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  1. 1. 蘇建維1,2,3 侯明志2,4 吳肇卿3,5 1台北榮民總醫院內科部胃腸科 2陽明大學醫學院醫學系 3陽明大學醫學院臨床醫學研究所 4台北榮民總醫院內視鏡診斷暨治療中心 5台北榮民總醫院教學研究部
  2. 2. 肝臟結節之分類 來源 良性 惡性 肝細胞 (hepatocellular) 腺瘤 (adenoma) 肝細胞癌 (hepatocellular carcinoma) 再生結節 (regeneration nodules) 纖維板層肝細胞癌 (fibrolamellar carcinoma) 結節性再生性增生 (nodular regenerative hyperplasia) 肝母細胞瘤 (hepatoblastoma) 局部結節性增生 (focal nodular hyperplasia) 膽管細胞 (cholangiocellular) 膽管腺瘤 (bile duct adenoma) 膽管癌 (cholangiocarcinoma) 膽管囊腺瘤 (biliary cystadenoma) 囊腺癌 (cystadenocarcinoma) 單純囊腫 (simple hepatic cyst) 多囊性肝疾病 (polycystic liver disease) 間質細胞(mesenchymal) 血管瘤 (hemangioma) 血管肉瘤 (angiosarcoma) 血管脂肪瘤 (angiolipoma) 淋巴瘤 (lymphoma) 異位性(heterotopic) 腎上腺/胰/脾(adrenal/pancreatic/splenic) 轉移癌 (metastases) 感染性(infectious) 膿瘍(abscess) 結核 (tuberculosis) 血吸蟲 (schistosomiasis)
  3. 3. Hemangioma: epidemiology • Hemangiomas are the most common benign mesenchymal tumors of the liver, with a prevalence range of 3-20% • They are thought to arise from congenital hamartomas that increase in size because of progressive ectasia or from dilatation of existing blood vessels in normally developed tissue • Size: range from a few mm to > 20cm • Age: all age groups, but are most commonly discovered between third and fifth decades of life
  4. 4. Hemangioma: gender • Gender: Female/male: 3:1; tend to be larger and more numerous in women • Hormonal influence is controversial – It may grow in size during pregnancy and in women taking oral contraceptives (OCP) – Estrogen receptors have been identified on some hemangioma – Estrogen treatment in vitro can cause proliferation of hemangioma vascular endothelial cells – Case-controlled study found no causal link between OCP use and hemangioma development – Hemangioma growth does occur in the absence of OCP use and in postmenopausal women or men
  5. 5. Hemangioma: clinical manifestations • Often are small and asymptomatic; detected as an incident mass on imaging • Some may present with RUQ abdominal pain, fullness, nausea, vomiting, easy satiety • Pain may secondary to infarction, hemorrhage, torsion or distension of the Glissen’s capsule • Hepatic biochemical tests are usually normal except in complications such as thrombosis, bleeding or biliary obstruction • Hemobilia may occur when bleeding into the biliary tree • Kasabach-Merritt syndrome: consumptive coagulopathy causing DIC
  6. 6. 奧地利 哈斯達特
  7. 7. Hepatic adenoma Paradis V. Clin Liver Dis 2010; 14:719-29
  8. 8. Adenoma: epidemiology (I) • Hepatic adenoma are benign epithelial liver tumors, seen most commonly in women of childbearing age • It tends to develop in individuals with a hormonal or metabolic abnormality that can stimulate hepatocyte porliferation • The number of reported cases of hepatic adenomas has increased dramatically since 1960s, coinciding with the introduction of oral contraceptives (OCP) • Annual incidence: 1 per million (no OC women)/30-40 per million (long-term users) • Usually larger in size, more numerous and more likely to bleed in patients taking OCP • It may regress with cession of OCP and increase in size during pregnancy.
  9. 9. Adenoma: epidemiology (II) • Adenomas are also seen in association with glycogen storage diseases • Incidence: 50% in type Ia; 25% in type III • Usually occur more commonly in males before the third decade of life
  10. 10. Adenoma: clinical manifestations • Often asymptomatic and noted incidentally on imaging studies • Up to 25% of patients present with abdominal pain in the epigastrum or RUQ abdomen • Acute or severe abdominal pain maybe caused by bleeding, rupture into peritoneum or tumor necrosis • The risk of bleeding increased with – Pregnancy – Prolonged OCP – Multiple adenoma – Larger lesions – Sub-capsular location
  11. 11. Subtypes of hepatocellular adenoma: more than a uniform benign tumor • Hepatocyte nuclear factor-1ɑ (HNF1ɑ) inactivating mutations: 36-46% • Inflammatory subtype (IHCA): 18%-44% • β-catenin: 13%-14% – 5%: β-catenin activating mutations – 7%: β-catenin mutations with IHCA features • Unclassified: 9%-23%
  12. 12. Pathogenesis of HNF1A-inactivated adenoma Nault JC, et al. Gastroenterology 2013; 144:888-902
  13. 13. Pathogenesis of Inflammatory adenoma Nault JC, et al. Gastroenterology 2013; 144:888-902
  14. 14. 奧地利 多瑙河
  15. 15. β-catenin-mutated hepatocellular adenoma Katabathina VS, et al. RadioGraphics 2011; 31:1529-43
  16. 16. Clinical and genetic determinants of occurrence of hepatic adenoma Nault JC, et al. Gastroenterology 2013; 144:888-902
  17. 17. Adenoma: diagnosis • Hepatic biochemical tests are usually normal – Alk-P and GGT may occasionally be elevated, particularly in patients with bleeding or multiple adenomas – AFP is usually normal • Percutaneous liver biopsy is usually not indicated (?) – Risk of bleeding – Lesions may have loci of malignancy that may be missed on biopsy – Often insufficient in providing the necessary tissue for histological diagnosis
  18. 18. 維也納 熊布倫宮
  19. 19. Focal Nodular hyperplasia (FNH) Venturi A, et al. J ultrasound 2007;10:116-127.
  20. 20. FNH: epidemiology • FNH accounts for 25 % of benign hepatic tumor and is second in frequency only to hemangioma. • It is more common in females (female/male ratio: 8/1). • Roughly 20% of all cases are characterized by multiple tumors. • Most of the lesions are identified between the third and fourth decades of life.
  21. 21. FNH: clinical manifestations • In the vast majority of cases, FNH is initially asymptomatic • No malignant transformation tendency in the follow-up • Hemorrhage and necrosis are rare (2-3%) • Oral contraceptives are not implicated, however, the risk of hemorrhage appears to be higher in women taking oral contraceptives • Typically, the lesion is a solid tumor, often in the right lobe, with a fibrous core and stellate projections • Technetium scan usually shows a hot spot because of the presence of Kupffer cells. Vascular on angiography, and septations may be detectable by angiography, helical CT scan, and, most reliably, MRI, but only rarely by sonography. • OP is indicated only for symptomatic lesions
  22. 22. 奧地利 魯斯特
  23. 23. Kuo YH, et al. J clinical ultrasound 2009; 37:132-137. 2.5 cm
  24. 24. Kuo YH, et al. J clinical ultrasound 2009; 37:132-137.
  25. 25. 血管瘤 (hemangioma) 局部結節性增生 (FNH) 腺瘤 (adenoma) 發生率 (%) 0.4-20 0.3-3 1x10-6 至1.2 x 10-4 好發年齡 30-50歲 30-50歲 各種年齡層 性別 (男:女) 1:2-6 1:5-17 1: 8-15 超音波所見回音性 高回音 (hyerechoic) 不一定 不一定 電腦斷層 靜脈性影像增強 中央疤 (central scar) 動脈相廣泛性影像增 強 磁振造影 腦脊髓液質地 肝臟質地 肝臟質地 T1時相影像為高訊號 (hyperintense)病灶 血管攝影 高血管性 高血管性 高血管性 核醫檢查 (Tc99m sulfur colloid scan) 紅血球吸收 吸收 因缺乏Kupffer 細胞, 減少吸收 鈣化 會 不會 不會 結節破裂機會 極少 無 可能
  26. 26. Hepatic Angiomyolipoma (AML) Lu HC, Chau GY, Su CW. Hepatic angiomyolipoma mimicking hepatocellular carcinoma. Gastroenterology 2009;136:1169
  27. 27. Hepatic Angiomyolipoma (AML) • A rare mesenchymal tumor of the liver, which is composed of a varying heterogeneous mixture of adipose tissue, proliferating blood vessels, and smooth muscle cells. • Image manifestations of hepatic AML differ widely due to the various proportions and distribution of the three components, which make it difficult to establish an accurate diagnosis. It is easily misdiagnosed as HCC before surgery. • The preoperative diagnostic accuracy was lesser than 32 % with the combined appliances of imaging survey and fine-needle aspiration biopsy.
  28. 28. AML: clinical manifestations • Yeh CN, Chen MF, et al. J Surg Oncol 2001;77:195-200 Median 40.5 years HMB-45
  29. 29. AML: clinical manifestations • Zeng JP, et al. Dig Dis Sci 2010;55:3235-40
  30. 30. Hepatic epithelioid hemangioendothelioma (HEHE) • A very rare vascular neoplasm of the liver that arises from endothelial cells, with an estimated incidence of 1 in 1,000,000 in the whole population • A borderline neoplasm at the middle of the spectrum, between the benign epithelioid hemangioma and highly aggressive epithelioid angiosarcoma • Immunohistochemical identification of epithelioid and positive dendritic cells for endothelial markers (Factor VIII-related antigen, CD34, CD31) is essential for diagnosis • Age: 12-86 years (mean: 41.7 years) • Gender: female predominant (61%) • May be associated with OCP, exposure to vinyl chloride, or major hepatic trauma • Clinical course: variable and unpredictable
  31. 31. Symptoms and signs of hepatic epithelioid hemangioendothelioma Mehrabi A, et al. Cancer 2006; 107:2108-21
  32. 32. Clinical and laboratory findings of hepatic epitheloid hemangioendothelioma in Taiwan Hsieh MS, Shun CT, et al. J Formos med Assoc 2010;109:219-27
  33. 33. Hepatic angiosarcoma • Primary hepatic angiosarcoma accounting for onely 0.1-2% of all malignant primary liver tumors • Highly malignant and rapidly progressive vascular tumor of endothelial cell origin • Environmental carcinogens: vinyl chloride, thorium dioxide, arsenic • Symptoms: abdominal pain, weakness, fever, and weight loss
  34. 34. Hepatic angiosarcoma: clinical manifestations Kim HR, et al. Ann Oncol 20:780-7
  35. 35. Hepatic TB Su CW, et al. Gastroenterol J Taiwan 2008;25:215-221
  36. 36. Hepatic TB: clinical manifestation • Hepatic TB was rare in immunocompetent patients • Bolukbas and colleagues reported that only 4 of 88 (4.5%) abdominal TB patients had hepatic involvement • It had diverse and non-specific clinical symptoms and signs including low grade fever, night sweat, cough, abdominal pain, hepatomegaly, body weight loss, fatigue, vomiting, diarrhea, dyspnea, and jaundice
  37. 37. Hepatic TB: clinical manifestation • There are three types of hepatic TB – The most common form is the miliary tuberculosis of liver associated with lung TB, with diffuse fine miliary micronodular lesions (less than 2 cm in diameter on CT scan) in the liver parenchyma. – The second type is the granulomatous disease or tuberculous hepatitis, presenting with jaundice or hepatomegaly, which is caused by caseating granulomas in the liver. – The least frequent type is the macronodular form (also named pseudotumor or tuberculoma), characterized by large (more than 2 cm) nodular lesions.
  38. 38. Hepatic TB Tai WC, Chuah SK, Lee CM, et al. J Intern Med Taiwan 2008;19:410-7
  39. 39. Hepatic TB • Differential diagnosis – Abscess: early in the evolution of the lesion, its appearance on contrast-enhanced images is similar to abscess, whereas more advanced lesions usually calcify – Metastases – Hepatocellular carcinoma – Masses with calcification: epitheloid hemangioendothelioma; fibrolamellar carcinoma – The finding of caseating granuloma in the liver biopsy is considered diagnostic of TB
  40. 40. 捷克 庫倫洛夫
  41. 41. Cystic lesion of liver
  42. 42. Cystadenoma: epidemiology • Occur more commonly in women, range in size from 2cm to 28 cm and can occur at extremes of age, although usually present in the fourth decade of life • No known association between cystadenomas and use of OCP
  43. 43. Cystadenoma: clinical manifestation • Most commonly found incidentally on abdominal imaging • May present with abdominal pain and anorexia • DDx: simple cyst – Sonography: Hypoechoic lesions with irregular walls and septations – Histological examination: • Contain blood or dark brown material • Microscopic: lined by mucus-secreting cuboidal or columnar epithelium, supported by cellular fibrosis stroma.
  44. 44. Polycystic liver disease • Secondary to a failure in intralobular bile duct involution during fetal development; the intralobular ducts subsequently become distorted and degenerate into cysts • Usually diagnosed in the fourth and fifth decades of life when symptoms develop • Frequently associated with autosomal dominant polycystic kidney disease
  45. 45. Polycystic liver disease: clinical manifestations • Abdominal discomfort, distention, nausea, and vomiting • Rupture or bleeding into a cyst may be associated with severe acute abdominal pain • Hepatic complications: – Infection, bleeding, rupture, portal hypertension, biliary obstruction , cholangiocarcinoma (rarely) • Hepatic biochemical tests: usually normal; obstructive jaundice, ascites • High-resolution brain CT scan for screening intracranial aneurysms
  46. 46. 捷克 庫倫洛夫