liver biopsy interpretation

Liver biopsy interpretation

Presenter - Dr. Dhanya A N Moderator – Dr. Ramesh S T

Contents • Indications of liver biopsy • Lab investigations • Techniques of liver biopsy • Needles of liver biopsy• Processing and staining • Normal histology • Approach to liver biopsy interpretation • Interpretation of different pathological

conditions

Indications of liver biopsy

• Make or confirm the diagnosis

• Assess the severity of liver damage

• Assess the prognosis of a given case

• Monitor the response to the treatment

Clinical and lab investigations

• History and general physical examination • Lab investigation

– Liver function tests – CBC– Prothrombin time, aPTT – Bleeding time – Clotting time – USG,CT, MRI

Liver function tests • Hepatic integrity

– Serum aspartate aminotransferase– Serum alanine aminotransferase– Serum lactate dehydrogenase

• Biliary excretory functions– Serum bilirubin– Serum alkaline transferase – gamma glutamyl transferase

• Hepatocyte synthetic function– Serum proteins– Coagulation proteins – Serum ammonia

Techniques of liver biopsy 1. Percutaneous - Transthoracic

– Subcostal • Blind procedure • Image guided – USG, CT,

MRI• Plugged liver biopsy

– Gelatin, gel foam plugged

2. Transvenous (Transjugular)

• Done in coagulation disorders or ascites

• Performed in a vascular catheterisation laboratory with videofluoroscopy equipment and proper cardiac monitoring

3. Laparoscopic liver biopsy

• Transvenous liver biopsy is not available,

• In patients who have a combination of a focal liver lesion and a coagulopathy.

Needles for liver biopsy

Broadly classified into • Suction needles

– Menghini, – Klatskin,

• Cutting needles – Vim-Silverman, – Tru-cut (commonly used)

• Spring-loaded cutting needles that have a triggering mechanism.

Vim silverman needle

Tru cut needle

Processing the sample

• Place on the filter paper • Fix immediately

– Buffered formalin (routine)– Alcohol (glycogen storage disorder)– 2.5% buffered gluteraldehyde (for EM)– Frozen sections (for fat)

• Fix overnight • Take sections • Stain

Special stains

Masson trichrome, stains blue color to collagen and red color to hepatocyes H & E stain of hepatic lobule

Special stains

Perls prussian blue for iron, heoatocytes have taken the blue stain

PAS positive in glycogen storage right side and after treating it with diastase, left side

Special stains

PAS+diastase for aplha1 antitrypsin deficiencyHapatocytes have taken magenta color

Oil Red O stain highlighting fat globules in a frozen section of theliver.

Special stains

Rhodanin stain for copper, hepatocytes have taken orange red color in the upper nodule

Congo red stain orange-staining of vascular amyloid deposition,characteristic apple-green birefringence under polarizedmicroscopy (inset)

Special stains

Orcein stain for elastic fibres is positive in two portal tracts (P) but not in the intervening area of collapse. A necrotic bridge (arrow) is also negative. Inset: This contrasts with an elastic fibre-rich septum in chronic liver disease.

PP

Reticulin stain of micronodular cirrhosisStains collagen

Adequacy of liver biopsy

• Biopsy length - > 1 cm • At least 10 portal tracts should be seen• Any amount of tissue that yields diagnosis • Transjugular biopsy : smaller, thinner,

fragmented tissue cores (4 fragmented cores) or at least 4-6 portal tracts

• Best is laparoscopic biopsy

Histology

Lobular model • 2-3 mm diameter lobule • Hexagonal shape • The central hepatic vein

(terminal hepatic vein)• Portal tracts at the

periphery • Portal tract- portal vein,

hepatic artery, bile duct

Conti..

• Hepatocytes around – central vein -centrilobular(zone3), – portal tract - periportal (zone 1), – in between mid zonal (zone 2)

• Hepatocytes – polygonal, central single nucleus, cells arranged in plates

• Sinusoids on either side of cell plate

• Sinusoids – lined by fenestrated endothelial cells

P

BD

Conti..• Space of disse – lies below the endothelial lining of

sinusoids has stellate cells • Kupffer cells- mononuclear phagocytic cells, on luminal

side of sinusoids

Conti..

Bile canaliculi – seen in between hepatocytes, 1-2 𝛍 diameter, drain into canal of hering, in turn drain into bile duct

Acute Injury Response of liver parenchyma to acute injury • Necrosis

– Hepatocytes swells– Blebs are formed and carry out organelles out of the cell– Cell rupture – Macrophage infiltration at the site of necrosis

• Apoptosis – Nuclear pyknosis, karyorrhexis– Acidophilic bodies – councilman bodies

Disease process continues • Spotty necrosis/ focal necrosis - Death of

individual hepatocytes or small groups of these cells

• Confluent necrosis – widespread parenchymal loss, a zonal loss of hepatocytes

• Bridging necrosis – necrosis link central veins to portal tracts or bridge the adjacent portal tract

• Panlobular and multilobular necrosis - confluent necrosis involving entire single lobules or several adjacent lobules respectively

Bridging necrosis

p

c

Panlobular and multilobular necrosis

Scar formation and regression

• Stellate cells – most important, myofibroblastic properties

Approach to liver biopsy interpretation • Architecture

– Maintained – Collapse – Fibrosis

• Hepatocellular changes – Necrosis – apoptosis

• Cholestasis – Canalicular – Ductular

• Portal tract – Inflammation– Edema – Bile ductular reaction– Ductopenia – Fibrosis

• Inflammatory infiltrate – Neutrophils – Eosinophil's– Mononuclear cell

Acute viral hepatitis


• Usually Pan lobular – Centrilobular – hepatitis B, C– Periportal – hepatitis A

• Hepatocytes – ballooning, pale granular cytoplasm or shrinkage, nuclear pyknosis – acidophilic bodies (Councilman bodies),

• Bilirubinostasis • Mononuclear and lymphocytic

infiltration • Spotty necrosis


bridging necrosis. curved lines of necrotic debris and collapse extend from a portal tract to cetral venule.

C

P


multilobular necrosis Portal tract (arrow) can be identified but the parenchyma has been replaced by inflammatory cells, necrotic debris

Fate and morphological sequel of acute viral hepatitis

• Resolution• Scarring• Chronic hepatitis• Cirrhosis• Acute liver failure • Hepatocellular carcinoma

Chronic hepatitis

Classic causes of chronic hepatitis• Hepatitis B, with or without HDV infection • Hepatitis C • Autoimmune hepatitis • Drug-induced hepatitis – methotrexate, OCP,

vitamin A, acetaminophin • Chronic hepatitis of unknown cause

Chronic hepatitis

The portal tract is heavily infiltrated with lymphocytes (H&E)

Interface hepatitis-process of inflammation and erosion of the hepatic parenchyma at its junction with portal tracts or fibrous septa (H&E)

Chronic hepatitis

Chronic hepatitis with lobular activity. Clumps of inflammatory cells, some of them associated with hepatocyte loss, extend through the parenchyma. The portal tract above is inflamed. (H&E.)

Chronic hepatitis B

the central part of the cytoplasm has a homogeneous ground-glass appearance. Sanded nuclei – fine granular, eiosinophilic

Cytoplasmic inclusions of HBsAg are present.

Chronic hepatitis C

• The portal tract is heavily infiltrated by lymphocytes,

• A lymphoid follicle with germinal center has formed

• 15-25% may have steatosis

Autoimmune hepatitis

• Female predilection • Chronic progressive hepatitis with features of

autoimmune diseases – Genetic predisposition– Associated with other autoimmune disorders – Therapeutic response to immunosuppression

Autoimmune hepatitis 1. Type 1

– Any age (Middle aged to old age)– Presence of antinuclear antibodies (ANA), anti

smooth muscle actin antibodies (SMA), anti soluble liver antigen/liver- pancreas antigen( anti-SLA/LP), anti mitochondrial (AMA) antibodies

• Type 2 – Children and teenagers – Anti liver kidney microsome-1 antibodies


Interface hepatitis Plasma cell predominates in the mononuclear inflammatory infiltrate


Hepatocytes rosettes in areas of activity Confluent necrosis, parenchymal collapsePlasma cell infiltration seen (characteristic)

Drug induced hepatitis

Conti..

Necroinflammatory score for chronic hepatitis (HAI/Knodell score)

Conti…

Grading for chronic hepatitis

Minimal activity (grade 1). Inflammation is confined to the portal tracts and there is no interface hepatitis. The lobular parenchyma is quiescent

Mild activity (grade 2). Focal interface hepatitis present (right periportal region) in addition to portal tract inflammation. A few lobular necroinflammatory foci are also seen at right

Grading for chronic hepatitis

Moderate activity (grade 3). More extensive interface hepatitis is present than in grade 2, but involving <50% of the circumference of most portal tracts.

Marked activity (grade 4). The portal tract is diffusely inflamed and shows extensive circumferential interface hepatitis. Similar changes affect virtually all portal tracts with this grade of activity, often with considerable lobular activity.

Cirrhosis • Results from interplay between parenchymal

damage, fibrinogenesis, fibrinolysis and hepatocellular regeneration

• Main Causes – Hepatitis B, C, – Alcohol abuse– Biliary diseases– Metabolic disorders – Drugs, toxins– Autoimmune hepatitis – Venous out flow obstruction

Criteria for cirrhosis 1. Fundamental

– Nodularity – Fibrosis

2. Relative • Fragmentation • Abnormal structure • Hepatocellular changes

– Regenerative hyperplasia – Pleomorphism – Large-cell dysplasia (large-cell change) – Small-cell dysplasia (small-cell change)

Classification

based on size of the nodule• Micronodule - < 3 mm causes - Alcohol, Metabolic, Hemachromatosis, Wilson's Disease

• Macronodule - > 3 mm causes – Viruses (B,C), Toxins, Poisoning

• Mixed – equal number of both nodules

Cirrhosis

Cirrhosis: micronodular pattern. Nodules are of lobular size or smaller , reticulin stain

Cirrhosis: macronodular pattern. Nodules are larger than 3 mm, reticulin stain

Fragmented sample

Cirrhosis: fragmented sample. A specimen obtained by the biopsy method has broken into rounded fragments peripherally circumscribed by fibrosis, reticulin stain

Abnormal structures

Cirrhosis: selective sampling. A nodule has been cored out of the connective tissue by the biopsy procedure, but a thin layer of connective tissue (arrow) has adhered to the nodule margin. (Needle biopsy, reticulin.)

Cirrhosis: distorted reticulin pattern. The distortion has resulted from abnormal and irregular hepatocyte growth patterns. (Needle biopsy, reticulin.)

Hepatocellular changes

Cirrhosis: hepatocellular regeneration. Liver-cell plates are two or more cells thick, indicating active growth. (Needle biopsy, H&E.)

Cirrhosis: large-cell dysplasia , nuclei of the enlarged hepatocytes irregular in shape and vary greatly in size and staining intensity. Cells are multinucleated. The normal hepatocytes at right and in the upper left-hand corner. (Wedge biopsy, H&E.)

Hepatocellular changes

Cirrhosis: small-cell dysplasia (small-cell change). The hepatocytes below and to the right have normal-sized nuclei, but their overall size is reduced. Nuclear– cytoplasmic ratios are therefore increased. (Needle biopsy, H&E.)

Assessment of cause for cirrhosis • Pattern of nodules

and fibrosis – regular– irregular

• Bile ducts – Ductular reaction– Ductopenia– fibrosis

• Blood vessels – Narrowing

– Ischemic changes• Steatohepatitis • Evidence of viral

infection • Abnormal deposits

– Iron – Copper, copper-

associated protein – α1-Antitrypsin

globules

Ishak score for Staging of fibrosis

Alcoholic liver disease

3 forms of alcoholic liver injury • Hepatocellular steatosis• Alcoholic hepatitis (steatohepatitis)• Steatofibrosis

Hepatic steatosis

There are large fat vacuoles in perivenular hepatocytes, displacing the nuclei to the edges of the cells. (Needle biopsy, H&E.)

Steatohepatitis

Alcoholic steatohepatitis. Ballooning, necrosis,. Inflammatory cells, mainly neutrophils. contain densely stained Mallory bodies (arrows). Many hepatocytes contain large fat vacuoles. (Needle biopsy, H&E.) ASH cannot be differentiated from NASH

Mallory bodies. The Mallory bodies in this example of steatohepatitis stain strongly for ubiquitin (arrows)

Steatofibrosis

Micro nodules entrapped in blue-staining fibrous tissue.Fat accumulation no longer seen, burned out stage. (masson trichrome stain)

Metabolic liver diseases

• Non alcoholic fatty liver disease• Hemochromatosis• Wilson disease • 𝛂1 antitrypsin deficiency• Glycogen storage diseases • Gaucher’s disease• Niemann–Pick disease

Non alcoholic fatty liver disease• NAFLD is a group of conditions that have in common

the presence of hepatic steatosis (fatty liver), in individuals who do not consume alcohol, or do so in very small quantities (less than 20 g of ethanol/week)

• NAFLD – Fatty liver– NASH– Fibrosis – Cirrhosis

• Associated with metabolic syndrome

Non alcoholic fatty liver disease

NASH predominantly mononuclear inflammatory cell in filtrate with both small and large fat droplets (H&E)

Steatofibrosis prominent at portal region, extending along the sinusoids in a chicken wire pattern around the hepatocytes ( masson trichrome )

NAFLD Score

Hemochromatosis • Excessive iron absorption, most of which is

deposited in parenchymal organs like liver, pancreas, heart, joints, endocrine organs

• Normal iron pool 2-6 gm in adults • 0.5 gm stored in liver (98% in hepatocytes)• Disease manifestation appear when the iron

load > 20gm

Hemochromatosis

• Mutations of TFR1, TFR2, HJV, HFE gene mutation lead to decrease production of hepcidin and increased absorption of iron and increased release into circulation

• Serum ferritin >1000 µg/L• Transferrin saturation > 45% • Serum iron > 150 µg/dl

Classification of hemochromatosis

Hemochromatosis

Hepatocytes showing iron over load, stained blue color in perl’s prussian blue stain, note the inflammation characteristically absent.

Wilson disease

• Autosomal recessive disorder • Mutation of the ATP7B gene, • Impaired copper excretion into bile and a

failure to incorporate copper into ceruloplasmin• Copper accumulate in liver and later brain• Serum ceruloplasmin < 20 mg/dl• 24 hr Urine copper > 100 𝛍g/dl• Total serum Cu < 60 𝛍g/dl

Wilson’s disease

Fatty change, mild to moderate hepatocytic necrosis, with inflammatory infiltrate, intranuclear glycogen inclusions also seen.

The upper nodule is strongly positive for copper, stained orange-red. The lower nodule is completely negative. (Wedge biopsy, rhodanine.)

Glycogen Storage Diseases

• A hereditary deficiency of one of the enzymes involved in the synthesis or sequential degradation of glycogen

• The liver is important in glycogen metabolism. • Type 1( von Gierke) is most common for liver –

absence of glucose 6 phosphatase

Von Gierke disease

type I glycogen storage disease, PAS positive and after treating with diastase hepatocytes are swollen and resemble plant cells ,the abundant glycogen displaces the organelles of affected cells to the periphery. Sinusoids are compressed. Slender periportal fibrous scars often develop

Gaucher’s disease

• Autosomal recessive disorders resulting from mutations in the gene encoding glucocerebrosidase

• Glucocerebrosidase - cleaves the glucose residue from ceramide.

• The enzyme defect, glucocerebroside accumulates in phagocytes, kupffer cells

Gaucher’s disease

Pale-staining, striated Kupffer cells containing stored lipid are present within sinusoids. The affected cells compress hepatocytes and sinusoids and may give rise to portal hypertension. Pericellular fibrosis is a common finding

Niemann–Pick disease

• Lysosomal accumulation of sphingomyelin due to an inherited deficiency of sphingomyelinase

Niemann–Pick disease

accumulation of sphingomyelin in both hepatocytes and macrophages. The latter are greatly swollen, foamy and diastase–PAS-positive to a variable extent , Niemann–Pick disease may progress to cirrhosis

𝛂1- Antitrypsin deficiency

• Autosomal recessive disorder • low levels of α1-antitrypsin• Normal functions – inhibitors of protease,

elastase, protease 3, cathepsin G which are released by neutrophils at the site of inflammation

• Mutated α1-antitrypsin protein abnormally folded inside the ER and lead to apoptosis of cell.

𝛂1- Antitrypsin deficiency

Hepatocytes near periportal region contain mutated proteins, and stained magenta color for PAS+diastase . May also show steatosis, necrosis and fibrosis

Cholestasis diseases

• Refers to impairment of bile flow.

• In light microscope- bile pigment within bile canaliculi, hepatocytes and other sites.

• Bile is seen in the form of bile thrombi (bile plugs) in dilated canaliculi

Large bile-duct obstruction

• Causes in children – Biliary atresia – Cystic fibrosis– Choledochal cyst

• Causes in adults – Gall stones– Malignancies of biliary tree, head of pancreas– Stricture from previous surgery

Large bile-duct obstruction

• Dilatation intercanaliculi

• Portal tract edema• Bile duct proliferation

at the margin of portal tract

• Mild inflammatory infiltrate

Chronic bile-duct obstruction and biliary cirrhosis(secondary biliary cirrhosis)

Bile duct obstruction persists, bile duct infarct and increasing fibrosis. Jigsaw puzzle shape

Primary biliary cirrhosis

• Autoimmune disease characterized by nonsuppurative, inflammatory destruction of small and medium sized intrahepatic bile ducts

• Antimitochondrial antibodies recognize E2 component of pyruvate dehydrogenase complex of mitochondrial membrane,

• Altered MHC II of bile ductal epithelial cells seen, causes autoactivation of T cells

Stages of primary biliary cirrhosis


Grannulomatous lesion surrounding bile duct with mononuclear cell infiltration

Florid duct lesion


Ductular reaction with periportal hepatitis A lymphoid aggregate and a follicle with a germinal Centre (arrow)


Scarring; bridging necrosis, septal fibrosis There is extensive scarring with irregular nodule formation. Aggregates of lymphocytes mark the former sites of bile ducts

Primary sclerosing cholangitis

• Inflammation and obliterative fibrosis of intrahepatic and extrahepatic bile ducts, with dilation of preserved segments

• Immunological mediated injury to bile duct• T cells in periductal region• Autoantibodies to HLA-B8, MHC antigens • pANCA can be noted in circulation • On cholangiographic demonstration of the characteristic

beading of bile ducts • May be associated with inflammatory bowel disease

Primary sclerosing cholangitis

A bile duct undergoing degeneration is entrapped in a dense, “onion-skin” concentric scar

Cholestasis of sepsis

• By 3 main mechanism1. Direct effect of intrahepatic bacterial

infection (abscess, bacterial cholangitis) 2. Ischemia relating to hypotension due to

sepsis ( when liver is cirrhotic)3. Response to circulatory microbial products

(most common)

Cholestasis of sepsis

Canalicular cholestasis – bile plug at centilobular canliculi , sometime associate with kuffer cell activity and mild poratl tract inflammation

Ductular cholestasis – dilated canal of hering and bile ductules at the interface of portal tracts and parenchyma become dilate and contains bile plug

Biliary atresia

• Partial or complete obstruction of the lumen of the extrahepati biliary tree within the first 3 months of life

• Most common cause of neonatal cholestasis • 2 types

– Fetal type (20%)– Perinatal type (80%)

Cont..

• Fetal form – Malrotation of abdominal viscera – Interruptured inferior vena cava – Polysplenia – Congenital heart disease

• Perinatal form– Viral (reovirus, rotavirus, CMV)– Autoimmune reaction

Biliary atresia

An expanded, inflamed portal tract at left contains many proliferated bile ducts, some of which are filled with inspissated bile.

Congenital hepatic fibrosis

• Autosomal recessive inherited condition • Due to Ductal plate malformation• Presents with hepatomegaly or portal

hypertension, usually in childhood but occasionally in adults

• Associated with polycystic disease of kidney• Misdiagnosed as cirrhosis

Congenital hepatic fibrosis

Several portal tracts are interconnected by bridging fibrous septa containing ductal plate malformations. The fibrosis surrounds normal parenchyma with a terminal venule (short arrow) preserved in a central position. Inset: Higher magnification of the abnormal duct structures seen at lower left (long arrow).

Indian childhood cirrhosis

• High mortality affecting young Indian children (and Indian subcontinent)

• Brass- and copper-containing vessels used for milk-feeding - identified as sources of copper contamination

• Large amounts of copper and copper-associated protein accumulate in affected hepatocytes

Indian childhood cirrhosis

Many liver cells are swollen (centre), and surrounded by fibrosis and mononuclear cells. Regenerating hepatocytes are organised into small clusters. Disease progress l/t micronodular cirrhosis (H&E.)

Granulomatous lesion

TB GranulomaSarcoid Granuloma

PBC Granuloma Fibrin Granuloma

http://www.granuloma.homestead.com/files/granuloma_apoptotic1.jpg

Nodules and tumors

Hepatocellular adenoma

Liver cells appear normal or contain fat vacuoles. Blood vessels but no portal tracts are seen within the lesion. (H&E.)

Focal nodular hyperplasia (FNH)

Central scar with arteriole, periphery shows fibrous septa with bile duct proliferation (arrow), surrounding the scar is the nodule consists of normal hepotocytes .

Nodular regenerative hyperplasia(NRH)

This abnormal, nodular growth pattern is not accompanied by fibrosis and therefore differs from cirrhosis. The parenchymal nodules (N) are often adjacent to nodule (at left) or surrounding portal tracts. The intervening liver shows flattened and compressed liver-cell plates and/or sinusoidal dilatation (H/E)

N

N

Bile-duct adenoma

This subcapsular tumour consists of closely packed well formed bile ducts set in a dense fibrous stroma. A dense collection of lymphocytes is seen at the edge of the lesion (bottom). (H&E.)

Hemangioma

Locate beneath the capsule. Blood-filled spaces are separated by fibrous septa. A thick capsule is seen at right. ( H&E.)

Hepatocellular carcinoma

• Precursors of hepatocellular carcinoma 1. Chronic cirrhosis 2. Large cell dysplasia 3. Small cell dysplasia 4. Macroregenerative nodule 5. Dysplastic nodule

Macroregenerative nodule

This low-magnification view demonstrates the increased size of the nodule at left compared with the cirrhotic nodules at right.

Dysplastic nodule

The dysplastic nodule at right shows hepatocytes arranged in pseudoacini, with a less cohesive growth pattern centrally. A cirrhotic nodule is present at lower left. Cells show nuclear atypia , (H&E)


Trabeculae-sinusoidal pattern, trabeculae are thicker and reticulin is often scanty or even absent, (HandE)

Reticulin is scanty in this example. Reticulin stain


Adenoid pattern.

Grading of HCC

Grade 1 (well differentiated) tumours have small, round nuclei prominent nucleoli almost similar to those of normal and cirrhotic liver. HandE

Grades 2 show progressive alterations in nuclear contour, chromatin coarseness and hyper chromaticity

Conti..

Grade 3- more nuclear atypia compared to grade 2 and nuclear crowding is seen

Grade 4 shows marked anaplasia with giant, multinucleated tumour cells and atypical mitotic figures

HCC - Fibrolamellar type

Occur under the age of 30yrs, occur as single large, hard, scirrhous tumor.Tumor cells are well differentiated, shows oncocytic change, separated by parellel lamellae of dense collagen bundles.

Heptatocellular carcinoma

• Immunostaining 1. Hep Par 1 (hepatocyte) 2. Polyclonal CEA 3. Cytokeratin 7/20 pair (−/− staining) 4. GPC-3/GS/HSP70 trio (recent and confirmative,

any 2 +ve indicates HCC) – Glypican- 3 (GPC-3)– Glutamine synthetase (GS) – Heat shock protein 70 (HSP70)

Hepatoblastoma

• Most common liver tumor of early childhood • Occur at the age of 3yr• 2 variants

– Epithelial – polygonal fetal or embryonal cells arranged in acini, tubules, papillary

– Mixed epithelial and mesenchymal – admixed with osteoid, chondroid, striated muscle

Hepatoblastoma

Epithelial type - The tumour grows in cords of small hepatocytes with a ‘light-and-dark’ cells due to the admixed clear (glycogenated) and eosinophilic liver cells.( H & E.)

cholangiocarcinoma

• Malignancy of the biliary tree, arising from the bile duct within and outside of the liver

• Risk factors – Chronic inflammatory conditions – Primary sclerosing cholangitis– Hepatolithiasis – Fibropolycystic disease

Conti..

• 2 types – Intra hepatic – Extra hepatic (perihilar, klatskin tumor)

• Premalignant lesions – biliary intraepithelial neoplasias (BilN)– Low grade BilN 1 and 2– High grade BilN3

cholangiocarcinoma

There are islands of adenocarcinoma in the connective tissue, well formed glands lined by malignant tumor epithelial cells. Lymphovascular and perivascular invasions are common

Liver allograft rejection

• Acute cellular rejection – Most common within one month, but can occur

later – Traid – – portal inflammation, – bile-duct damage & – endothelitis

• Chronic rejection – Occur after 6 months of transplantation

Host vs graft reaction

Acute rejection- Heterogeneous portal inflammation consisting of lymphocytes, plasma cells and scattered neutrophils infiltrates the bile duct (between arrows) and the portal vein branch at top. (Needle biopsy, H&E.)

Endotheliitis in acute rejection. An efferent vein shows lymphocytic infiltration of its wall. The endothelium is focally lifted off the underlying vein wall and partially destroyed. (Needle biopsy, H&E.)

Graft vs host reaction

Chronic (ductopenic) rejection. An hepatic artery branch (arrow) is present in the portal tract but the corresponding interlobular bile duct has disappeared as a result of rejection. A sparse lymphocytic infiltrate remains. (Explanted donor liver, H&E.)

Vanishing duct syndrome

• Neonatal age– Biliary atresia – Alagalie syndrome

• Adult age– PBC– PSC– Overlap syndrome– Drug induced– Chronic graft vs host rejection– Idiopathic

Summary

• Acute severe liver injury and in advanced stages of fibrosis/cirrhosis – etiological diagnosis usually not possible

• Drug induced liver injury can present with any form of liver injury. Hence we cannot exclude if clinically suspected.

• Fibrosis with normal liver architecture – suspect congenital hepatic fibrosis

Summary

• Excess iron in liver is not always hemochromatosis. Infact most common cause is alcoholic cirrhosis

• Clinically suspected cirrhosis but no fibrosis on biopsy than look for NRH, and hepatic venous outflow obstruction

• Poorly differentiated HCC and cholangiocarcinoma difficult to differentiate – use IHC

References

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3 Gill RM, Kakar s, Washington K. non neoplastic liver diseases and masses of the liver. In: Greenson JK, Hornick JL, Longacre TA, Reuter VE, Sternberg’s diagnositc surgical pathology. 6th ed. China: Wolters Kluwer; 2015. 1663-1704

4 Lefkowitch HJ. SCHEUER’S Liver Biopsy Interpretation. 8th ed. China: Reed Elsevier; 2010

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