Histogenesis of epithelial neoplasms of human gallbladder I. Dysplasia

In order to find a relationship between normal gallbladder epithelium and dysplastic epithelium, histological and histochemical examinations were made on gallbladder specimens obtained from cholecystetomies and special attention was paid to the relationship of the different metaplasias. Epithelial pseudostratification increases in mitotic figures and hyperchromatism accord well with the degrees of dysplasia of surface epithelium. The relationship of the ratio of cell and nuclear size and complexity of glandular branching is more meaningful in degrees of dysplasia of glandular epithelium. Epithelial dysplasia in the surface and glandular epithelium was divided into three types: mild, moderate and severe. This classification was made on the basis of specimens containing dysplasia selected from an extensive gallbladder material. The frequency of dysplasias of different degrees was clarified in 71 cholecystectomia gallbladders. No dysplastic changes were demonstrated in 47 gallbladders (66.2%), and in 10 of these metaplasia was present, 24 gallbladders (33.8%) exhibited dysplastic changes; metaplasia was present in 20 cases (83.3%) and in 14 (58.3%) in the dysplastic region. Severe dysplasia was present only in one case, moderate in 6 and mild dysplasia alone in 17 cases. Dysplasia was found in glands only in 3 cases. In dysplastic epithelium, the mucin reaction was similar to that in the metaplastic epithelium. It contained mainly nonsulphated acid mucin and neutral mucin. With gradually increasing degree of dysplasia the amount of mucin. With gradually increasing degree of dysplasia the amount of mucin clearly decreased. The present results indicate that dysplasia often develops in metaplastic epithelium.     

Flat elevated lesions of the colon and rectum: a spectrum of neoplastic and nonneoplastic entities

The aim of this prospective study is to establish the frequency and the type (neoplastic and nonneoplastic) lesions defined endoscopically as flat elevated lesion (FEL) in the colon and rectum, as well as to compare flat adenomas (FAs) to polypoid lesions of the same size with morphometric and immunohistochemical analysis. One hundred nineteen patients were studied through fibrocolonoscopy with chromoscopy (indigo carmine spray). All detected lesions (total of 195) were removed, and FELs measuring 10 mm or smaller were also selected. Using histopathologic criteria, they were divided in neoplastic (adenomas and carcinomas) and nonneoplastic ones. In neoplastic lesions, the following parameters were evaluated to compare FAs with polypoid lesions: morphometric studies with Index of Structural Atypia (ISA) and Stratification Index (SI), evaluation of cellular proliferation with label index of Ki-67, and expression of p53 protein. Of 195 lesions resected, only 33 (17%) met the endoscopic requirements for FELs. Twelve (36.4%) were neoplastic and 21 (63.6%) considered nonneoplastic. Among the FAs, there were a percentage of high-grade (severe dysplasia) significantly more frequent than observed in polypoid lesions (16.7% vs 2.6%). In addition, the SI, Ki-67 label index and p53 positivity were significantly higher in FAs. The ISA also reached significant differences between both groups of adenomas. Non-neoplastic FELs included different entities such as hyperplasic polyps, focuses of colitis, normal mucosa, and scars. The endoscopic elements analyzed were shared between nonneoplastic FELs and FAs. A central depression, when air was properly insufflated, considered typical in neoplastic lesions, was frequently observed in nonneoplastic lesions. Following the endoscopic criteria of FELs, nonneoplastic lesions predominated over the adenomatous lesions, demonstrating that FELs and FAs are not homologous terms. The frequency of high-grade dysplasia was significantly more elevated in the adenomatous FELs than in polypoid adenomas. The ISA, SI, p53 expression, and Ki-67 label index were helpful in differentiating adenomatous FELs from polypoid lesions. Flat elevated lesions selected by endoscopic criteria are, in fact, a heterogeneous population of lesions.     

Absence of epithelial atypia in B3-lesions of the breast is associated with decreased risk for malignancy

IntroductionLesions of uncertain malignant potential (B3) represent a heterogeneous group with an overall risk for malignancy of 9.85–35.1% after total resection. Positive predictive values (PPV) for malignancy vary depending on B3 subtype.The aim of this study was to evaluate the PPV for malignancy in B3 lesions and to determine the clinical significance of atypia-dependent sub-classification (a = without epithelial atypia; b = with epithelial atypia) of B3 into B3a and B3b and papillary lesions (PL) in PLa and PLb.Methods219 patients with histopathologically proven B3 lesions on core needle/vacuum-assisted biopsy who subsequently underwent diagnostic excision biopsy were included in this study. PPVs for malignancy were reported for B3 in general and all B3 sub-categories. Logistic regression analysis identified associations between B3-subgroups and outcome after excision biopsy as well as the impact of clinical and diagnostic findings on excision diagnosis.ResultsThe overall PPV rate was 10.0% (22/219). Excision histology exhibited a higher malignancy rate in PLb (2/7; PPV: 28.6%) than in PLa (6/127; PPV: 4.7%) (p = 0.057) and in B3b (12/50; PPV: 24.0%) compared to B3a category (8/165; PPV: 4.8%) (p < 0.001).DiscussionThese findings support the necessity of B3 lesion sub-classification into B3a and B3b and of PL into PLa and PLb when considering epithelial atypia. The determination of atypia status represents a relevant factor in risk-stratification for clinical management of B3 lesions. Should future studies using the sub-classification of PL confirm these results, observation may be a safe option for the clinical management of patients with asymptomatic PLa lesions.     

Three-year Trends in Diagnosis of B3 Breast Lesions and Their Upgrade Rates to Malignant Lesions

BackgroundB3 breast lesions are a heterogeneous group with uncertain malignant potential and, as such, provide a source of diagnostic difficulty. We calculated the prevalence of B3 lesions at our center along with the upgrade rates (positive predictive value) to in situ or invasive malignancy.Materials and MethodsWe searched our pathology database over a 3-year period to include all B3 biopsies. The subsequent excision for each biopsy was reviewed, and the rate of upgrade was calculated by subtype. These results were compared against data published in large United Kingdom studies.ResultsA total of 9206 breast biopsies were identified, of which 614 (6.7%) were classified as B3. Lesions displaying epithelial atypia were the most common subtype of lesion, with a prevalence of 39.6%. Lesions displaying epithelial atypia were upgraded to malignancy in 35.7% of cases. Among non-atypical cases, papillary lesions were the most common diagnosis (32.1%) with an upgrade rate of 2%. In situ lobular neoplasia (10.4%) was the third most frequently encountered diagnosis, and was upgraded to malignancy in 10.9% of cases. The upgrade rate in the remaining non-atypical lesions was invariably low (0%-2.6%).ConclusionsHerein, we have shown an overall B3 rate in keeping with published data, whereas lesions displaying epithelial atypia showed upgrade rates to malignancy comparable with that of large United Kingdom studies. In our study, lesions without epithelial atypia showed very low rates of upgrade. A wide range of upgrade rates is seen in cases of lobular neoplasia, which highlights the need for uniformity of nomenclature and reporting within this subtype to accurately ascertain the true risk of upgrade associated with these lesions.     

不典型胎盘早剥37例分析

目的：通过对不典型胎盘早剥的临床分析，以期提高早期诊断率。方法：对我院的临床资料进行分析。结果：胎盘早剥的发生为0．29％。产前确诊率33．93％，漏诊率66，07％，应用催产素（9．73％）、胎膜早破（32．43％）是不典型胎盘早剥的主要发病诱因，而胎心改变（67．56％）、早产（0．54％）是其主要的临床表现。结论：诱因不明确、症状不典型、后壁胎盘、Ⅰ度胎盘早剥及B超检查呈阴性是漏诊的主要原因。注重病史和诱因并予以综合分析、动态观察、反复检查，才能提高早期诊断率。     

Effects of endoscopic sphincterotomy on biliary epithelium: a case-control study

AIM: To study the long-term effects of endoscopic sphincterotomy on biliary epithelium.METHODS: This is a prospective case-control study. A total of 25 patients with a median age of 71 years (range 49-89 years) and prior endoscopic sphincterotomy (ES) for benign disease formed the first group. The median time from ES was 42 mo (range 8-144 mo). Another 25 patients with a median age of 76 years (range 44-94 mo) and similar characteristics who underwent current endoscopic retrograde cholangiopancreatography (ERCP) and ES for benign disease formed the second group (control group). Brush cytology of the biliary tree with p53 immunocytology was performed in all patients of both groups. ERCPs and recruitment were conducted at the Endoscopic Unit of Aretaieion University Hospital and Tzaneio Hospital, Athens, from October 2006 to June 2010.RESULTS: No cases were positive or suspicious for malignancy. Epithelial atypia was higher in the first group (32% vs 8% in the second group, P = 0.034). Acute cholangitis and previous biliary operation rates were also higher in the first group (acute cholangitis, 60% vs 24% in the second group, P = 0.01; previous biliary operation, 76% vs 24% in the second group, P = 0.001). Subgroup analysis showed that previous ES was the main causal factor for atypia, which was not related to the time interval from the ES (P = 0.407). Two patients (8%) with atypia in the first group were p53-positive.CONCLUSION: ES causes biliary epithelial atypia that represents mostly reactive/proliferative rather than premalignant changes. The role of p53 immunoreactivity in biliary atypia needs to be further studied.     

二乙基亚硝胺诱发肝癌前病变大鼠模型的建立

目的:研究二乙基亚硝胺诱发大鼠肝癌前病变的时效关系与量效关系.方法:Wistar♂大鼠100只,体质量均衡随机分5组;每84h1次分别腹腔注射二乙基亚硝胺0、25、50、75、100mg/kg造模.每组体质量排序分10小组,年龄配对;造模时程最短0d,间隔14d延长,最长126d,灌注固定肝脏.常规石蜡包埋,6μm切片,HE染色,观察病变性质后显微照相;使用Image-Pro Plus软件,分别形态计量10、20、40倍物镜下汇管区(R1)、肝索(R2)、肝细胞核(R3)的体积构成比,观察每10个高倍镜视野下的核分裂像;计算各动物异型性指数[Ei=(1-R1)-1·(R3)·(R2)-1].Prism 4软件回归"二乙基亚硝胺导致异型性指数"的时效曲线及曲线下面积,进而导致曲线下面积的量效关系.结果:以异型性指数(肝细胞核/浆体积比校正值),回归0、25、50、75、100mg/kg二乙基亚硝胺造模的半效时程(95%CI)分别为70347(0-)、1734(937-3211)、1536(948-2490)、1530(890-2632)、1183(955-1466)h,曲线下面积分别为0.0064、0.0084、0.0123、0.0165、0.0167[异型性指数·log(h)].以曲线下面积,回归二乙基亚硝胺诱发肝细胞癌前病变的半效剂量为48.255mg/kg.50.000mg/kg造模各时程的异型性指数与核分裂像总数之间呈直线正相关(y=0.0023x-0.0056,r=0.9217,n=10,P<0.01).结论:以异型性指数为指标,每84h腹腔注射1次二乙基亚硝胺,诱发♂大鼠肝细胞癌前病变的最佳造模剂量为48.255mg/kg(约50.000mg/kg),最佳造模累积连续时程为64d.核分裂像计数验证了异型性指数的临床预警价值.