肝脏病理

Welcome,肝脏疾病病理学诊断,Outline of Guidelines,Classification of liver diseases,LIVER,Liver Biopsy,Liver Biopsy,Confirm the diagnosis Serological blood tests Establish degree of fibrosis Serology Biopsy not representative Identify cirrhosis Determine optimum therapy,Liver biopsy adequacy,“Most hepatopathologists are satisfied with a biopsy specimen containing at least six to eight portal tracts”.Bravo AA et al NEJM 344, 495; 2001.We should not be primarily concerned with the size of biopsy that “satisfies” the pathologist.The correct question is:What size of biopsy will provide a reliable assessment for the patients management?,Liver biopsy adequacy,Guido M and Rugge M. Semin Liv Dis 24, 89; 2004.In most diffuse liver diseases examination of 12-15 complete portal tracts is necessary.20mm of a 1.4mm diameter (17 gauge) needle biopsy.Progressively longer samples of thinner biopsies are needed.,36-1 肝脏活检标本的评价,整体情况 -低倍镜汇管区 中、高倍镜肝小叶 中、高倍镜中央静脉 中、高倍镜,LOBULE VS ACINUS,肝小叶,肝板、肝窦,肝脏,EM,肝脏,EM (cont.),汇管区和中央静脉,36-2 常用诊断名词的定义,嗜酸性小体气球样变性Ductule叶间胆管碎宵状坏死,灶状坏死带状坏死融合性坏死大片坏死桥接坏死,Acidophil body,Ballooning Degeneration,Fatty Degeneration Alcoholic liver disease,Ductule,Interlobular bile duct,Necrosis, piecemeal,Necrosis, focal,Necrosis, Zonal,Necrosis, Confluent,Necrosis, Massive,Necrosis, Bridging,Drug and Toxin- Induced Liver Disease,36-3 肝小叶淋巴细胞浸润伴有或不伴有肝细胞变性或坏死,急性医源性急性病毒性 (HAV, HBVB,HCV, CMV, EBV etc)自身免疫性癌髓外造血白血病/淋巴瘤原发性胆管性肝硬化,36-4 肝小叶多形核细胞浸润伴有或不伴有肝细胞变性或坏死,酒精性肝炎细菌/真菌感染医源性反应败血症“手术性”肝炎病毒感染（CMV),Autoimmune Hepatitis,36-5 肝细胞坏死伴轻微炎症反应,急性病毒感染纤维化性胆汁淤积性肝炎肝静脉血液外溢缺血嗜肝病毒引起的大片坏死医源或毒素反应创伤肿瘤,36-6 汇管区淋巴细胞或和浆细胞浸润,急性病毒性肝炎自身免疫性肝炎胆管阻塞移植物抗宿主反应淋巴瘤/白血病,肝小叶炎症或变性或坏死轻微,肉芽肿或肿瘤原发性胆汁性肝硬化原发性硬化性胆管炎排斥反应病毒性肝炎Wilson病,Primary biliary cirrhosis,Antimitochondrial antibody,36-7 汇管区多形核细胞浸润 -,肝小叶炎症或变性或坏死轻微,顺行性胆管炎胆道阻塞高营养医源性病毒性肝炎,“胆管溶解性”,36-8 汇管区嗜酸性粒细胞浸润,自身免疫性肝炎髓外造血医源反应寄生虫感染原发性胆汁性肝硬化原发性硬化性胆管炎排斥反应,Liver biopsy from a 25 y-o Laotian showing a granulomatous reaction against the ovum (HE).,36-9 肉芽肿性炎症,儿童慢性肉芽肿病克隆氏病异物反应原发性肝脏肉芽肿病免疫性胆管炎细菌、真菌、立克次氏体、病毒感染脂肪性肉芽肿恶性肿瘤医源性反应原发性胆汁性肝硬化肉瘤样病,36-10 肝纤维化,淀粉样桥接性纤维化中央透明变性纤维化先天性肝纤维化先天性梅毒囊性纤维化灶性结节状增生肝脏门脉区纤维化肝脏静脉性血液外溢，慢性阻塞性代谢性疾病中央静脉周围纤维化肿瘤,肝纤维化,肝硬化 = 肝细胞再生 + 纤维化,36-11 胆汁淤积,良性家族性胆汁淤积妊娠性胆汁淤积医源性手术后性胆汁淤积败血症,细胞内淤胆,Intrahepaptic Cholestasis,Extrahepaptic Cholestasis,36-12 淤血或出血伴有肝窦扩张,肝静脉血外溢静脉阻塞性疾病心力衰竭医源反应肿瘤压迫结节性再生性增生和回管区硬化门脉阻塞,肝淤血,肝出血,36-13 色素沉积,胆色素铁脂褐素其它外源性色素福尔马林色素,胆色素 bile pigment,Hemochromatosis,Prussian blue iron stain,Lipofuscin,36-14 细胞内包含体,腺病毒抗胰靡蛋白酶缺乏支链淀粉血症大泡脂肪变微泡脂肪变“糖原性”胞核巨线粒体“毛玻璃”细胞HSVMallory hyaline,ALPHA-1-ANTITRYPSIN STORAGE,MEGAMITOCHONDRIA,GROUND GLASS CELLS,Alpha-1-antitrypsin deficiency,CMV hepatitis,Glycogen Nuclei,A 30-year-old woman in the 30th week of pregnancy with Fulminant hepatic failure,herpes simplex virus,Mallory hyaline,36-15 脂肪变显著不伴有或轻微坏死,酒精性脂肪性肝炎妊娠脂肪肝灶性脂肪变肝细胞腺瘤、癌医源、毒素反应代谢性疾病非酒精性脂肪性肝炎非特异性脂肪变Wilson病,36-16 组织中出现不常见细胞,髓外造血巨核细胞转移瘤储备细胞（肝、Kupffer或Ito),髓外造血,36-17 “几乎正常”的肝活检,肝汇管区纤维化医源性反应Missed lesion结节状再生或增生蓄积或代谢性疾病,36-18 缺少(观察不到)正常结构,胆管中央静脉肝细胞汇管区汇管静脉肝窦,36-19 肝脏代谢性疾病的光镜诊断,36-20 肝脏代谢性疾病的电镜和非特异性光镜诊断,36-21 肝脏代谢性疾病非诊断的光镜和电镜特点,高酪氨酸血症肝脏,Glycogen storage, Liver, LM,Glycogen storage, Liver, EM,肝脏疾病诊断,病因学形态（LM & EM)组化和免疫组化血清学、酶学检查临床表现,Alcoholic Fatty Liver,Alcoholic Fatty Liver,Cirrhosis,FibrosisRegenerating Nodule,Micronodular cirrhosis,Micronodular cirrhosis:,Hepatic Adenoma,Hepatocellular Carcinoma,Hepatic metastasis:,Hepatic metastasis:,Amoebic Liver Abscess:,Hepar Lobatum (cong. Syphilis):,HCC- The Global Perspective The Big Five Cancers,The Major Etiological Factors,Chronic hepatitis - types B or CCirrhosis/chronic liver disease of any type Aflatoxin exposureMales, increasing age,8% - High,2-7% - Intermediate,2% - Low,Data from CDC,Chronic HBV Infection - Geographic Distribution,Prospective Study of HCC Development in HBsAg Seropositive Male Chinese,HCC DEVELOPMENT 19,223 (HBsAg -ve) 9 22,707 Mean follow-up = 8.9 years Male Chinese 3,454 (HBsAg +ve) 152 Relative risk = 98.4 (50.2-193),Beasley, 1982,Beasley 1986,“The lifetime risk of developing Hepatocellular carcinomaIn a Chinese male carrier Of the hepatitis B virusIs between 40 and 50%”,Chronic Viral Hepatitis & HCC,Okuda , 1999,Anti-HCV Prevalence,5% - High,1.1-5% - Intermediate,0.2-1% - Low,0.2-1% - Low,Chronic HCV Infection - Geographic Distribution,Thank Your Attend