Polypoid Dysplastic Lesions Research Articles

Influence of SCENIC recommendations on terminology used for histopathologic diagnosis of inflammatory bowel disease-associated dysplasia.

BACKGROUNDPublished in 2015, the International Consensus Recommendations on Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients (SCENIC) recommended abandoning the use of diagnostic term “dysplasia-associated lesion or mass (DALM)” for polypoid dysplastic lesions detected in patients with inflammatory bowel disease (IBD). The aim of this study was to investigate whether this recommendation had any influence on diagnostic terminologies used by pathologists in their practice.METHODSWe retrospectively reviewed all pathology reports for surveillance colonoscopic biopsies from ulcerative colitis (UC) patients in our institution during 1/2012-12/2014 (pre-SCENIC) and 1/2016-12/2018 (post-SCENIC). These included 1203 biopsies from 901 UC patients during the pre-SCENIC period and 1273 biopsies from 977 UC patients during the post-SCENIC period. Their corresponding endoscopic findings and histopathologic diagnoses were recorded. Clinical indications for total colectomy for UC patients and corresponding histopathologic findings in colectomy specimens were also recorded and compared.RESULTSA total of 347 and 419 polyps/polypoid lesions were identified during the pre-SCENIC and post-SCENIC periods, among which 60 and 104 were dysplastic/adenomatous, respectively. More polypoid dysplastic lesions were simply diagnosed as “adenoma” during the post-SCENIC period in comparison with the pre-SCENIC period (97.1% vs 65.0%; P < 0.001). The number of cases with a comment in pathology reports regarding the distinction between DALM and sporadic adenoma was also significantly decreased during the post-SCENIC period (5.8% vs 38.3%; P < 0.001). In addition, the term “dysplasia” was more consistently used for random biopsies during the post-SCENIC period. Furthermore, the terms “sessile serrated adenoma/polyp” (SSA/P) and “serrated epithelial change” (SEC) were more consistently used for polypoid lesions and random biopsies, respectively, during the post-SCENIC period, although these were not specifically addressed in the SCENIC recommendations. The indications for colectomy remained unchanged, however, despite the standardization of diagnostic terminologies.CONCLUSIONThe SCENIC recommendations relieve pathologists from the burden of distinguishing DALM from sporadic adenoma in IBD patients, which helps the standardization of diagnostic terminologies used by pathologists. The consistent use of the diagnostic terminologies may help reduce potential confusions to clinicians and patients.

Patients with Endoscopically Visible Polypoid Adenomatous Lesions Within the Extent of Ulcerative Colitis Have an Increased Risk of Colorectal Cancer Despite Endoscopic Resection.

Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). Few studies have looked at long-term outcomes of endoscopically visible adenomatous lesions removed by endoscopic resection in these patients. We aimed to assess the risk of developing CRC in UC patients with adenomatous lesions that develop within the segment of colitis compared to the remainder of an ulcerative colitis cohort. We identified patients with a confirmed histological diagnosis of UC from 1991 to 2004 and noted outcomes till June 2011. The Kaplan-Meier method was used to estimate cumulative probability of subsequent CRC. Factors associated with risk of CRC were assessed in a Cox proportional hazards model. Twenty-nine of 301 patients with UC had adenomatous lesions noted within the segment of colitis. The crude incidence rate of developing colon cancer in patients with UC was 2.45 (95% CI 1.06-4.83) per 1000 PYD and in those with UC and polypoid adenomas within the extent of inflammation was 11.07 (95% CI 3.59-25.83) per 1000 PYD. Adjusted hazards ratio of developing CRC on follow-up in UC patients with polypoid dysplastic adenomatous lesions within the extent of inflammation was 4.0 (95% CI 1.3-12.4). The risk of developing CRC is significantly higher in UC patients with polypoid adenomatous lesions, within the extent of inflammation, despite endoscopic resection. Patients and physicians should take the increased risk into consideration during follow-up of these patients.

Endoscopy in the Diagnosis and Management of Complications of Inflammatory Bowel Disease

The role of endoscopy in inflammatory bowel disease (IBD) has grown over the last decade in both diagnostic and therapeutic realms. It aids in the initial diagnosis of the disease and also in the assessment of the extent and severity of disease. IBD is associated with development of multiple complications such as strictures, fistulae, and colon cancers. Endoscopy plays a pivotal role in the diagnosis of colon cancer in patients with IBD through incorporation of chromoendoscopy for surveillance. In addition, endoscopic resection with surveillance is recommended in the management of polypoid dysplastic lesions without flat dysplasia. IBD-associated benign strictures with obstructive symptoms amenable to endoscopic intervention can be managed with endoscopic balloon dilation both in the colon and small intestine. In addition, endoscopy plays a major role in assessing the neoterminal ileum after surgery to risk-stratify patients after ileocolonic resection and assessment of a patient with ileoanal pouch anastomosis surgery and management of postsurgical complications. Our article summarizes the current evidence in the role of endoscopy in the diagnosis and management of complications of IBD.

Histological evaluation in ulcerative colitis.

This review summarizes diagnostic problems, challenges and advances in ulcerative colitis (UC). It emphasizes that, although histopathological examination plays a major role in the diagnosis and management of UC, it should always be interpreted in the context of clinical, endoscopic, and radiological findings. Accurate diagnosis requires knowledge of the classic morphological features of UC, as well as a number of atypical pathological presentations that may cause mis-classification of the disease process, either in resection or biopsy specimens. These atypical pathological presentations include rectal sparing and patchiness of disease at initial presentation of UC in pediatric patients or in the setting of medically treated UC, cecal or ascending colon inflammation in left-sided UC, and backwash ileitis in patients with severe ulcerative pancolitis. Loosely formed microgranulomas, with pale foamy histiocytes adjacent to a damaged crypt or eroded surface, should not be interpreted as evidence of Crohn’s disease. Indeterminate colitis should only be used in colectomy specimens as a provisional pathological diagnosis. Patients with UC are at risk for the development of dysplasia and carcinoma; optimal outcomes in UC surveillance programs require familiarity with the diagnostic criteria and challenges relating to UC-associated dysplasia and malignancy. Colon biopsy from UC patients should always be evaluated for dysplasia based on cytological and architectural abnormalities. Accurate interpretation and classification of dysplasia in colon biopsy from UC patients as sporadic adenoma or UC-related dysplasia [flat, adenoma-like, or dysplasia-associated lesion or mass (DALM)] requires clinical and endoscopic correlation. Isolated polypoid dysplastic lesions are considered to be sporadic adenoma if occurring outside areas of histologically proven colitis, or adenoma-like dysplasia if occurring in the diseased segment. Recent data suggest that such lesions may be treated adequately by polypectomy in the absence of flat dysplasia in the patient. UC patients with DALM or flat high-grade dysplasia should be treated by colectomy because of the high probability of adenocarcinoma. The natural history of low-grade dysplasia (LGD) is more controversial: while multifocal LGD, particularly if detected at the time of initial endoscopic examination, is treated with colectomy, unifocal flat LGD detected during surveillance may be managed by close follow-up with increased surveillance. The surveillance interval and treatment options for UC patients with dysplasia are reviewed in detail.

Diagnostic Problems and Advances in Inflammatory Bowel Disease

This review summarizes current diagnostic problems and advances with regard to patterns of inflammation and dysplasia in ulcerative colitis and Crohn's disease. Ulcerative colitis and Crohn's disease have a variety of characteristic but non-specific pathologic features. In approximately 5% of inflammatory bowel disease cases, a definite diagnosis of ulcerative colitis or Crohn's disease cannot be established, in which case the term “indeterminate” colitis is used. Most cases of indeterminate colitis are related to fulminant colitis, a condition in which the classic features of ulcerative colitis or Crohn's disease may be obscured by severe ulceration with early superficial fissuring ulceration, transmural lymphoid aggregates, and relative rectal sparing. Approximately 20% of patients with indeterminate colitis develop severe pouch complications, which is intermediate in frequency between ulcerative colitis (8–10%) and Crohn's disease (30–40%). In order to establish a diagnosis of ulcerative colitis or Crohn's disease, it is important to evaluate pathologic material in conjunction with clinical, laboratory, radiologic, and endoscopic features and to recognize the variety of changes that may be seen in fulminant ulcerative colitis. There are a number of exceptions to the classic principles of inflammatory bowel disease pathology that may lead to diagnostic confusion. For instance, apparent skip lesions on biopsy analysis may occur in patients with ulcerative colitis in the following settings; long term oral or topical therapy, focal ascending colon, cecum and/or appendiceal involvement in patients with left sided ulcerative colitis, upper gastrointestinal involvement in patients with ulcerative colitis, and at initial presentation of ulcerative colitis in pediatric patients. In all of these circumstances, the finding of patchy disease and/or rectal sparing should not be misinterpreted as either evidence against a diagnosis of ulcerative colitis, or as representing skip areas characteristic of Crohn's disease. Patients with ulcerative colitis and Crohn's disease are at increased risk for the development of dysplasia and carcinoma. Recent studies suggest that given a similar duration and extent of disease, patients with Crohn's disease have a similar risk of dysplasia and cancer as patients with ulcerative colitis. Dysplasia in ulcerative colitis may be classified as flat or elevated (dysplasia associated lesion or mass [DALM]). Patients with flat high grade dysplasia are generally treated with colectomy. However, there is recent evidence to suggest that patients with flat low grade dysplasia, particularly if detected at the time of initial endoscopic exam, or if its multifocal or synchronous, should also be treated with colectomy. Elevated lesions in ulcerative colitis (DALM) are subdivided into “adenoma-like” and “non-adenoma-like” lesions based on their endoscopic appearance. Recent data suggests that adenoma-like lesions, regardless of the grade of dysplasia, or the location of the lesion (i.e., inside or outside areas of established colitis) may be treated adequately by polypectomy if there are no other areas of flat dysplasia in the patient. Although there are some histologic and molecular features that can help differentiate sporadic adenomas from adenoma-like polypoid dysplastic lesions related to ulcerative colitis, none of these adjunctive techniques can help distinguish these lesions definitively in any single patient. Patients with a non-adenoma-like DALM, (irregular, broad based, or strictured lesion) should be treated with colectomy because of the high probability of adenocarcinoma. The surveillance and treatment options for patients with flat and elevated dysplasia in ulcerative colitis are reviewed in detail.

P53 and β Catenin Expression in Chronic Ulcerative Colitis–Associated Polypoid Dysplasia and Sporadic Adenomas

In patients with chronic ulcerative colitis (CUC), polypoid dysplastic lesions (PDLs) are morphologically similar to sporadic adenomas (SAs), but may be biologically distinct from them and are managed differently. p53 mutations have been shown to occur at an earlier phase in the progression of CUC-associated neoplasia when compared with sporadic colon carcinogenesis. In contrast, APC gene mutations are common and occur at an earlier stage in the development of SA. beta catenin is a cell membrane protein that accumulates in the nucleus of colon cancer cells in response to APC gene mutations. This study was performed to test the hypothesis that CUC-associated PDLs have a different molecular profile than do CUC-associated SAs and therefore may be distinguished on this basis. Mucosal biopsy specimens of 38 benign polypoid epithelial neoplasms (17 CUC-associated PDLs and 21 CUC-associated SAs) from 33 patients with CUC and 13 SAs from patients without CUC (controls) were immunohistochemically stained for p53 and beta catenin and graded as follows: 0 = no staining, 1+ = <50% of cells positive, and 2+ = > or =50% of cells positive. The results were correlated with the clinical and histologic features and compared between the two CUC-associated polyp subgroups. Overall, six (16%) polyps were p53-positive, of which five were CUC-associated PDLs (one 1+ and four 2+) and one was a CUC-associated SA (1+) (p = 0.05). Strong (2+) p53 positivity was detected, however, in only CUC-associated PDLs (4 of 5; 80%). Nine of 32 polyps evaluated for beta catenin were positive and included 1 (8%) of 12 CUC-associated PDLs and 8 (40%) of 20 CUC-associated SAs (p = 0.06). Two of the nine beta catenin polyps were strongly positive, and both were CUC-associated SAs. Non-CUC-associated (control) SAs were positive for p53 and beta catenin in 2 (15%) of 13 and 6 (46%) of 13 cases, but none in a strong (2+) fashion. No differences were observed in p53 or beta catenin staining, between CUC-associated and non-CUC-associated SAs. Neither p53 nor beta catenin expression correlated with any clinical or pathologic features, including size and degree of dysplasia of the polyps. CUC-associated PDLs and CUC-associated SAs may have a different molecular genotype. In patients with CUC, the combination of strong p53 expression and absent or weak beta catenin expression is evidence in favor of a CUC-associated PDL in diagnostically difficult lesions. Furthermore, CUC-associated and non-CUC-associated SAs have a similar P53 and beta catenin immunophenotype and thus provide evidence that they are pathogenetically related neoplasms regardless of the presence or absence of colitis.

Adenomas and adenoma-like DALMs in chronic ulcerative colitis: a clinical, pathological, and molecular review.

Dysplasia in chronic ulcerative colitis (CUC) is categorized as either flat or associated with a raised lesion or mass (dysplasia-associated lesion or mass [DALM]). One specific subtype of DALM consists of an isolated discrete "adenoma-like" polypoid dysplastic lesion that is difficult to distinguish from a sporadic adenoma that occurs coincidentally in patients with CUC. Sporadic adenomas are, by definition, also polypoid dysplastic lesions, but their development is unrelated to the underlying colitis. The clinical distinction between CUC-associated polypoid dysplastic lesions and sporadic adenomas is important because the former is an indication for colectomy whereas the latter is usually treated by simple polypectomy. This review focuses on the clinical, pathological, and molecular aspects of polypoid dysplastic lesions and sporadic adenomas in CUC. There are a variety of clinical and pathological features that can be used to distinguish these lesions, but none of these features are entirely specific for either type of neoplasm. Furthermore, there is recent evidence to suggest that the molecular pathogenesis of CUC-associated polypoid dysplasia is different, in terms of the order and timing of genetic events, in comparison to sporadic adenomas and, thus, this information may be used to distinguish these lesions in the near future. Few studies have evaluated the natural history of CUC-related polypoid dysplastic lesions and sporadic adenomas. However, recent reports indicate that the majority of these lesions will follow a relatively benign course with a low risk of progression to flat dysplasia or adenocarcinoma. This review also summarizes the current provisional treatment recommendations for CUC patients with an adenoma-like polypoid dysplastic lesion.

Polypoid dysplasia in Barrett's esophagus: A clinicopathologic, immunohistochemical, and molecular study of five cases

Dysplasia in Barrett's esophagus (BE) is a precursor to adenocarcinoma and most commonly occurs as a flat, grossly undetectable lesion. Rarely, dysplasia in BE may grow as a polypoid lesion. Most BE-associated polypoid dysplastic lesions have been referred to as “adenomas” because of their histological similarity to a colonic adenoma. BE-associated polypoid dysplastic lesions have been less well characterized than the flat type. Therefore, our aim was to characterize the clinicopathologic and molecular features of five cases of BE-associated polypoid dysplasia and to review the literature on this entity. The cases were evaluated clinically, histologically, immunostained for MIB-1 and p53, and genotyped for loss of heterozygosity (LOH) at the adenomatous polyposis coli (APC) locus. Mucosal biopsy specimens of five BE patients without dysplasia, and five BE cases with high-grade flat dysplasia, were used as controls. The study patients were all male (average age, 71 years) who presented with symptoms of gastroesophageal reflux disease. Endoscopically, all five cases had a well-defined sessile or pedunculated polypoid lesion ranging from 0.4 to 1.5 cm in size in the mid (n = 1) or distal (n = 4) esophagus and were associated with specialized-type BE (four long segment, one short segment). Histologically, the polyps consisted of intestinalized epithelium with low- and high-grade dysplasia. All five cases contained adenocarcinoma (four within the polyp, one in adjacent BE). All polyps showed increased cell proliferation in the form of surface MiB-1 staining and showed positive p53 staining. Three of three (100%) informative cases showed LOH at the APC locus in the dysplastic epithelium and in areas of adenocarcinoma. All five flat dysplasia controls also showed surface MIB-1 staining and p53 positivity, and three of three informative controls showed LOH for APC. None of the nondysplastic BE controls showed any of these findings. Three patients were treated with esophagectomy and two with polypectomy. All were alive, without metastasis, from 2 months to 6 years later. A literature review of esophageal “adenomas” uncovered 12 cases. Four of these had no clinical or pathological information, two were, in fact, gastric heterotopic lesions, one was composed entirely of intestinal-type epithelium, and five were polypoid dysplastic lesions similar to the cases described here (three male, two female; mean age, 59 years). Four of these five cases were associated with adenocarcinoma in the polyp (two intramucosal, two submucosal). In summary, BE-associated polypoid dysplasia share similar clinical, pathological, and molecular features as flat dysplasia and are often associated with adenocarcinoma. Thus, we agree with other authors who recommend that the term adenoma, which usually carries a benign connotation, be abandoned in favor of a descriptive diagnostic term, such as “BE-associated polypoid dysplasia.” BE patients with this lesion should be considered strong candidates for esophageal resection similar to lesions of this kind that occur in inflammatory bowel disease.

Polypoid dysplasia and adenomas in inflammatory bowel disease: a clinical, pathologic, and follow-up study of 89 polyps from 59 patients.

Dysplasia in inflammatory bowel disease (IBD) is categorized as either flat or associated with a raised lesion or mass (dysplasia-associated lesion or mass [DALM]). One specific subtype of a dysplasia-associated lesion or mass consists of isolated discrete nodules or polyps that are difficult to distinguish from sporadic adenomas. Because the clinical management of these two lesions is different, we performed this study to (1) evaluate the clinical presentation, pathologic features, and natural history of polypoid dysplastic lesions and sporadic adenomas in patients with IBD and (2) determine whether there are clinical, endoscopic, or pathologic findings useful in differentiating between these two lesions. The morphologic features of 89 benign polypoid epithelial neoplasms from 59 patients with IBD (51 with ulcerative colitis, 8 with Crohn's colitis) were evaluated and correlated with the clinical, endoscopic, and follow-up data. In a separate analysis, patients were categorized arbitrarily as having (1) a probable sporadic adenoma if the polypoid epithelial neoplasm was not located within areas of histologically proven colitis, (2) a probable IBD-associated polypoid dysplasia if the lesion developed within an area of colitis, and associated flat dysplasia or an adenocarcinoma was detected during follow-up evaluation or (3) an indeterminate polyp, which was seen in the remainder of the cases. The clinical, endoscopic, and histologic data were compared among these three patient and polyp subgroups. There were 35 males and 24 females (median age, 57 years; range, 27-85 years). Median duration of disease was 10 years. Forty-nine percent of the patients had pancolitis; 66% had histologically active disease at the time of presentation. Nearly 70% of patients had only one polyp; the majority occurred in either the left colon or the rectum (66%). Most polyps were described as a sessile nodule, whereas only 7 (7.8%) were pedunculated. Polyps ranged from 2 mm to 50 mm (median, 5 mm); most had a tubular architecture (84.3%) and contained low-grade dysplasia (64%). In addition, most polyps had mildly increased lamina propria and intraepithelial neutrophilic and mononuclear inflammation. At follow-up evaluation (40 patients; median follow-up time, 13 months; range, 1-78 months), a further neoplastic lesion developed in 20%; low-grade flat dysplasia was seen in 5 (12.5%), and adenocarcinoma developed in 3 (7.5%). However, dysplasia or adenocarcinoma did not develop in the patients who had polyps located outside of areas of histologically proven colitis. In addition, at least one more benign polypoid epithelial neoplasm developed in 15 of 40 patients (37.5%). Patients with probable IBD-associated polypoid dysplasia had a statistically significant (p < 0.05), longer disease duration than patients with probable sporadic adenoma. A statistically significant, higher proportion of polyps with tubullovillous or villous architecture, an admixture of normal and dysplastic epithelium at the surface of the polyps, and increased lamina propria mononuclear inflammation was noted in probable IBD-associated polypoid dysplastic lesions compared with those considered to be sporadic adenomas. Several clinical and pathologic features may be useful to help categorize a polypoid dysplastic lesion as a sporadic adenoma or an IBD-related neoplasm in a patient with IBD. This distinction is important because the natural history of these two lesions (as shown by the results of this study) and their subsequent management are quite different.