This document provides an overview of liver biopsy interpretation. It discusses the indications for liver biopsy, techniques used, histological examination and staining, and the approach to interpreting different pathological conditions of the liver seen on biopsy. Key points include the use of biopsy to diagnose and assess liver damage and prognosis, techniques including percutaneous and transjugular biopsies, examining features such as necrosis, inflammation, fibrosis and cirrhosis, and interpreting conditions like viral hepatitis, autoimmune hepatitis, non-alcoholic fatty liver disease, and hemochromatosis.

1. Liver biopsy interpretation
Presenter - Dr. Dhanya A N
Moderator – Dr. Ramesh S T

2. 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

3. 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

4. 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

5. 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

6. Techniques of liver biopsy
1. Percutaneous
- Transthoracic
– Subcostal
• Blind procedure
• Image guided – USG, CT,
MRI
• Plugged liver biopsy
– Gelatin, gel foam
plugged

7. 2. Transvenous (Transjugular)
• Done in coagulation
disorders or ascites
• Performed in a vascular
catheterisation laboratory
with videofluoroscopy
equipment and proper
cardiac monitoring

8. 3. Laparoscopic liver biopsy
• Transvenous liver
biopsy is not available,
• In patients who have a
combination of a focal
liver lesion and a
coagulopathy.

9. 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.

11. Vim silverman needle

12. Tru cut needle

13. 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

14. Special stains
Masson trichrome, stains blue color to
collagen and red color to hepatocyesH & E stain of hepatic lobule

15. 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

16. Special stains
PAS+diastase for aplha1 antitrypsin deficiency
Hapatocytes have taken magenta color
Oil Red O stain highlighting fat
globules in a frozen section of the
liver.

17. 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 polarized
microscopy (inset)

18. 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.
P
P
Reticulin stain of micronodular cirrhosis
Stains collagen

19. 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

20. 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

21. 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

22. Conti..
• Space of disse – lies below the endothelial lining
of sinusoids has stellate cells
• Kupffer cells- mononuclear phagocytic cells, on
luminal side of sinusoids

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

24. 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

25. 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

26. • 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

27. Bridging necrosis
p
c

28. Panlobular and multilobular necrosis

29. Scar formation and regression
• Stellate cells – most important, myofibroblastic properties

30. 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

31. Acute viral hepatitis

32. 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

33. Acute viral hepatitis
bridging necrosis. curved lines of necrotic debris and
collapse extend from a portal tract to cetral venule.
C
P

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

35. Fate and morphological sequel of
acute viral hepatitis
• Resolution
• Scarring
• Chronic hepatitis
• Cirrhosis
• Acute liver failure
• Hepatocellular carcinoma

36. 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

37. 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)

38. 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.)

39. 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.

40. Chronic hepatitis C
• The portal tract is
heavily infiltrated by
lymphocytes,
• A lymphoid follicle
with germinal
center has formed
• 15-25% may have
steatosis

41. Autoimmune hepatitis
• Female predilection
• Chronic progressive hepatitis with features of
autoimmune diseases
– Genetic predisposition
– Associated with other autoimmune disorders
– Therapeutic response to immunosuppression

42. 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

43. Autoimmune hepatitis
Interface hepatitis
Plasma cell predominates in the mononuclear inflammatory infiltrate

44. Autoimmune hepatitis
Hepatocytes rosettes in areas of activityConfluent necrosis, parenchymal collapse
Plasma cell infiltration seen (characteristic)

45. Drug induced hepatitis

46. Conti..

47. Necroinflammatory score for
chronic hepatitis (HAI/Knodell score)

48. Conti…

49. 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

50. 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.

51. 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

52. 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)

53. 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

54. Cirrhosis
Cirrhosis: micronodular pattern.
Nodules are of lobular size or smaller
, reticulin stain
Cirrhosis: macronodular pattern.
Nodules are larger than 3 mm, reticulin
stain

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

56. 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.)

57. 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.)

58. 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.)

59. 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

60. Ishak score for Staging of fibrosis

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

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

63. 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)

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

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

66. 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

67. 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 )

68. NAFLD Score

69. 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

70. 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

71. Classification of hemochromatosis

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

73. 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

74. 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.)

75. 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

76. 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

77. 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

78. 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

79. Niemann–Pick disease
• Lysosomal accumulation of sphingomyelin due
to an inherited deficiency of sphingomyelinase

80. 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

81. 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.

82. 𝛂1- Antitrypsin deficiency
Hepatocytes near periportal region contain mutated
proteins, and stained magenta color for PAS+diastase .
May also show steatosis, necrosis and fibrosis

83. 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

84. 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

85. Large bile-duct obstruction
• Dilatation
intercanaliculi
• Portal tract edema
• Bile duct proliferation
at the margin of
portal tract
• Mild inflammatory
infiltrate

86. Chronic bile-duct obstruction and
biliary cirrhosis(secondary biliary
cirrhosis)
Bile duct obstruction persists, bile duct infarct and increasing fibrosis.
Jigsaw puzzle shape

87. 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

88. Stages of primary biliary cirrhosis

89. Primary biliary cirrhosis
Grannulomatous lesion
surrounding bile duct with
mononuclear cell infiltration
Florid duct lesion

90. Primary biliary cirrhosis
Ductular reaction with periportal hepatitis A lymphoid aggregate and
a follicle with a germinal Centre (arrow)

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

92. 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

93. Primary sclerosing cholangitis
A bile duct undergoing degeneration is entrapped
in a dense, “onion-skin” concentric scar

94. Cholestasis of sepsis
• By 3 main mechanism
1. 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)

95. 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

96. 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%)

97. Cont..
• Fetal form
– Malrotation of abdominal viscera
– Interruptured inferior vena cava
– Polysplenia
– Congenital heart disease
• Perinatal form
– Viral (reovirus, rotavirus, CMV)
– Autoimmune reaction

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

99. 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

100. 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).

101. 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

102. 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.)

103. Granulomatous lesion

104. TB Granuloma
Sarcoid Granuloma
PBC Granuloma Fibrin Granuloma

105. Nodules and tumors

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

107. 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 .

108. 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

109. 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.)

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

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

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

113. 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)

114. Hepatocellular carcinoma
Trabeculae-sinusoidal pattern, trabeculae are
thicker and reticulin is often scanty or even
absent, (HandE)
Reticulin is scanty in this example.
Reticulin stain

115. Hepatocellular carcinoma
Adenoid pattern.

116. 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

117. 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

118. 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.

119. 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)

120. 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

121. 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.)

122. 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

123. 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

124. 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

125. 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

126. 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.)

127. 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.)

128. Vanishing duct syndrome
• Neonatal age
– Biliary atresia
– Alagalie syndrome
• Adult age
– PBC
– PSC
– Overlap syndrome
– Drug induced
– Chronic graft vs host rejection
– Idiopathic

129. 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

130. 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

132. References
1. Theise ND. Liver and gall bladder. In: kumar,
Abbas, Aster, Robbins and Cotran Pathologic
Basis of Disease. 9th ed. New Delhi: Reed
Elsevier India Private limited; 2014. 185-263
2. Desmet VJ, Rosai J. Liver. In: Rosai J, Rosai and
ackerman’s surgical pathology. 10th ed. New
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