Hyperplastic polyps, serrated adenomas, and the serrated polyp neoplasia pathway

It was previously though that adenomas gave rise to colorectal cancers and that other polyps were harmless. Serrated polyps—hyperplastic polyps, serrated adenomas, and sessile serrated adenomas—show distinct patterns of genetic and epigentic mutation that suggest their role in an alternative pathway of colorectal cancer development. In parallel with these findings are improved demographic and histologic data that also indicate that a subset of serrated polyps are precursors of cancer.     

The serrated pathway of colorectal carcinogenesis

The serrated neoplastic pathway describes a molecular and morphologic continuum, whereby a subset of architecturally serrated polyps progress to colorectal cancers that show BRAF mutation and widespread gene promoter hypermethylation. A subtype of hyper plastic polyp called sessile serrated adenoma has been firmly placed as the dominant precursor lesion in this pathway, whereas the role of the serrated adenoma in this or an alternate serrated pathway requires clarification. The existence of at least one serrated pathway to colorectal carcinogenesis is well established, and research efforts are focused on better defining serrated polyp subtypes macroscopically, histologically, and at the molecular level to ensure optimal clinical management.     

Aspirin reduces the incidence of metastasis in a pre-clinical study of Braf mutant serrated colorectal neoplasia

Background Aspirin reduces the incidence of conventional adenomas driven by APC mutation and thus colorectal cancer. The effect of aspirin on the ~20% of colorectal cancers arising via BRAF mutation is yet to be established.Methods Braf^V637E/+;Villin-Cre^ERT2/+ mice were allocated to a control (n = 86) or aspirin-supplemented (n = 83) diet. After 14 months the incidence of murine serrated lesions, carcinoma and distant metastases were measured by histological examination. RNA was extracted from carcinomas from each cohort and subjected to sequencing to identify differentially expressed genes and molecular pathways.Results Aspirin did not reduce the incidence of murine serrated lesions or carcinoma when compared to control, however, did significantly reduce lesion size (P = 0.0042). Among the mice with carcinoma there was a significant reduction in the incidence of distant metastasis with aspirin treatment (RR 0.69, 95% CI 0.48–0.90, P = 0.0134). Key pathways underlying metastasis of carcinoma cells include NOTCH, FGFR and PI3K signalling, were significantly downregulated in carcinomas sampled from mice on an aspirin-supplemented diet.Conclusions Aspirin reduces the incidence of metastatic Braf mutant carcinoma, although this is not due to a reduction in primary disease. The reduction in metastasis could be attributed to a delay or prevention of molecular changes within the primary site driving metastatic growth.Subject terms: Cancer prevention, Metastasis, Colon cancer, Cancer models     

Chemoprevention of colorectal cancer in inflammatory bowel disease

Introduction: Patients with inflammatory bowel disease are at an increased risk of colorectal cancer when compared to the general population. Chronic inflammation is thought to be the underlying cause, and medications that reduce inflammation have the potential to reduce the risk of colorectal cancer.

Areas covered: After conducting a PubMed search for relevant literature, we examined several classes of medications that have been studied as potential chemopreventive agents. These include 5-aminosalicylates, thiopurines, tumor necrosis factor antagonists, ursodeoxycholic acid, NSAIDs, and statins.

Expert commentary: While each class of medications has some data to support its use in chemoprevention, the majority of the evidence in each case argues against the routine use of these medications solely for a chemopreventive benefit.     

Genetic and epigenetic aberrations occurring in colorectal tumors associated with serrated pathway

To clarify molecular alterations in serrated pathway of colorectal cancer (CRC), we performed epigenetic and genetic analyses in sessile serrated adenoma/polyps (SSA/P), traditional serrated adenomas (TSAs) and high‐methylation CRC. The methylation levels of six Group‐1 and 14 Group‐2 markers, established in our previous studies, were analyzed quantitatively using pyrosequencing. Subsequently, we performed targeted exon sequencing analyses of 126 candidate driver genes and examined molecular alterations that are associated with cancer development. SSA/P showed high methylation levels of both Group‐1 and Group‐2 markers, frequent BRAF mutation and occurrence in proximal colon, which were features of high‐methylation CRC. But TSA showed low‐methylation levels of Group‐1 markers, less frequent BRAF mutation and occurrence at distal colon. SSA/P, but not TSA, is thus considered to be precursor of high‐methylation CRC. High‐methylation CRC had even higher methylation levels of some genes, e.g., MLH1, than SSA/P, and significant frequency of somatic mutations in nonsynonymous mutations (p < 0.0001) and insertion/deletions (p = 0.002). MLH1‐methylated SSA/P showed lower methylation level of MLH1 compared with high‐methylation CRC, and rarely accompanied silencing of MLH1 expression. The mutation frequencies were not different between MLH1‐methylated and MLH1‐unmethylated SSA/P, suggesting that MLH1 methylation might be insufficient in SSA/P to acquire a hypermutation phenotype. Mutations of mismatch repair genes, e.g., MSH3 and MSH6, and genes in PI3K, WNT, TGF‐β and BMP signaling (but not in TP53 signaling) were significantly involved in high‐methylation CRC compared with adenoma, suggesting importance of abrogation of these genes in serrated pathway.     

Inflammatory bowel disease-related colorectal cancer: Past,present and future perspectives

Inflammatory bowel disease-related colorectal cancer (IBD-CRC) is one of the most serious complications of IBD contributing to significant mortality in this cohort of patients. IBD is often associated with diet and lifestyle-related gut microbial dysbiosis, the interaction of genetic and environmental factors, leading to chronic gut inflammation. According to the “common ground hypothesis”, microbial dysbiosis and intestinal barrier impairment are at the core of the chronic inflammatory process associated with IBD-CRC. Among the many underlying factors known to increase the risk of IBD-CRC, perhaps the most important factor is chronic persistent inflammation. The persistent inflammation in the colon results in increased proliferation of cells necessary for repair but this also increases the risk of dysplastic changes due to chromosomal and microsatellite instability. Multiple pathways have been identified, regulated by many positive and negative factors involved in the development of cancer, which in this case follows the ‘inflammation-dysplasia-carcinoma’ sequence. Strategies to lower this risk are extremely important to reduce morbidity and mortality due to IBD-CRC, among which colonoscopic surveillance is the most widely accepted and implemented modality, forming part of many national and international guidelines. However, the effectiveness of surveillance in IBD has been a topic of much debate in recent years for multiple reasons — cost-benefit to health systems, resource requirements, and also because of studies showing conflicting long-term data. Our review provides a comprehensive overview of past, present, and future perspectives of IBD-CRC. We explore and analyse evidence from studies over decades and current best practices followed globally. In the future directions section, we cover emerging novel endoscopic techniques and artificial intelligence that could play an important role in managing the risk of IBD-CRC.     

MicroRNA expression in inflammatory bowel disease-associated colorectal cancer

MicroRNAs (miRNAs) are non-coding RNA molecules composed of 19–25 nucleotides that regulate gene expression and play a central role in the regulation of several immune-mediated disorders, including inflammatory bowel diseases (IBD). IBD, represented by ulcerative colitis and Crohn’s disease, is characterized by chronic intestinal inflammation associated with an increased risk of colorectal cancer (CRC). CRC is one of the most prevalent tumors in the world, and its main risk factors are obesity, physical inactivity, smoking, alcoholism, advanced age, and some eating habits, in addition to chronic intestinal inflammatory processes and the use of immunosuppressants administered to IBD patients. Recent studies have identified miRNAs associated with an increased risk of developing CRC in this population. The identification of miRNAs involved in this tumorigenic process could be useful to stratify cancer risk development for patients with IBD and to monitor and assess prognosis. Thus, the present review aimed to summarize the role of miRNAs as biomarkers for the diagnosis and prognosis of IBD-associated CRC. In the future, therapies based on miRNA modulation could be used both in clinical practice to achieve remission of the disease and restore the quality of life for patients with IBD, and to identify the patients with IBD at high risk for tumor development.     

Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway

Human gut microbiota is being increasingly recognized as a player in colorectal cancers (CRCs). Evidence suggests that Fusobacterium nucleatum (F. nucleatum) may contribute to disease progression and is associated with CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) in CRCs; however, to date, there are no reports about the relationship between F. nucleatum and molecular features in the early stage of colorectal tumorigenesis. Therefore, we investigated the presence of F. nucleatum in premalignant colorectal lesions. In total, 465 premalignant lesions (343 serrated lesions and 122 non‐serrated adenomas) and 511 CRCs were studied. We determined the presence of F. nucleatum and analyzed its association with molecular features including CIMP, MSI and microRNA‐31 status. F. nucleatum was detected in 24% of hyperplastic polyps, 35% of sessile serrated adenomas (SSAs), 30% of traditional serrated adenomas (TSAs) and 33% of non‐serrated adenomas. F. nucleatum was more frequently detected in CIMP‐high premalignant lesions than in CIMP‐low/zero lesions (p = 0.0023). In SSAs, F. nucleatum positivity increased gradually from sigmoid colon to cecum (p = 0.042). F. nucleatum positivity was significantly higher in CRCs (56%) than in premalignant lesions of any histological type (p < 0.0001). In conclusion, F. nucleatum was identified in premalignant colorectal lesions regardless of histopathology but was more frequently associated with CIMP‐high lesions. Moreover, F. nucleatum positivity increased according to histological grade, suggesting that it may contribute to the progression of colorectal neoplasia. Our data also indicate that F. nucleatum positivity in SSAs may support the “colorectal continuum” concept.     

Increased risk of colorectal neoplasia in inflammatory bowel disease patients with post-inflammatory polyps: A systematic review and meta-analysis

BACKGROUNDInflammatory bowel disease (IBD) patients with post-inflammatory polyps (PIPs) may carry an increased risk of colorectal neoplasia (CRN) including dysplasia and cancer. Current guidelines recommend active colonoscopy follow-up for these patients. However, the evidence for guidelines is still poor. In addition, some recent high-quality reports present a different view, which challenges the current guidelines. We hypothesize that IBD patients with PIPs are at increased risk of CRN.AIMTo evaluate the risk of CRN in IBD patients with and without PIPs.METHODSA systematic search of PubMed, Embase, Cochrane Library, and Web of Science was performed to identify studies that compared the risk of CRN in IBD patients with and without PIPs. In addition, we screened the reference lists and citation indices of the included studies. Quality assessment was performed using the Newcastle–Ottawa Scale. Pooled odds ratio (OR) was calculated using the random-effects model to explore the final pooled effect size of the included studies and determine whether PIPs increase the risk of CRN. Sensitivity analysis, subgroup analysis, and assessment of publication bias were performed to examine the sources of heterogeneity.RESULTSTwelve studies with 5819 IBD patients, including 1281 (22.01%) with PIPs, were considered eligible for this meta-analysis. We found that IBD patients with PIPs were at an increased risk of CRN as compared to those without PIPs [OR 2.01; 95% confidence interval (CI): 1.43–2.83]. The results were similar when colorectal cancer was used as the study endpoint (OR 2.57; 95%CI: 1.69–3.91). Furthermore, the risk of CRN was still increased (OR 1.80; 95%CI: 1.12–2.91) when restricted to ulcerative colitis patients. Heterogeneity was high among the included studies (I² = 75%). Subgroup analysis revealed that the high heterogeneity was due to the study design. Sensitivity analysis showed that the main statistical outcomes did not essentially change after excluding any one of the included studies. No significant publication bias was found in the funnel plots.CONCLUSIONIBD patients with PIPs have an increased risk of CRN as compared with those without PIPs, which support the current guidelines. However, a high-quality randomized controlled trial is warranted.     

The serrated neoplasia pathway of colorectal tumors: Identification of MUC5AC hypomethylation as an early marker of polyps with malignant potential

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.     

Invasive Fusobacterium nucleatum may play a role in the carcinogenesis of proximal colon cancer through the serrated neoplasia pathway

The prevalence of invasive Fusobacterium nucleatum (Fn) within the serrated neoplasia pathway of the proximal colon has seldom been investigated. We examined the invasive Fn and bacterial biofilms in 35 proximal hyperplastic polyps (HPs), 33 sessile serrated adenomas (SSAs), 48 proximal colorectal cancers (CRCs) and 10 matched metastatic lymph nodes using 16S rRNA fluorescence in situ hybridization (FISH). Samples of normal mucosa, traditional adenomas (TAs), distal HPs, distal CRCs and matched lymph nodes with or without metastases were used as controls. The prevalence of invasive Fn within proximal HPs (65.7%) and SSAs (78.8%) were significantly higher than that of proximal TAs (28.9%) and distal TAs (24.4%; p < 0.05). Invasive Fn was detected in markedly more proximal CRCs (89.6%) than in distal CRCs (42.2%; p < 0.05). Moreover, invasive Fn was detected in a significantly higher proportion of matched metastatic lymph nodes (100%) than that within nonmetastatic lymph nodes (40.0%; p < 0.001). Bacterial biofilms were found on 52.1% of proximal CRCs, 55.6% of distal CRCs and 48.5% of SSAs. Biofilms were positive for Fn in 47.9% of proximal CRCs, 48.9% of distal CRCs and 27.3% of SSAs. However, the presence of Fn in biofilms was not related to invasive Fn within colorectal tissues (p = 0.415). Invasive Fn may play a role in the carcinogenesis of proximal colon developing via the serrated neoplasia pathway, but might have a less important role in the TA‐carcinoma sequence. Bacterial biofilms may not contribute to the invasion of Fn into tumor tissues.     

Associations between single-nucleotide polymorphisms and inflammatory bowel disease-associated colorectal cancers in inflammatory bowel disease patients: a meta-analysis

Purpose

To assess the correlation between single-nucleotide polymorphisms (SNPs) and inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) in IBD patients.

Methods

A systematic search of PubMed, EmBase, and Cochrane databases was performed. Five genetic models (allelic, dominant, recessive, heterozygous and homozygous models) were used to analyze the associations, and trial sequential analysis was used to analyze the robustness of the results.

Results

We collected and analyzed the results of seven trials including a total of 2287 patients in our meta-analysis. A total of 8 SNPs were tested in IBD patients. For rs1800629 of TNF-α, the allelic model showed that polymorphism at this locus significantly increased the risk of IBD-associated CRC in IBD patients (OR 4.45, 95% CI 3.18–6.21, P < 0.001). The results also showed a significant association between rs1800629 and an IBD-associated CRC population (heterozygous model: OR 4.335, 95% CI 2.329–8.069, P < 0.001; homozygous model: OR 11.5, 95% CI 2.498–52.592, P = 0.002; dominant model: OR 4.986, 95% CI 2.754–9.026, P < 0.001; recessive model: OR 7.208, 95% CI 1.588–32.72, P = 0.01). Other studies have found that mutation of rs1143627 of IL1B (allelic model: OR 2.97; 95% CI 1.74–5.05, P < 0.001) and rs1050152 of OCTN1 (allelic model: OR 1.637, 95% CI 1.078–2.485, P = 0.021) increased the proportion of IBD-associated CRC in the population. Moreover, there were significant associations between IBD-associated CRC and ITLN rs2274910, gene desert rs1551398 and rs4871611, FCGR2A rs1801274, and S100-Z rs7712957 in the allelic model.

Conclusion

Associations between SNPs and the proportion of IBD-associated CRC in IBD patients were examined, and further investigation of additional SNPs and their association with the risk of morbidity is needed.

     

Involvement of ephrins and their receptors in oncogenesis

Ephrins are membrane-linked ligands with an autocrine and/or immediate paracrine action. Ephrins were previously involved in embryonic neurogenesis, axonal guidance and/or retraction. Here, we will present data of the literature describing their roles in angiogenesis and in tumor progression. The capacity for ephrins to act in opposite directions will be discussed.     

Altered gene expression and oncogenesis of B-cell neoplasia

B-cell malignancies reveal a number of consistent translocations involving the C-MYC, BCL and IG genes. In common, these rearrangements usually lead to an inability of the involved B-cells to respond to normal regulatory controls for expression of the genes. This usually lead to over-production of the protein products of the genes at inappropriate times of the cell growth cycle and appears to allow a survival advantage to the B-cell. The result of these changes almost certainly plays a prominent role in the development of B-cell neoplasia. Classification of these lymphoma's at a molecular level may be of benefit to determine the prognosis and treatment in addition to providing a useful marker of disease. Determining the molecular basis of these B-cell lymphomas may help our understanding of their pathogenesis. This in turn could lead to more rational treatment aimed at altering the abnormal molecular changes and returning the neoplastic cells to normal cell development.     

Evolving roles of magnifying endoscopy and endoscopic resection for neoplasia in inflammatory bowel diseases

Magnifying endoscopy is a useful technique to differentiate neoplasia from non-neoplastic lesions. Data regarding the clinical utility of magnifying endoscopy for neoplasia in patients with inflammatory bowel disease (IBD) has been emerging. While Kudo’s pit pattern types III-V are findings suggestive of neoplasia in non-IBD patients, these pit patterns are predictive of IBD-associated neoplasia as well. However, active chronic inflammatory processes, particularly regenerative changes, can mimic neoplastic pit patterns and may affect a meticulous evaluation of pit pattern diagnosis in patients with IBD. The clinical evidence regarding the utility of magnifying endoscopy with narrow band imaging or endocytoscopy has also been evolving in regard to the diagnosis of IBD-associated neoplasia. These advanced endoscopic techniques are promising for multiple reasons; not only for making an accurate diagnosis of neoplasia, but also in determining if endoscopic resection is appropriate for such lesions in patients with IBD. In this review, we discuss the diagnostic accuracy and limitations of magnifying endoscopy in assessing IBD-associated neoplasia and examine the feasibility and outcomes of endoscopic resection for these lesions.     

Role of Wnt pathway in medulloblastoma oncogenesis

To clarify the roles of Wnt pathway in medulloblastoma oncogenesis, immunohistochemical staining of beta-catenin and Wnt-1 and genomic analyses of CTNNB1 (beta-catenin) and AXIN1 (axin 1) were examined in 23 sporadic cases. Accumulation of beta-catenin in tumor cells was immunohistochemically proven in 5 cases; 2 cases showed positive immunoreactivity for Wnt-1 and another 2 showed mutation of either CTNNB1 or AXIN1. AXIN1 mutation was in exon 3, corresponding to GSK-3beta binding site and CTNNB1 mutation was in exon 3, corresponding to its phosphorylation site. Disruption of these proteins could result in upregulation of the Wnt signaling and accumulation of beta-catenin, followed by cell proliferation and medulloblastoma oncogenesis.     

Colonoscopic surveillance improves survival after colorectal cancer diagnosis in inflammatory bowel disease

Background:

Colonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse.

Method:

The aim of this study was to compare tumour stage and survival of IBD patients with CRC who were a part of a surveillance programme with those who were not. A nationwide pathology database (PALGA (pathologisch anatomisch landelijk geautomatiseerd archief)) was consulted to identify IBD patients with CRC treated in all eight university hospitals in The Netherlands over a period of 15 years. Patients were assigned to the surveillance group when they had undergone one or more surveillance colonoscopies before a diagnosis of CRC. Patients who had not undergone surveillance served as controls. Tumour stage and survival were compared between the two groups.

Results:

A total of 149 patients with IBD-associated CRC were identified. Twenty-three had had colonoscopic surveillance before CRC was discovered. The 5-year CRC-related survival rate of patients in the surveillance group was 100% compared with 74% in the non-surveillance group (P=0.042). In the surveillance group, only one patient died as a consequence of CRC compared with 29 patients in the control group (P=0.047). In addition, more early tumour stages were found in the surveillance group (P=0.004).

Conclusions:

These results provide evidence for improved survival from colonoscopic surveillance in IBD patients by detecting CRC at a more favourable tumour stage.     

结直肠锯齿状息肉患者临床与内镜特征

目的探讨结直肠锯齿状息肉(SA)的临床和内镜特征。方法选取2016年11月至2018年10月间漳州正兴医院收取完成结肠镜检查的6 440名检查者,其中包括60例结直肠锯齿状病变患者,分析比较不同年龄段和不同性别的检查者的一般资料,并探讨锯齿状息肉患者的相关因素。结果 60例息肉锯齿状病变患者中,男46例,女14例,年龄25～78岁,平均(52. 3±12. 6)岁。锯齿状息肉患者中,青年组(<45岁) 17例,同年龄段的结肠镜检查者2 544例,锯齿状息肉检出率为0. 7%(17/2 544),同年龄段检出结肠息肉共476例,锯齿状病变占结肠息肉的3. 6%(17/476);中年组(年龄≤45岁且<60岁) 26例,同年龄段的结肠镜检查者2 530例,锯齿状息肉检出率为1. 0%(26/2 530),同年龄段检出结肠息肉共775例,锯齿状病变占结肠息肉的3. 4%(26/775);老年组(年龄≥60岁) 17例,同年龄段的结肠镜检查者1 366例,锯齿状息肉检出率为1. 2%(17/1 366);同年龄段检出结肠息肉共418例,锯齿状病变占结肠息肉的4. 1%(17/418)。锯齿状息肉单发19例,多发锯齿状息肉41例。纳入所有单发性息肉,多发性锯齿状息肉每例选取较大的2枚代表性锯齿状息肉纳入分析。共纳入101枚锯齿状息肉,其中增生性息肉(HP)为71枚,无蒂锯齿状腺瘤/息肉(SSA/P)为25枚,TSA为5枚。HP与SSA/P的内镜特征比较显示,HP在结直肠远端的比例为69. 0%,明显高于SSA/P的32. 0%,差异有统计学意义(P <0. 05);息肉形态方面,HP扁平型、半球型、亚蒂和有蒂的比例分别为50. 7%、38. 0%、8. 5%和2. 8%,SSA/P扁平型、半球型、亚蒂和有蒂的比例分别为64. 0%、20. 0%、8. 0%和8. 0%,HP与SSA/P的不同形态比例分布,两者差异无统计学意义(P> 0. 05);息肉直径方面,HP≤5mm、6～10mm、11～20mm和> 20mm的比例分别为60. 6%、21. 1%、15. 5%和2. 8%,而SSA/P相应的比例分别为28. 0%、40. 0%、16. 0%和16. 0%,两者病变直径比较,差异有统计学意义(P <0. 05);病理内瘤变方面,HP低级别内瘤变发生率为28. 2%,无高级别内瘤患者,而SSA/P内瘤变发生率为64. 0%,其中低级别内瘤变11例,高级别内瘤变4例,高级别内瘤并黏膜内癌1例,SSA/P内瘤变发生率明显高于HP,差异有统计学意义(P <0. 05)。结论SSA/P患者病变较HP大,一般> 0. 5mm,SSA/P内瘤变发生率高,临床要重视SSA/P患者的内镜和病理诊断,降低SSA/P漏诊率。     

结直肠锯齿状病变病理诊断及鉴别诊断

结直肠癌是最常见及致死率最高的癌症之一,其发生机制有两个主要通路:即经典的“腺瘤-腺癌”通路和锯齿状通路。锯齿状通路因其独特的分子病理学改变,而被认为是独立于经典的“腺瘤-腺癌”通路之外的结直肠癌发生路径。Longacre和Fenoglia Preiser于1990年对大肠“混合性增生性腺瘤样息肉”(mixed hyperplastic adenomatous polyps,MHAP)进行重新评估,并首次使用“锯齿状腺瘤”(serrated adenoma,SA)来定义此类病变。锯齿状病变的组织学分类及致癌的分子机制已部分阐明。然而,在实际工作中,病理医生,特别是年轻的病理医生对锯齿状病变分类及诊断仍存困惑。本文拟就锯齿状病变的分类、临床病理学特征、诊断及鉴别诊断要点进行讨论。