Granulomas in the liver

doi:10.1053/j.semdp.2006.11.003

Seminars in Diagnostic Pathology

Volume 23, Issues 3–4, August–November 2006, Pages 161-169

https://doi.org/10.1053/j.semdp.2006.11.003 Get rights and content

Granulomatous diseases of the liver span a huge range of infectious, drug-related, and immunologic disorders. Familiarity with the different types of granulomas as well as how they present in different diseases can be helpful in narrowing the pathologic differential diagnosis. This review surveys both common and unusual granulomatous diseases with emphasis on practical diagnosis.

Section snippets

Morphology of granuloma types found in the liver

It is important to note the type and location of granulomas in the liver as these factors may aid in the differential diagnosis.6, 7, 8, 9 Granulomas may be intrinsic to the disease or only incidental. The types of granulomas seen are listed in Table 1, and examples are shown in Figure 1.

Microgranulomas are small collections of macrophages within the hepatic parenchyma, often associated with other inflammatory cells or apoptotic hepatocytes (Figure 1A). As the name implies, they are small,

Diagnostic evaluation of hepatic granulomas

The pathologist plays a key role in the etiologic diagnosis and classification of granulomatous liver disease. Infections may often be identified morphologically more quickly than it takes to culture the organisms. In suspected drug reactions, the finding of granulomatous hepatitis may serve to confirm the diagnosis. Thus, it is important to evaluate the biopsy carefully and systematically. The types and locations of granulomas should be identified. Microgranulomas and lipogranulomas are

Conclusion

The finding of granulomas on liver biopsy can have diverse clinical implications, from none in the case of lipogranulomas and incidental nonnecrotizing epithelioid granulomas, to being a central finding of great significance in the case of granulomatous infections and drug reactions. Attention should be paid to the numbers and types of granulomas, their location within the hepatic acinus, and the types of secondary injury (duct lesions, vasculitis, and hepatitis) present. Granulomas from

Acknowledgments

This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

References (148)

M. Marazuela et al.
Hepatic fibrin-ring granulomas: a clinicopathologic study of 23 patients
Hum Pathol
(1991)
A. Moreno et al.
Hepatic fibrin-ring granulomas in visceral leishmaniasis
Gastroenterology
(1988)
M. Nenert et al.
Epstein-barr virus infection and hepatic fibrin-ring granulomas
Hum Pathol
(1988)
B.H. Stricker et al.
Fibrin ring granulomas and allopurinol
Gastroenterology
(1989)
M. Vanderstigel et al.
Allopurinol hypersensitivity syndrome as a cause of hepatic fibrin-ring granulomas
Gastroenterology
(1986)
J.F. Emile et al.
The presence of epithelioid granulomas in hepatitis c virus-related cirrhosis
Hum Pathol
(1993)
B. Portmann et al.
Sequential and diagnostic features in primary biliary cirrhosis based on serial histologic study in 209 patients
Gastroenterology
(1985)
R.G. Lee et al.
Granulomas in primary biliary cirrhosis: a prognostic feature
Gastroenterology
(1981)
K.G. Ishak et al.
Drug-induced and toxic granulomatous hepatitis
Baillieres Clin Gastroenterol
(1988)
J.S. Hunt et al.
Granulomatous hepatitis: a complication of b.C.G. immunotherapy
Lancet
(1973)

M. Trevenzoli et al.

Sepsis and granulomatous hepatitis after bacillus calmette-guerin intravesical installation

J Infect

(2004)

I.C. Roberts-Thomson et al.

Granulomatous hepatitis and cholangitis associated with giardiasis

Gastroenterology

(1982)

M. Elisaf et al.

Aprindine-induced hepatic granulomata

J Hepatol

(1992)

J.K. Korinek et al.

Trichosporon hepatitis

Gastroenterology

(1983)

N.S. Sarachek et al.

Diltiazem and granulomatous hepatitis

Gastroenterology

(1985)

G.P. Jori et al.

Hydralazine disease associated with transient granulomas in the liverA case report

Gastroenterology

(1973)

C. Cho et al.

Sarcoidlike granulomas as an early manifestation of whipple’s disease

Gastroenterology

(1984)

M. Braun et al.

Mesalamine-induced granulomatous hepatitis

Am J Gastroenterol

(1999)

E. Bjornsson et al.

Norfloxacin-induced eosinophilic necrotizing granulomatous hepatitis

Am J Gastroenterol

(2000)

W. Britton

Type iv hypersensitivity

A. Zumla et al.

Granulomatous infections: etiology and classification

Clin Infect Dis

(1996)

S. Gordon

Mononuclear phagocytes in immune defense

J. Ma et al.

Regulation of macrophage activation

Cell Mol Life Sci

(2003)

M.C. Sneller

Granuloma formation, implications for the pathogenesis of vasculitis

Cleve Clin J Med

(2002)

H. Denk et al.

Guidelines for the diagnosis and interpretation of hepatic granulomas

Histopathology

(1994)

P.T. Harrington et al.

Granulomatous hepatitis

Rev Infect Dis

(1982)

J.H. Lefkowitch

Hepatic granulomas

J Hepatol

(1999)

P.J. Scheuer

Hepatic granulomas

Br Med J (Clin Res Ed)

(1982)

P. Christoffersen et al.

Lipogranulomas in human liver biopsies with fatty changeA morphological, biochemical and clinical investigation

Acta Pathol Microbiol Scand [A]

(1971)

P. Petersen et al.

Ultrastructure of lipogranulomas in human fatty liver

Acta Pathol Microbiol Scand [A]

(1979)

H.P. Dincsoy et al.

Lipogranulomas in non-fatty human liversA mineral oil induced environmental disease

Am J Clin Pathol

(1982)

I.R. Wanless et al.

Mineral oil lipogranulomata in liver and spleenA study of 465 autopsies

Arch Pathol Lab Med

(1985)

J.R. Srigley et al.

Q-feverThe liver and bone marrow pathology

Am J Surg Pathol

(1985)

M. Ruel et al.

Fibrin ring granulomas in hepatitis a

Dig Dis Sci

(1992)

D.H. Lobdell

‘Ring’ granulomas in cytomegalovirus hepatitis

Arch Pathol Lab Med

(1987)

L. de Bayser et al.

Hepatic fibrin-ring granulomas in giant cell arteritis

Gastroenterology

(1993)

E. Murphy et al.

Fibrin-ring granulomas: a non-specific reaction to liver injury?

Histopathology

(1991)

V. Tahan et al.

Prevalence of hepatic granulomas in chronic hepatitis b

Dig Dis Sci

(2004)

R.D. Goldin et al.

Granulomas and hepatitis c

Histopathology

(1996)

K. Harada et al.

Epithelioid cell granulomas in chronic hepatitis c: immunohistochemical character and histological marker of favourable response to interferon-alpha therapy

Histopathology

(1998)

R. Ozaras et al.

The prevalence of hepatic granulomas in chronic hepatitis c

J Clin Gastroenterol

(2004)

J. Ludwig et al.

Granulomas in primary sclerosing cholangitis

Liver

(1995)

Y. Nakanuma et al.

Quantitation of hepatic granulomas and epithelioid cells in primary biliary cirrhosis

Hepatology

(1983)

P. Scheuer

Primary biliary cirrhosis

Proc R Soc Med

(1967)

S. Sherlock

Primary biliary cirrhosis

Mt Sinai J Med

(1977)

H.D. Hercules et al.

Value of liver biopsy in sarcoidosis

Arch Pathol Lab Med

(1984)

E. Lehmuskallio et al.

The liver in sarcoidosis

Acta Med Scand

(1977)

S.M. Rasmussen et al.

SarcoidosisA clinical study with special reference to the choice of biopsy procedure

Acta Med Scand

(1976)

K. Devaney et al.

Hepatic sarcoidosisClinicopathologic features in 100 patients

Am J Surg Pathol

(1993)

J.A. Winkelstein et al.

Chronic granulomatous diseaseReport on a national registry of 368 patients

Medicine (Baltimore)

(2000)

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Granulomas in the liver

Section snippets

Morphology of granuloma types found in the liver

Diagnostic evaluation of hepatic granulomas

Conclusion

Acknowledgments

Hum Pathol

Gastroenterology

Hum Pathol

Gastroenterology

Gastroenterology

Hum Pathol

Gastroenterology

Gastroenterology

Baillieres Clin Gastroenterol

Lancet

J Infect

Gastroenterology

J Hepatol

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Am J Gastroenterol

Am J Gastroenterol

Type iv hypersensitivity

Granulomatous infections: etiology and classification

Clin Infect Dis

Mononuclear phagocytes in immune defense

Regulation of macrophage activation

Cell Mol Life Sci

Granuloma formation, implications for the pathogenesis of vasculitis

Cleve Clin J Med

Guidelines for the diagnosis and interpretation of hepatic granulomas

Histopathology

Granulomatous hepatitis

Rev Infect Dis

Hepatic granulomas

J Hepatol

Hepatic granulomas

Br Med J (Clin Res Ed)

Lipogranulomas in human liver biopsies with fatty changeA morphological, biochemical and clinical investigation

Acta Pathol Microbiol Scand [A]

Ultrastructure of lipogranulomas in human fatty liver

Acta Pathol Microbiol Scand [A]

Lipogranulomas in non-fatty human liversA mineral oil induced environmental disease

Am J Clin Pathol

Mineral oil lipogranulomata in liver and spleenA study of 465 autopsies

Arch Pathol Lab Med

Q-feverThe liver and bone marrow pathology

Am J Surg Pathol

Fibrin ring granulomas in hepatitis a

Dig Dis Sci

‘Ring’ granulomas in cytomegalovirus hepatitis

Arch Pathol Lab Med

Hepatic fibrin-ring granulomas in giant cell arteritis

Gastroenterology

Fibrin-ring granulomas: a non-specific reaction to liver injury?

Histopathology

Prevalence of hepatic granulomas in chronic hepatitis b

Dig Dis Sci

Granulomas and hepatitis c

Histopathology

Epithelioid cell granulomas in chronic hepatitis c: immunohistochemical character and histological marker of favourable response to interferon-alpha therapy

Histopathology

The prevalence of hepatic granulomas in chronic hepatitis c

J Clin Gastroenterol

Granulomas in primary sclerosing cholangitis

Liver

Quantitation of hepatic granulomas and epithelioid cells in primary biliary cirrhosis

Hepatology

Primary biliary cirrhosis

Proc R Soc Med

Primary biliary cirrhosis

Mt Sinai J Med

Value of liver biopsy in sarcoidosis

Arch Pathol Lab Med

The liver in sarcoidosis

Acta Med Scand

SarcoidosisA clinical study with special reference to the choice of biopsy procedure