以阑尾炎起病的阑尾上皮性肿瘤15例临床病理分析

目的:探讨以阑尾炎起病的阑尾上皮性肿瘤的临床病理学特征.方法:对15例以阑尾炎起病的阑尾上皮性肿瘤的临床病理资料进行回顾性分析.结果:15例以阑尾炎起病的阑尾上皮性肿瘤中,6例为低级别阑尾黏液性肿瘤(low-grade appendiceal mucinous neoplasm,LAMN),其余9例为前驱病变,包括8例锯齿状病变及1例绒毛状-管状腺瘤,其中锯齿状病变为6例无蒂锯齿状腺瘤/息肉(sessile serrated adenoma/polyp,SSA/P)及2例传统型锯齿状腺瘤(traditional serrated adenoma,TSA).14例以"急性阑尾炎"起病,1例以"慢性阑尾炎"起病.SSA/P镜下见锯齿状结构、隐窝扩张呈L或倒T形;TSA见显著的锯齿状轮廓和异位隐窝,具有细胞异型性;锯齿状病变的黏膜肌层完整.LAMN内衬轻度异性的黏液性上皮,管壁纤维化或破裂,管壁内及浆膜见无细胞性黏液池.9例获得随访包括5例前驱病变及4例LAMN,随访时间1.0~81.5个月,患者均无病生存.结论:阑尾锯齿状病变及LAMN均可因急性阑尾炎起病,锯齿状病变大多数为镜下偶然发现.外科医生应提高对这些病变的认识,以避免医源性穿孔导致的腹膜假黏液瘤.病理医生应将该类阑尾病变标本全部取材以便于鉴别诊断,报告阑尾切缘情况.     

结直肠锯齿状病变8例临床病理分析

目的：分析结直肠锯齿状病变的病理分类及鉴定诊断要点。方法运用形态学方法回顾性分析72例结直肠腺瘤性息肉及83例结直肠增生性息肉的临床资料,综合文献标准对其进行分类。结果72例结直肠腺瘤性息肉及83例结直肠增生性息肉中8例结直肠病变腺体有锯齿状结构,其中4例为锯齿状形态的增生性息肉( hyperplastic polyps, HP),2例为传统锯齿状腺瘤( traditional serrated adenoma, TSA),1例为广基锯齿状腺瘤( sessile serrated adenoma, SSA),1例为混合性息肉(mixed polyposis, MP)。每一种病变在形态上均有与同其他各型组织学相异的特征。结论利用形态学方法能够对各类结直肠锯齿状病变进行诊断和鉴别,提升对结直肠锯齿状病变的认识,提升临床诊断的正确率。     

结直肠锯齿状病变104例形态学及细胞增殖活性的观察

目的 探讨结直肠锯齿状病变增生性息肉(HP)、广基锯齿状腺瘤(SSA)、传统锯齿状腺瘤(TSA)的临床特征,组织病理学诊断,鉴别诊断及细胞增殖状况.方法 复习北京军区总医院2002年11月至2007年12月2628例病理诊断为结直肠息肉/腺瘤的病理切片,从中收集104例结直肠锯齿状病变,综合文献标准进行分类,观察各类型病变临床病理学特征,以及细胞增殖指数Ki-67的表达特点.结果 104例锯齿状病变中包括HP 60例,TSA 20例,SSA 11例,混合性锯齿状息肉/腺瘤7例,混合件锯齿状息肉/腺瘤+普通腺瘤6例.对各型组织学特征进行总结归纳.免疫组织化学显示正常结肠黏膜Ki-67阳性细胞位于基底(隐窝下1/3),呈间隔分布;51例HP中阴性或阳性细胞数最<25%的40例(78%),大多数阳性位于隐窝下1/3(基底);15例TSA中11例阳性细胞数量在25%～50%或>50%,其中大多数位于隐窝中1/3,少数(2例)隐窝弥漫分布;SSA的数量与分布和TSA相似;相比之下低级别管状腺瘤26例中24例(92%)阳性数量>50%,18例(69%)分布于隐窝表面,6例(23%)弥漫分布;高分化管状腺癌10例全部呈弥漫分布,7例Ki-67阳性指数在70%左右.阳性细胞多少与分布部位差异有统计学意义,阳性细胞)χ2=34.601,P=0.000,阳性分布χ2=63.077,P=0.000.结论 HP、SSA、TSA组织学鉴别诊断的主要难点是在HP与SSA两者之间,SSA锯齿状隐窝基底扩张结构特征是诊断的关键,比细胞学改变更重要.TSA与SSA的主要形态鉴别在于TSA锯齿状腺体有明显异型增生(普通腺瘤样增生)以及几乎所有TSA异型增生的腺体都不与黏膜肌相邻(ECF现象).细胞增殖指数Ki-67数量及分布的表达可为HP、SSA及TSA鉴别诊断提供一定帮助.锯齿状腺瘤中TSA和SSA的Ki-67表达指数都比普通腺瘤要低.     

结直肠锯齿状病变发病情况及其恶性潜能的病理学观察

目的 分析结直肠锯齿状病变发生情况,并对锯齿状腺瘤与普通腺瘤的恶性潜能进行病理学比较观察.方法 收集北京军区总医院、海军总医院、解放军第二五二医院、河北省巨鹿县医院、北京中医药大学东直门医院约5年中病理诊断为结直肠各类息肉和腺瘤的病例5347例,进行回顾性分析,经3名病理医师4～5轮阅片从中筛选出腺体具有锯齿状特征的息肉及腺瘤共258例,按文献标准分类,观察传统锯齿状腺瘤(TSA)及普通腺瘤异型增生程度.随机收集普通腺瘤(管状腺瘤160例及绒毛管状腺瘤27例)187例,浸润性腺癌36例作为对照.对部分TSA、广基锯齿状腺瘤(SSA)、管状腺瘤、浸润性腺癌进行免疫组织化学(Max Vision法)Ki-67、p53、β-catenin染色.结果 五所医院的5347例结直肠息肉/腺瘤中共筛选出锯齿状病变258例,占4.8%.其中增生性息肉(HP)112例,占锯齿状病变43.4%(112/258);TSA 78例,占锯齿状病变30.2%(78/258);SSA26例,占锯齿状病变10.1%(26/258);锯齿状病变合并高级别黏膜内肿瘤及浸润性腺癌11例,占锯齿状病变4.3%(11/258).重点观察62例TSA的异型增生等级.62例TSA呈中度异型增生13例,高级别黏膜内肿瘤4例,浸润性腺癌癌旁有TSA成分2例.中度以上异型增生占30.6%(19/62),高级别黏膜内肿瘤和浸润性腺癌占9.6%(9/62).收集的普通腺瘤187例,其中中度异型增生27例,高级别黏膜内肿瘤12例,13例在不同部位伴有浸润性腺癌,中度以上异型增生占27.8%(52/187),高级别黏膜内肿瘤和浸润性癌占13.3%(25/187).TSA与普通腺瘤比较X2=19.373,P=0.000.北京军区总医院19个月期间结直肠同时、不同部位具有锯齿状腺瘤及普通腺瘤13例(管状或绒毛管状腺瘤),其中锯齿状腺瘤13例中12例旱轻度异型增生,1例呈轻-中度异型增生;13例管状腺瘤中7例呈轻度异型增生,2例呈轻-中度异型增生,4例呈中度异型增生(两者相比X2=5.432,P=0.052).对两组病例进行了Ki-67、p53、β-catenin检测,在锯齿状腺瘤(TSA、SSA)和普通腺瘤(管状)中的表达差异无统计学意义(P>0.05),但锯齿状腺瘤与腺癌表达差异有统计学意义(P=0.000).结论 结直肠锯齿状病变发病率似较低.锯齿状腺瘤有明显恶性潜能.与普通腺瘤相比,锯齿状腺瘤合并高级别黏膜内肿瘤及浸润性癌的病例有所减少.     

结直肠癌前病变与结直肠腺癌免疫表型及基因突变分析

目的 分析结直肠癌前病变与结直肠腺癌免疫表型及基因突变特征,比较两种结直肠癌前病变癌变机制的差异.方法 收集2006年1月至2012年6月间诊断的53例结直肠锯齿状病变,包括30例增生性息肉、20例广基锯齿状腺瘤(SSA)及3例混合性息肉;同时选取45例传统腺瘤、50例结直肠腺癌.采用免疫组织化学EnVision法检测30例增生性息肉、20例SSA、3例混合性息肉以及45例传统腺瘤DNA错配修复(MMR)蛋白MLH1、MSH2、MSH6及甲基转移酶MGMT蛋白的表达情况;采用Sanger直接测序法检测10例SSA、10例传统腺瘤、l例混合性息肉及50例结直肠腺癌中KRAS、BRAF及PIK3CA基因的突变情况.结果 (1)MLH1蛋白在增生性息肉中仅3例阴性(10％),在SSA、传统腺瘤中均呈阳性.MSH2、MSH6及MGMT蛋白在增生性息肉及SSA中的阴性率明显高于传统腺瘤,差异均具有统计学意义(P＜O.01).(2)结直肠SSA和传统腺瘤中KRAS基因突变比例为5/10,5/10;1例混合性息肉存在KRAS基因突变.(3)结直肠腺癌中,KRAS、BRAF及PIK3CA基因突变率分别为48％ (24/50)、6％ (3/50)及4％(2/50).结论 结直肠锯齿状病变与传统腺瘤在免疫表型及基因突变等方面存在着一定的差异,MMR与MGMT在“锯齿状肿瘤”癌变通路中起着重要的作用.KRAS基因突变是结直肠腺癌癌变过程中发生较早的重要遗传学改变.     

锯齿状腺瘤中端粒酶、p53表达与锯齿状腺癌的关系

目的对锯齿状腺瘤(traditional serrated adenoma,TSA)、传统腺瘤(traditional adenoma,TA)及锯齿状腺癌(serrated ade-nocarcinoma,SAC)中端粒酶、p53及Ki-67的免疫表型进行分析和比较。方法运用免疫组化MaxVision快捷法对52例TSA、50例TA及51例SAC组织标本中端粒酶、p53、Ki-67的表达进行检测。结果端粒酶在TSA、TA与SAC组表达差异均有显著性,SAC组阳性率高于TSA(P<0.01),TSA组高于TA组(P<0.01);Ki-67在TSA与TA组表达差异无显著性(P>0.05),SAC组阳性率则明显高于TSA和TA组(P<0.01);p53在SAC组阳性率高于TA组(P<0.01),TA组高于TSA组(P<0.01)。结论 TSA是一种具有增殖活性的腺瘤,端粒酶的激活可能在其癌变过程中起一定作用。     

结直肠锯齿状病变及癌变组织中PI3Kp110α、PI3Kp110β的表达及意义

目的探讨PI3Kp110α、PI3Kp110β在结直肠锯齿状病变及其癌变组织中的表达及意义。方法采用免疫组化和Western blot法检测PI3Kp110α、PI3Kp110β在结直肠正常黏膜、管状腺瘤、锯齿状病变及来自管状腺瘤和锯齿状腺瘤癌变组织中的表达,并分析二者表达与临床病理特征的关系。结果 PI3Kp110α、PI3Kp110β在腺癌组、不同级别锯齿状腺瘤组及高级别管状腺瘤组中均呈高表达,且明显高于增生性息肉、低级别管状腺瘤及正常黏膜组织(P0.05),但组间相比差异无显著性(P0.05)。锯齿状腺瘤中PI3Kp110α、PI3Kp110β的表达与肿瘤大小有关、肿瘤数目有关(P0.05)。腺癌组中PI3Kp110α、PI3Kp110β表达与肿瘤分化程度及淋巴结转移有关(P0.05)。结论 PI3Kp110α与PI3Kp110β在锯齿状腺瘤及腺瘤癌变中呈高表达,二者可能是促进腺瘤恶变的危险因素,联合检测PI3Kp110α和PI3Kp110β在结直肠锯齿状腺瘤中的表达有助于判断其恶性潜能。     

结直肠癌中的BRAF基因突变

约15%结直肠癌患者有BRAF基因突变。BRAF通过激活MAPK通路和抑制促凋亡因子BIM,导致细胞异常增殖和分化。结直肠癌的"锯齿状"成瘤途径,即"畸形隐窝灶-增生性息肉-锯齿状腺瘤-癌"途径。BRAF基因突变参与这条途径并与CpG岛甲基化和微卫星不稳定性均有密切关系。KRAS基因状态为预测抑制表皮生长因子受体的单克隆抗体临床疗效的分子标记物,有研究发现一部分KRAS未发现突变而存在BRAFV600E基因突变的患者对爱必妥等药物也无效,故野生型BRAF基因对爱必妥等药物的有效性也是必需的。近年来也出现针对突变型KRAS和BRAF的分子靶向抑制剂,除了表皮生长因子受体抑制剂,分子靶向药物使有BRAF/KRAS突变的患者有了更多的选择。     

超声诊断急性阑尾炎115例的临床价值

目的探讨超声在急性阑尾炎临床诊断上的价值。方法选取2008年2月～2009年12月在本院门诊及住院治疗的经手术及病理证实的急性阑尾炎患者115例,并对该组患者手术前超声诊断,术后病理检查,比较超声及术后病理检查的结果,分析其声像图特征。结果 115例患者中,手术病理诊断急性单纯性阑尾炎36例,超声诊断33例,诊断符合率为91.67%,漏诊2例;手术病理诊断急性化脓性阑尾炎55例,超声诊断52例,诊断符合率为94.55%,漏诊3例;手术病理诊断急性坏疽性阑尾炎16例,超声诊断16例,诊断符合率为100%;手术病理诊断穿孔型阑尾炎6例,超声诊断5例,诊断符合率为83.33%,漏诊1例;手术病理诊断阑尾周围脓性2例,超声诊断2例,诊断符合率为100%。结论超声检查对急性阑尾炎具有明确诊断及鉴别诊断的价值,其声像图变与病理改变基本一致,适用于所有具有阑尾炎临床表现的患者,有利于临床医师治疗方案的选择。     

超声诊断急性阑尾炎115例的临床价值

目的 探讨超声在急性阑尾炎临床诊断上的价值.方法 选取2008年2月～2009年12月在本院门诊及住院治疗的经手术及病理证实的急性阑尾炎患者115例,并对该组患者手术前超声诊断,术后病理检查,比较超声及术后病理检查的结果,分析其声像图特征.结果 115例患者中,手术病理诊断急性单纯性阑尾炎36例,超声诊断33例,诊断符合率为91.67%,漏诊2例;手术病理诊断急性化脓性阑尾炎55例,超声诊断52例,诊断符合率为94.55%,漏诊3例;手术病理诊断急性坏疽性阑尾炎16例,超声诊断16例,诊断符合率为100%;手术病理诊断穿孔型阑尾炎6例,超声诊断5例,诊断符合率为83.33%,漏诊1例;手术病理诊断阑尾周围脓性2例,超声诊断2例,诊断符合率为100%.结论 超声检查对急性阑尾炎具有明确诊断及鏊别诊断的价值,其声像图变与病理改变基本一致,适用于所有具有阑尾炎临床表现的患者,有利于临床医师治疗方案的选择.     

Serrated colorectal polyps and polyposis

Serrated polyps represent a heterogeneous group of lesions, some of which have well-documented malignant potential. The histological classification of serrated polyps has evolved over the last two decades to recognize three major subtypes: hyperplastic polyp, sessile serrated adenoma/polyp and traditional serrated adenoma. Sessile serrated adenoma/polyp remains under-diagnosed while it represents up to 25% of all serrated polyps and is the precursor lesion to colorectal carcinoma evolving though the serrated neoplasia pathway with BRAF mutation and CpG island methylator phenotype. Pathologists need to be aware of the World Health Organisation criteria to correctly diagnose each entity as patient management guidelines are based upon the use of this classification. Serrated polyposis is an under-recognized syndrome with unknown genetic cause conferring an increased risk of colorectal carcinoma. Pathologists have a pivotal role in identifying these patients who should undergo yearly surveillance colonoscopy.     

Demographic and pathological characteristics of serrated polyps of colorectum

AIMS: To characterize a series of colorectal polyps, focusing on the clinicopathological features of serrated adenoma (SA), mixed polyp (MP) and the recently recognized sessile serrated adenoma (SSA). METHODS AND RESULTS: Eight hundred and ninety-one conventional adenomas (AD), 298 hyperplastic polyps (HP), 27 SSA, 10 MP and 24 traditional SA were obtained from patients during colonoscopic examination. SSA were more likely to be proximally located than other polyps. All SA, MP and SSA and a randomly selected subset of HP (n = 61) and ADs (n = 93) were assessed for expression of mucin, MLH1, MGMT, and Ki67. SSA expressed more MUC5AC than either HP or SA. Loss of MLH1 was not observed in any serrated polyps and in only one AD. Loss of MGMT occurred in 13% of AD, and showed no correlation with histological type, size or location. Loss of MGMT occurred in 24% of SSA, MP and SA (combined), and was more frequent in proximal lesions and larger lesions. SSA had a higher proliferative index than HP. In MP, the proliferative index of the non-dysplastic component was closer to HP than SSA, while the dysplastic component was intermediate between SA and AD. CONCLUSIONS: SSA differ from other serrated polyps of colorectum in terms of location, morphology and immunophenotype.     

Colorectal serrated pathway cancers and precursors

The serrated pathway (SP) can be viewed as two parallel, but partially overlapping, arrays of colorectal precursor lesions, and their respective endpoint carcinomas, that are distinct from those of the conventional adenoma–carcinoma sequence (APC‐pathway). In this review we focus at the outset on the clinical impact, pathological features, molecular genetics and biological behaviours of the various SP cancers. Then we summarize the clinicopathological features, classification and molecular profiles of the two main precursor lesions that anchor the respective pathways: (i) sessile serrated adenoma/polyp (SSA/P), also called sessile serrated lesion (SSL), and (ii) traditional serrated adenoma (TSA). Activating mutations of the RAS–RAF–MAPK pathway initiate and sustain the lesions of the SP, and CpG island methylation of the promoter regions of tumour suppressor and DNA repair genes play the major role in their neoplastic progression. The SP includes microsatellite stable (MSS) carcinomas that are among the most biologically aggressive colorectal carcinomas (CRC), and also accounts for the great preponderance of sporadic hypermutated, mismatch repair (MMR)‐deficient or microsatellite instable (MSI) CRC. The identification, removal and appropriate classification of at‐risk SP precursors and surveillance of individuals who harbour these lesions present a challenge and opportunity for CRC prevention and mortality reduction.     

Filiform serrated adenomatous polyposis arising in a diverted rectum of an inflammatory bowel disease patient

A 54-year-old man, previously colectomized for inflammatory bowel disease, developed carcinoma in the inflamed rectum stump. The malignant growth was surrounded by a filiform polyposis, grossly considered as pseudopolyps. The histology disclosed, however, a morphology corresponding to the recently described filiform subset of serrated adenoma (FSA). The clustering of the FSA amounted to a filiform serrated adenomatous polyposis, a hitherto unreported observation. It is speculated that neoplastic transformation of pre-existing pseudopolyps and prolaps-related events lead to this peculiar morphology. Minor zones with a villous structure were admixed as were small areas of traditional serrated adenoma and patches of flat dysplasia. Although a combined gastric and intestinal (positivity for MUC5AC, MUC2, MUC6, CDX2) immunoprofile characterized the adenomatous component, a downregulation of the gastric mucin along with a loss of the serrated attribute accompanied the malignant transformation. An added dynamic shift during the adenoma carcinoma sequence included the acquisition of CK7 expression in the malignant portion. Gastric mucin may play a role in the initial step of the neoplastic evolution and CK7 may denote neoplastic progression. This case confirms the notion of a widely variegated morphology of precursor lesions of colorectal carcinoma arising in a chronically inflamed bowel as opposed to the generally more monotonous appearance of adenomas in a sporadic context.