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Liver and Gallbladder Surgical Pathology
This document summarizes surgical liver and biliary pathology presented by Dr. Noel C. Santos. It discusses focal liver lesions including tumors and tumor-like lesions of the liver. It also discusses diseases of the gallbladder and bile ducts. Primary and metastatic liver tumors are classified and various pathologies of the liver, bile ducts, and gallbladder are described including hepatocellular carcinoma and cholangiocellular carcinoma.
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Liver and Gallbladder Surgical Pathology
- 1. SURGICALSURGICAL LIVERLIVER andand BILIARYBILIARYPATHOLOGYPATHOLOGY of Dr. Florencio C. Dizonof Dr. Florencio C. Dizon By Dr. Noel C. Santos, M.D.
- 2. LIVER PATHOLOGYLIVER PATHOLOGY Focal liver lesionsFocal liver lesions – Tumor-like lesions and tumorsTumor-like lesions and tumors Liver transplantationLiver transplantation Diseases of gallbladder and bile ductsDiseases of gallbladder and bile ducts – Diseases of gall bladderDiseases of gall bladder – Diseases of extrahepatic bile ductsDiseases of extrahepatic bile ducts – TumorsTumors
- 3. Focal liver lesionsFocalliver lesions Tumor-like lesions of the liverTumor-like lesions of the liver – FNHFNH, NRH, mesenchymal hamartoma, cysts,, NRH, mesenchymal hamartoma, cysts, inflammatory pseudotumor, abscessus, infarctusinflammatory pseudotumor, abscessus, infarctus Benign liver tumorsBenign liver tumors – Non epithelialNon epithelial:: haemangiomahaemangioma, fibroma,, fibroma, angiomyolipoma etcangiomyolipoma etc – EpithelialEpithelial:: adenomaadenoma (HCA, CCA)(HCA, CCA) Malignant liver tumorsMalignant liver tumors – Non epithelialNon epithelial: haemangiosarcoma, -endothelioma: haemangiosarcoma, -endothelioma embryonal sarcoma, lymphomaembryonal sarcoma, lymphoma – EpithelialEpithelial:: hepatocellular cc, cholangiocellular cc.,hepatocellular cc, cholangiocellular cc., mixed, hepatoblasomamixed, hepatoblasoma
- 4. Classification of livercystsClassification of liver cysts I.I. ParasiticParasitic II.II. Non parasiticNon parasitic A. SoliterA. Soliter B. HerediterB. Herediter 1. Non communitating ductal1. Non communitating ductal 2. DPM („ductal plate malformatio”-2. DPM („ductal plate malformatio”- communitating)communitating) •• CHF (cong. hepatic fibrosis)CHF (cong. hepatic fibrosis) •• ARPKDARPKD •• syndromes (Meckel-Gruber, Ivemark)syndromes (Meckel-Gruber, Ivemark) 3. Isolated hepatic3. Isolated hepatic *Witzleben, G. L., Ruchelli, E.*Witzleben, G. L., Ruchelli, E.
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- 7. II. Non parasiticII.Non parasitic C.C. Systemic biliary dilatativeSystemic biliary dilatative 1. Without choledochus cyst1. Without choledochus cyst („simple” Caroli disease)(„simple” Caroli disease) 2. With choledochus cyst2. With choledochus cyst D. OtherD. Other 1.1. Traumatic, infarctusTraumatic, infarctus 2. Duodenal duplication2. Duodenal duplication 3.3. Tumors with cystTumors with cyst •• cystadenoma/-carcinomacystadenoma/-carcinoma •• mesenchymal hamartomamesenchymal hamartoma •• giant cavernous haemangiomagiant cavernous haemangioma •• teratomateratoma •• otherother 4.4. PeliosisPeliosis *Witzleben, G. L., Ruchelli, E.*Witzleben, G. L., Ruchelli, E. Classification of liver cystsClassification of liver cysts
- 8. 1 cm Mesenchymal hamartoma(children, benign)
- 9. Peliosis hepatis (dilatedsinusoids)
- 10. Tumor-like focal liverlesionsTumor-like focal liver lesions – Focal nodular hyperplasia (FNH)Focal nodular hyperplasia (FNH) – InflammatorInflammatoryy pseudotumorpseudotumor – Mesenchymal hamartomaMesenchymal hamartoma – NoduNodulalar regenerar regeneratitiv hyperplasiav hyperplasia – InfarctInfarct – Granulomas (Boeck, tbc etc)Granulomas (Boeck, tbc etc)
- 11. Focal nodular hyperplasia(FNH) - Female predominance, - Well circumsized, - No capsule - Central scar (fibrous septa radiate, “focal cirrhosis”) - Color (pale, fatty, haemorrhagic etc.) - Bile ducts: numerous, tortuous - Inflammatory cells
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- 13. 1 cm Focal nodularhyperplasia
- 14. 1 cm Focal nodularhyperplasia (cental fibrosis)
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- 16. Classification of primaryliverClassification of primary liver tumorstumors Epithelial Hepatocellular adenoma Cholangiocellular adenoma/cystadenoma Biliary papilloma/papillomatosis Hepatocellular carcinoma -Cholangiocellular carcinoma Mixed carcinoma Hepatoblastoma Nonepithelial Haemangioma Angiolipoma/myolipoma Fibroma Haemangiosarcoma Haemangioendothelioma Carcinoid, lymphoma, etc Benign Malignant
- 17. 1 cm Haemangioma hepatis (themost common primary liver tumor)
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- 19. Hepatocellular adenoma - Femalepredominance - Associated with oral contraceptives, anabolic steroids - Sharply demarcated, - Encapsulated - Homogenous structure, but hemorrhage, necrosis common, - Steatosis, no bile ducts in the tumor
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- 21. 1 cm Adenoma hepatocellulare(extended bleeding, rupture might occur)
- 22. Cytological smear, HEstain Fine needle aspiration from the liver
- 23. Border of liver andtumor (after formalin fixation).
- 25. Hepatocellula adenoma withextended peliosis. The tumor cells are similar to normal hepatocytes. HE stain
- 26. Classification of primaryliverClassification of primary liver tumorstumors Epithelial Hepatocellular adenoma Cholangiocellular adenoma/cystadenoma Biliary papilloma/papillomatosis Hepatocellular carcinoma -Cholangiocellular carcinoma Mixed carcinoma Hepatoblastoma Nonepithelial Haemangioma Aangiolipoma/myolipoma Fibroma Haemangiosarcoma Haemangioendothelioma Carcinoid, lymphoma, etc Benign Malignant
- 27. Hepatocellular carcinoma - Cirrhosis(70%) - Association with HBV/HCV/alkohol etc - Gross: uneven border, usually no capsule, haemorrhage, necrosis - Hist: trabecular, pseudoglandular (acinar), clear cell, scirrhous, fibrolamellar (grades I-IV) - Progression: infiltration of capsule (if exists), venous invasion
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- 31. Different histological typesof HCC HCC, trabecular HCC, pseudoglandular HCC, anaplastic HCC, venous invasion
- 32. Characteristics of HCCCharacteristicsof HCC 5% of malignant tumors5% of malignant tumors 564 000564 000 new cases annuallynew cases annually (in 2000) and similar death(in 2000) and similar death Incidence is dubbled in the pastIncidence is dubbled in the past 20 yrs (Japan, USA, Sweden,20 yrs (Japan, USA, Sweden, France)France) 7.7. in malesin males 9.9. in femelsin femels Characteristic geographyCharacteristic geography Etiological factors:Etiological factors: HBV, HCVHBV, HCV,, AFB1 (80%), alkohol etcAFB1 (80%), alkohol etc Unknown 35% HBV/HDV 5% HBV 15% HCV 45% Koff RS, et al.Koff RS, et al. ViralViral Hepatitis.Hepatitis. 2nd ed. 1994.2nd ed. 1994.
- 33. HBV, HCV HCC Mutagen effects Cirrhosis! Aflatoxin Fusarium toxin Hepatocarcinogenesis Etiological factors Alcohol Androgens Metabolic diseases Schistosoma
- 34. proto Onkogenes c-myc, N-ras, c-fos HCC Citokines TGF-α,HGF ! IGF-I, IGF-II., TGF-β, Tumor suppressor genes p53, p16, RB Hepatocarcinogenesis LOH 1p,1q, 2q, 4q, 5q, 6q, 9p, 9q, 10q, 11p, 13q, 16p, 16q, 17p, 22/APC Adhesion molecules Integrins, E-cadherin, β-catenin ! Ampl. Chromos- region 1q, 8q
- 35. p53p53 ((p53,p14p53, p14 ARFARF , MDM2), MDM2) wntwnt ((ββ-catenin-catenin)) RB1RB1 ((p16p16 INK4aINK4a ,, p15p15 INK4bINK4b ,, RB1RB1, CDK4,, CDK4, cyclin D1)cyclin D1) Most common altered pathways in HCCMost common altered pathways in HCC Edamoto et al. Int.J.Cancer 2003.106:334-341Edamoto et al. Int.J.Cancer 2003.106:334-341 Suriawinata A. and Ruliang Xu, Seminars in liver Disease, 2004Suriawinata A. and Ruliang Xu, Seminars in liver Disease, 2004
- 36. Classification of tumorsof bile duct and gall bladderClassification of tumors of bile duct and gall bladder originorigin)) Intrahepatic cholangiocarcinoma (ICC)Intrahepatic cholangiocarcinoma (ICC) (synonim: cholangiocellular carcinoma)(synonim: cholangiocellular carcinoma) •• peripheralperipheral ((CK7CK7+, CK20-)+, CK20-) •• hilar (Klatskin tumor)hilar (Klatskin tumor) from d. hepaticus (bifurcatio)from d. hepaticus (bifurcatio) (CK7+/CK20+)(CK7+/CK20+) Extrahepatic bile duct carcinomaExtrahepatic bile duct carcinoma (EBDC)(EBDC) CK7CK7++ /CK20/CK20++ Gallbladder carcinomaGallbladder carcinoma CK7CK7++ /CK20/CK20++ ICC osztályozása a májtumor TNM szerint; EBDC osztályozása „saját” TNM szerintICC osztályozása a májtumor TNM szerint; EBDC osztályozása „saját” TNM szerint Cabibi et al. P.R.P., 2001, 22:114-23; Okuda et al. J. Gastroent.Hepatol. 2002, 17:1049-55Cabibi et al. P.R.P., 2001, 22:114-23; Okuda et al. J. Gastroent.Hepatol. 2002, 17:1049-55
- 37. Most common metastaticMostcommon metastatic liver tumorsliver tumors Gastrointestinal tract, gallbladder,Gastrointestinal tract, gallbladder, bile ducts , pancreasbile ducts , pancreas LungLung KidneyKidney BreastBreast MelanomaMelanoma neuroendocrinneuroendocrin
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- 41. Cholangiocellular carcinoma. Ductus choledocus Tumor,protruding from the Liver
- 42. Case reportCase report 54y male54 y male Jaundice, 3 wJaundice, 3 weekeekss CT: enlarged tumor like alteration in the headCT: enlarged tumor like alteration in the head region of the pancreas, multiple foci in theregion of the pancreas, multiple foci in the liverliver Liver biopsy (frozen saLiver biopsy (frozen sammple)ple)
- 43. Liver Glandular tumor withfibrotic stroma
- 44. DiagnosisDiagnosis Cholangiocellular (Cholangiocellular (““bileduct”) adenomabile duct”) adenoma
- 45. Attention!Attention! It might mimicCCC or metastatic tumorIt might mimic CCC or metastatic tumor (especially on frozen section)(especially on frozen section)
- 46. Biliary hamartoma (vonMeyenburg complex)
- 47. Biliary hamartoma (vonMeyenburg complex)
- 48. Gallbladder 1. Tumorlike lesions -inflammatory origin (polyp, xanthogranulomatous cholecystitis etc) - hyperplasia (papillary, adenomyomatous) - Heterotopic tissue (pancreas, stomach, endocrin) - other
- 49. Gallbladder 2. Tumors Benign - adenoma -cystadenoma - papillomatosis - mesenchymal Malignant - epithelial - adenocarcinoma - adenosquamosus cc. - squamosus cc. - differenciálatlan - cystadenocarcinoma - mesenchymal - endocrin - carcinoid
- 50. Gallbladder carcinoma Gross - infiltrating -exophytic Histology - adenocarcinoma Immunohistochem - CEA - CA 19-9 Other - TNM - occult carcinoma - in situ carcinoma
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- 54. Thank you forlistening……Thank you for listening……
- 55. SURGICALSURGICAL LIVERLIVER andand BILIARYBILIARYPATHOLOGYPATHOLOGY of Dr. Florencio C. Dizonof Dr. Florencio C. Dizon By Dr. Noel C. Santos, M.D.