课件：结直肠锯齿状息肉最新报道.pptx

结直肠锯齿状息肉最新报道 Update on serrated polyps of the colorectum,姜惠峰 山东大学齐鲁医院（青岛） 2014-03-19,1,-,简要介绍锯齿状病变专家共识推荐规范 增生性息肉(MVHP)与SSA/P的新认知 传统型锯齿状腺瘤(TSA)伴异型增生,2,-,简要介绍锯齿状病变专家共识推荐规范 2010年在Cleveland举行，由美国胃肠病学会(ACG)支持、美国国立卫生研究院(NIH)赞助 专家组成员：endoscopy, surgery, pathology, epidemiology, and/or molecular aspects of serrated lesions and/or serrated polyposis.,3,-,经与会专家组讨论15年MEDLIAN文献，形成共识报告，目的是总结锯齿状息肉病理、分子病理和内镜特征，提高这种疾病威胁的意识，描述内镜特征，强调该疾病精确探查和完全切除的重要性，提供有关该病切除后处理的推荐规范。,4,-,Key conclusions and recommendations of the consensus group Pathology 1 Serrated lesions of the colorectum should be classified histologically as hyperplastic polyp (HP), sessile serrated adenoma/polyp(SSA/P) with or without cytologic dysplasia, or traditional serrated adenoma (TSA). Exceptions and subcategories are discussed in the text. Clinicians and pathologists within institutions should work collaboratively to achieve a common usage and understanding of terminology of serrated lesions. 2 SSA/P and TSA are pre-cancerous lesions. SSA/P is the principal precursor of hypermethylated colorectal cancers (cancers with the CpG Island Methylator Phenotype CIMP). This pathway occurs primarily in the proximal colon.,5,-,3 SSA/P is distinguished from HP pathologically by findings of crypt distortion, particularly in the crypt base, in SSA/P. We recommend that a single unequivocal architecturally distorted, dilated, and/or horizontally branched crypt, particularly if it is associated with inverted maturation, is sufficient for a diagnosis of SSA/P. Most large serrated lesions in the proximal colon are SSA/Ps. 4 SSA/P with cytological dysplasia is a more advanced lesion in the progression to cancer compared to SSA/P without cytological dysplasia.,6,-,Endoscopy 5 SSA/P and hyperplastic polyps in the proximal colon have a distinct endoscopic appearance, which includes a “mucus cap”, color usually similar to normal mucosa, and indistinct edges. All colonoscopists should be able to recognize serrated lesions. 6 Detection of proximal colon serrated lesions by individual endoscopists is highly correlated with adenoma detection. Pending development of specific detection targets for proximal colon serrated lesions, endoscopists should measure their adenoma detection rates as a check on adequate detection of serrated lesions. 7 All serrated lesions proximal to the sigmoid colon should be fully resected during colonoscopy. All serrated lesions in the rectosigmoid colon 5 mm in size should be fully resected.,7,-,Surveillance 8 Serrated polyposis is defined by the World Health Organization (see text for details). Patients with serrated polyposis require close endoscopic follow-up with control of polyp burden by endoscopy or by surgical resection if the number, size or location of serrated polyps precludes endoscopic resection or if a cancer is diagnosed. 9 First degree relatives of patients with SPS should undergo colonoscopy at age 40 or 10 years before the age at diagnosis of SPS. Colonoscopy should be at 5 year intervals or more often if polyps are found. 10 There are few longitudinal observational studies after removal of serrated lesions on which recommendations for postpolypectomy surveillance can be based. Recommendations are mostly based on features of serrated lesions for which there is evidence of an association with increased risk of cancer or advanced neoplasms, including: proximal colon location, large size, increasing number, and histologic features including SSA/P histology . Am J Gastroenterol, 2012 ,107(9): 13151330.,8,-,序言(introduction),锯齿状病变(serrated lesions)的真正发病率，尤其是结肠近段，可能高于先前的报道；相当数量的内镜医师漏掉了半数以上的锯齿状病变。 流行病学 尸解研究显示25-50%的白种成人有一个及以上锯齿状病变。内镜检出率很低。锯齿状病变最常见于乙状结肠和直肠，其分布依据组织学类型变化，70-95%的锯齿状病变为HPs，左半结肠为主；SSA/Ps占5-25%，右半结肠为主，TSA少于SSA/Ps，左半结肠常见。,9,-,结直肠锯齿状病变是1/3结直肠癌的前驱病变（癌前病变）。 源于锯齿状病变的癌常发生于近端结肠。 结直肠锯齿状病变根据WHO标准病理学分三大类，即增生性息肉(HPs)、广基型锯齿状腺瘤/息肉(SSA/P)伴或不伴细胞异型增生及传统型锯齿状腺瘤(TSA)。,10,2019,-,11,2019,-,对SSA/P的认识时间相对较短，其诊断对低年资病理医生常有困难； SSA/P诊断频率文献报道也是变化甚大。MVHP与SSA/P交界性病变依然是一个诊断问题。 近年来对SSA/P的诊断阈值趋向降低，认为在MVHP背景中即使是有1个确定的结构扭曲、扩张和/或水平分支的SSA/P样隐窝，也可以诊断SSA/P(Am J Gastroenterol.2012, 107(9): 13151330)。,12,2019,-,SSA/P和TSA是恶性前病变，而SSA/P是结直肠癌主要的锯齿状前驱病变。 结直肠锯齿状病变的内镜表现独特，一般不如经典腺瘤性息肉易发现。 近端至乙状结肠病变或所有直乙状结肠病变5mm，应完全切除。 锯齿状息肉切除后随访监测，减少间隔性结直肠癌。,13,2019,-,SSA/P诊断标准有不同的意见： 增生性息肉(MVHP)与SSA/P的区分以及诊断SSA/P需要特征性隐窝的分布范围和数量标准是困难的问题 美国胃肠病协会指南建议假若1个隐窝具有SSA/P的特征，就可诊断SSA/P；而WHO(2010)的标准是至少3个或相邻2个特征性隐窝，可诊断SSA/P。 SSA/P在息肉状病变中的比例实际并不低，14.7%。 锯齿状息肉漏诊率依然很高。,14,-,锯齿状息肉(serrated polyps) 一组异质性病变，具有不同的大体、组织学和分子遗传学特征；通过serrated pathway发展为癌 上皮成分以锯齿状(燕尾状或星状)结构为特征 WHO分类：增生性息肉(hyperplastic polyps,HPs) 广基锯齿状腺瘤/息肉(sessile serrated adenoma/polyp,SSA/P)with or without cytological dysplasia 传统型锯齿状腺瘤(traditional serrated adenoma,TSA),15,2019,-,临床表现,增生性息肉(HPs) 结肠远端（左半结肠）最常见 GCHP总是左半结肠，而MVHP远端结肠和直肠最常见，但全结肠均可见 广基病变，1-5mm，罕见超过1cm；近端HPs大于远端 内镜下珠状晶莹透明，扁平状,16,2019,-,组织病理学,增生性息肉(HPs) 75% 三种类型具有分布和分子学的差异 细胞学“成熟”，隐窝拉长伴程度不等的锯齿状 隐窝笔直，增生区位于下三分之一 隐窝上皮假乳头状，即腺腔呈锯齿状 隐窝基底狭窄，衬覆未分化细胞，有NECs间隔,17,2019,-,组织病理学-增生性息肉(HPs)（续）,MVHPs：59%，上皮细胞含粘液小泡，有或无杯状细胞间隔（杯状细胞数目减少）；锯齿状明显 GCHPs：34%，杯状细胞为主；锯齿状特点模糊（仅限于表浅隐窝），上述两亚型细胞核温和，无非典型 MPHPs：少见，粘液缺失；可有明显的锯齿状；反应性核非典型 MVHP最常见，其次是GCHP，MPHP罕见,18,2019,-,增生性息肉重要的特征,胞核圆或卵圆，无复层，核质比小 核仁不明显 核分裂底部三分之一明显 隐窝对称、大小一致，拉长、狭窄，抵达粘膜肌,19,2019,-,HP的鉴别诊断,粘膜脱垂，上皮反应性改变，管状腺瘤,20,2019,-,临床表现,广基锯齿状腺瘤/息肉(SSA/P) 少有临床症状 近端结肠常见 超半数5mm，10-20% 1cm 扁平至广基，表面光滑，黄梨色，边界模糊,21,2019,-,组织病理学,SSA/P 15-25% 细胞学温和，隐窝拉长伴明显的锯齿状 特征：正常隐窝结构扭曲，导致增生带改变，增生带位于隐窝一侧-不对称增生，这现象也称隐窝异常划分(crypt compartmentalization aberration,CCA )；Ki67标记更突出增生带 隐窝基底部扩张、形状异常“L”或倒“T”型 平坦型病变锯齿状见于隐窝基底并扩张10%的隐窝,22,2019,-,组织病理学-SSA/P（续）,核圆或卵圆，和混合笔杆样核，核非典型不明显，常呈泡状核、核仁明显 核分裂见于隐窝任何部分，中部和浅表更多见 超半数的隐窝成熟障碍 有些区域隐窝笔直，类似MVHP，但不足病变的一半；,23,2019,-,SSA/P诊断标准有不同的意见： 增生性息肉(MVHP)与SSA/P的区分以及诊断SSA/P需要特征性隐窝的分布范围和数量标准是困难的问题 美国胃肠病协会指南建议假若1个隐窝具有SSA/P的特征，就可诊断SSA/P；而WHO(2010)的标准是至少3个或相邻2个特征性隐窝，可诊断SSA/P。 SSA/P在息肉状病变中的比例实际并不低，14.7%。 锯齿状息肉漏诊率依然很高。,24,2019,-,25,2019,-,26,2019,-,(Am J Surg Pathol, 2014;38:158166),27,2019,-,组织病理学-SSA/P（续）,细胞学异型在结构简单的SSA/P缺乏 但朝向癌进展时，连结MLH1基因甲基化及MSI 除了经典腺瘤(细长的核和嗜碱性胞质)外，可见核仁明显、泡状核、嗜酸性胞质的立方细胞-锯齿状异型增生(serrated dysplasia) 这些进展期病变较早的文献称“mixed SSA/P-tubular adenoma”，由于这些病变的细胞学异型区域的生物学与经典腺瘤不同，因而适于称“SSA/P with cytological dysplasia”，这些病变更具侵袭性,28,2019,-,SSA/P伴细胞异型增生 同义词：混合型SSA/P-管状腺瘤（ SSA/P with cytologic dysplasia）、混合型增生性息肉-传统腺瘤（mixed HP-TA）或混合型增生性/腺瘤性息肉（mixed hyperplastic/adenomaous polyps） 特征：非异型增生性HP或SSA锯齿状成分和异型增生性成分，如经典腺瘤、TSA或形态学上多种独特的非TSA型异型增生。两种成份显示类似的分子生物学表达特征，提示来源于先前的非异型性SP，如SSA，是进展至癌的中间步骤。,29,2019,-,A HP pSSA type 1-3(B-D),30,2019,-,鉴别诊断： HP and TSA,31,2019,-,临床表现,传统锯齿状腺瘤(TSA) 较少见，1-2%，主要位于远端结肠 内镜下类似经典腺瘤，但是较SSA/P更鲜红、更突起（肥大），偶有蒂,32,2019,-,组织病理学,传统锯齿状腺瘤(TSA) “锯齿状腺瘤”(“serrated adenoma”)：任何显示锯齿状和细胞学异型的病变 TSA：整体观呈复杂性绒毛状结构，伴细胞学异型，而有别于经典腺瘤或SSA/P伴细胞异型 特征(hallmark)：异位隐窝形成(ectopic crypt formation, ECF)，即隐窝基底远离粘膜肌,33,2019,-,传统型锯齿状腺瘤(TSA)伴异型增生 两种形态的异型增生：锯齿状异型增生和经典腺瘤性异型增生(serrated dysplasia and conventional adenomatous dysplasia) 分类：TSA with serrated dysplasia,TSA with conventional adenomatous dysplasia and tubullovillous adenoma with serrated dysplasia,后一种类型含少量serrated dysplasia,34,-,形态和分子病理学特征： TSA with serrated dysplasia-息肉小、与BRAF突变高度相关；TSA with convetional adenomatous dysplasia and tubullovillous adenoma with serrated dysplasia，息肉较大，更多KRAS突变，后二者具有-catenin表达，而前者无表达；但是，CpG岛甲基化和BRAF突变很少见于经典腺瘤。 (Modern Pathology, advance online publication, 7 March 2014),35,-,TSA重要的鉴别特征,病变息肉样或有蒂，深染笔杆样核、复层、核仁明显 核分裂达浅表区 胞质嗜酸性 异位隐窝形成(ECF) 局灶异型性(低或高级别上皮内瘤),36,2019,-,TSA的鉴别诊断,SSA/P and tubular adenoma,37,2019,-,Am J Gastroenterol, 2012 ; 107(9): 13151330.,38,2019,-,不同的锯齿状病变隐窝与粘膜肌的关系模式图,39,2019,-,HP,40,2019,-,增生性息肉,SSA/P,41,2019,-,HPsMVHP(left),42,2019,-,Hyperplastic polyp MVHP,43,2019,-,44,2019,-,GCHP,45,2019,-,MPHP,46,2019,-,borderline sessile serrated lesion,A.介于HP和SSA/P之间，仅有隐窝 扩张；B.SSA/P,47,2019,-,Mucosal prolapse polyps.,48,2019,-,SSA/P,49,2019,