Waist circumference (WC) and its allometric counterpart, "a body shape index" (ABSI), are risk factors for colorectal cancer; however, it is uncertain whether associations with these body measurements are limited to specific molecular subtypes of the disease.

Data from 2,772 colorectal cancer cases and 3,521 controls were pooled from four cohort studies within the Genetics and Epidemiology of Colorectal Cancer Consortium. Four molecular markers (BRAF mutation, KRAS mutation, CpG island methylator phenotype, and microsatellite instability) were analyzed individually and in combination (Jass types). Multivariable logistic and multinomial logistic models were used to assess the associations of WC and ABSI with overall colorectal cancer risk and, in case-only analyses, to evaluate heterogeneity by molecular subtype, respectively.

Higher WC (ORper 5 cm = 1.06, 95% confidence interval, 1.04-1.09) and ABSI (ORper 1-SD = 1.07, 95% confidence interval, 1.00-1.14) were associated with elevated colorectal cancer risk. There was no evidence of heterogeneity between the molecular subtypes. No difference was observed regarding the influence of WC and ABSI on the four major molecular markers in proximal colon, distal colon, and rectal cancers, as well as in early- and late-onset colorectal cancers. Associations did not differ in the Jass-type analysis.

Higher WC and ABSI were associated with elevated colorectal cancer risk; however, they do not differentially influence all four major molecular mutations involved in colorectal carcinogenesis but underscore the importance of maintaining a healthy body weight in colorectal cancer prevention.

The proposed results have potential utility in colorectal cancer prevention.

Gastrointestinal polyposis disorders are a group of syndromes defined by clinicopathologic features that include the predominant histologic type of colorectal polyp and specific inherited gene mutations. Adenomatous polyposis syndromes comprise the prototypical familial adenomatous polyposis syndrome and other recently identified genetic conditions inherited in a dominant or recessive manner. Serrated polyposis syndrome is defined by arbitrary clinical criteria. The diagnosis of hamartomatous polyposis syndromes can be suggested from the histologic characteristics of colorectal polyps and the association with various extraintestinal manifestations. Proper identification of affected individuals is important due to an increased risk of gastrointestinal and extragastrointestinal cancers.

This study aimed to investigate clinicopathological and molecular tumour features associated with intratumoral pks+ Escherichia coli (pks+E.coli+), pks+E.coli- (non-E.coli bacteria harbouring the pks island), Enterotoxigenic Bacteroides fragilis (ETBF) and Fusobacterium nucleatum (F. nucleatum).

We screened 1697 tumour-derived DNA samples from the Australasian Colorectal Cancer Family Registry, Melbourne Collaborative Cohort Study and the ANGELS study using targeted PCR.

Pks+E.coli+ was associated with male sex (P < 0.01) and APC:c.835-8 A > G somatic mutation (P = 0.03). The association between pks+E.coli+ and APC:c.835-8 A > G was specific to early-onset CRCs (diagnosed<45years, P = 0.02). The APC:c.835-A > G was not associated with pks+E.coli- (P = 0.36). F. nucleatum was associated with DNA mismatch repair deficiency (MMRd), BRAF:c.1799T>A p.V600E mutation, CpG island methylator phenotype, proximal tumour location, and high levels of tumour infiltrating lymphocytes (Ps < 0.01). In the stratified analysis by MMRd subgroups, F. nucleatum was associated with Lynch syndrome, MLH1 methylated and double MMR somatic mutated MMRd subgroups (Ps < 0.01).

Intratumoral pks+E.coli+ but not pks+E.coli- are associated with CRCs harbouring the APC:c.835-8 A > G somatic mutation, suggesting that this mutation is specifically related to DNA damage from colibactin-producing E.coli exposures. F. nucleatum was associated with both hereditary and sporadic MMRd subtypes, suggesting the MMRd tumour microenvironment is important for F. nucleatum colonisation irrespective of its cause.

Despite advances in endoscopic treatment, patients with serrated polyposis syndrome (SPS) occasionally require surgery due to numerous or unresectable polyps, recurrence, and treatment-related adverse events.

We retrospectively evaluated 43 patients with SPS undergoing diagnosis and treatment at Omori Red Cross Hospital from 2011 to 2022. Resection of all polyps ≥3 mm in size was planned during the clearing phase; endoscopic control was defined as complete, endoscopic polyp removal. During the surveillance phase, patients underwent annual colonoscopy and resection of newly detected polyps ≥3 mm in size.

Thirty-eight patients (88%) achieved endoscopic control, two (5%) required surgery after endoscopic treatment because of colorectal cancer (CRC), and three (7%) have not yet achieved endoscopic control and are planning treatment. Endoscopic control was achieved with a median of four colonoscopies at 8 months. Ten polyps (median value) were resected per patient during the clearing phase. Three polyps ≥50 mm in size, six located in the appendiceal orifice, and seven with severe fibrosis could be resected by endoscopic submucosal dissection (ESD). All patients underwent treatment with a combination of cold snare polypectomy (CSP), endoscopic mucosal resection/hot polypectomy, and/or ESD. No case required surgery due to difficulty with endoscopic treatment. Delayed bleeding was observed in 2 cases (0.3%). Twenty-one patients underwent colonoscopies during the surveillance phase. Fifty-three polyps were resected using CSP; no CRC, sessile serrated lesions with dysplasia, or advanced adenoma were detected.

SPS can be effectively, efficiently, and safely controlled with appropriate endoscopic management.

Patients with serrated polyposis syndrome (SPS) have an increased risk to develop colorectal cancer (CRC). Due to an abundance of serrated polyps, these CRCs are assumed to arise mainly through the serrated neoplasia pathway rather than through the classical adenoma-carcinoma pathway. We aimed to evaluate the pathogenetic routes of CRCs in patients with SPS.

We collected endoscopy and pathology data on CRCs and polyps of patients with SPS under treatment in our center. Our primary end point was the proportion of BRAFV600E mutated CRCs, indicating serrated pathway CRCs (sCRCs). CRCs lacking BRAFV600E most likely inferred a classical adenoma-carcinoma origin (aCRCs). We assessed patient, polyp, and CRC characteristics and stratified for BRAFV600E mutation status.

Thirty-five patients with SPS harbored a total of 43 CRCs. Twenty-one CRCs (48.8%) carried a BRAFV600E mutation, 10 of which lacked MLH1 staining and 17 (81%) were located in the proximal colon. Twenty-two CRCs (51.1%) did not carry a BRAFV600E mutation and were MLH1 proficient. Of these 22 putatively aCRCs, 17 (77.3%) were located distally and one-third (36.4%) harbored a pathogenic KRAS or NRAS mutation. In patients with BRAFwt -CRCs, a higher ratio of the median number of conventional adenomas versus serrated polyps was found (4 vs 13) than patients with BRAFV600E -CRCs (1 vs 14).

Our study indicates that in patients with SPS, the ratio of sCRCs:aCRCs on average is 50:50. This elevated sCRC:aCRC ratio in patients with SPS, when compared with non-SPS patients, correlates well with the differences in the ratios of the numbers of sessile serrated lesions and conventional adenomas in patients with SPS and non-SPS patients, respectively.

Serrated polyps are pathological neoplastic lesions in the colon with subtle gross morphology leading to underreporting during colonoscopy. While detection rates are increasing in average-risk adult screening colonoscopy, the rate of detection during pediatric colonoscopy is unknown. Serrated polyposis syndrome is characterized by the presence of multiple serrated polyps in the colon and an increased risk of developing colorectal cancer. Cancer prevention relies on early recognition, endoscopic clearance of all polyps > 5 mm, and continued interval surveillance or prophylactic colectomy. We report the diagnosis and management of serrated polyposis syndrome in a young adolescent patient and highlight the subtle features of serrated polyps that may go unrecognized leading to underreporting in childhood.

Serrated polyposis syndrome (SPS), a type of colorectal polyposis characterized by multiple serrated polyps, is associated with a high risk of colorectal carcinoma (CRC). This study aimed to clarify the clinicopathological characteristics of SPS in Japan.

We investigated the clinicopathological characteristics of patients with SPS from the "Multicenter Study on Clinicopathological Characteristics of SPS (UMIN 000032138)" by the Colorectal Serrated Polyposis Syndrome (SPS) Study Group. In this study, patients were diagnosed with SPS based on the 2019 World Health Organization (WHO) SPS diagnostic criteria.

Ninety-four patients were diagnosed with SPS in 10 institutions between January 2001 and December 2017. The mean number (± standard deviation [SD]) of resected lesions per patient was 11.3 ± 13.8. The mean age at diagnosis of SPS was 63.3 ± 11.6 years, and 58 patients (61.7%) were male. Eighty-seven (92.6%) and 16 (17.0%) patients satisfied WHO diagnostic criteria I and II, respectively. Nine patients (9.6%) satisfied both criteria I and II. Carcinoma (T1-T4) were observed in 21 patients (22.3%) and 24 lesions. Of the 21 patients with CRC, 19 (90.4%) satisfied diagnostic criterion I, 1 (4.8%) satisfied diagnostic criterion II, and 1 (4.8%) satisfied diagnostic criteria I and II. There was no notable difference in the prevalence of CRC among patients who met diagnostic criterion I, II, and both I and II.

Patients with SPS have a high risk of CRC and should undergo regular surveillance colonoscopy. Raising awareness of this syndrome is crucial.

Although serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, the carcinogenic mechanisms remain unknown. We investigated clinicopathological characteristics and genetic abnormalities in colorectal polyps and CRC to elucidate carcinogenic mechanisms in SPS.

We retrospectively analyzed clinicopathological features of colorectal polyps in 44 SPS patients, and examined mutations of genes including APC, RAS, BRAF, and TP53, and microsatellite instability (MSI) in CRC tissues.

Of the 44 patients, 25 (56%) fulfilled WHO criterion 1, 11 (25%) fulfilled criterion 2, and 8 (18%) fulfilled both. A total of 956 polyps were observed; 642 (67%) hyperplastic polyps (HP), 204 (21%) sessile serrated lesions (SSL), 10 (1%) traditional serrated adenoma (TSA), and 100 (11%) adenomas. The median numbers of polyps (/patient) were 10.5 (IQR 2.75-23) HPs, 4.0 (2.0-6.0) SSLs, 0 (0-0) TSA, and 1 (0-3.3) adenoma. SSL and HP located preferentially in the proximal and distal colon, respectively. Twenty-two CRCs were found in 18 patients. Based on the histological coexistence of SSL/TSA, BRAF mutation and MSI, 5 CRCs (26%) were classified as serrated-neoplasia pathway. Conversely, based on the coexistence of adenoma, APC/RAS and TP53 mutations, 11 CRCs (58%) were classified as adenoma-carcinoma pathway. The remaining three were unclassifiable. Most CRCs through adenoma-carcinoma pathway were located in the left-side colorectum and patients bearing those met criterion 2, characterized by many HP and advanced adenomas. Adenoma was a significant risk factor for CRC.

Our results suggest that more than half of the CRCs, particularly those in the left-side colorectum, developed through the adenoma-carcinoma pathway in SPS patients. Adenoma was a risk factor for CRCs, suggesting its importance in colorectal carcinogenesis.

Serrated polyposis syndrome (SPS) is characterized by development of numerous serrated lesions throughout the colorectum and increased risk of colorectal cancer (CRC). However, SPS has been an underrecognized CRC predisposition syndrome, and the true risk of CRC in SPS, both overall and in surveillance, is not known. The aim of this systematic review and meta-analysis is to describe the risk of CRC in patients with SPS.

Electronic databases were searched on March 25, 2021, for studies describing CRC risk in SPS. Random-effects meta-analysis was performed to assess pooled risk of CRC among SPS patients. Primary outcomes were risk of CRC at time of SPS diagnosis and during surveillance following diagnosis of SPS. Secondary outcomes included risk of CRC prior to diagnosis of SPS and effect of World Health Organization subtype on CRC risk.

Thirty-six studies including 2788 patients with SPS were included in the analysis. Overall risk of CRC in SPS was 19.9% (95% confidence interval [CI], 15.3%-24.5%). CRC risk at the time of diagnosis was 14.7% (95% CI, 11.4%-18.8%), while risk during surveillance was 2.8% (95% CI, 1.8%-4.4%), or 7 cases per 1000 person-years. SPS patients also had a high incidence of history of CRC prior to SPS diagnosis (7.0%; 95% CI, 4.6%-11.7). Subgroup analysis did not reveal any significant differences based on World Health Organization subtype.

Our meta-analysis demonstrated that patients with SPS have an elevated risk of CRC, which is highest at the time of diagnosis and suggests the importance of early SPS recognition and screening to modify CRC risk. The persistently elevated CRC risk during surveillance supports current guidelines recommending heightened surveillance protocols.

Patients with serrated polyposis syndrome (SPS) and their first-degree relatives (FDRs) have increased colorectal cancer (CRC) risk. Patients with sporadic sessile serrated lesion (SSL) have risk for progression to CRC. Yet familial risks of common extracolonic cancers and even CRC in these cohorts are poorly understood. Our aim was to examine cancer risk for patients with SPS and sporadic SSL and their close and more distant relatives using a large population database.

Patients with SPS (n = 59) from hereditary patient registries were eligible for study. Sporadic SSL (n = 754) and sex- and age-matched normal colonoscopy controls (n = 1,624) were selected from clinical data linked to the Utah Population Database. Cox models adjusting for the number of relatives, degree of relatedness, and person-years at risk were used to estimate CRC, extracolonic, and any-site adenocarcinoma/carcinoma cancer risk in patients and their relatives.

Compared with controls, CRC risk was elevated 10-fold in patients with SPS (P = 0.04) and 5-fold in their FDRs (P = 0.001). Any-site adenoma/carcinoma risk was increased 2.6-fold in FDRs of patients with SPS. No elevated risks of other common extracolonic cancers were observed in SPS and family members. The FDRs, second-degree relatives, and third-degree relatives of patients with both SSL and adenomatous polyps exhibited a 50% increased CRC risk.

Patients with SPS and their FDRs have an increased CRC risk, confirming other reports. Interestingly, patients with SSL were noted to have an increased risk of prostate cancer. Relatives of individuals with both sporadic SSL and adenomas, irrespective of size or dysplasia on examination, may have an elevated CRC risk, suggesting closer colonoscopy surveillance in this population.

The serrated pathway of carcinogenesis has been the subject of intense investigation over the past 2 decades, but many gaps in our understanding still need to be resolved. Serrated polyp precursors include hyperplastic polyps, sessile serrated polyps, and traditional serrated adenomas. These are considered discrete entities, but there is emerging molecular data to suggest that they may be more closely related to each other than currently believed. The recent US Multi-Society Task Force surveillance guidelines for patients with serrated polyps are admittedly based on low quality evidence. In this brief review, we discuss the limitations in endoscopic detection and pathologic interpretation of serrated polyps and the implications of these diagnostic difficulties on risk prediction and postpolypectomy surveillance recommendations.

Serrated polyps are classified into hyperplastic polyps, sessile serrated adenomas/polyps, and traditional serrated adenomas. Although all serrated polyps share characteristic colonic crypts serrations, distinguishing hyperplastic polyps from sessile serrated adenomas/polyps is challenging. Traditional serrated adenomas are cytologically dysplastic lesions; sessile serrated adenomas/polyps develop cytologic dysplasia as they progress to colorectal cancer. A flat and pale appearance of serrated polyps may make detection difficult. Endoscopic mucosal resection has higher rates of complete resection. Close surveillance is recommended for sessile serrated adenomas/polyps, sessile serrated adenomas/polyp with dysplasia, hyperplastic polyps ≥10 mm, and traditional serrated adenomas.

Researchers are searching in vain for a coherent genetic explanation for serrated polyposis. We hypothesize that there is no consistent monogenetic inheritance.

The purpose of this study was to describe the serrated polyposis phenotype, assessing features of mendelian inheritance, and to compare these features with patients with a solitary sessile serrated lesion.

This was a retrospective review of a prospectively maintained database comparing patients with serrated polyposis versus solitary sessile serrated lesions.

The study was conducted at a single-institution tertiary referral center.

Patients with serrated polyposis meeting World Health Organization criteria type I (≥5 serrated polyps proximal to the sigmoid, ≥2 of which are ≥10 mm in diameter) and isolated sessile serrated lesions were included MAIN OUTCOME MEASURES:: Disease phenotype was the main outcome measured.

A total of 46 serrated polyposis patients were identified. Median age of first sessile serrated lesion was 66 years (interquartile range, 42-70 y). A total of 60.3% were current or past smokers (mean = 38.6 packs per year). Serrated polyposis patients had a higher number of all types of polyps (26.3 vs 4.4) and a higher rate of high-grade dysplasia (19.6% vs 3.7%) compared with patients with a solitary sessile serrated lesion. A total of 36.2% of patients had personal history of noncolorectal cancers, including skin, prostate, breast, thyroid, and renal cell cancers and leukemia. In addition, 32.6% had a family history of colorectal cancer in first- or second-degree relatives; these cancers were not young age of onset. Breast and prostate cancers were also common (family history of any cancer, 83.0%). Ten patients underwent genetic testing: 4 had negative panels, 1 had a pathogenic variant in MSH2, 1 an IVS7 deletion in PTEN, 2 negative APC sequencing (1 negative MYH), and 1 a pathogenic variant in Chek2.

RNF4 was not sequenced. Genetic analysis was performed on a subset of patients.

The rate of associated cancers suggests an underlying genetic predisposition to disordered growth, but serrated polyposis does not have typical features of dominant inheritance. The association with smoking suggests that familial/environmental factors play a role. See Video Abstract at http://links.lww.com/DCR/B84. POLIPOSIS SERRADA SÉSIL: ¿NO ES UN SÍNDROME HEREDITARIO?: Los investigadores están buscando en vano una explicación genética coherente para la póliposis serrados. Suponemos que no existe una herencia monogenética consistente.1) Describir el fenotipo de póliposis serrada, evaluando las características de la herencia mendeliana, 2) comparar estas características con pacientes con una lesión serrada sésil solitaria.Revisión retrospectiva de una base de datos mantenida prospectivamente que compara pacientes con póliposis serrada versus lesiones serradas sésiles solitarias.Institución única, centro de referencia terciario.Pacientes con póliposis serrada que cumplen con los Criterios de la Organización Mundial de la Salud Tipo I (≥ 5 pólipos serrados proximales al sigmoideo, ≥2 de los cuales tienen ≥10 mm de diámetro) y lesiones serradas sésiles aisladas.Fenotipo de la enfermedad.Se identificaron un total de 46 pacientes con póliposis serrada. La edad mediana de la primera lesión serrada sésil fue de 66 años (RIC: 42-70 años). El 60.3% eran fumadores actuales o pasados (medio 38.6 paquetes / año). Los pacientes con póliposis serrada tuvieron un mayor número de todos los tipos de pólipos (26.3 versus 4.4) y una mayor tasa de displasia de alto grado (19.6% versus 3.7%) en comparación con los pacientes con una lesión serrada sésil solitaria. El 36.2% de los pacientes tenían antecedentes personales de cánceres no colorectales, incluyendo los cánceres de piel, próstata, mama, tiroides, células renales y leucemia. El 32.6% tenía antecedentes familiares de cáncer colorectal en familiares de primer o segundo grado; estos cánceres no eran de inicio de edad temprana. El cáncer de mama y próstata también fue frecuente (antecedentes familiares de cualquier tipo de cáncer: 83.0%). 10 pacientes se sometieron a pruebas genéticas: 4 tenían paneles negativos, 1 tenía una variante patogénica en MSH2, 1 una eliminación IVS7 en PTEN, 2 secuenciación APC negativa (1 MYH negativa) y 1 variante patogénica en Chek2.RNF4 no fue secuenciado. El análisis genético se realizó en un subconjunto de pacientes.La tasa de cánceres asociados sugiere una predisposición genética subyacente al crecimiento desordenado, pero la póliposis serrada no tiene características típicas de herencia dominante. La asociación con el tabaquismo sugiere que los factores familiares / ambientales juegan un papel. Consulte Video Resumen en http://links.lww.com/DCR/B84. (Traducción-Dr. Yesenia Rojas-Khalil).

Approximately 35% of patients with colorectal cancer (CRC) have a family history of the disease attributed to genetic factors, common exposures, or both. Some families with a history of CRC carry genetic variants that cause CRC with high or moderate penetrance, but these account for only 5% to 10% of CRC cases. Most families with a history of CRC and/or adenomas do not carry genetic variants associated with cancer syndromes; this is called common familial CRC. Our understanding of familial predisposition to CRC and cancer syndromes has increased rapidly due to advances in next-generation sequencing technologies. As a result, there has been a shift from genetic testing for specific inherited cancer syndromes based on clinical criteria alone, to simultaneous testing of multiple genes for cancer-associated variants. We summarize current knowledge of common familial CRC, provide an update on syndromes associated with CRC (including the nonpolyposis and polyposis types), and review current recommendations for CRC screening and surveillance. We also provide an approach to genetic evaluation and testing in clinical practice. Determination of CRC risk based on family cancer history and results of genetic testing can provide a personalized approach to cancer screening and prevention, with optimal use of colonoscopy to effectively decrease CRC incidence and mortality.

Colorectal cancer (CRC) has been ranked as the third most prevalent cancer worldwide. Indeed, it represents 10.2% of all cancer cases. It is also the second most common cause of cancer mortality, and accounted for about 9.2% of all cancer deaths in 2018. Early detection together with a correct diagnosis and staging remains the most effective clinical strategy in terms of disease recovery. Thanks to advances in diagnostic techniques, and improvements of surgical adjuvant and palliative therapies, the mortality rate of CRC has decreased by more than 20% in the last decade. Cancer biomarkers for the early detection of CRC, its management, treatment and follow-up have contributed to the decrease in CRC mortality. Herein, we provide an overview of molecular biomarkers from tumor tissues and liquid biopsies that are approved for use in the CRC clinical setting for early detection, follow-up, and precision therapy, and of biomarkers that have not yet been officially validated and are, nowadays, under investigation.

Our understanding of serrated colorectal polyps has increased dramatically over the past two decades and has led to a modern classification scheme for these lesions. Sessile serrated polyps with dysplasia represent the most clinically significant serrated polyp; however, the morphologic heterogeneity of dysplasia in sessile serrated polyps has only recently been recognized and correlated with MLH1 immunohistochemistry. Detailed morphologic analysis of traditional serrated adenomas has led to the recognition of flat and early forms of this polyp. Robust data on the risk of metachronous lesions in patients with serrated polyps are also beginning to emerge. This review will summarize our current understanding of serrated polyps and associated carcinomas with a focus on diagnostic criteria, morphologic heterogeneity, molecular findings, and natural history. Controversial issues in the diagnosis and classification of these polyps are also discussed.

Define the morphologic and molecular features of colonic polyps with subtle histologic features.

Two hundred specimens were obtained of surveillance colonoscopies. Endoscopic findings were reviewed. Histologic features of the polyps were compared with the flat mucosa. Next-generation sequencing was performed on 30 study polyps and 20 control samples.

Polyps with subtle changes comprised 12% of all polyps. All polyps were sessile and small (<0.5 cm) and were located predominantly in the distal colon (60%). Synchronous hyperplastic, sessile serrated, and dysplastic polyps were found in 30%, 7%, and 51% of patients, respectively. A total of 169 (84.5%) polyps showed wide, nonserrated crypts, increased intraluminal mucus, and patent openings. KRAS alterations were present in 30% of polyps.

Most polyps with subtle histologic features have recognizable morphologic changes. About one-third harbored KRAS alterations. These polyps should not be regarded as variants of hyperplastic polyps.

Serrated adenomas are genetically heterogeneous, and the histological classification into sessile serrated (SSA) adenoma and traditional serrated adenoma (TSA) does not reflect the molecular landscape. The objective of this study was to assess clinical or pathological factors associated with BRAF-V600E mutation in serrated adenomas. Systematic review and meta-analysis was performed by searching electronic databases from January 2011 to January 2019 for studies assessing the association of BRAF-V600E mutation with clinical or pathological features of serrated adenomas. Odds ratio (OR) was calculated for each factor; a P-value <0.05 was considered significant. Forty studies assessing 3511 serrated adenomas (2375 SSAs and 1136 TSAs) were included. BRAF-V600E mutation was significantly associated with proximal localisation (OR = 2.71; P < 0.00001) and CIMP-H status (OR = 4.81; P < 0.0001) in both SSA and TSA, with polyp size <10 mm (OR = 0.41; P = 0.02) in TSA, and with endoscopic pit pattern II-O (OR = 13.11; P < 0.00001) and expression of MUC5A5 (OR = 4.43; P = 0.003) and MUC6 (OR = 2.28; P < 0.05) in SSA. Conversely, BRAF mutation was not associated with age <70 years (OR = 1.63; P = 0.34), age <60 years (OR = 0.86; P = 0.79), female sex (OR = 0.77; P = 0.12), flat morphology (OR = 1.52; P = 0.16), presence of any dysplasia (OR = 1.01; P = 0.59), serrated dysplasia (OR = 1.23; P = 0.72) and invasive cancer (OR = 0.67; P = 0.32), nuclear β-catenin expression (OR = 0.73; P = 0.21) and p53 overexpression (OR = 1.24; P = 0.82). In conclusion, BRAF-V600E mutation is associated with proximal localisation and CIMP-H status in both SSA and TSA, with size <10 mm only in TSA, and with expression of MUC5A5 and MUC6 and endoscopic pit pattern II-O at least in SSA. In serrated adenomas, BRAF-V600E mutation does not seem to be associated with age and sex, with the prevalence of dysplasia and cancer and with the morphology of the dysplastic component.

Dysplasia in colonic sessile serrated adenomas (SSAs)/sessile serrated polyps often shows loss of MLH1 expression as determined with immunohistochemistry, but the significance of loss of MLH1 expression in non-dysplastic crypts in these polyps is less well studied. The purpose of this study was to evaluate the prevalence of loss of MLH1 expression in non-dysplastic crypts in SSAs, and to evaluate its significance with regard to progression of these polyps.

Four hundred SSAs, including 158 SSAs without dysplasia, 219 SSAs with dysplasia (SSAD), and 23 SSAs with invasive adenocarcinoma (SSAC), were evaluated immunohistochemically for loss of MLH1 expression in both non-dysplastic and dysplastic portions of the polyps. Seventy-one of 400 (18%) SSAs showed loss of MLH1 expression in non-dysplastic crypts. The prevalence of MLH1-deficient non-dysplastic crypts was higher in polyps with dysplasia or carcinoma (7%, 22%, and 52% in SSAs, SSADs, and SSACs, respectively; P < 0.0001). When SSAs with MLH1-deficient dysplasia and those with MLH-1-proficient dysplasia were compared, those with MLH1-deficient dysplasia were more likely to have MLH1-deficient non-dysplastic crypts (66% versus 8.1%, P < 0.0001) and a greater number of discrete foci (3.6 foci versus 1.1 foci, P = 0.008). Also, non-dysplastic crypts with loss of MLH1 expression were more likely to be contiguous with the dysplasia when the dysplasia also showed loss of MLH1 expression (26% versus 0%, P = 0.02).

Our results suggest that loss of MLH1 expression in non-dysplastic crypts in SSAs precedes the development of MLH1-deficient dysplasia and adenocarcinoma, and may be a biomarker of an advanced serrated polyp even in the absence of dysplasia.

The pathologist can contribute to recognizing hereditary causes of colorectal cancer via morphology. By identifying so-called index patients, it is possible to take preventive measures in affected families. The precise definition of the clinical presentation and the histopathological phenotype help to narrow the spectrum of expected genetic alterations. Novelties within Lynch syndrome include the recognition of EPCAM as a fifth gene locus, as well as the newly defined Lynch-like syndrome with evidence of somatic mismatch repair (MMR) mutations. With regard to polyposis-associated syndromes, the spectrum of polyps, whether serrated, hamartomatous or classic adenoma, is of crucial importance. The resulting differential diagnosis includes (attenuated) familial adenomatous polyposis ([a]FAP), MUTYH-associated polyposis (MAP), polymerase proofreading-associated polyposis (PPAP), phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS), Peutz-Jeghers syndrome and juvenile polyposis, each with a specific genetic background.

Colorectal carcinoma (CRC) is the third most common cancer in men and the second most common cancer in women across the world. Most CRCs occur sporadically, but in 15-35% of cases, hereditary factors are important. Some patients with an inherited predisposition to CRC will be diagnosed with a "genetic polyposis syndrome" such as familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), polymerase proofreading associated polyposis (PPAP), NTHL1-associated polyposis, MSH3-associated polyposis or a hamartomatous polyposis syndrome. Individuals with ≥10 colorectal polyps have traditionally been referred for genetic diagnostic testing to identify APC and MUTYH mutations which cause FAP and MAP respectively. Mutations are found in most patients with >100 adenomas but in only a minority of those with 10-100 adenomas. The reasons that diagnostic laboratories are not identifying pathogenic variants include mutations occurring outside of the open reading frames of genes, individuals exhibiting generalized mosaicism and the involvement of additional genes. It is important to identify patients with an inherited polyposis syndrome, and to define the mutations causing their polyposis, so that the individuals and their relatives can be managed appropriately.

Hyperplastic polyps, once considered to have no malignant potential, are now recognized to be part of a larger group of polyps known as serrated polyps. Serrated polyps can progress to CRC through an epigenetic pathway known as CpG Island Methylator Phenotype (CIMP), characterized by hypermethylation of specific DNA regions such as the promoter regions of the DNA mismatch repair genes like MLH1. The CIMP pathway is tightly linked with mutations of the oncogene BRAF. There are three subtypes of serrated polyps - hyperplastic polyps, sessile serrated polyps (SSPs) and traditional serrated adenomas (TSAs). TSAs harbor cytologic dysplasia whereas hyperplastic polyps and SSPs are nondysplastic lesions. Currently, only SSPs and TSAs are believed to progress to CRC whereas hyperplastic polyps are thought to be benign with no malignant potential. This article will review the current evidence while highlighting some of the issues regarding serrated polyps.

One challenge has been pathologically distinguishing hyperplastic polyps from SSPs, which is an important distinction, given the potential for progression of SSPs to CRC. Other challenges regarding serrated polyps include adequate detection and resection. Surveillance guideline recommendations for some serrated polyps have been changed in current guidelines to reflect the malignant potential, recommending closer surveillance intervals than the 10-year follow-up that has been traditionally provided for hyperplastic polyps.

Given the difficulties in diagnosing as well as resecting, it is important for endoscopists to know how to detect, resect and manage follow-up in patients with serrated polyps.

The purpose of this review is to summarize the management of serrated colorectal polyps (SPs), with a particular focus on the most common premalignant SP, sessile serrated adenoma or polyp (SSA/P). These lesions present a challenge for endoscopists with respect to detection and resection, and are also susceptible to pathologic misdiagnosis.

Patients with SSA/Ps are at an increased risk of future colorectal neoplasia, including advanced polyps and cancer. Reasonable benchmarks for SP detection rates are 5-7% for SSA/Ps and 10-12% for proximal SPs. Certain endoscopic techniques such as chromoendoscopy, narrow band imaging, water immersion, and wide-angle viewing may improve SSA/P detection. Emerging endoscopic techniques such as underwater polypectomy, suction pseudopolyp technique, and piecemeal cold snare polypectomy are helpful tools for the endoscopist's armamentarium for removing SSA/Ps. Proper orientation of SSA/P specimens can improve the accuracy of pathology readings. Patients with confirmed SSA/Ps and proximal HPs should undergo surveillance at intervals similar to what is recommended for patients with conventional adenomas. Patients with SSA/Ps may also be able to lower their risk of future polyps by targeting modifiable risk factors including tobacco and alcohol use and high-fat diets. NSAIDs and aspirin appear to be protective agents. SPs and SSA/Ps in particular are important colorectal cancer precursors that merit special attention to ensure adequate detection, resection, and surveillance.

The influence of lifestyle factors on survival following a diagnosis of colorectal cancer (CRC) is not well established. We examined associations between lifestyle factors measured before diagnosis and CRC survival. The Melbourne Collaborative Cohort Study collected data on alcohol intake, cigarette smoking and physical activity, and body measurements at baseline (1990-1994) and wave 2 (2003-2007). We included participants diagnosed to 31 August 2015 with incident stages I-III CRC within 10-years post exposure assessment. Information on tumor characteristics and vital status was obtained. Tumor DNA was tested for microsatellite instability (MSI) and somatic mutations in oncogenes BRAF (V600E) and KRAS. We estimated hazard ratios (HRs) for associations between lifestyle factors and overall and CRC-specific mortality using Cox regression. Of 724 eligible CRC cases, 339 died (170 from CRC) during follow-up (average 9.0 years). Exercise (non-occupational/leisure-time) was associated with higher CRC-specific survival for stage II (HR = 0.25, 95% CI: 0.10-0.60) but not stages I/III disease (p for interaction = 0.01), and possibly for colon and KRAS wild-type tumors. Waist circumference was inversely associated with CRC-specific survival (HR = 1.25 per 10 cm increment, 95% CI: 1.08-1.44), independent of stage, anatomic site and tumor molecular status. Cigarette smoking was associated with lower overall survival, with suggestive evidence of worse survival for BRAF mutated CRC, but not with CRC-specific survival. Alcohol intake was not associated with survival. Survival did not differ by MSI status. We have identified pre-diagnostic predictors of survival following CRC that may have clinical and public health relevance.

Colorectal cancer (CRC), one of the most common cancers, is a major public health issue globally, especially in Westernized countries. Up to 35% of CRCs are thought to be due to heritable factors, but currently only 5% to 10% of CRCs are attributable to high-risk mutations in known CRC susceptibility genes, predominantly the mismatch repair genes (Lynch syndrome) and adenomatous polyposis coli gene (APC; familial adenomatous polyposis). In this era of precision medicine, high-risk mutation carriers, when identified, can be offered various risk management options that prevent cancers and improve survival, including risk-reducing medication, screening for early detection, and surgery. The practice of clinical genetics is currently transitioning from phenotype-directed single gene testing to multigene panels, now offered by numerous providers. For CRC, the genes included across these panels vary, ranging from well established, clinically actionable susceptibility genes with quantified magnitude of risk, to genes that lack extensive validation or have less evidence of association with CRC and, therefore, have minimal clinical utility. The current lack of consensus regarding inclusion of genes in CRC panels presents challenges in patient counseling and management, particularly when a variant in a less validated gene is identified. Furthermore, there remain considerable challenges regarding variant interpretation even for the well established CRC susceptibility genes. Ironically though, only through more widespread testing and the accumulation of large international data sets will sufficient information be generated to (i) enable well powered studies to determine if a gene is associated with CRC susceptibility, (ii) to develop better models for variant interpretation and (iii) to facilitate clinical translation.

Polyps of the gastrointestinal tract are very common lesions and most frequently sporadic in nature. Some polyp subtypes are associated with rare hereditary polyposis syndromes, including juvenile polyposis syndrome, Peutz-Jeghers syndrome, and Cowden syndrome. However, many sporadic benign lesions of the gastrointestinal tract can mimic some of these syndromic hamartomatous polyps. The role of the surgical pathologist is to raise the possibility of a hereditary condition in case of suggestive polyp histology and to look for clinical information to support the suspected diagnosis. In this review, the clinical presentation and the pathology associated with these rare hamartomatous polyposis syndromes are discussed in an attempt to provide pathologists clues in suggesting one such syndrome on the basis of histologic findings and clinical context. Identification of affected individuals is important because of the increased gastrointestinal and other malignancies. Recently, new adenomatous polyposis syndromes have been discovered, expanding the genetic causes of patient diagnosed with multiple colonic adenomas. By being aware of the clinical phenotype and the tumor spectrum associated with gastrointestinal polyposis syndromes, surgical pathologists can play a critical role in recommending genetic counseling when suspicious of such a diagnosis. This may lead to the identification of a genetic cause and appropriate surveillance of affected family members to screen for associated malignancies.

Colorectal cancer (CRC) is the fourth most common cancer amongst men and women. Between 3 and 6% of all CRCs are attributed to well-defined inherited syndromes, including Lynch syndrome, familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), and several hamartomatous polyposis conditions. Identification of these patients through family history and appropriate genetic testing can provide estimates of cancer risk that inform appropriate cancer screening, surveillance and/or preventative interventions. This narrative review examines the hereditary colorectal cancer and polyposis syndromes, their genetic basis, clinical management, and evidence supporting cancer screening.

We investigated whether patients with multiple serrated polyps, but not meeting the World Health Organization criteria for serrated polyposis syndrome, and their relatives have similar risks for colorectal cancer (CRC) as those diagnosed with serrated polyposis.

We collected data from patients with more than 10 colonic polyps, recruited in 2008-2009 from 24 hospitals in Spain for a study of causes of multiple colonic polyps. We analyzed data from 53 patients who met the criteria for serrated polyposis and 145 patients who did not meet these criteria, but who had more than 10 polyps throughout the colon, of which more than 50% were serrated. We calculated age- and sex-adjusted standardized incidence ratios (SIRs) for CRC in both groups, as well as in their first-degree relatives.

The prevalence of CRC was similar between patients with confirmed serrated polyposis and multiple serrated polyps (odds ratio, 1.35; 95% confidence interval [CI], 0.64-2.82; P = .40). The SIR for CRC in patients with serrated polyposis (0.51; 95% CI, 0.01-2.82) did not differ significantly from the SIR for CRC in patients with multiple serrated polyps (0.74; 95% CI, 0.20-1.90; P = .70). The SIR for CRC also did not differ significantly between first-degree relatives of these groups (serrated polyposis: 3.28, 95% CI, 2.16-4.77; multiple serrated polyps: 2.79, 95% CI, 2.10-3.63; P = .50). Kaplan-Meier analysis showed no differences in the incidence of CRC between groups during the follow-up period (log-rank, 0.6).

The risk of CRC in patients with multiple serrated polyps who do not meet the criteria for serrated polyposis, and in their first-degree relatives, is similar to that of patients diagnosed with serrated polyposis.

Serrated polyps have long been considered to lack malignant potential but accumulating data suggest that these lesions may cause up to one-third of all sporadic colorectal cancer. Serrated polyps are classified into three subtypes, including sessile serrated adenomas/polyps (SSA/Ps), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). SSA/P and TSA harbour malignant potential but TSA represents only 1-2%, wheras SSA/P constitute up to 20% of all serrated lesions. HPs are most common (80%) of all serrated polyps but are considered to have a low potential of developing colorectal cancer. Due to their subtle appearence, detection and removal of serrated polyps pose a major challenge to endoscopists. Considering that precancerous serrated polyps are predominately located in the right colon could explain why interval cancers most frequently appear in the proximal colon and why colonoscopy is less protective against colon cancer in the proximal compared to the distal colon. Despite the significant impact on colorectal cancer incidence, the aetiology, incidence, prevalence, and natural history of serrated polyps is incompletely known. To effectively detect, remove, and follow-up serrated polyps, endoscopists and pathologists should be well-informed about serrated polyps. This review highlights colorectal serrated polyps in terms of biology, types, diagnosis, therapy, and follow-up.

Ethanol in alcoholic beverages is a causative agent for colorectal cancer. Colorectal cancer is a biologically heterogeneous disease, and molecular subtypes defined by the presence of somatic mutations in BRAF and KRAS are known to exist. We examined associations between lifetime alcohol intake and molecular and anatomic subtypes of colorectal cancer. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 38,149 participants aged 40-69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between lifetime alcohol intake and colorectal cancer risk. Heterogeneity in the HRs across subtypes of colorectal cancer was assessed. A positive dose-dependent association between lifetime alcohol intake and overall colorectal cancer risk (mean follow-up = 14.6 years; n = 596 colon and n = 326 rectal cancer) was observed (HR = 1.08, 95% CI: 1.04-1.12 per 10 g/day increment). The risk was greater for rectal than colon cancer (phomogeneity  = 0.02). Alcohol intake was associated with increased risks of KRAS+ (HR = 1.07, 95% CI: 1.00-1.15) and BRAF-/KRAS- (HR = 1.05, 95% CI: 1.00-1.11) but not BRAF+ tumors (HR = 0.89, 95% CI: 0.78-1.01; phomogeneity  = 0.01). Alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- tumors originating via specific molecular pathways including the traditional adenoma-carcinoma pathway but not with BRAF+ tumors originating via the serrated pathway. Therefore, limiting alcohol intake from a young age might reduce colorectal cancer originating via the traditional adenoma-carcinoma pathway.

Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance.

In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded.

In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4).

The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias.

This review article deals with the analysis and the detection of the morphological features associated with somatic mutations, mostly BRAFV600E mutation, on both cytological and histological samples of carcinomas. Few authors demonstrated that some architectural and specific cellular findings (i.e. polygonal eosinophilic cells defined as "plump cells" and sickle-shaped nuclei) are able to predict BRAF V600E mutation in both cytological and histological samples of papillary thyroid carcinoma (PTC) as well as in other carcinomas. In the current review article we evaluated the first comprehensive analysis of the morphological prediction of BRAFV600E and other somatic mutations in different malignant lesions with the description of the possible mechanisms beneath these morphologic features. The detection of predictive morphological features, mostly on FNAC, may add helpful information to the stratification of the malignant risk and personalized management of cancers. Additionally, the knowledge of the molecular mechanism of different oncogenic drivers can lead to the organ-specific triaging selection of cases and can provide significant insight for targeted therapies in different malignant lesions.

Serrated polyposis syndrome (SPS) is associated with an increased colorectal cancer (CRC) risk, although the magnitude of the risk remains uncertain. Whereas intensive endoscopic surveillance for CRC prevention is advised, predictors that identify patients who have high CRC risk remain unknown. We performed a multicentre nationwide study aimed at describing the CRC risk in patients with SPS and identifying clinicopathological predictors independently associated with CRC.

From March 2013 through September 2014, patients with SPS were retrospectively recruited at 18 Spanish centres. Data were collected from medical, endoscopy and histopathology reports. Multivariate logistic regression was performed to identify CRC risk factors.

In 296 patients with SPS with a median follow-up time of 45 months (IQR 26-79.7), a median of 26 (IQR 18.2-40.7) serrated polyps and 3 (IQR 1-6) adenomas per patient were detected. Forty-seven patients (15.8%) developed CRC at a mean age of 53.9±12.8, and 4 out of 47 (8.5%) tumours were detected during surveillance (cumulative CRC incidence 1.9%). Patients with >2 sessile serrated adenomas/polyps (SSA/Ps) proximal to splenic flexure and ≥1 proximal SSA/P with high-grade dysplasia were independent CRC risk factors (incremental OR=2, 95% CI 1.22 to 3.24, p=0.006). Patients with no risk factors showed a 55% decrease in CRC risk (OR=0.45, 95% CI 0.24 to 0.86, p=0.01).

Patients with SPS have an increased risk of CRC, although lower than previously published. Close colonoscopy surveillance in experienced centres show a low risk of developing CRC (1.9% in 5 years). Specific polyp features (SSA/P histology, proximal location and presence of high-grade dysplasia) should be used to guide clinical management.

Serrated polyposis is a rare disorder characterised by the presence of multiple serrated polyps in the large intestine, and an increased personal and familial risk of colorectal cancer. Knowledge of the molecular characteristics of colonic lesions which develop in this syndrome is fragmented, making it difficult to understand the underlying genetic basis of this condition. We conducted a systematic review and meta-analysis of all studies which evaluated the molecular characteristics of colorectal neoplasms found in individuals with serrated polyposis. We identified 4561 potentially relevant studies, but due to a lack of consensus in the reporting of findings, only fourteen studies were able to be included in the meta-analysis. BRAF mutation was found in 73% (95% CI 65-80%) of serrated polyps, 0% (95% CI 0-3%) of conventional adenomas and 49% (95%CI 33-64%) of colorectal cancers. In contrast, KRAS mutation was present in 8% (95% CI 5-11%) of serrated polyps, 3% (95% CI 0-13%) of conventional adenomas and 6% (95% CI 0-13%) of colorectal cancers. Absence of MLH1 immunostaining was found in 3% (95% CI 0-10%) of serrated polyps and 53% (95% CI 36-71%) of colorectal cancers. Overall, microsatellite instability was found in 40% (95% CI 18-64%) of colorectal cancers arising in the setting of serrated polyposis. Our results indicate that diverse molecular pathways are likely to contribute to the increased predisposition for colorectal cancer in individuals with serrated polyposis. We also propose a set of minimum standards for the reporting of future research in serrated polyposis as this is a rare syndrome and collation of research findings from different centres will be essential to identify the molecular mechanisms involved in the pathogenesis of this condition.

The serrated neoplasia pathway accounts for 20-30% of colorectal cancers (CRC), which are characterized by extensive methylation (CpG island methylation phenotype, CIMP), frequent BRAF mutation and high microsatellite instability (MSI). We recently identified MUC5AC mucin gene hypomethylation as a specific marker of MSI CRC. The early identification of preneoplastic lesions among serrated polyps is currently challenging. Here, we performed a detailed pathological and molecular analysis of a large series of colorectal serrated polyps and evaluated the usefulness of mucin genes MUC2 and MUC5AC to differentiate serrated polyps and to identify lesions with malignant potential. A series of 330 colorectal polyps including 218 serrated polyps [42 goblet cell-rich hyperplastic polyps (GCHP), 68 microvesicular hyperplastic polyps (MVHP), 100 sessile serrated adenoma (SSA) and eight traditional serrated adenoma (TSA)] and 112 conventional adenomas was analyzed for BRAF/KRAS mutations, MSI, CIMP, MLH1 and MGMT methylation, and MUC2 and MUC5AC expression and methylation. We show that MUC5AC hypomethylation is an early event in the serrated neoplasia pathway, and specifically detects MVHP and SSA, arguing for a filiation between MVHP, SSA and CIMP-H/MSI CRC, whereas GCHP and TSA arise from a distinct pathway. Moreover, MUC5AC hypomethylation specifically identified serrated lesions with BRAF mutation, CIMP-H or MSI, suggesting that it may be useful to identify serrated neoplasia pathway-related precursor lesions. Our data suggest that MVHP should be recognized among HP and require particular attention.

Background/Aim. Serrated polyposis syndrome (SPS) is a rare condition characterized by multiple serrated polyps throughout the colon and rectum. The aim of this study was to evaluate the clinicopathological characteristics of SPS in Koreans. Methods. This retrospective analysis of prospectively collected data was performed using information from the endoscopy, clinical records, and pathology database system of Uijeongbu St. Mary's Hospital. Consecutive patients satisfying the updated 2010 World Health Organization criteria for SPS between June 2011 and May 2014 were enrolled. Results. Of the 17,552 patients who underwent colonoscopies during the study period, 11 (0.06%) met the criteria for SPS. The mean age of these patients was 55.6 years. Ten patients (91%) were males. None had a family history of CRC or a first-degree relative with SPS. Seven patients (64%) had synchronous advanced adenoma. One patient had coexistence of SPS with CRC that was diagnosed at the initial colonoscopy. Five patients (45%) had more than 30 serrated polyps. One of the patients underwent surgery and 10 underwent endoscopic resection. Conclusion. The prevalence of SPS in this study cohort was comparable to that in Western populations. Considering the high risk of CRC, correct diagnosis and careful follow-up for SPS are necessary.

Goblet cell--rich hyperplastic polyps (GCRHP) are morphologically subtle compared to microvesicular hyperplastic polyps (MVHP) and are believed to be the most commonly unrecognized serrated polyp, though this has not been systematically studied. We hypothesize that a gastrointestinal pathologist's review of endoscopically but not histologically apparent polyps will identify previously missed GCRHPs, a finding that may be clinically significant if the addition of this subtype of serrated polyp contributes to sufficient numeric criteria for a clinical diagnosis of serrated polyposis syndrome (SPS). Two blinded reviews were performed on 160 endoscopically but not histologically apparent polyps by a gastrointestinal pathologist, separated by a 6 month "washout period." A final review diagnosis of GCRHP was applied to all polyps with complete agreement on both reviews. Patient records were then searched to determine if the addition of a GCRHP resulted in sufficient numeric criteria for a clinical diagnosis of SPS. Fourteen (9%) polyps were reclassified as GCRHPs. The majority (n = 12, 86%) were originally called "colonic mucosa with surface hyperplastic change (CMWSHC)." Two polyps (1%) were re-classified as MVHPs. No other serrated or adenomatous polyps were identified. For each patient, the addition of a hyperplastic polyp did not result in a clinical diagnosis of SPS, though one patient fell short of this diagnosis by only one polyp. GCRHPs are the most commonly underdiagnosed serrated polyp and are often called CMWSHC. The addition of previously missed GCRHPs is unlikely to contribute to a diagnosis of SPS in an individual patient.

The sessile serrated polyp (SSP), also known as sessile serrated adenoma, is the evil twin among the colorectal cancer precursors. As will be described, these lesions have multiple aliases (serrated adenoma, serrated polyp, or serrated lesion among others), they hang out in a bad neighborhood (the poorly prepped right colon), they hide behind a mask of mucus, they are difficult for witnesses (pathologists) to identify, they are difficult for police (endoscopists) to find, they are difficult to permanently remove from the society (high incomplete resection rate), they can be impulsive (progress rapidly to colorectal cancer (CRC)), and enforcers (gastroenterologists) do not know how best to control them (uncertain surveillance recommendations). There is no wonder that there is a need to understand these lesions well, learn how best to prevent the colonic mucosa from going down this errant path or, if that fails, detect these deviants and eradicate them from the colonic society. These lesions should be on endoscopists' most wanted list.