Colorectal Serrated Lesions Research Articles

How to "pick up" colorectal serrated lesions and polyps in daily histopathology practice: From terminologies to diagnostic pitfalls.

Over the last decade, our knowledge of colorectal serrated polyps and lesions has significantly improved due to numerous studies on this group of precursor lesions. Serrated lesions were misleading as benign before 2010, but they are currently reclassified as precancerous lesions that contribute to 30% of colorectal cancer through the serrated neoplasia pathway. The World Health Organization updated the classification for serrated lesions and polyps of the colon and rectum in 2019, which is more concise and applicable in daily practice. The responsible authors prescribe that "colorectal serrated lesions and polyps are characterized by a serrated (sawtooth or stellate) architecture of the epithelium." From a clinical standpoint, sessile serrated lesion (SSL) and SSL with dysplasia (SSLD) are the two most significant entities. Despite these advancements, the precise diagnosis of SSL and SSLD based mainly on histopathology remains challenging due to various difficulties. This review describes the nomenclature and the terminology of colorectal serrated polyps and lesions and highlights the diagnostic criteria and obstacles encountered in the histopathological diagnosis of SSL and SSLD.

Safety and efficacy of underwater EMR for 10- to 20-mm colorectal serrated lesions (SEA CLEAR study)

Colorectal serrated lesions (SLs) are precursors of colorectal carcinoma via the serrated neoplasia pathway. However, the success rate of endoscopic resection of large SLs is low. Therefore, this study aimed to determine the safety and efficacy of underwater EMR (UEMR) for SLs sized 10 to 20mm. This 2-center, prospective, observational study included patients with at least 1 SL sized 10 to 20mm. We resected the SLs by UEMR and performed tattooing at the resection site. Surveillance colonoscopy was performed 12 months postoperatively to evaluate local recurrence. The primary outcome was the complete resection rate of UEMR, which was defined as en bloc resection with no serrated tissue in the 4 marginal biopsy samples and histologically negative margins. UEMR was performed for 65 SLs in 58 patients, with a median lesion size of 14mm. The en bloc, R0 resection, and complete resection rates were 87.7% (57 of 65), 61.5% (40 of 65), and 60.0% (39 of 65), respectively. Adverse events included 1 (1.5%) immediate bleeding and 1 (1.5%) delayed perforation. Surveillance colonoscopy was performed in 50 patients with 57 scars, and the rates of identification for tattoos and scars were 94.7% (54 of 57) and 100% (57 of 57), respectively. The recurrence rate was 5.3% (3 of 57), and all 3 recurrent lesions were completely resected endoscopically. This 2-center prospective study demonstrated that UEMR for SLs sized 10 to 20mm was comparable to previous conventional EMR outcomes.

Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas

BackgroundAberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions.MethodsSMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (n = 199) and adjacent normal colonic tissues (n = 112).ResultsSMOC1 was abundantly expressed in normal colon and SSLs while it was significantly downregulated in TSAs, advanced adenomas and cancers. Mean immunohistochemistry scores were as follows: normal colon, 24.2; hyperplastic polyp (HP), 18.9; SSL, 23.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 15.8; TSA, 5.4; TSA with high grade dysplasia (HGD)/EIC, 4.7; non-advanced adenoma, 21.4; advanced adenoma, 11.9; EIC, 10.9. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components.ConclusionOur results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 expression may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.

Serum DNA methylome of the colorectal cancer serrated pathway enables non-invasive detection.

The clinical relevance of the colorectal cancer serrated pathway is evident, but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway and to evaluate circulating cell-free DNA (cfDNA) methylomes as a potential source of biomarkers for the non-invasive detection of serrated lesions. We collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and individuals with no colorectal findings. First, we quantified cfDNA methylation with the MethylationEPIC array. Then, we compared the methylation profiles with tissue and serum datasets. Finally, we evaluated the utility of serum cfDNA methylation biomarkers. We identified a differential methylation profile able to distinguish high-risk serrated lesions from no serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions. Serum methylation profiles are pathway-specific, clearly separating serrated lesions from conventional adenomas. The combination of ninjurin 2 (NINJ2) and glutamate-rich 1 (ERICH1) methylation discriminated high-risk serrated lesions and SAC with 91.4% sensitivity (64.4% specificity), while zinc finger protein 718 (ZNF718) methylation reported 100% sensitivity for the detection of SAC (96% specificity). This is the first study exploring the serum methylome of serrated lesions. Differential methylation of cfDNA can be used for the non-invasive detection of colorectal serrated lesions.

Colorectal serrated lesions and polyps in the Danish population: A large nationwide register-based cohort study

Abstract Background and study aims Colorectal serrated lesions and polyps (SPs) include hyperplastic polyps (HP), sessile serrated lesions-/+dysplasia (SSL/SSL-D), and traditional serrated adenomas (TSA). From 20% to 30% of colorectal cancers (CRC) develop from SP. We present incidence and baseline characteristics of SP in a Danish cohort. Patients and methods We used The Danish Pathology Registry to include all SPs in the Danish population from January 1, 2000 to December 31, 2021. Based on the unique Danish personal identification number and SNOMED-codes, combined with the age and sex of patients, and date of procedure, we determined the incidence of the SP subtypes, anatomical location, and changes over time. Results During the period from 2000 to 2021, a total of 292,761 SPs were removed from 163,840 patients: 51,649 SSLs, 5959 SSL-Ds, 224,860 HDs, and 10,293 TSAs. The median age of patients was 64.1 years (range 55.2–71.6) and 53.3% were male. We found a general increase in SPs from 3525 in 2000 to 25,853 in 2021 and a rise in the SSL proportion from 1.7% in 2006 to 38% in 2021. Half of all patients had more than one lesion at endoscopy with conventional adenomas being the most common. CRC was found along with SPs in 3.3% of procedures, while 1% to 2.5% of the patients developed metachronous CRC. Conclusions We found an increasing number of SPs, especially SSLs. From 2019 to 2021 the number of SPs seem to stabilize, while the proportion of SSLs keeps rising. Synchronous lesions were common along all subtypes of SP.

Association between metabolic syndrome and early-stage colorectal cancer

BackgroundAccumulating studies have suggested metabolic syndrome (MetS) contributed to colorectal cancer (CRC) development. However, advanced CRC might decrease the detection proportion of MetS due to chronic malnutrition, we included patients with early-stage CRC to examine the associations among MetS, onset age, and different tumorigenesis pathways of CRC.MethodsWe conducted a retrospective study that included 638 patients with early-stage CRC from January 2014 to December 2018. Patient information was collected from the medical record system and further refined during the follow-up. Stratified analyses of the associations between MetS and different stratification factors were determined by the Cochran‒Mantel‒Haenszel test.ResultsThere were 16 (13.3%) and 111 (21.4%) cases suffering from MetS in the early-onset and late-onset CRC groups, respectively. MetS coexisted in early-stage CRC patients ≥ 50 years of age more frequently than patients < 50 years of age (OR 1.77; 95% CI 1.01 to 3.12), but not for women patients (OR 0.84; 95% CI 0.79 to 0.90). MetS patients were associated with a higher risk of advanced serrated lesions than that of conventional adenomas (OR 1.585; 95% CI 1.02 to 2.45), especially in patients ≥ 50 years (OR 1.78; 95% CI 1.11 to 2.85).ConclusionsMetabolic dysregulation might partly contribute to the incidence of colorectal serrated lesions. Prevention of MetS should be highly appreciated in the early diagnosis and early treatment of the colorectal cancer system, especially in patients ≥ 50 years.

Usefulness of analyzing endoscopic features in identifying the colorectal serrated sessile lesions with and without dysplasia.

Sessile serrated lesions (SSLs) are often missed on colonoscopy, and studies have shown this to be an essential cause of interstitial colorectal cancer. The SSLs with dysplasia (SSL-D+), in particular, have a faster rate of carcinogenesis than conventional tubular adenomas. Therefore, there is a clinical need for some endoscopic features with independent diagnostic value for SSL-D+s to assist endoscopists in making immediate diagnoses, thus improving the quality of endoscopic examination and treatment. To compare the characteristics of SSLs, including those with and without dysplasia (SSL-D+ and SSL-D-), based on white light and image-enhanced endoscopy, to achieve an immediate differential diagnosis for endoscopists. From January 2017 to February 2023, cases of colorectal SSLs confirmed by colonoscopy and histopathology at the Gastrointestinal Endoscopy Center of Beijing Tsinghua Changgung Hospital were collected. The general, endoscopic, and histopathological data were reviewed and analyzed to determine the diagnostic utility. Univariate analysis was used to find potential diagnostic factors, and then multivariate regression analysis was performed to derive endoscopic features with independent diagnostic values for the SSL-D+. A total of 228 patients with 253 lesions were collected as a result. There were 225 cases of colorectal SSL-D-s and 28 cases of SSL-D+s. Compared to the colorectal SSL-D-, the SSL-D+ was more common in the right colon (P = 0.027) with complex patterns of depression, nodule, and elevation based on cloud-like surfaces (P = 0.003), reddish (P < 0.001), microvascular varicose (P < 0.001), and mixed type (Pit II, II-O, IIIL, IV) of crypt opening based on Pit II-O (P < 0.001). Multifactorial logistic regression analysis indicated that lesions had a reddish color [odds ratio (OR) = 18.705, 95% confidence interval (CI): 3.684-94.974], microvascular varicose (OR = 6.768, 95%CI: 1.717-26.677), and mixed pattern of crypt opening (OR = 20.704, 95%CI: 2.955-145.086) as the independent predictors for SSL-D+s. The endoscopic feature that has independent diagnostic value for SSL-D+ is a reddish color, microvascular varicose, and mixed pattern of crypt openings.

Local recurrence rates after resection of large colorectal serrated lesions with or without margin thermal ablation

Introduction Serrated lesions (SLs) including traditional serrated adenomas (TSA), large hyperplastic polyps (HP) and sessile serrated lesions (SSLs) are associated with high incomplete resection rates. Margin ablation combined with EMR (EMR-T) has become routine to reduce local recurrence while cold snare polypectomy (CSP) is becoming recognized as equally effective for large SLs. Our aim was to evaluate local recurrence rates (LRR) and the use of margin ablation in preventing recurrence in a retrospective cohort study. Methods Patients undergoing resection of ≥15 mm colorectal SLs from 2010-2022 were identified through a pathology database and electronic medical records search. Hereditary CRC syndromes, first follow-up > 18 months or no follow-up, surgical resection were excluded. Primary outcome was LRRs (either histologic or visual) during the first 18-month follow-up. Secondary outcomes were LRRs according to size, and resection technique. Results 191 polyps in 170 patients were resected (59.8% women; mean age, 65 years). The mean size of polyps was 22.4 mm, with 107 (56.0%) ≥20 mm. 99 polyps were resected with EMR, 39 with EMR-T, and 26 with CSP. Mean first surveillance was 8.2 mo. Overall LRR was 18.8% (36/191) (16.8% for ≥20 mm, 17.9% for ≥30 mm). LRR was significantly lower after EMR-T when compared with EMR (5.1% vs. 23.2%; p = 0.013) or CSP (5.1% vs. 23.1%; p = 0.031). There was no difference in LRR between EMR without margin ablation and CSP (p = 0.987). Conclusion The local recurrence rate for SLs ≥15 mm is high with 18.8% overall recurrence. EMR with thermal ablation of the margins is superior to both no ablation and CSP in reducing LRRs.

Rates of synchronous advanced neoplasia and colorectal cancer in patients with colonic serrated lesions.

Serrated lesions (SL) have been associated with significant risks of developing colorectal cancer (CRC). Data on synchronous findings after SL detection during colonoscopy is limited. Study aim was to evaluate the rate of synchronous advanced neoplasia (S-AN) and synchronous CRC (S-CRC) in colonoscopies where SLs were detected. We conducted a retrospective study of screening aged patients 45-74year with colorectal SL (sessile serrated polyp [SSP] or traditional serrated adenoma [TSA]) detected during an elective colonoscopy. Primary outcome was risk of S-AN in patients with SL. Secondary outcomes included risk of S-AN or S-CRC stratified by SL characteristics. The study included 1262 patients with 1649 SLs (1214 with SSPs and 48 with TSAs). 47.2% were female and 22.9% of exams were screening colonoscopies, 48.2% surveillance, 28.9% diagnostic. The overall rates of S-AN and S-CRC were 15.1% and 1.3%, respectively. Presence of SSPs ≥ 10mm was associated with higher rates of S-AN, (18.1 vs. 12.2%, Odds-Ratio [OR] = 1.61 [95% Confidence Interval [CI] 1.17-2.23], p = 0.004). SSP dysplasia was predictive of S-AN, (30.3 vs 14.1%, OR = 2.68 [95%CI 1.24-5.78], p = 0.012) but not S-CRC. SSP number (≥ 3) and location (proximal) were not predictors of S-AN or S-CRC. Patients with SLs are at high-risk of S-AN and S-CRC. Findings of SSPs ≥ 10mm and SSP dysplasia are associated with high-risk of S-AN. Endoscopists should exercise heightened vigilance for synchronous findings when SLs are detected, especially SSPs ≥ 10mm or when bowel preparation is suboptimal. Studies contrasting synchronous risk of other polyp types are needed to confirm these results.

Morphological and molecular characterization of colorectal sessile serrated lesions with dysplasia

In sessile serrated lesions (SSLs) with adenomatous dysplasia, the dysplastic component and the serrated component without dysplasia should be considered as part of the same lesion, classified as SSL with dysplasia. However, some of these lesions may actually represent collisions between a serrated polyp and a conventional adenoma. Further supporting the "collision theory", conventional adenomatous dysplasia may be found in association with hyperplastic polyps (HPs). In order to determine the molecular and biological landscape of conventional type dysplasia in serrated lesions, we collected 17 cases of colorectal serrated lesions with adenomatous dysplasia, classifying them as SSL with dysplasia (n=10) or as mixed lesions comprising a HP component and a conventional adenomatous component (n=7). We characterized the dysplastic and the non-dysplastic component of each lesion, after microdissection, through the targeted mutational analysis of 11 commonly altered genes in colorectal cancer (AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN and TP53). We also characterized MMR and p53 status by immunohistochemistry. Overall, 14/17 (82.4%) cases harbored a mutation in at least one of the two components. The most altered genes were BRAF in 10/17 (58.8%) cases, APC in 2/17 (11.8%) and TP53 in 4/17 (23.5%). Among the SSL with dysplasia, the mutational profile was concordant between the two components in 7/10 (70%) cases, while among the mixed lesions, the mutational profile was concordant in 1/7 (14.3%). In all but two cases of SSL with dysplasia, MMR status was concordant between the two components of the serrated lesions. Our findings suggest that adenomatous dysplasia may develop in SSL as part of the serrated lesion, even if some SSL with dysplasia may actually be collision lesions. On the other hand, the polyps that are morphologically classifiable as mixed lesions composed of a HP and a conventional adenomatous component are more likely to be collision lesions.

Linked color imaging improves visibility of colorectal serrated lesion by high color contrast to surrounding mucosa.

This study aimed to objectively evaluate the efficacy of linked color imaging (LCI) in diagnosing colorectal serrated lesions by utilizing visibility scores and color differences. We examined 89 serrated lesions, including 36 hyperplastic polyps (HPs), 47 sessile serrated lesions (SSLs), and six traditional serrated adenomas (TSAs). Visibility changes were scored by six endoscopists as follows: 4, excellent; 3, good; 2, fair; and 1, poor. Furthermore, images obtained by white-light imaging (WLI) or LCI were assessed using the CIELAB color space in the lesion and adjacent mucosa. We calculated the mean color values (L*, a*, and b*) measured at five regions of interest of the sample lesion and surrounding mucosa and derived the color difference (ΔE*). The visibility scores of both HPs and SSLs in LCI were significantly higher than that in WLI (HPs, 3.67/2.89, P < 0.001; SSLs, 3.07/2.36, P < 0.001). Furthermore, SSLs showed a significantly higher L* value and significantly lower a* and b* values in LCI than the adjacent mucosae (L*, 61.76/58.23, P = 0.016; a*, 14.91/17.58, P = 0.019; b*, 20.42/24.21, P = 0.007), while WLI produced no significant difference in any color value. A similar trend was apparent in HPs. In all serrated groups, LCI revealed significantly greater ΔE* values between the lesion and adjacent mucosa than WLI (HPs, 11.54/6.12; SSLs, 13.43/7.67; TSAs, 35.00/22.48). Linked color imaging showed higher color contrast between serrated lesions and the surrounding mucosae compared with WLI, indicating improved visibility of colorectal serrated lesion using LCI.

Arterial stiffness is associated with high-risk colorectal adenomas and serrated lesions: A cross-sectional study in a Taiwanese population

BackgroundLittle is currently known about the association between arterial stiffness and colorectal serrated lesions. This study was aimed toward an investigation of the association between arterial stiffness and colorectal precancerous lesions, including colorectal adenomas and serrated lesions. Methods7262 eligible adult subjects who underwent health check-ups with colonoscopies and brachial-ankle pulse wave velocity (baPWV) were recruited. Patients were categorized as polyp-free, low-risk and high-risk adenomas, and low-risk and high-risk serrated lesions based on the presence of polyps. The severity of arterial stiffness was categorized into four subgroups based on the baPWV quartile. ResultsAfter adjusting for multiple covariates, the baPWV values were found to be positively correlated with the occurrence of low-risk adenomas. With respect to high-risk polyps, the third and highest baPWV quartiles were significantly associated with the occurrence of both high-risk adenomas and high-risk serrated lesions. A more significant association was found in the highest baPWV quartiles combined with smoking in cases classified with high-risk serrated lesions. ConclusionsIncreased arterial stiffness was independently associated with precancerous colorectal lesions, not only adenomas but also high-risk serrated lesions. Individuals with increased arterial stiffness, especially those who are smokers, should be more aware of the risk of colorectal cancer.

Serrated Colorectal Lesions: An Up-to-Date Review from Histological Pattern to Molecular Pathogenesis

Until 2010, colorectal serrated lesions were generally considered as harmless lesions and reported as hyperplastic polyps (HPs) by pathologists and gastroenterologists. However, recent evidence showed that they may bear the potential to develop into colorectal carcinoma (CRC). Therefore, the World Health Organization (WHO) classification has identified four categories of serrated lesions: hyperplastic polyps (HPs), sessile serrated lesions (SSLs), traditional serrated adenoma (TSAs) and unclassified serrated adenomas. SSLs with dysplasia and TSAs are the most common precursors of CRC. CRCs arising from serrated lesions originate via two different molecular pathways, namely sporadic microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP), the latter being considered as the major mechanism that drives the serrated pathway towards CRC. Unlike CRCs arising through the adenoma–carcinoma pathway, APC-inactivating mutations are rarely shown in the serrated neoplasia pathway.

Comprehensive analyses of microRNA and mRNA expression in colorectal serrated lesions and colorectal cancer with a microsatellite instability phenotype.

MicroRNA (miRNA) expression is dysregulated in human tumors, thereby contributing to tumorigenesis through altered expression of mRNA. Thus, identification of the relationships between miRNAs and mRNAs is important for evaluating the molecular mechanisms of tumors. In addition, elucidation of the molecular features of serrated lesions is essential in colorectal tumorigenesis. Here, we examined the relationships of miRNA and mRNA expressed in serrated lesions, including 26 sessile serrated lesions (SSLs), 12 traditional serrated adenomas (TSAs), and 11 colorectal cancers (CRCs) with a microsatellite instability (MSI) phenotype using crypt isolation. We divided the samples into the first and second cohorts for validation. Array-based expression analyses were used to evaluate miRNAs and mRNAs with opposite expression patterns in isolated tumor glands. In addition, we validated the relationships of miRNA/mRNA pairs in the second cohort using real-time polymerase chain reaction. We found that the expression of miRNA-5787 was correlated with reciprocal expression of two mRNAs, that is, SRRM2 and POLR2J3, in SSL samples. In TSA samples, two pairs of miRNAs/mRNAs showing opposite expression patterns, that is, miRNA-182-5p/ETF1 and miRNA-200b-3p/MYB, were identified. Ultimately, three pairs of miRNAs/mRNAs with opposite expression patterns, including miRNA-222-3p/SLC26A3, miRNA-6753-3p/FABP1, and miRNA-222-3p/OLFM4, were retained in CRC with an MSI phenotype. Finally, we performed transfection with an miR-222-3p mimic to confirm the expression of SLC26A3 and OLFM4; the results showed that ectopic expression of miR-222-3p moderately suppressed OLFM4 and downregulated SLC26A3 to some extent. Overall, our results provided basic insights into the evaluation of colorectal tumorigenesis of serrated lesions and CRC with an MSI phenotype.

Endoscopic features of isolated and traditional serrated adenoma-associated superficially serrated adenomas of the colorectum.

Superficially serrated adenoma (SuSA) is a recently proposed subtype of colorectal serrated lesions. It is characterized by distinct clinicopathological and molecular features, including mixed serrated and adenomatous histology and frequent genetic alterations involving KRAS and RSPO. This study aimed to characterize the endoscopic features of isolated and traditional serrated adenoma (TSA)-associated SuSAs. We retrospectively evaluated the endoscopic findings of 25 isolated SuSAs and 21 TSA-associated SuSAs that were histologically and molecularly characterized. SuSAs appeared as a sessile polyp or slightly elevated lesion located mostly in the sigmoid colon and rectum (88%). The size was between 3 and 20 mm (median, 6 mm). Most of them exhibited KRAS mutations (96%) and RSPO fusions/overexpression (92%). Endoscopically, many lesions had a whitish color (84%), a distinct border (96%), an irregular border (76%), and a lobulated surface (72%). However, diminutive lesions exhibited overlapping features with hyperplastic polyps. On narrow-band imaging, vessel patterns were invisible or appeared as lacy microvessels in most lesions (80%). Chromoendoscopy invariably showed stellar or elongated/branched stellar pits, indicating a serrated microarchitecture. Most TSA-associated SuSAs typically presented as polyps with a two-tier raised appearance, consisting of whitish lower and reddish higher components corresponding to a SuSA and a TSA, respectively. SuSAs exhibit several characteristic endoscopic features on white-light and image-enhanced endoscopy. Diminutive lesions exhibit endoscopic features overlapping with hyperplastic polyps. Nonetheless, the endoscopic diagnosis of larger and TSA-associated SuSAs may be feasible.

Underwater endoscopic mucosal resection of adenomas and colorectal serrated lesions: a prospective clinical study.

BackgroundUnderwater endoscopic mucosal resection (UEMR) without submucosal injection has been described as an alternative technique to the endoscopic resection of adenomas and colorectal serrated lesions. We aimed to assess the feasibility, safety, and efficacy of UEMR in a Brazilian setting.MethodsThis was a prospective observational study of consecutive patients who underwent UEMR between January and July 2019, in a single tertiary care center. Inclusion criteria were lesions without endoscopic stigmata of deep submucosal invasion in patients referred for endoscopic resection of colorectal adenomas, and serrated lesions detected in a previous colonoscopy. The following features were assessed: complete resection rate, en bloc resection rate, resection time, adverse events, and resection infeasibility.ResultsA total of 36 patients underwent UEMR for 51 colorectal lesions. The mean/median lesion size was 16.24/13 mm and the mean/median resection time was 16.97/9.19 min. Histopathology revealed the following: tubular adenoma (43.1%), tubulovillous adenoma (13.7%), serrated lesions (41.2%), and intramucosal adenocarcinoma (2%). Complete resection was achieved in 86.3% of cases; 52.9% of the lesions were removed en bloc, while 47.1% were resected in a piecemeal fashion. UEMR was feasible in 96.1% of cases and failed on 2 occasions, requiring conversion to standard endoscopic mucosal resection. Minor intraoperative bleeding occurred in 5 patients (9.8%) and only 1 presented with delayed bleeding (2%), all controlled endoscopically.ConclusionUEMR for removal of adenomas and colorectal serrated lesions was demonstrated to be feasible, safe and effective.

Immunohistochemical Examination is Highly Sensitive and Specific for Detection of the V600E BRAF Mutation in Colorectal Serrated Lesions.

Mutations in BRAF are important events in colorectal serrated lesions and specific genetic markers for the serrated pathway. However, examination of BRAF mutations is not easy in routine histopathologic analyses. Here, the authors examined 73 colorectal serrated lesions, including 21 hyperplastic polyps, 32 traditional serrated adenomas, and 30 sessile serrated lesions, for comparison of BRAF mutation status with immunopositive expression of the anti-BRAF V600E mutation-specific antibody VE1. Thirty-two tubular adenomas (TAs) were examined as controls. In addition, 5 examples of sessile serrated lesion with dysplasia were included. Mutations in BRAF (exon 15; V600E) and KRAS (exon 2) were analyzed in serrated lesions and TAs using pyrosequencing. Finally, the authors compared BRAF mutations with immunohistochemical expression of VE1 antibodies against the BRAF V600E mutation, which was examined based on quantitative analyses and correlations between semiquantitative (0, 1+, or 2+) and quantitative results in colorectal serrated lesions. The cut-off value of VE1 expression (32%) was set based on receiver operating characteristic curve analysis. In the current study, mutations in BRAF were well correlated with VE1 expression in serrated lesions, although no TAs without BRAF mutations were immunopositive. In contrast, serrated lesions and TAs with mutations in KRAS were not stained for VE1 expression. In serrated lesions, although the sensitivity was 96.2% to 100%, the specificity was 90.0% to 100%. In addition, there was also good correlation between semiquantitative and quantitative results. Analysis of BRAF V600E expression may be pathologically useful, particularly in routine histopathologic diagnosis.

Colorectal non-invasive epithelial lesions: an update on the pathology of colorectal serrated lesions and polyps

Colorectal non-invasive epithelial lesions: an update on the pathology of colorectal serrated lesions and polyps

Endoscopic Biopsy in Differential Diagnosis of Colorectal Serrated Lesions

Background. Preoperative biopsy is recommended for morphological verification of colorectal epithelial neoplasms prior to their endoscopic resection. However, histological reports for endoscopic biopsy and resected lesions are not reliably consistent.Aim. Assessment of sensitivity, specificity and accuracy of endoscopic biopsy in differential diagnosis of colorectal serrated adenomas and risk factors for variance between biopsy results and morphological examination of completely resected lesions.Materials and methods. The assay used data on 56 morphologically verified serrated adenomas diagnosed and resected in 50 patients (14 men, 36 women; average age 66.9 ± 10.5 years). Biopsy was taken from all tumours before endoscopic resection. Results of morphological examination of biopsy samples and resected tumours were analysed and compared. Sensitivity, specificity and accuracy of biopsy was assessed, with the tumour size and type and biopsy forceps system taken as criteria.Results. The identified cases included 22 (39.3%) right-colon, 21 (37.5%) left-colon and 13 (23.2%) rectal lesions of 28.5 ± 2.6 mm average size. Polypoid were 17 (30.3%), non-polypoid — 6 (10.7%) and spreading — 33 (59%) of the tumours. Full consistency of morphological examination was observed for 12 cases (21.4%). In 9 cases (16%), dysplasia was established as mild-graded with biopsy, whilst the eradicated tumours contained severe dysplastic foci. Foci of adenocarcinoma were detected in 10 tumours (including 2 with submucosal invasion), but only 2 cases were correctly diagnosed for malignant adenoma with biopsy. Tumour morphology was misidentified in 32 cases (57.1%).Conclusions. Preoperative forceps biopsy is shown to possess low sensitivity in differential diagnosis of serrated colorectal lesions and very low sensitivity to predict malignant serrated adenomas.

Significance of gene mutations in the Wnt signaling pathway in traditional serrated adenomas of the colon and rectum.

Recent studies have shown that colorectal serrated lesions, which include sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs), are precursors of colorectal cancer. However, the molecular mechanisms underlying the carcinogenesis, particularly in TSAs, remain largely uncharacterized. To clarify their molecular and clinicopathological characteristics, we performed mutation and methylation analyses of cancer-associated genes in 78 serrated lesions, including TSAs, SSAs and microvesicular hyperplastic polyps. Target exon sequence analysis was performed with 39 genes, including genes known to be frequently mutated in colorectal cancers and/or serrated lesions. We also used bisulfite pyrosequencing to assess the methylation status of various cancer-associated genes and marker genes of the CpG island methylator phenotype (CIMP). The prevalence of mutations in genes associated with Wnt signaling was significantly higher in TSAs than SSAs (65% vs. 28%, p < 0.01). Among those, RNF43 mutations were observed in 38% of TSAs and 17% of SSAs. In immunohistochemical studies of 39 serrated lesions, the prevalence of abnormal nuclear β-catenin accumulation was significantly higher in TSAs (57%) than SSAs (8%) (P = 0.01). SMOC1 methylation was detected in 54% of TSAs but in no SSAs (p < 0.01). Additionally, SMOC1 methylation was more prevalent among TSAs with KRAS mutation (82%) than with BRAF mutation (38%, p = 0.03). Lesions with CIMP-high or RNF43 mutations were detected only in TSAs with BRAF mutation, suggesting two distinct carcinogenic pathways in TSAs. Mutations in genes associated with Wnt signaling play a greater role in the carcinogenesis of TSAs than SSAs.