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Liver and intrahepatic bile ducts-nontumor
Reviewers: Komal Arora, M.D. (see Reviewers page)
Revised: 16 May 2012, last major update May 2012 - IN PROGRESS
Copyright: (c) 2004-2012, PathologyOutlines.com, Inc.
Table of contents
Primary references, normal anatomy, normal histology, embryology, normal physiology, patterns of hepatic injury, biopsy, diagnostic patterns
Developmental
anomalies/cysts: accessory lobe, Alagille’s syndrome, Bloom syndrome, Byler’s disease, Caroli’s disease, choledochal cyst, congenital hepatic fibrosis, Down’s syndrome, extrahepatic biliary atresia, foregut cyst, intrahepatic biliary atresia, multiple hilar cysts, polycystic liver disease, solitary cyst, von Meyenburg complex
Metabolic
diseases: general, alpha-1-antitrypsin deficiency, cystic fibrosis, erythropoietic protoporphyria, familial apolipoprotein A-I amyloidosis, galactosemia, Gaucher, glycogen storage disease, GM2 gangliosidosis, heme oxygenase-1 deficiency, hemochromatosis, hereditary fructose intolerance, hereditary hepatic coproporphyria, hereditary tyrosinemia, mucopolysaccharidosis, Niemann-Pick, porphyria cutanea tarda, primary hyperoxaluria, Wilson’s disease, Wolman disease, Zellweger syndrome
General
concepts: ascites, cirrhosis, cirrhosis-features to report, differential diagnosis of fibrosis, fulminant hepatitis / massive hepatic necrosis, hepatic failure
Hepatitis (acute and chronic): general, acute hepatitis-general, prolonged resolving acute hepatitis, chronic hepatitis-general, chronic hepatitis-grading and staging
Hepatitis
(non-infectious): alcoholic, autoimmune, drug/toxin induced, granulomatous, neonatal, nonalcoholic steatohepatitis, total parenteral nutrition related
Infectious
(non-viral) disorders: Aspergillus, bacterial, Blastomycosis, Candida, Clonorchis sinensis, Coccidiodomycosis, Coxiella, Cryptococcus, dengue fever, Echinococcal cyst, Echovirus, Entamoeba histolytica, Fasciola hepatica, granulomatous, Histoplasma, malakoplakia, microsporidia, Mucor, Mycobacteria, Orientia tsutsugamushi, Penicillium, pyogenic abscess, Reye’s syndrome, Salmonella, Schistosomiasis, visceral larva migrans, visceral leishmaniasis
Viral
hepatitis: general, acute viral hepatitis, chronic viral hepatitis, adenovirus, CMV, EBV, hepatitis A, hepatitis B, hepatitis C, Delta agent, hepatitis E, hepatitis G, herpes, HHV6, HIV
Biliary
tract disease: cholestasis, acute large duct obstruction, ascending cholangitis, autoimmune cholangitis, cholangitis lenta, chronic large duct obstruction, hyperalimentation, oriental cholangiohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, secondary biliary cirrhosis
Jaundice: physiology, unconjugated hyperbilirubinemia, conjugated hyperbilirubinemia
Vascular
disorders: general, arterial disorders, Budd-Chiari, hepatoportal sclerosis, hemorrhagic hereditary telangiectasia, peliosis hepatis, portal hypertension, portal vein obstruction, veno-occlusive disease
Systemic
diseases/conditions: amyloidosis, congestive heart failure, Crohn’s disease, diabetes mellitus, hemolytic anemia, myeloproliferative disorders, pregnancy, rheumatoid arthritis, sarcoidosis, sickle cell disease, ulcerative colitis
Transplantation: liver transplant-general, adult to adult liver donor transplantation, hyperacute graft rejection, acute graft rejection, chronic graft rejection, post-bone marrow transplant, acute graft versus host disease, chronic GVHD, posttransplant lymphoproliferative disorder, pseudopeliotic steatosis
Go to Liver and intrahepatic
bile ducts - tumor chapter
Primary references
top
AJCC
Cancer Staging Manual (7th Ed)
American Journal of Clinical Pathology
American Journal of Surgical Pathology
Archives of Pathology and Laboratory Medicine
Human Pathology
Modern Pathology
Websites: Loyola
University review by Dr. Emilio Orfei
Please refer to these primary references for more detailed discussions and photographs
Transplantation
Adult to adult live donor liver transplantation
Elective voluntary directed liver donation to a patient by a relative or friend, to overcome shortage of cadaveric organs
Usually right-lobe transplants since left lobe grafts have inadequate volume
Preliminary report suggests that biliary tract complications are common, are amenable to surgical intervention, don’t adversely affect patient or graft survival, Hum Path 2001;32:814
Also called humoral rejection
Rare in liver
Antibody mediated process with necrotizing arteritis, neutrophils and ischemic damage
Due to preformed antibodies against donated organ and antibody-complement mediated damage to endothelium
Cell mediated, potentially reversible
Either resolves or progresses to chronic graft rejection
Banff International Consensus Document criteria: mixed portal inflammation, cholangiolitis and endothelialitis, Hepatology 1997;25: 658
Treatment: cautious increase in immunosuppression (even if posttransplant lymphoproliferative disorder)
Micro: portal infiltrate of lymphocytes and variable eosinophils and neutrophils that damage bile ducts and venous endothelium; no /minimal hepatocyte damage; also loss of bile ducts, arteritis, central ischemic damage with ballooning degeneration and hepatocyte dropout
Micro images: moderate acute rejection with bile duct damage, severe acute rejection, loss of bile ducts
DD: EBV associated hepatitis, terbinafine drug reaction, Hepatitis C, primary biliary cirrhosis
Usually irreversible injury of hepatic allografts, likely secondary to ischemic damage to hepatocytes or direct immunologic damage to bile ducts with total loss (vanishing bile duct syndrome)
May have insidious onset with no acute component
Micro: vanishing bile duct syndrome: loss of intrahepatic bile ducts, minimal portal inflammation; obliterative endarteritis - occlusion by subintimal fibrosis and foam cell change in large and medium sized hilar hepatic arteries and portal vein and distal branches near hilum; also associated ischemic changes of centrilobular ballooning degeneration, pericellular fibrosis and possibly cirrhosis; changes more variable in portal vein; however pathognomonic arterial changes are rarely present in needle biopsies
Micro images: portal vein with foam cell change and luminal obliteration
References: Archives 2004;128:64 (portal vein changes), AJSP 1999;23:1328 (reversibility)
Post-bone marrow transplantation
Weight gain, tenderness, edema, ascites typically occurs just after donor marrow administration
Within first 30 days, have fungal and CMV infection, veno-occlusive disease or nodular regenerative hyperplasia
Poor outcome likely if severe liver toxicity or severe liver dysfunction
Death due to septicemia, pneumonia, bleeding, multiorgan failure
Laboratory: elevated serum bilirubin, fall in urinary sodium excretion
Micro: centrilobular necrosis, veno-occlusive disease
Acute graft versus host disease (GVHD)
Frequent complication of allogeneic hematopoietic cell transplantation
Liver damage due to donor lymphocytes attacking liver epithelial cells, appears 10-50 days after bone marrow transplant
Usually affects skin, GI tract, liver
Responds to immunosuppressive therapy
Diagnosis: elevated serum alkaline phosphatase > 2x normal, liver biopsy with typical features and no other cause for cholestatic liver disease after ultrasound, biopsy and follow-up.
Micro: damage to > 50% of bile ducts with vacuolated cytoplasm, nuclear pleomorphism and necrosis of individual cells (apoptosis); lymphocytic infiltrate of portal tracts and veins (endothelialitis) with lifting of endothelium from its basement membrane; may also have ballooning degeneration or acidophil bodies
Note: inflammatory infiltrate is limited because of bone marrow suppression early after transplant
DD: viral hepatitis and drug related hepatitis (little bile duct damage)
References: AJSP 2000;24:1004
After day 100 post-transplant
Biopsy provides diagnosis and prognostic information
Poor prognostic features: piecemeal necrosis, fibrosis, cirrhosis
Micro: brisk lymphocytic infiltrate, bile duct damage with total loss of interlobular bile ducts (vanishing bile duct syndrome), endothelialitis; may be piecemeal necrosis but no extensive hepatocellular damage
DD: drug reaction (may also cause loss of bile ducts)
Post liver transplant lymphoproliferative disorder
Due to immunosuppressive drugs for solid organ transplantation (including liver), particularly cyclosporine
Usually presents at 6-17 months post-transplant as systemic illness; only 2-3% of liver grafts are involved
Tumors usually of host origin
Strongly associated with EBV
Also associated with acute rejection in 80% of biopsies, which can be treated even if EBV present, AJSP 2001;25:324
Treatment: reduction in dose of tacrolimus or cyclosporine
Case reports: 61 year old man with hiccups due to post-transplant diffuse large B cell lymphoma (Archives 2003;127:248), B cell lymphomas and anaplastic plasmacytoma (AJSP 2000;24:733), distinct EBV+ diffuse large B cell lymphomas in abdomen and brain (Hum Path 1999;30:1262)
Micro:
Early lesions: formerly called plasmacytic hyperplasia; infectious mononucleosis like, composed of small lymphocytes, plasma cells, scattered immunoblasts
Polymorphic lesions: medium sized lymphocytes with mitotic activity, plasma cells, immunoblasts
Monomorphic lesions: resemble high grade lymphoma; most cells are large and plantlike
Micro images: H&E, CD20, EBV
Pediatric cases
All cases related to EBV
Often involves Waldeyer’s ring
Favorable prognosis for early lesions and nonmalignant lesions (polymorphous subtype)
Malignant lesions often diffuse large B cell lymphoma
Poor prognostic factors: 3+ sites of involvement, allograft involvement
Micro images: infectious mononucleosis-like lesion, polymorphous subtype with monotypic light chain expression, EBV+, diffuse large B cell lymphoma-like lesion
References: Archives 2001;125:337
Formerly called lipopeliosis
Pathophysiology: steatotic hepatocytes are present in donor liver; preservation injury causes their death with loss of fat; fat droplets accumulate to form fat globules that mimic dilated sinusoids (week 1); then surrounded by macrophages and cleared by 3-4 weeks Micro: apparent sinusoidal engorgement by large fat globules, although fat globules are actually outside sinusoids when collagen IV immunostaining is performed; variable damaged hepatocytes
References: AJSP 2002;26:134
End of Liver and intrahepatic bile ducts - Non tumor chapter
