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A case of liver sarcoidosis mimicking cirrhosis
Clinical Imaging 31 (2007) 47 – 49
A case of liver sarcoidosis mimicking cirrhosis Spyridon P. Dourakisa,4, Demosthenis D. Cokkinosb, Aspasia S. Soultatia, Alexandra Alexopouloua, Vasiliki Nezia, Athanasios J. Archimandritisa a
2nd Department of Internal Medicine, University of Athens Medical School, Hippocration General Hospital, 114 Vas Sofias Avenues, 11527, Athens, Greece b Radiology Department, Hippocration General Hospital, 114 Vas Sofias Avenues, 11527, Athens, Greece Received 3 June 2006; received in revised form 10 September 2006; accepted 25 September 2006
Abstract Although autopsy series report liver granulomas in up to 70% of patients, computed tomography detection of hepatic and splenic lesions is described in 5% and 15% of sarcoidosis cases, respectively. A rather rare case of liver sarcoidosis mimicking macronodular cirrhosis is presented by this current article. Imaging findings in our patient were in compliance with the diagnosis of liver cirrhosis, although liver biopsy findings eventually revealed sarcoid granulomas located in the portal and lobular areas without fibrotic lesions. Histological and imaging modalities in liver sarcoidosis are discussed. D 2007 Elsevier Inc. All rights reserved. Keywords: Sarcoidosis; Sarcoid hepatic granulomas; Liver macronodular cirrhosis; Abdominal CT imaging
1. Introduction
2. Case report
Sarcoidosis is a disseminated disease defined by the presence of noncaseous granulomas. Digestive localizations are rare and the stomach is the most affected. Sarcoidosis presenting as a liver disease is uncommon, although hepatic granulomas can be identified in approximately two thirds of patients with systemic sarcoidosis. Clinical presentation includes weight loss, hepatomegaly and abnormal liver function tests [1]. A cholestatic syndrome characterized by pruritus and jaundice, hepatic failure or portal hypertension can develop, yet liver involvement is usually clinically silent. Diagnosis of liver sarcoidosis is based on compatible clinicopathological findings from the liver in addition to an injury of at least one more organ or tissue characteristic of the disease [2]. Sarcoid disease of the liver is not infrequently coupled with chronic liver disease and differential diagnosis on that ground is challenging.
A 46 -year-old female patient diagnosed with sarcoidosis was admitted to our hospital for diagnostic evaluation of hepatosplenic enlargement and parenchymal heterogeneity demonstrated in sonographic and magnetic resonance imaging (MRI) findings. Laboratory evaluation on admission revealed the following values: erythrocyte sedimentation rate, 82 mm; C-reactive protein, 15.30 mg/dl, positive antinuclear antibody (titer, 1:160); smooth muscle (1:360) and antineutrophil cytoplasmic antibodies; angiotensinconverting enzyme, 189 mg/dl (normal values, 8– 52 mg/dl); bilirubin, 0.58 mg/dl; alanine and aspartate aminotransferases, 19 and 34 IU/l, respectively; g-glutamyltranspeptidase, 158 IU/l; alkaline phosphatase, 162 IU/l. A contrast-enhanced abdominal computed tomography (CT) scan was performed (Fig. 1). The liver showed a lobular outline, increased size mainly affecting the left lobe and parenchymal inhomogeneity, with fibrous bands surrounding nodular areas, considered at that point as suggestive of macronodular cirrhosis. The upper intrahepatic part of the inferior vena cava and the hepatic veins were compressed. The spleen was also enlarged (with a
4 Corresponding author. 28 Achaias St., 115 23 Athens, Greece. Tel.: +30 210 6918464, +30 6932272477; fax: +30 210 6993693. E-mail address: [email protected] (S.P. Dourakis). 0899-7071/07/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.clinimag.2006.09.020
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S.P. Dourakis et al. / Clinical Imaging 31 (2007) 47 – 49
Fig. 1. Contrast-enhanced abdominal and chest CT imaging: Inhomogeneity and increased size of the liver, with fibrous bands surrounding nodular areas and spleen enlargement, are revealed. In chest CT, high-resolution slice shows micronodular infiltrations in the upper lobes, predominantly on the right. Peripheral intralobular septal thickening is also noted. Contrast-enhanced slice in mediastinal window depicts subcarinal and hilar lymphadenopathy.
craniocaudal diameter of 13 cm) with diffusely decreased attenuation and no focal lesions. A subcapsular effusion was noted in the posterior part of the spleen. Multiple enlarged lymph nodes were observed throughout the abdomen. Chest CT scan findings, completed with high-resolution and contrast-enhanced slices, revealed mediastinal, epiphrenic and axillary lymphadenopathy. The lungs showed micronodular infiltrations in the upper and middle zones. The interstitial peribronchovascular space and peripheral intralobular septa were also affected. A liver biopsy was performed, revealing sarcoid granulomas in the portal and lobular areas and mild lipoid and endolobular inflammatory reaction. No fibrotic lesions were demonstrated. Gallium citrate Ga 67 (5 mCi) scanning was performed and increased absorption was demonstrated in the orbits, bilateral upper pulmonary zones, diffuse hepatic areas, bilateral inguinal, submaxillary, lateral sphage areas and the right colic flexure.
3. Discussion Sarcoidosis can cause progressive liver disease with a wide array of histologic and imaging features that can mimic those of other primary liver diseases. Although imaging studies were suggestive of a cirrhotic liver, no
fibrotic lesions were demonstrated on biopsy studies in our patient. Although autopsy series report liver granulomas in up to 70% of patients, CT detection of hepatic and splenic lesions is described in 5% and 15% of sarcoidosis cases, respectively. Patterns of involvement described include diffuse organomegaly, retroperitoneal lymphadenopathy or a nodular pattern of organ involvement, predominately affecting the splenic parenchyma [3–5]. Hepatosplenic involvement or isolated hepatic lesions (like those demonstrated in our case) are less common [4]. Sarcoid hepatic granulomas manifest as multiple nodules, variable in size, (ranging from 1 mm to 3 cm in diameter) revealed in periportal rather than intraparenchymal locations [6]. Besides granulomatous formation, three broad categories of histologic change can be found: cholestatic, associated with bile duct lesions similar to primary biliary cirrhosis or periductal fibrosis reminiscent of primary sclerosing cholangitis (58%); necroinflammatory, including spotty necrosis or chronic portal inflammation (41%); and vascular, consisting of sinusoidal dilatation and nodular regenerative hyperplasia (20%). Fibrosis can also be demonstrated consisting of periportal (13%), bridging (2%) or cirrhotic lesions (6%) [7]. Cirrhosis and focal fibrosis were suggested to emerge on the ground of ischemia secondary to primary granulomatous phlebitis of portal and hepatic veins [8]. There are several reports of
S.P. Dourakis et al. / Clinical Imaging 31 (2007) 47 – 49
hepatic sarcoidosis presenting associated with chronic hepatitis C virus (HCV) infection, suggesting that HCV itself could induce a granulomatous reaction in chronic HCV-infected patients through the stimulation of the cellular immune system [9]. Regarding liver sarcoidosis, imaging modalities include ultrasonography and CT for detection and differentiation of focal liver lesions [10]. For differentiation of regenerative and dysplastic nodules, contrast-enhanced CT and MRI are the most commonly used modalities. On contrast-enhanced CT, liver nodules present low attenuation and decreased vascularity compared to the surrounding parenchyma [11,12]. Punctate calcifications are also revealed. Nodules can manifest as low-density intrahepatic septa rather than discrete nodules [13]. Hepatic lesions are important for clinical surveillance, as they can improve or disappear following initiation of corticosteroid therapy, but after longterm follow-up, they can reappear and liver cirrhosis can then develop. On MRI, the liver parenchyma is heterogeneous with discrete nodules, contour irregularity, intrahepatic vessel spiculation and/or high periportal signal intensity [14]. In our case, there was hepatomegaly and lobular liver contour, but the nodules were not typically hypoattenuating. The parenchyma showed inhomogeneity, with fibrous bands surrounding the nodules. The findings were more suggestive of macronodular cirrhosis. The enlarged spleen showed no focal lesions and its heterogeneity was considered a result of rapid acquisition of images after contrast injection. Lymphadenopathy was seen throughout the abdomen. Inferior vena cava and hepatic vein compression and a small subcapsular splenic effusion were also observed. In conclusion, liver sarcoidosis can mimic cirrhosis, and on that ground liver images should be considered with skepticism.
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References [1] Amarapurkar DN, Patel ND, Amarapurkar AD. Hepatic sarcoidosis. Indian J Gastroenterol 2003;22:98 – 100. [2] Loginov AS, Aruin LI, Shepeleva SD, Shatalova OL, Tkachev VD, Petrova OP. Sarcoidosis and sarcoid-like granulomas in the liver. Ter Arkh 1990;62:51 – 5. [3] Thanos L, Zormpala A, Brountzos E, Nikita A, Kelekis D. Nodular hepatic and splenic sarcoidosis in a patient with normal chest radiograph. Eur J Radiol 2002;41:10 – 1. [4] Scott GC, Berman JM, Higgins JL. CT patterns of nodular hepatic and splenic sarcoidosis: a review of the literature. J Comput Assist Tomogr 1997;21:369 – 72. [5] Farman J, Ramirez G, Brunetti J, Tuvia J, Ng C, Rotterdam H. Abdominal manifestations of sarcoidosis. CT appearances Clin Imaging 1995;19:30 – 3. [6] Kanel GC, Reynolds TB. Hepatic granulomas. In: Kalowitz N, editor. Liver and biliary diseases. Baltimore7 Williams and Wilkins, 1992. pp. 406 – 14. [7] Devaney K, Goodman ZD, Epstein MS, Zimmerman HJ, Ishak KG. Hepatic sarcoidosis Clinicopathologic features in 100 patients. Am J Surg Pathol 1993;17:1272 – 80. [8] Moreno-Merlo F, Wanless IR, Shimamatsu K, Sherman M, Greig P, Chiasson D. The role of granulomatous phlebitis and thrombosis in the pathogenesis of cirrhosis and portal hypertension in sarcoidosis. Hepatology 1997;26:554 – 60. [9] Bonnet F, Morlat P, Dubuc J, et al. Sarcoidosis-associated hepatitis C virus infection. Dig Dis Sci 2002;47:794 – 6. [10] Hauenstein K, Heller T. Modern, non-invasive diagnostic of focal liver lesions. Rontgenpraxis 2005;55:207 – 21. [11] Kataoka M, Nakata Y, Hiramatsu J, et al. Hepatic and splenic sarcoidosis evaluated by multiple imaging modalities. Intern Med 1998;37:449 – 53. [12] Folz SJ, Johnson CD, Swensen SJ. Abdominal manifestations of sarcoidosis in CT studies. J Comput Assist Tomogr 1995;19:573 – 9. [13] Tsukada T, Katayama N, Taniguchi M, et al. Liver sarcoidosis showing low-density intrahepatic septa on postcontrast computed tomography. Gastroenterol Jpn 1993;28:730 – 3. [14] Kessler A, Mitchell DG, Israel HL, Goldberg BB. Hepatic and splenic sarcoidosis: ultrasound and MR imaging. Abdom Imaging 1993; 18:159 – 63.
A case of liver sarcoidosis mimicking cirrhosis Spyridon P. Dourakisa,4, Demosthenis D. Cokkinosb, Aspasia S. Soultatia, Alexandra Alexopouloua, Vasiliki Nezia, Athanasios J. Archimandritisa a
2nd Department of Internal Medicine, University of Athens Medical School, Hippocration General Hospital, 114 Vas Sofias Avenues, 11527, Athens, Greece b Radiology Department, Hippocration General Hospital, 114 Vas Sofias Avenues, 11527, Athens, Greece Received 3 June 2006; received in revised form 10 September 2006; accepted 25 September 2006
Abstract Although autopsy series report liver granulomas in up to 70% of patients, computed tomography detection of hepatic and splenic lesions is described in 5% and 15% of sarcoidosis cases, respectively. A rather rare case of liver sarcoidosis mimicking macronodular cirrhosis is presented by this current article. Imaging findings in our patient were in compliance with the diagnosis of liver cirrhosis, although liver biopsy findings eventually revealed sarcoid granulomas located in the portal and lobular areas without fibrotic lesions. Histological and imaging modalities in liver sarcoidosis are discussed. D 2007 Elsevier Inc. All rights reserved. Keywords: Sarcoidosis; Sarcoid hepatic granulomas; Liver macronodular cirrhosis; Abdominal CT imaging
1. Introduction
2. Case report
Sarcoidosis is a disseminated disease defined by the presence of noncaseous granulomas. Digestive localizations are rare and the stomach is the most affected. Sarcoidosis presenting as a liver disease is uncommon, although hepatic granulomas can be identified in approximately two thirds of patients with systemic sarcoidosis. Clinical presentation includes weight loss, hepatomegaly and abnormal liver function tests [1]. A cholestatic syndrome characterized by pruritus and jaundice, hepatic failure or portal hypertension can develop, yet liver involvement is usually clinically silent. Diagnosis of liver sarcoidosis is based on compatible clinicopathological findings from the liver in addition to an injury of at least one more organ or tissue characteristic of the disease [2]. Sarcoid disease of the liver is not infrequently coupled with chronic liver disease and differential diagnosis on that ground is challenging.
A 46 -year-old female patient diagnosed with sarcoidosis was admitted to our hospital for diagnostic evaluation of hepatosplenic enlargement and parenchymal heterogeneity demonstrated in sonographic and magnetic resonance imaging (MRI) findings. Laboratory evaluation on admission revealed the following values: erythrocyte sedimentation rate, 82 mm; C-reactive protein, 15.30 mg/dl, positive antinuclear antibody (titer, 1:160); smooth muscle (1:360) and antineutrophil cytoplasmic antibodies; angiotensinconverting enzyme, 189 mg/dl (normal values, 8– 52 mg/dl); bilirubin, 0.58 mg/dl; alanine and aspartate aminotransferases, 19 and 34 IU/l, respectively; g-glutamyltranspeptidase, 158 IU/l; alkaline phosphatase, 162 IU/l. A contrast-enhanced abdominal computed tomography (CT) scan was performed (Fig. 1). The liver showed a lobular outline, increased size mainly affecting the left lobe and parenchymal inhomogeneity, with fibrous bands surrounding nodular areas, considered at that point as suggestive of macronodular cirrhosis. The upper intrahepatic part of the inferior vena cava and the hepatic veins were compressed. The spleen was also enlarged (with a
4 Corresponding author. 28 Achaias St., 115 23 Athens, Greece. Tel.: +30 210 6918464, +30 6932272477; fax: +30 210 6993693. E-mail address: [email protected] (S.P. Dourakis). 0899-7071/07/$ – see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.clinimag.2006.09.020
48
S.P. Dourakis et al. / Clinical Imaging 31 (2007) 47 – 49
Fig. 1. Contrast-enhanced abdominal and chest CT imaging: Inhomogeneity and increased size of the liver, with fibrous bands surrounding nodular areas and spleen enlargement, are revealed. In chest CT, high-resolution slice shows micronodular infiltrations in the upper lobes, predominantly on the right. Peripheral intralobular septal thickening is also noted. Contrast-enhanced slice in mediastinal window depicts subcarinal and hilar lymphadenopathy.
craniocaudal diameter of 13 cm) with diffusely decreased attenuation and no focal lesions. A subcapsular effusion was noted in the posterior part of the spleen. Multiple enlarged lymph nodes were observed throughout the abdomen. Chest CT scan findings, completed with high-resolution and contrast-enhanced slices, revealed mediastinal, epiphrenic and axillary lymphadenopathy. The lungs showed micronodular infiltrations in the upper and middle zones. The interstitial peribronchovascular space and peripheral intralobular septa were also affected. A liver biopsy was performed, revealing sarcoid granulomas in the portal and lobular areas and mild lipoid and endolobular inflammatory reaction. No fibrotic lesions were demonstrated. Gallium citrate Ga 67 (5 mCi) scanning was performed and increased absorption was demonstrated in the orbits, bilateral upper pulmonary zones, diffuse hepatic areas, bilateral inguinal, submaxillary, lateral sphage areas and the right colic flexure.
3. Discussion Sarcoidosis can cause progressive liver disease with a wide array of histologic and imaging features that can mimic those of other primary liver diseases. Although imaging studies were suggestive of a cirrhotic liver, no
fibrotic lesions were demonstrated on biopsy studies in our patient. Although autopsy series report liver granulomas in up to 70% of patients, CT detection of hepatic and splenic lesions is described in 5% and 15% of sarcoidosis cases, respectively. Patterns of involvement described include diffuse organomegaly, retroperitoneal lymphadenopathy or a nodular pattern of organ involvement, predominately affecting the splenic parenchyma [3–5]. Hepatosplenic involvement or isolated hepatic lesions (like those demonstrated in our case) are less common [4]. Sarcoid hepatic granulomas manifest as multiple nodules, variable in size, (ranging from 1 mm to 3 cm in diameter) revealed in periportal rather than intraparenchymal locations [6]. Besides granulomatous formation, three broad categories of histologic change can be found: cholestatic, associated with bile duct lesions similar to primary biliary cirrhosis or periductal fibrosis reminiscent of primary sclerosing cholangitis (58%); necroinflammatory, including spotty necrosis or chronic portal inflammation (41%); and vascular, consisting of sinusoidal dilatation and nodular regenerative hyperplasia (20%). Fibrosis can also be demonstrated consisting of periportal (13%), bridging (2%) or cirrhotic lesions (6%) [7]. Cirrhosis and focal fibrosis were suggested to emerge on the ground of ischemia secondary to primary granulomatous phlebitis of portal and hepatic veins [8]. There are several reports of
S.P. Dourakis et al. / Clinical Imaging 31 (2007) 47 – 49
hepatic sarcoidosis presenting associated with chronic hepatitis C virus (HCV) infection, suggesting that HCV itself could induce a granulomatous reaction in chronic HCV-infected patients through the stimulation of the cellular immune system [9]. Regarding liver sarcoidosis, imaging modalities include ultrasonography and CT for detection and differentiation of focal liver lesions [10]. For differentiation of regenerative and dysplastic nodules, contrast-enhanced CT and MRI are the most commonly used modalities. On contrast-enhanced CT, liver nodules present low attenuation and decreased vascularity compared to the surrounding parenchyma [11,12]. Punctate calcifications are also revealed. Nodules can manifest as low-density intrahepatic septa rather than discrete nodules [13]. Hepatic lesions are important for clinical surveillance, as they can improve or disappear following initiation of corticosteroid therapy, but after longterm follow-up, they can reappear and liver cirrhosis can then develop. On MRI, the liver parenchyma is heterogeneous with discrete nodules, contour irregularity, intrahepatic vessel spiculation and/or high periportal signal intensity [14]. In our case, there was hepatomegaly and lobular liver contour, but the nodules were not typically hypoattenuating. The parenchyma showed inhomogeneity, with fibrous bands surrounding the nodules. The findings were more suggestive of macronodular cirrhosis. The enlarged spleen showed no focal lesions and its heterogeneity was considered a result of rapid acquisition of images after contrast injection. Lymphadenopathy was seen throughout the abdomen. Inferior vena cava and hepatic vein compression and a small subcapsular splenic effusion were also observed. In conclusion, liver sarcoidosis can mimic cirrhosis, and on that ground liver images should be considered with skepticism.
49
References [1] Amarapurkar DN, Patel ND, Amarapurkar AD. Hepatic sarcoidosis. Indian J Gastroenterol 2003;22:98 – 100. [2] Loginov AS, Aruin LI, Shepeleva SD, Shatalova OL, Tkachev VD, Petrova OP. Sarcoidosis and sarcoid-like granulomas in the liver. Ter Arkh 1990;62:51 – 5. [3] Thanos L, Zormpala A, Brountzos E, Nikita A, Kelekis D. Nodular hepatic and splenic sarcoidosis in a patient with normal chest radiograph. Eur J Radiol 2002;41:10 – 1. [4] Scott GC, Berman JM, Higgins JL. CT patterns of nodular hepatic and splenic sarcoidosis: a review of the literature. J Comput Assist Tomogr 1997;21:369 – 72. [5] Farman J, Ramirez G, Brunetti J, Tuvia J, Ng C, Rotterdam H. Abdominal manifestations of sarcoidosis. CT appearances Clin Imaging 1995;19:30 – 3. [6] Kanel GC, Reynolds TB. Hepatic granulomas. In: Kalowitz N, editor. Liver and biliary diseases. Baltimore7 Williams and Wilkins, 1992. pp. 406 – 14. [7] Devaney K, Goodman ZD, Epstein MS, Zimmerman HJ, Ishak KG. Hepatic sarcoidosis Clinicopathologic features in 100 patients. Am J Surg Pathol 1993;17:1272 – 80. [8] Moreno-Merlo F, Wanless IR, Shimamatsu K, Sherman M, Greig P, Chiasson D. The role of granulomatous phlebitis and thrombosis in the pathogenesis of cirrhosis and portal hypertension in sarcoidosis. Hepatology 1997;26:554 – 60. [9] Bonnet F, Morlat P, Dubuc J, et al. Sarcoidosis-associated hepatitis C virus infection. Dig Dis Sci 2002;47:794 – 6. [10] Hauenstein K, Heller T. Modern, non-invasive diagnostic of focal liver lesions. Rontgenpraxis 2005;55:207 – 21. [11] Kataoka M, Nakata Y, Hiramatsu J, et al. Hepatic and splenic sarcoidosis evaluated by multiple imaging modalities. Intern Med 1998;37:449 – 53. [12] Folz SJ, Johnson CD, Swensen SJ. Abdominal manifestations of sarcoidosis in CT studies. J Comput Assist Tomogr 1995;19:573 – 9. [13] Tsukada T, Katayama N, Taniguchi M, et al. Liver sarcoidosis showing low-density intrahepatic septa on postcontrast computed tomography. Gastroenterol Jpn 1993;28:730 – 3. [14] Kessler A, Mitchell DG, Israel HL, Goldberg BB. Hepatic and splenic sarcoidosis: ultrasound and MR imaging. Abdom Imaging 1993; 18:159 – 63.