Mixed Polyps Research Articles

Endoscopic double-layered suturing: an updated technique for clip closure of large mucosal defects after endoscopic submucosal dissection

Video 1Endoscopic submucosal dissection of a large, laterally spreading-type granular mixed polyp in the ascending colon followed by closure of the ulcer bed using modified double-layered endoscopic suturing with endoscopic clips.

Endoscopic features with associated histological and molecular alterations in serrated polyps with dysplasia: Retrospective analysis of a tertiary case series

BackgroundSerrated polyps are incompletely understood lesions and include serrated sessile lesion (SSL) without or with dysplasia and traditional serrated adenoma (TSA). AimsWe investigated prevalence and characteristics of serrated lesions, especially SSL with dysplasia (mixed polyps). MethodsThis retrospective study analyzed data from consecutive patients referred for colonoscopy at a tertiary care center. Endoscopic and histopathological characteristics of identified lesions were studied. SSLs with dysplasia were molecularly analyzed for mutations and microsatellite instability. ResultsAmong 1147 patients, a total of 436 polyps were found, including 288 adenomas (66.1 %) and 114 serrated lesions (SLDR 26.2 %). PDR was 34.5 % and ADR was of 30.2 %. Serrated lesions included 75 hyperplastic polyps (17.2 %), 24 SSLs without dysplasia (5.5 %), 6 SSLs with dysplasia (mixed polyps) (1.4 %) and 9 TSA (2.1 %). The mixed polyps were evaluated molecularly: these analyses found no KRAS mutation, a single NRAS mutation in one lesion, the Val600Glu BRAF mutation in four lesions in both their serrated non-dysplastic and dysplastic areas, and microsatellite instability in four lesions, limited to the dysplastic areas. ConclusionOur single-center experience confirms the high prevalence of serrated lesions, a part of which are SSL with dysplasia. These lesions seem to carry specific molecular alterations.

Type 17 mucosal-associated invariant T cells contribute to neutrophilic inflammation in patients with nasal polyps

Immune regulation in chronic rhinosinusitis with nasal polyps (CRSwNP) with a neutrophilic endotype remains unclear. Mucosal-associated invariant T (MAIT) cells are tissue-resident innate T lymphocytes that respond quickly to pathogens and promote chronic mucosal inflammation. We investigated the roles of MAIT cells in neutrophilic CRSwNP. Nasal tissues were obtained from 110 CRSwNP patients and 29 control subjects. Peripheral and tissue MAIT cells and their subsets were analyzed by flow cytometry. Polyp derived MAIT cells were analyzed by RNA-sequencing and used to study their effects on neutrophils. Endotypes of CRSwNP were classified into paucigranunlocytic (n=21), eosinophilic (n=29), neutrophilic (n=37), and mixed granulocytic (n=23). Frequencies of MAIT cells were significantly higher in neutrophilic (3.62%) and mixed granulocytic (3.60%) polyps than in control mucosa (1.78%). MAIT cell percentages positively correlated with local neutrophil counts. MAIT cells were more enriched in tissues than in matched PBMCs. The frequencies of MAIT1 subset or IFN-γ+ MAIT cells were comparable among control tissues and CRSwNP subtypes. The proportions of MAIT17 subset or IL-17A+MAIT cells were significantly increased in neutrophilic or mixed granulocytic polyps compared to controls. RNA-sequencing revealed type 17 and pro-neutrophil profiles in neutrophilic polyp derived MAIT cells. In patients with neutrophilic CRSwNP, the proportions of the MAIT and the MAIT17 were positively correlated with local pro-inflammatory cytokines and symptom severity. In vitro experiments demonstrated that neutrophilic polyps derived MAIT cells promoted neutrophil migration, survival, and activation. MAIT cells from neutrophilic CRSwNP present type 17 functional properties and promote neutrophil infiltration in nasal mucosa.

Type 2 and Type 17 Invariant Natural Killer T Cells Contribute to Local Eosinophilic and Neutrophilic Inflammation and Their Function Is Regulated by Mucosal Microenvironment in Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by heterogeneous inflammatory endotypes of unknown etiology. Invariant natural killer T (iNKT) cells are multifunctional innate T cells that exhibit Th1-, Th2-, and Th17-like characteristics. We investigated functional relationships between iNKT cells and inflammatory subtypes of CRSwNP. Eighty patients with CRSwNP and thirty-two control subjects were recruited in this study. Flow cytometry was used to analyze the frequencies and functions of iNKT cells and their subsets in peripheral blood mononuclear cells (PBMCs) and tissues. Polyp tissue homogenates were used to study the multifunctionality of iNKT cells. iNKT cells were significantly increased in polyps (0.41%) than in control mucosa (0.12%). iNKT cells were determined in the paucigranunlocytic (n=20), eosinophilic (n=22), neutrophilic (n=23), and mixed granulocytic (n=13) phenotypes of CRSwNP. The percentages of iNKT cells and HLA-DR+PD-1+ subsets were lower in eosinophilic or mixed granulocytic polyps than those of other phenotypes. iNKT cells and subsets were enriched in polyp tissues than in matched PBMCs. The evaluation of surface markers, transcription factors, and signature cytokines indicated that the frequencies of iNKT2 and iNKT17 subsets were significantly increased in eosinophilic and neutrophilic polyps, respectively, than in the paucigranulocytic group. Moreover, the production of type 2 (partially dependent on IL-7) and type 17 (partially dependent on IL-23) iNKT cells could be stimulated by eosinophilic and neutrophilic homogenates, respectively. Our study revealed that type 2 and type 17 iNKT cells were involved in eosinophilic and neutrophilic inflammation, respectively, in CRSwNP, while different inflammatory microenvironments could modulate the functions of iNKT cells, suggesting a role of iNKT cells in feedback mechanisms and local inflammation.

Применение эозинофильно-нейтрофильного индекса ЭНИ и показателя степени интенсивности воспалительной инфильтрации для оценки воспалительного процесса при полипозном риносинусите

Introduction. Identification of the cellular composition of polyps in polypous rhinosinusitis (PRS) is important. In practice, to determine the quantitative indicators of the number and ratio of eosinophilic and neutrophilic leukocytes in polyp tissue, the eosinophil-neutrophil index (ENI) was introduced, which is equal to the ratio of the arithmetic mean number of eosinophils to the arithmetic mean number of neutrophils in 10 considered fields of view at a magnification of the microscope ×400, and the indicator degree of cellular inflammatory infiltration. Objective. To conduct a pathomorphological study of the tissue of resected nasal polyps with the determination of ENI parameters and the degree of cellular inflammatory infiltration in various PRS phenotypes and evaluate the possibility of using these indicators as predictors of PRS drug control. Materials and methods. We examined 292 people (126 men, 166 women), mean age 52.12±13.04 years, with bilateral PRS, which were divided into 4 phenotypic groups: I group: PRS without concomitant bronchial asthma (BA) and respiratory allergies; IIa group: PRS + allergic BA (aBA) and allergic rhinitis (AR); IIb group: PRS + AR without BA; III group: PRS + nonallergic BA (nBA). During pathological examination, polyps were divided into 3 histological types: «eosinophilic,» «neutrophilic,» and «mixed»; the ENI index was determined, 3 degrees of inflammatory infiltration were established: weak (I degree) when the arithmetic mean of eosinophils, lymphocytes, neutrophils, macrophages, histiocytes, and mast cells in 10 representative fields of view does not exceed 200 cells; moderate (II degree) when the arithmetic mean varies from 201 to 400 cells; and significant (III degree) where the arithmetic mean is > 400 cells. In the PRS+BA groups, the state of BA control was determined using the ACQ-7 (Asthma Control Questionnaire). An analysis of the dynamics of ENI indicators and the degree of inflammatory infiltration was carried out depending on the effectiveness of conservative therapy with topical glucocorticoids (GCs) during the observation period of 1 year. The patients were divided into 3 groups: group 1, patients with positive dynamics, with a decrease in the degree of nasal polyps; group 2, the severity of polyps remained at the same level; group 3, the prevalence of polyps was higher than a year ago. Results. In all phenotypes of PRS, the eosinophilic type of inflammation prevails. The minimum indicators of ENI (11 [6;16]) and the degree of inflammatory infiltration (1 [1; 1]) were in the PRS +AR group, the highest intensity of inflammation was found in the PRS+nBA group (2.03 [2; 2]). According to the cellular composition of polyps in group 1, eosinophilic polyps were 87%; neutrophilic, 8%; mixed type, 5%; in group 2a, 97% of eosinophilic and 3% of mixed type in the absence of neutrophilic polyps, in group 2b ORS + AR, eosinophilic polyps were detected in 100%; in group 3, eosinophilic 88%, neutrophilic 6%, and mixed polyps 6% were diagnosed. Changes in ENI parameters and the intensity of inflammatory infiltration depending on the effectiveness of conservative therapy were revealed. In the group with positive dynamics, there was a decrease in these two indicators after 6 months of using intranasal GCs, in the absence of dynamics during therapy there were no changes in these indicators, and with low drug control, their increase was noted, which after the next 12 months was manifested by aggressive growth of polyps. At the same time, a correlation was found between the increase in the magnitude of indicators of local inflammation of the tissue of nasal polyps with a deterioration in the degree of control of BA of any etiology and the absence of significant correlations between blood eosinophilia and the level of eosinophilic infiltration of polypous tissue. Conclusions. 1. During the pathological examination of the surgical material, it is necessary to establish the histological type of nasal polyps (eosinophilic, neutrophilic, and mixed) to determine the further tactics of treating patients with PRS. 2. Pathological determination of the density of the inflammatory infiltrate in the tissue of resected nasal polyps with the calculation of ENI in clinical practice is necessary to control the dynamics of the course of inflammation, predict the possibility of relapse, and adjust the treatment of patients with PRS. 3. Correlation analysis in patients with PRS did not reveal a significant relationship between the severity of tissue eosinophilic infiltration of polyp tissue and the level of eosinophils in the peripheral blood, so the determination of peripheral blood eosinophilia is not enough to characterize local inflammation in PRS. 4. A decrease in ENI and the degree of density of the inflammatory infiltrate in nasal polyps in dynamics indicates the effectiveness of the ongoing conservative therapy. 5. An increase in the intensity of inflammatory infiltration in the tissues of polyps is accompanied by a deterioration in the medical control of asthma in phenotypes of PRS in combination with aBA and nBA.

Molecular characteristics of colorectal hyperplastic polyp subgroups.

The importance of hyperplastic polyps during colorectal carcinogenesis is appreciated related to the understanding of serrated pathway. The morphologic subtypes of hyperplastic polyps in carcinogenesis and the nomenculature of lesions with both hyperplastic and adenomatous areas are controversial. We aimed to reveal the molecular properties of hyperplastic polyp subtypes and the molecular changes in polyps containing both hyperplastic and adenomatous areas. Matherial and Methods: 49 hyperplastic polyps [19 microvesicular (MVHP), 19 goblet-rich (GRHP), 11 mucin-poor (MPHP)] and 10 mixed hyperplastic and adenomatous polyps were analysed for KRAS, BRAF mutations and MSI with real-time PCR. 68,4% of MVHPs and 81% of MPHPs which were localized in right colon had BRAF mutations. While none of the GRHPs showing a KRAS mutation with a rate of 73% was localized in the ascending colon, 63% of them were localized in the rectosigmoid area. In five (50%) of the mixed polyps, KRAS mutation was detected both in the hyperplastic and adenoma components. There was no BRAF mutation in any of the mixed polyps. However, in two cases, the hyperplastic component was MSI-H and the adenoma area was MSS. Hyperplastic polyps, even if smaller than 5 mm, are precancerous lesions bearing different mutations. GRHPs with predominant KRAS mutations and MVHPs and MPHSs with predominant BRAF mutations are precancerous. Although the molecular investigations for HPP/SP are not necessary the morphological subtyping should be included if the case is diagnosed with HPP/SP as it will be useful for attracting the gastroenterologist's attention.

Comparative analysis of bile components in patients with different types of gallstones

Objective To study the relationship among bile components and different gallstone types through comparing and analyzing gallbladder bile contents in patients with different types of gallstones. Methods A retrospective study of 542 consecutive patients with gallstones or gallbladder polyps was conducted. The stone composition type and 14 kinds of bile components from these patients were analyzed. The bile parameters consisted of potassium (K+ ), sodium (Na+ ), chlorine (Cl-), calcium (Ca2+ ), bicarbonate (HCO3-), magnesium (Mg2+ ), aspartate aminotransferase (AST), glutamyltranspeptidase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), total bile acid (TBA), cholesterol (CHO), lactate dehydrogenase (LDH) and pH. Finally, the content of these bile components among the different types of stones and gallbladder polyps were compared. According to the composition determined by Fourier transform infrared spectroscopy (FTIR), the gallstone patients were divided into five groups. Results Compared with other groups, the content of K+ , GGT, ALP, TBIL, TBA and CHO in the calcium carbonate stone group were lower (P 0.05). In addition, there was no difference in bile contents among the pigment gallstone group, mixed stone group and polyp group (P>0.05). Conclusions In gallstone patients, the bile components of patients with calcium carbonate stones is significantly different. The high cholesterol content in bile is the main feature of cholesterol stone patients, and there is no significant difference in bile composition between patients with pigment stones and mixed stones. Key words: Cholecystolithiasis; Bile; Gallbladder polyps; Cholesterol; Bile acid; Calcium carbonate stones

1591 Melanosis Coli Aids Endoscopic Differentiation of Polyp Histology in Cowden Syndrome

INTRODUCTION: Cowden syndrome is a rare disorder related to germline mutations in the PTEN gene. Although considered a hamartomatous polyposis syndrome, emerging evidence has shown colorectal polyposis with mixed histologic types (including adenomas) to be most common. This can make endoscopic surveillance difficult. Melanosis coli is characterized by dark pigmentation of the colon. Adenomatous and hyperplastic polyps remain pale in this setting and are easily visualized, but there are no published reports on the appearance of hamartomatous polyps. CASE DESCRIPTION/METHODS: A 55-year-old man with intellectual disability was referred to our institution for consideration of colectomy due to colorectal polyposis. He was then referred to GI Genetics clinic for further evaluation prior to surgery. His history included innumerable colon polyps on previous colonoscopies. Available pathology included multiple colon polyp types including tubulovillous and tubular adenoma, serrated adenoma, hyperplastic and inflammatory polyps. His family history included twin brother with brain tumor, mother with breast cancer and stomach cancer and father with brain cancer. Examination showed macrocephaly with head circumference of 62 cm. Cowden syndrome was suspected and genetic testing was performed. This showed a pathogenic mutation in the PTEN gene and confirmed the diagnosis. Surveillance colonoscopy was performed. This showed diffuse melanosis and polyposis of the colon. There were 4 colon polyps that were pale and visually consistent with adenomas. These were resected and returned as 3 tubular adenomas and a serrated adenoma with minimally apparent melanosis on histologic assessment. There were multiple diminutive polyps throughout the colon that were dark and appeared visually consistent with hamartomas. Many of these were sampled and were consistent with hamartomatous polyps with prominent melanosis histologically. Given the ability to endoscopically differentiate between neoplastic and benign polyp histologies, ongoing surveillance colonoscopy was recommended and colectomy was avoided. DISCUSSION: Polyposis with mixed polyp histology is common in Cowden syndrome and complicates endoscopic surveillance. In our patient with melanosis coli, hamartomatous polyps remained dark and matched the surrounding mucosa while adenomas and serrated adenomas were pale and easily distinguishable. This is the first report of the appearance of hamartomas in the setting of melanosis to our knowledge.

Molecular characterization of “sessile serrated” adenoma to carcinoma transition in six early colorectal cancers

Colorectal cancer (CRC) is a heterogeneous group of diseases both from the morphological and molecular point of view. The sessile serrated adenoma/polyp (SSA/P) has been proposed as the precursor lesion of CRCs characterized by CpG island methylator phenotype (CIMP), DNA mismatch repair (MMR) system deficiency, and BRAF gene mutations. However, no study so far investigated the molecular landscape of “sessile serrated” adenoma to carcinoma transition in early CRCs. Six formalin-fixed paraffin-embedded CRCs developed within SSA/P were profiled for the immunohistochemical expression of MMR proteins (MLH1, MSH2, MSH6, PMS2, and Ep-CAM), p16, and β-catenin. DNA was extracted from the two components of each sample, after microdissection, and characterized for CIMP status and by applying a custom hotspot multigene mutational profiling of 164 hotspot regions of eleven CRC-associated genes (AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN, and TP53). Five out of the six CRCs shared the same molecular profile (i.e. CIMP positive, MSI status, and BRAF mutation) with their SSA/P components. One out of five CRCs was also APC mutated, whereas another one showed an additional TP53 mutation. The remaining case was CIMP negative and MMR proficient in both the components, harbored a BRAF mutation in the SSA/P counterpart, whereas the CRC one was APC and TP53 mutated and showed p16 and β-catenin dysregulation. This study provides the molecular evidence that SSA/P, even without cytological dysplasia, is a precursor lesion of CRC and that conventional CRC might arise from mixed polyp.

Duodenal polyp with mixed features – a case report

Epithelial polyps are a common finding in the colorectum. They are less common in small bowel in absence of any polyposis syndromes. These polyps are conventionally divided into adenomatous polyps and serrated polyps, with the latter further subdivided into hyperplastic polyps, traditional serrated adenomas and sessile serrated polyps. Polyps with mixed features displaying more than one type of morphology have been described but are less common. Tubular adenomas are common in the colorectum with a lifetime prevalence of 30–50% in industrialised countries.1 Mixed adenoma-serrated polyps comprise only <1% of all colorectal polyps,1 with no duodenal variant case reports identified in the literature. We present a case of a mixed polyp in the duodenum without any known history of polyposis syndrome.

Gastrointestinal poliplerin boyutları, lokalizasyonu ve histopatolojik tiplerine göre değerlendirilmesi: bir yıllık periyod

Aim: It was aimed to document gastrointestinal system polyps and evaluated with respect to their frequency, size, anatomic location and histopathologic features. Material and Method: 56 gastrointestinal polyps that were histopathologically diagnosed during the period 2014-2015 were included in the study. Polyps were noted according to their localization, age, gender, size and histopathologic types. Results: 59 % of the patients were males and 41% of the patients were females. Their mean age was 61.7 years. The mean diameter of the adenomatous polyps was 10.12 mm. The mean diameter of the hyperplastic polyps was 5.7 mm.18 cases were diagnosed as tubular adenomas(32 %). 16 cases were diagnosed as tubulovillous adenomas (28%), 21 cases were diagnosed as hyperplastic polyps (37.5%), 1 case was diagnosed as mixed polyps,1 case was diagnosed as juvenile polyps. 10 cases of hyperplastic polyps were localized sigmoid colon (% 47.6) and 6 cases were localized rectum (% 28.5). 16 cases of adenomatous polyps were localized sigmoid colon (% 47). Ages ranged from 4 to 84 years were diagnosed as all polyps. Gender were 33 men and 23 female. Conclusion: In this study, it was showed that the oldest groups of tubulovillous adenoma, the most common groups of hyperplastic polyps, the most common gender of male, the most common location of sigmoid colon.

Evaluation of Gastrointestinal Polyps According to Their Size, Localization and Histopathologic Types; Annual Period

Aim: It was aimed to document gastrointestinal system polyps and evaluated with respect to their frequency, size, anatomic location and histopathologic features. Material and Method: 56 gastrointestinal polyps that were histopathologically diagnosed during the period 2014-2015 were included in the study. Polyps were noted according to their localization, age, gender, size and histopathologic types. Results: 59 % of the patients were males and 41% of the patients were females. Their mean age was 61.7 years. The mean diameter of the adenomatous polyps was 10.12 mm. The mean diameter of the hyperplastic polyps was 5.7 mm.18 cases were diagnosed as tubular adenomas(32 %). 16 cases were diagnosed as tubulovillous adenomas (28%), 21 cases were diagnosed as hyperplastic polyps (37.5%), 1 case was diagnosed as mixed polyps,1 case was diagnosed as juvenile polyps. 10 cases of hyperplastic polyps were localized sigmoid colon (% 47.6) and 6 cases were localized rectum (% 28.5). 16 cases of adenomatous polyps were localized sigmoid colon (% 47). Ages ranged from 4 to 84 years were diagnosed as all polyps. Gender were 33 men and 23 female. Conclusion: In this study, it was showed that the oldest groups of tubulovillous adenoma, the most common groups of hyperplastic polyps, the most common gender of male, the most common location of sigmoid colon.

Clinicopathological features of a kindred with SCG5-GREM1–associated hereditary mixed polyposis syndrome

Since first characterized in 1997, patients with hereditary mixed polyposis syndrome (HMPS) have been difficult to identify because of lack of well-established diagnostic criteria. Recently, HMPS was found to be caused by a duplication on chromosome 15 spanning the 3' end of the SCG5 gene and a region upstream of the GREM1 locus. Clinical testing for the duplication is available; however, the clinical characteristics of hereditary mixed polyposis to support testing are ill defined. The clinicopathological findings of 10 HMPS patients with confirmed germline SCG5-GREM1 duplication were reviewed. Mean age at presentation was 33.3 years. Fifty-one colonoscopies yielded 207 polyp specimens, all of which were reexamined. Adenomas (n = 80) and a fairly unique polyp composed of a mixture of hyperplastic polyp and inflammatory polyp-type changes (n = 74) were the most common findings; however, other polyps, including hyperplastic (n = 28), mixed inflammatory polyp/adenoma (n = 8), inflammatory polyp (n = 7), prolapse-type polyp (n = 6), and lymphoid aggregates (n = 4), were encountered. None of the patients developed colorectal malignancy during surveillance, demonstrated extracolonic manifestations, or underwent colectomy on follow-up (mean, 26.2 years). SCG5-GREM1 duplication-associated polyposis is characterized by a few polyps per endoscopy with a mixture of phenotypes, most commonly adenoma and nondysplastic mixed hyperplastic/inflammatory polyps. Nine of 10 patients had at least 1 mixed hyperplastic-inflammatory polyp, which is the characteristic lesion of SCG5-GREM1 duplication-associated HMPS.

The frequency of early colorectal cancer derived from sessile serrated adenoma/polyps among 1858 serrated polyps from a single institution.

Sessile serrated adenoma/polyps (SSAPs) are suspected to have a high malignant potential, although few reports have evaluated the incidence of carcinomas derived from SSAPs using the new classification for serrated polyps (SPs). The aim of study was to compare the frequency of cancer coexisting with the various SP subtypes including mixed polyps (MIXs) and conventional adenomas (CADs). A total of 18,667 CADs were identified between April 2005 and December 2011, and 1858 SPs (re-classified as SSAP, hyperplastic polyp (HP), traditional serrated adenoma (TSA), or MIX) were removed via snare polypectomy, endoscopic mucosal resection, or endoscopic sub-mucosal dissection. Among 1160 HP lesions, 1 (0.1%) coexisting sub-mucosal invasive carcinoma (T1) was detected. Among 430 SSAP lesions, 3 (0.7%) high-grade dysplasia (HGD/Tis) and 1 (0.2%) T1 were detected. All of the lesions were detected in the proximal colon, with a mean tumor diameter of 18 mm (SD 9 mm). Among 212 TSA lesions, 3 (1%) HGD/Tis were detected but no T1 cancer. Among 56 MIX lesions, 9 (16%) HGD/Tis and 1 (2%) T1 cancers were detected, and among 18,677 CAD lesions, 964 (5%) HGD/Tis and 166 (1%) T1 cancers were identified. Among the resected lesions that were detected during endoscopic examination, a smaller proportion (1%) of SSAPs harbored HGD or coexisting cancer, compared to CAD or MIX lesions. Therefore, more attention should be paid to accurately identifying lesions endoscopically for intentional resection and the surveillance of each SP subtype.

Abstract B85: Racial differences in the risk of serrated polyps and conventional adenomas in a younger aged, uninsured population in South Carolina

Abstract Compared to European Americans (EA), African Americans (AA) have higher colorectal cancer (CRC) incidence and are diagnosed with CRC at younger ages. The reasons for these disparities are poorly understood, but one contributing factor could be reduced access to high-quality preventative care. To address CRC disparities, this study assessed whether a racial difference in risk of large bowel polyps (precursors to most CRC) persists within a younger-aged, uninsured population in South Carolina (SC) undergoing screening colonscopy. We analyzed data from a multi-site statewide CRC screening program in SC to explore the risk of large bowel polyps among AA and EA. Eligible patients were uninsured, asymptomatic, had no personal history of colorectal neoplasia, and were between the ages 45-64 years (AA) or 50-64 years (EA). Using generalized linear regression, we estimated risk ratios and 95% confidence intervals (CI) as measures of the association between race and risk for one or more conventional adenomas or serrated polyps adjusting for age, sex, family history of CRC, and clinical site. Serrated polyps (SP) were defined as one or more hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, and mixed adenomatous polyps. SP were first classified in a single category since not all project pathologists used up-to-date pathologic terminology and there was a high-level of variability among clinical sites in use of newer SP categories (i.e., sessile, traditional adenomas). Serrated adenomas included any SP with serrated adenomatous features (sessile, traditional, or mixed). Advanced SP were defined as SP with large size (an estimated ≥ 1 cm). Conventional adenomas (CA) were defined as tubular, tubulovillous, or villous polyps. Advanced CA were defined as adenomas with at least 25% villous component (TVA), high-grade dysplasia (HGD), or large size. We also stratified polyps separately according to colonic region (proximal or distal colorectum), large size, and advanced CA histology (TVA, HGD). Of the 237 subjects enrolled (127 AA, 91 EA, 19 other), 233 had a complete exam (i.e., to the cecum). Our results suggested a lower risk of SP among AA compared to EA: any SP (RR 0.50 (95% CI 0.30-0.84)), any serrated adenoma (RR 0.35 (95% CI 0.11-1.14)), and any large SP (RR 0.27 (95% CI 0.09-0.85)). Although not always statistically significant, the trend in the results indicate that the risk of CA was higher in AA compared to EA: any CA 1.17 (95% CI 0.77-1.79), large CA 2.16 (95% CI 0.70-6.66), proximal large CA 4.24 (95% CI 1.0-18.01), and any advanced CA 1.38 (95% CI 0.55-3.42). In patients under 55 years of age (median age), AA compared to EA had higher risk of advanced CA histology lesions RR 4.11 (95% 1.05 -16.11), but otherwise risks were similar in the age groups. Overall, our findings suggest that it is important to consider type of polyp and age when assessing risk in different racial groups. Our results in this unique study population are consistent with an earlier study showing that AA have a lower risk of metachronous SP and among younger patients, an increased risk of conventional adenomas, especially advanced lesions. The persistence of these observations within a study population comprised of all medically underserved individuals implies that the unique features of the epidemiology of colorectal neoplasia in AA cannot be completely attributed to access to care barriers. Citation Format: Kristin Wallace, Anthony Alberg, Bridgette Blankenship, Heather Brandt, Renay Caldwell, James Dunn, Patricia Hegedus, Brenda Hoffman, Courtney Marsh, March Seabrook, Marylou Stinson, Annie Thibault, Franklin Berger. Racial differences in the risk of serrated polyps and conventional adenomas in a younger aged, uninsured population in South Carolina. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B85.

The Mendelian colorectal cancer syndromes.

A small minority of colorectal cancers (CRCs) (≤5%) are caused by a single, inherited faulty gene. These diseases, the Mendelian colorectal cancer (CRC) syndromes, have been central to our understanding of colorectal carcinogenesis in general. Most of the approximately 13 high-penetrance genes that predispose to CRC primarily predispose to colorectal polyps, and each gene is associated with a specific type of polyp, whether conventional adenomas (APC, MUTYH, POLE, POLD1, NTHL1), juvenile polyps (SMAD4, BMPR1A), Peutz-Jeghers hamartomas (LKB1/STK11) and mixed polyps of serrated and juvenile types (GREM1). Lynch syndrome (MSH2, MLH1, MSH6, PMS2), by contrast, is associated primarily with cancer risk. Major functional pathways are consistently inactivated in the Mendelian CRC syndromes: certain types of DNA repair (proofreading of DNA replication errors, mismatch repair and base excision repair) and signalling (bone morphogenetic protein (BMP), Wnt signalling and mTOR). The inheritance of the CRC syndromes also varies: most are dominant but some of the DNA repair deficiencies are recessive. Some of the Mendelian CRC genes are especially important because they play a role through somatic inactivation in sporadic CRC (APC, MLH1, SMAD4, POLE). Additional Mendelian CRC genes may remain to be discovered and searches for these genes are ongoing, especially in patients with multiple adenomas and hyperplastic polyps.

Histological characterization of traditional serrated Adenomas compared to conventional Adenomas

Background: Among the recently described and more rapidly progressing colorectal serrated lesions traditional serrated adenoma (TSA) is the rarest subtype. The morphologic distinction between TSA and conventional adenoma, especially villous/tubulovillous adenoma (VA/TVA), may be difficult, because there is a significant histological overlap between these lesions. According to the literature, there are three characteristic features usually present in TSAs: ectopic crypt foci (ECF), luminal serration and typical cytology with columnar epithelial cells with eosinophilic cytoplasm and elongated, centrally placed nuclei. Currently, TSA diagnosis needs at least two of the three features above with at least one present in 50% of the polyp. Aims: The aim of our study was to evaluate the presence of these morphological features in TSAs and TVAs, and define which features are most helpful in distinguishing TSA from TVA. Results: A total of 115 polyps diagnosed as TSA or TVA were reviewed and 11 polyps were selected and classified as TSA on the basis of the current diagnostic criteria. As a control group, we studied 104 TVAs and determined the same features. Both ECF and typical cytology were seen in 10 of the 11 TSAs (91%), luminal serration was present in 73%. To the extent of more than 50% of the polyp, typical cytology was noted in 7 cases (64%), ECF and luminal serration was seen in 3 TSAs (27%). Of the 104 TVAs, typical cytology was present in 35 cases (34%), ECF was found in 9% and luminal serration was noted in 20%. Typical cytological features were seen only in 3 TVAs (3%) to the extent of more than 50% of the adenoma. Luminal serration in more than half of the specimen was seen only in one TVA. The presence of all three morphological features simultaneously was observed in 6 of the 11 TSAs (55%), and only in 3 of the 104 TVAs (3%). Two TVAs showed typical TSA-like patterns to a considerable degree. Conclusions: In conclusion, ECF proved to be the most helpful morphological feature regarding the diagnosis of TSA, although it is not specific to TSA and is not seen in every case of TSA. Luminal serration and TSA-like cytology are frequently present in TVAs, but they are only visible in extreme cases in more than 50% of the adenoma. Some polyps show a mixed morphology, with TSA-like and conventional adenoma-like areas. These cases may be regarded as „mixed polyps”. This study was supported by the Hungarian Scientific Research Fund (OTKA-K111743 grant).

Wide spectrum of neuroendocrine differentiation in identical appearing colon polyps: A report of 2 mixed endocrine-glandular polyps

To the Editor, Mixed endocrine glandular tumors of the gastrointestinal tract are rare lesions. In these tumors, the glandular and neuroendocrine components display a broad spectrum of combinations with marked variability in histopathology, immunohistochemical properties and clinical prognosis. We hereby report two cases of colonic tubulovillous adenomas, concomitantly containing a neuroendocrine component. While one polyp contained benign microcarcinoid, the other showed a poorly differentiated infiltrative neuroendocrine cancer. CASE 1

Defined morphological criteria allow reliable diagnosis of colorectal serrated polyps and predict polyp genetics.

Criteria for the diagnosis of serrated colorectal lesions (hyperplastic polyp, sessile serrated adenoma without or with dysplasia--which we called mixed polyp--and traditional serrated adenoma) for which consensus has been reached should be validated for applicability in daily practice in terms of inter-observer reproducibility and their association with clinical features and (epi)genetic events. A study set was created from a consecutive series of colorectal polyps (n = 1,926) by selecting all sessile serrated adenomas, traditional serrated adenomas and mixed polyps. We added consecutive series of hyperplastic polyps, classical adenomas and normal mucosa samples for a total of 200 specimens. With this series, we conducted an inter-observer study, encompassing ten pathologists with gastrointestinal pathology experience from five European countries, in three rounds in which all cases were microscopically evaluated. An assessment of single morphological criteria was included, and these were correlated with clinical parameters and the mutation status of KRAS, BRAF and PIK3CA and the methylation status of MLH1. Gender, age and localisation were significantly associated with certain types of lesions. Kappa statistics revealed moderate to good inter-observer agreement for polyp classification (κ = 0.56 to 0.63), but for single criteria, this varied considerably (κ = 0.06 to 0.82). BRAF mutations were frequently found in hyperplastic polyps (86 %, 62/72) and sessile serrated adenomas (80 %, 41/51). KRAS mutations occurred more frequently in traditional serrated adenomas (78 %, 7/9) and less so in classical adenomas (20 %, 10/51). Single morphological criteria for sessile serrated adenomas showed significant correlation with BRAF mutation (all p ≤ 0.001), and those for classical adenomas or traditional serrated adenoma correlated significantly with KRAS mutation (all p < 0.001). Therefore, single well-defined morphological criteria are predictive for genetic alterations in colorectal polyps.

A histopathological study of 23 cases of benign epithelial polyps of intestine

Background: Intestinal polyps of the colon and rectum consist of hyperplastic polyps, adenomas and mixed polyps. The aim is to study the benign intestinal polyps histopathologically and classify them into specific groups, frequency of each subgroup and their sex and age incidence. Here aim is also to find their premalignant potential. Methods: It is a retrospective pathological study of 23 cases of intestinal polyps which included 16 resected intestinal specimens and 7 polypectomies. Haematoxylin and eosin stained paraffin sections were studied microscopically and categorised under WHO classification with special note to their malignant potential. Results: The present study was done with 23 cases of benign polyps of the intestine during the period 2011-2013. Juvenile polyps constituted 52% of polyps followed by equal incidence of villous, tubular and tubulovillous adenomas - each 8.6%. Hyperplastic polyps, pseudopolyps (Crohns disease), inflammatory fibroid polyp and ectopic pancreas were the least common group with equal incidence (4.3%). In the age group 0-9 years (47.8%) the juvenile polyps were seen. The oldest patient was 73 years. The male to female ratio was 16:7. Tubular and tubulovillous adenomas showed malignant change with age incidence 52 and 73 years respectively. Rectum was the most common site of polyps (39%). In each case of PeutzJeghers syndrome and Familial adenomatous polyposis, polyps were multiple. Conclusion: Juvenile polyps the most common type, found commonly in rectum and in the age group of 0-9 years.Familial Adenomatous Polyposis and PeutzJeghers polyps are not uncommon since they were diagnosed in this study of small number of cases.The incidence of malignancy in polyps is 9%. Malignant potential is seen in tubular and tubulovillous polyps.Ectopic pancreas can present as a polyp.