Various Granulomatous lesions in the liver -pathology

1. Dr. Karishma A. Korgaonker
Moderator : Dr . Zulfikar

2. Granuloma
•What ??

3. aggregates of macrophages
Modified
macrophages>epitheloid
cells>giant cells
Admixed with other
inflammatory cells

4. • Why???

5. Granuloma contd…
Chronic inflammation
Granulomas : cellular
attempt to contain offending
agent ,difficult to eradicate

6. How ????

8. •Where????

9. *Granulomatous lesions in
liver*
• >present in 3 – 15% liver biopsies
• >cause unknown in half the cases
• >requires careful histological evaluation of
granuloma and associated changes.

10. Classification ( etiology)
*Infectious
A. bacterial
B. parasitic
C. viral
D. fungal
*Non infectious
A. Liver disorders
B. Chronic gastrointestinal
diseases
C. Vasculitides
D. Foreign material
E. Systemic disorders
F. Drugs
G. Inherited diseases
H. Neoplasm

11. Infectious etiology…..
A. Bacterial
B. Parasitic
C. Viral
D. fungal

12. Bacteria
Mycobacterium tuberculosis =
• miliary tuberculosis
• range from asymptomatic to fever, right
upper quadrant pain ,hepatomegaly
• Tuberculoma

13. Microscopy
Two granulomatous lesions consisting of
epitheloid cells ,multinucleated giant cells and
marginal lymphocytes , the larger one shows
areas of caseous necrosis

14. • Histologic hallmark:
• epitheloid granuloma
with caseation and giant cells surrounded
by ring of lymphocytes and histiocytes
• Fibrosis and calcification in older cases
• Elevated bilirubin ,transaminase
• Dispropotionately high alkaline phosphate
Test : Culture

15. Mycobacterium avium
intracellulare
• common in immunocompromised patients
• Liver involved in 50% of disseminated diseases
• Immunocompetent : discrete epitheloid
granulomas with neutrophils ,lymphocytes , giant
cells and necrosis is rare

16. • Immunocompromised : aggregates of
foamy macrophages in the parenchyma
and portal tracts
• Test : Culture
• AFB : weak in immunocompetent
• Other mycobacteria : M. Kansasi

17. LEPROSY
Both tuberculoid and lepromatous leprosy
involve the liver
Lesions depend on type of leprosy

18. • Lepromatous leprosy >aggregates of
foamy histiocytes in portal tracts and
lobules
>Numerous AFB
>Minimal inflammation
Tuberculoid leprosy
>Discrete tuberculoid granulomas with giant
cells
>Bacilli rare

19. CAT SCRATCH DISEASE
Bartonella henselae
Isolated lymphadenopaty in area draining
cat scratch innoculation
 2% develop liver lesions

20. *Characteristic lesions
1) Irregular
2) Stellate microabscessess surrounded by
an inner layer of palisading histiocytes
and rim of lymphocytes with an
outermost thick layer of fibrous tissue
3) Outer fibrous zone is pronounced in the
liver

21. Catscratch..
• Test : exposure to cat
• Silver
impregnation stain

22. BRUCELLOSIS
• Exposure to farm animals ,
contaminated food.
• Liver involved in half the cases
• Test : History, serology

23. Microscopy :
Microgranulomas seen consisting of
lymphocytes,plasma cells and
macrophages.

24. TULAREMIA
• Granulomatous disease
• Francisella tularensis
• Transmitted though contact with
rodents

25. • Lesion in occur in lymph nodes
,spleen ,liver ,lungs and heart
• Necrosis surrounded by perimeter of
granulomatous reaction
• Resemble tuberculosis

26. Benign Tertiary syphilis
• Appearance of gummas – hallmark
• Granulomatous lesions composed of
central area of coagulative
necrosis,epitheloid macrophages ,
occasional giant cells and fibrosis

27. Actinomycosis :
Colonies of
actinomycosis with
cuff of inflammatory
cells
Silver impregnation

28. Infectious etiology…..
A. Bacterial
B. Parasitic
C. Viral
D. Fungal

29. Parasites
 Schistosomiasis
S.mansoni and S. japonicum
Granuloma formation and hepatic fibrosis
 portal hypertension, spleenomegaly ,
oesophageal varices

30. Continued..
• Gross: liver enlarged and nodular( pin
head granuloma)
• C/s: portal fibrosis: pipestem or symmers
fibrosis

31. Schistosoma egg provoked granulomatous
reaction . Granuloma contains macrophages ,
concentric ring of fibroblasts and collagen fibres
with few lymphocytes, eosinophils

32. Visceral leishmaniasis
Leishmania donovani -Obligate
intracellular parasite
Hepatospleenomegaly ,pancytopenia,
 lymphadenopathy
Culture and histological examination

33. L.D bodies seen within the swollen kupffer
cells . These are small round bodies 2-4
micrometers seen in spleenic and hepatic
aspirates . Kupffer cell involvement indicate
chronic cases

34. Toxocariasis
• Visceral lava migrans
• Rare disease in chidren
• Infestation of nematode ova excreted
in dog feaces

35. Enterobius vermicularis ( pin worm)
• Rare
• Central necrosis with eggs and worms
Fasciola hepatica = calculi ,cholangitis
with granuloma

36. Infectious etiology…..
A.Bacterial
B.Parasitic
C.Viral
D.Fungal

37. VIRAL INFECTIONS
• EBV =
Infectious mononucleosis
Infects B – lymphocytes
Lymphocytosis seen
Paul bunnell antibodies
•

38. • CMV :
• Congenital and opportunistic
pathogen
• Brain, liver
• Symptoms vary depending on
immunity
• *Epitheloid granuloma
• * Fibrin ring granuloma

39. Hepatitis C =
Common cause of chronic hepatitis
,cirrhossis and hepatocellular
carcinoma
 epitheloid
granulomas

40. Infectious etiology…..
A. Bacterial
B. Parasitic
C. Viral
D. Fungal

41. Fungal
• Immunocompromised
• Hepatomegaly
• Abdominal pain
• Increase in transaminase and bilirubin
• H and E when numerous
• Culture – gold standard

42. Fungal…
Candidiasis: granulomatous lesions
with suppurative area and variable
necrosis
• Occasionally giant cells present

43. Histoplasma –
 portal lymphocytichistiocytic
inflammatory lesion
Sinusoidal kupfer cell hyperplasia
Necrotising caseating granulomas

44. Fungal…
Aspergillosis: minimal to marked
neutrophilic infiltrate , granulomatous
inflammation

45. Cryptococcus: variable
inflammatory reaction depending on
immune status
Asymptomatic to necrotizing reaction

46. Non infectious causes
. Chronic liver diseases
 . Chronic GI disease
. Vasculitides
 . Adverse drug reaction
 . Metal toxicity
 .Foreign material
 .Inherited disorders
 .Reaction to neoplasms
 . Sarcoidosis

47. Chronic liver disease
Primary biliary cirrhosis = portal or
lobular granulomas with duct lesions
Primary sclerosing cholangitis = non –
necrotising , well formed epitheloid
granulomas

48. Primary biliary cirhossis=Small caseating
granuloma seen with *absence of bile ducts
and ductules *

49. Liver in
=
>Small bile
duct lined by
degenerated
epithelium .
>Lymphocytes
and plasma
cells seen .

50. Ulcerative
colitis
Small bile
duct
surrounded
by cuff of
inflammatory
cells

51. Polyarteritis nodosa
• : Systemic vasculitis of small /
medium sized muscular arteries
• PAN asso. Wt chronic Hepatitis
• Kidneys > heart > liver > GIT are
involved

52. Reactions to Neoplasm
Hodgkins disease
Primary hepatic tumour
Metastasis:

53. Foreign body
• TALC
• STARCH

54. Chronic granulomatous disease :
 failure of phagocytic cells to kill
organisms
recurrent bouts of infection
 formation of granuloma in many
organs
The nitroblue-tetrazolium (NBT) test

55. Sarcoidosis
Multisystem granulomatous disease
Secondary to lungs and lymph node
May resemble primary biliary
cirrhosis
•

56. Sarcoidosis
Microscopy shows
>typical >>non –
caseating
epitheloid
granulomas.
>>portal or
periportal areas

57. Diagnosis
 bilateral hilar lymphadenopathy on
xray
Peripheral lymphadenopathy
Cutaneous lesions, eye involvment

58. Adverse Drug reactions
• Poorly or well formed granuloma
• Examples : allopurinol , nitrofurantoin
, phenytoin ,hydralazine

59. ***Granulomatous inflammation + significant
hepatocellular injury = drug associated injury

60. Classification ( morphology)
• Divided into following morphologic categories
a) Epitheloid granuloma
b) Fibrin ring granuloma
c) Lipogranuloma
d) Microgranuloma
e) Foamy macrophagic aggregates
f) Granulomatous inflammation
g) Stellate abscess

61. Epitheloid granuloma
Discrete lesions with discrete edges
Infectious etiology
Architecture of liver destroyed
in necrotising granuloma
Examples:
Tuberculosis,brucellosis,leprosy,syphilis

62. Fibrin ring granulomas
Epitheloid granuloma with a central lipid
vacuole surrounded by a fibrin ring
Examples: Q-fever ,CMV,EBV, drug
reactions, MAI infections

63. Lipogranuloma
Contain lipid
Mineral oils in food
Not associated with fatty liver disease

64. Microgranuloma
3-7 cells in cross section mixed with
inflammatory cells
Non – specific
Rarely seen in listeria

65. Foamy macrophages
aggregates
Immunocompromised
Little inflammatory response
Seen in : MAI, Lepromatous leprosy,
Histoplasmosis, Leishmaniasis

66. Granulomatous inflammation
(with or without prominent suppurative
inflammation )
Poorly formed granulomas
Indistinct edges
Seen in : tularemia ,

67. Stellate abscess along with
granulomatous inflammation
Actinomycosis
Tularemia
Chronic granulomatous disease

68. ????Questions to ask
• ?Morphology of granuloma
• ?Accompanying inflammatory infiltrate
• ?Location of granuloma

69. • ?Nature of necrosis if present
• ?Is there anything in the granuloma other
associated morphological changes
• ?Need for special stains

70. Diagnosis
Blood tests = evaluate liver function
Blood cultures = identify the cause
Biopsy = to confirm the diagnosis.

71. Diagnosis…..
Imaging tests
• Ultrasonography
• computed tomography (CT)
• magnetic resonance imaging (MRI)
*These tests are useful in showing the age
of the granuloma which may calcify with
age

72. The underlying disorder is treated.
When cause is unknown, treatment is
usually withheld, and follow-up with
periodic liver function tests is instituted.
 Corticosteroids may benefit patients with
progressive hepatic sarcoidosis
Treatment

73. Prognosis
 Hepatic granulomas caused by drugs or
infection regress completely after
treatment.
Sarcoid granulomas may disappear
spontaneously or persist for years,without
causing clinically important liver disease.
•

74. Prognosis ….
• Progressive fibrosis and portal
hypertension (sarcoidal cirrhosis) may
develop.
• In schistosomiasis, progressive portal
scarring (pipestem fibrosis) is typical;
marked splenomegaly and variceal
hemorrhage can occur.

75. References
• Rosai and Ackerman’s surgical pathology 10th edition
volume one pg 962 -963
• http://www.pathologyportal.org/97th/pdf/companion05h0
3.pdf
• http://www.merckmanuals.com/professional/hepatic_and
_biliary_disorders/liver_masses_and_granulomas/hepati
c_granulomas.html
• Davidsons principles and practice of medicine 19th
edition
• Colour atlas of liver pathology by R.S patrick
• Robbins and Cotran Pathologic basis of disease