus of possible intramucosal cancer after 14 months, and one of 15 (6.7%) to mHGD after 29 months. Seven of 15 (46.7%) uHGD have regressed, five to no dysplasia and two to LGD, over the course of follow-up ranging from 24 to 73 months (mean ± SD, 43.3 ± 19.9). All three patients with short-segment Barrett’s esophagus with uHGD regressed. Fisher’s exact test revealed that Barrett’s length ≥3 cm and presence of hiatal hernia approached significance ( p < 0.08) in predicting uHGD progression to mHGD/DALM/cancer. However, use of the log-rank test to account for differences in length of follow-up show no significance for hiatal hernia or Barrett’s length. CONCLUSIONS: Barrett’s uHGD has a high risk for progressing to mHGD or cancer. Justification of an observational approach to uHGD should be discouraged. Markers of uHGD progression, as well as regression, are needed.

Long-term follow-up of Barrett's high-grade dysplasia.

The management of Barrett's high-grade dysplasia (HGD) remains controversial. The aims of this study were to evaluate prospectively the outcome of unifocal HGD (uHGD) in patients with Barrett's esophagus, and to determine demographic and endoscopic features predictive of progression to multifocal HGD (mHGD) and/or adenocarcinoma. Consecutive Barrett's patients in whom uHGD was found at initial endoscopy or during surveillance underwent intensification of medical treatment and repeat endoscopy. The study endpoint was progression to mHGD or adenocarcinoma or HGD in conjunction with a dysplasia-associated lesion or mass (DALM). HGD diagnosis was confirmed by a second, blinded pathologist. A total of 15 Barrett's patients with uHGD met inclusion criteria and have been prospectively followed for a mean +/- SD of 36.8 +/- 23.2 months. All were white and male, with a mean age +/- SD of 61.4 +/- 14.9 yr. Barrett's length varied from 1 to 13 cm (mean, +/- SD, 6.8 +/- 4 cm). Overall, eight (53.3%) uHGD progressed: four of 15 (26.7%) to frank cancer between 17 and 35 months of follow-up, two of 15 (13.3%) to mHGD with DALM in conjunction with one or more foci of possible intramucosal cancer after 12-91 months of follow-up, one of 15 (6.7%) to mHGD with a focus of possible intramucosal cancer after 14 months, and one of 15 (6.7%) to mHGD after 29 months. Seven of 15 (46.7%) uHGD have regressed, five to no dysplasia and two to LGD, over the course of follow-up ranging from 24 to 73 months (mean +/- SD, 43.3 +/- 19.9). All three patients with short-segment Barrett's esophagus with uHGD regressed. Fisher's exact test revealed that Barrett's length > or =3 cm and presence of hiatal hernia approached significance (p < 0.08) in predicting uHGD progression to mHGD/DALM/cancer. However, use of the log-rank test to account for differences in length of follow-up show no significance for hiatal hernia or Barrett's length. Barrett's uHGD has a high risk for progressing to mHGD or cancer. Justification of an observational approach to uHGD should be discouraged. Markers of uHGD progression, as well as regression, are needed.

Dysplasia and cancer in the dextran sulfate sodium mouse colitis model. Relevance to colitis-associated neoplasia in the human: a study of histopathology, B-catenin and p53 expression and the role of inflammation.

Animal models of colitis, which develop dysplasia and cancer similar to human ulcerative colitis are needed to further investigate the dysplasia cancer sequence. This study describes the expression of B-catenin and p53 along with the histopathology and inflammation scores as they relate to dysplasia and cancer in the dextran sulfate sodium (DSS) colitis model. Swiss Webster mice were fed with 5% DSS as follows: group A, four cycles of DSS, 84 days total (1 cycle = 7 days DSS + 14 days H(2)O); group B, four cycles DSS followed by 120 days H(2)O, 204 days total; group C, 7 days DSS followed by 180 days H(2)O, 187 days total; group D, 7 days DSS followed by 90 days H(2)O, 97 days total. The incidences of dysplasia and/or cancer were 15.8, 37.5, 18.1 and 0% in groups A-D, respectively. Dysplasia and/or cancer occurred as flat lesions or as dysplasia-associated lesion or mass (DALM) as observed in the human. Thirty-three percent of cancers had associated dysplasia. Within group A, inflammation scores were significantly higher in animals with dysplasia and/or cancer compared with those without dysplasia and/or cancer (P < 0. 05-P < 0.0001). Inflammation scores were significantly higher in animals with cancers versus those with dysplasia (P < 0.015) and in flat dysplasia and/or cancer versus DALM (P < 0.0042). B-catenin showed translocation from the cell membrane to the cytoplasm and/or nucleus in 100% of DALM and 5.8% of flat dysplasia and/or cancer. A total of 94.2% of flat dysplasia and/or cancer had exclusive cell membrane expression compared with 0% DALM (P < 0.0001). Only 7.4% of dysplasia and/or cancer showed nuclear expression of p53. In colitis-associated dysplasia and/or cancer in the DSS model: (i) histology resembles that in the human; (ii) inflammation plays a significant role in the dysplasia cancer sequence and whether dysplasia and/or cancer grows as a flat lesion or a DALM; (iii) the early molecular pathways are different for flat dysplasia and/or cancer versus DALM, with nuclear/cytoplasmic translocation of B-catenin as an early event in DALM but not flat dysplasia and/or cancer; and (iv) p53 has little or no role in dysplasia and/or cancer. This well characterized model provides an excellent vehicle for studying the roles of inflammation, the molecular events and the role of chemopreventive agents in colitis-associated neoplasia.

Distinction between dysplasia-associated lesion or mass (DALM) and adenoma in patients with ulcerative colitis

Polyps with epithelial dysplasia in ulcerative colitis (UC) represent either dysplasia-associated lesions or masses (DALMs) or sporadic adenomas. DALMs are frequently associated with associated carcinoma and are an indication for colectomy. Removal of the polyp is treatment of choice for sporadic adenomas. Differentiating between these 2 lesions is not always easy. The goal of this study was to distinguish DALMs from adenomas in patients with UC on a genetic basis. We evaluated genetic alterations in DALMs and compared them with a previously published set of dysplastic polyps in patients with UC that were considered adenomas for the following reasons: (1) polyps were located outside of current active disease; (2) polyps had histological features of sporadic adenomas; and (3) patients displayed a uneventful follow-up after polypectomy (UC-adenomas). In addition, adenomas not associated with UC were studied. Genetic alterations on chromosome 3p were assessed for the markers D3S1766, D3S2409, and D3S2387. LOH with or without microsatellite instability was found in 70%, 37%, and 57% of cases of DALM, respectively. In contrast, UC-adenomas lesions exhibited genetic alterations in 8.3%, 11.7%, and 15.3% for the respective markers. Spontaneous adenomas exhibited genetic alterations in 10.5%, 7.1%, and 0% of cases, which were not significantly different from the UC-adenoma results. These results indicate that UC-adenomas are genetically and biologically similar to sporadic adenomas and that UC-adenomas may biologically represent sporadic adenomas, supporting on a genetic basis the criteria chosen to diagnose adenomas in UC. Genetic markers on chromosome 3p may be useful in the differential diagnosis between DALM and UC-adenomas.

Surveillance colonoscopy in inflammatory bowel disease

Surveillance colonoscopy and systematic colonic biopsy in patients with ulcerative colitis of long duration appears to reduce the risk of colorectal cancer mortality. Patients with pan ulcerative colitis should undergo surveillance at one to 2 year intervals between 10 and 20 years of disease duration and annually thereafter. Biopsies should be taken from flat mucosa in all 4 colonic quadrants every 10 cm. Pseudopolyps need not be biopsied, but irregular mass legions and typical appearing adenomas should be biopsied or removed and the flat mucosa around them should be sampled separately. Sporadic tubular adenomas in older patients and adenomas proximal to the colitis do not mandate colectomy. High- or low-grade dysplasia in flat mucosa verified by an expert pathologist and dysplasia associated lesion or mass (DALM) are indications for colectomy. Patients should understand that surveillance colonoscopy in ulcerative colitis is not fully protective in preventing colorectal cancer mortality.

Adenomas in Chronic Ulcerative Colitis: Colectomy or Continued Surveillance?

In chronic ulcerative colitis, surveillance colonoscopy is used to identify patients at risk for cancer. A well-accepted indication for colectomy is the DALM (dysplasia-associated lesion or mass). However, patients with chronic ulcerative colitis also develop sporadic adenomas based on their age rather than the cancer potential of the colitis. These sporadic adenomas are mass lesions that by definition contain dysplasia, and thus there is inherent difficulty in differentiating them from classic DALMs. Two groups recently reported their experience following patients with chronic …

Colonoscopic polypectomy in chronic colitis: Conservative management after endoscopic resection of dysplastic polyps

Background & Aims: Adenomatous polyps are by definition dysplastic and pathologically indistinguishable from the dysplasia-associated lesion or mass (DALM) described in 1981. Yet, adenomatous polyps in noncolitic colons are usually removed definitively endoscopically, whereas DALMs are regarded as harbingers of colon cancer, mandating colectomy. Methods: Since 1988, all of our patients with chronic ulcerative or Crohn's colitis and dysplastic polyps and no coexistent dysplasia in flat mucosa underwent colonoscopic polypectomy. Biopsy specimens were obtained also adjacent to polypectomy sites, from strictures, and throughout the colon at 10-cm intervals. Follow-up colonoscopies and biopsies were performed within 6 months after polypectomy and yearly thereafter. Results: Colonoscopy in 48 patients with chronic colitis (mean duration, 25.4 years) resected 70 polyps (60 in colitic and 10 in noncolitic mucosa). Polyps were detected on screening colonoscopies (29%) and on surveillance (71%). Pathology was tubular adenoma in all polyps from noncolitic mucosa and low-grade dysplasia (57), high-grade dysplasia (2), or carcinoma (1) in polyps from colitic mucosa. Subsequent colonoscopies (mean follow-up, 4.1 years) revealed additional polyps in 48% but no carcinomas. Surgical resection (6 patients) for recurrent polyps confirmed colonoscopic findings. No dysplasia or cancers in flat mucosa were found at surgery or on follow-up colonoscopies. Conclusions: In patients with chronic colitis who have no dysplasia in flat mucosa, colonoscopic resection of dysplastic polyps can be performed effectively, just as in noncolitic colons. GASTROENTEROLOGY 1999;117:1295-1300

Villous, hypermucinous mucosa in long standing ulcerative colitis shows high frequency of K-rasmutations

BACKGROUNDK-rasmutation is one of the first genetic alterations in classical colorectal carcinogenesis.AIMSTo investigate the role of K-ras mutations in carcinogenesis, in long standing ulcerative colitis.METHODSA total of 161 microdissected and...

Endoscopic appearance of dysplasia and cancer in inflammatory bowel disease.

Dysplastic alteration of mucosa may occur in flat or raised mucosal lesions. Over 95% of dysplastic foci occur in flat mucosa. Flat dysplasia is occasionally visible macroscopically as areas of discolouration, velvety-villous appearance, or peculiar fine nodular thickening. The prevalence of macroscopically visible flat dysplasia is unknown. Raised dysplasia or DALM (dysplasia associated lesion or mass) occurs in less than 5% of patients with dysplasia. DALMs are polypoid structures of firm consistency, discoloured mucosa and irregular nodularity. DALMs cannot be distinguished endoscopically from early malignancy. The presence of DALMs has an ominous significance.

Surgical treatment of inflammatory bowel disease--a review of some current opinions and controversies.

There are many controversial issues regarding the treatment of patients with inflammatory bowel disease. From this review we have concluded that the longer surgery for Crohn's disease is delayed, the higher the rate is of pre- and postoperative complications. A plea is thus made for relatively early surgical intervention. For Crohn's disease, the general policy today is to perform resections, even if relatively limited ones, rather than to perform by-passes of the macroscopically involved intestine. Indeterminate colitis, as well as self-limiting colitis, are differential diagnoses that the surgeon must be aware of, especially when selecting the appropriate operative method. Due to the existent risk of cancer in ulcerative colitis, some authors advocate prophylactic colectomy after 10 to 15 years, but the most current policy seems to be one of close surveillance, with surgery only in the cases of severe dysplasia or if a so called dysplasia associated lesion or mass (DALM) is diagnosed. Coloproctectomy has been the standard procedure for patients with ulcerative colitis, however, good or even excellent results are often seen after ileorectal anastomosis and pelvic pouch operations. Although all patients cannot benefit from the latter operation it is likely that it will become the principal operation for patients with ulcerative colitis.

Dysplasia-associated lesion or mass (DALM) detected by colonoscopy in long-standing ulcerative colitis: An indication for colectomy

In performing colonoscopy over a 4-yr period on 112 patients with long-standing ulcerative colitis, a dysplasia-associated lesion or mass (DALM) was found in 12. This appeared as either a single polypoid mass (5 cases), a plaquelike lesion (2 cases), or multiple polyps (5 cases). In 7 of these 12 cases carcinoma was subsequently found. This was particularly true in the 5 cases of single polypoid masses where all 5 contained invasive carcinoma. In none of the cases associated with malignancy did multiple biopsies of the DALM reveal invasive carcinoma. In only 2 of the 7 patients with carcinoma was the dysplasia “severe,” being “mild” or “moderate” in the remaining 5. In the 27 patients with dysplasia found incidentally in random biopsies of flat mucosa only one carcinoma was found, in contrast to the 7 cancers in 12 patients with DALM. This difference leads us to regard the finding of DALM, especially a single polypoid mass, as highly significant in patients with long-standing ulcerative colitis. It carries a sufficiently high risk of cancer, thereby constituting a strong indication for colectomy.