Radiologic Mimics of Cirrhosis

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1 Gastrointestinal Imaging Pictorial Essay Jha et al. Radiologic Mimics of Cirrhosis Gastrointestinal Imaging Pictorial Essay Priyanka Jha 1 Liina Poder Zhen J. Wang ntonio C. Westphalen enjamin M. Yeh Fergus V. Coakley Jha P, Poder L, Wang ZJ, Westphalen C, Yeh M, Coakley FV Keywords: cirrhosis, liver, liver disease, pseudocirrhosis DOI: /JR Received July 30, 2009; accepted after revision September 15, Z. J. Wang was supported by an NII training grant (1 T32 E001631). 1 ll authors: Department of Radiology, University of California, San Francisco, 505 Parnassus ve., ox 0628, M-372, San Francisco, C ddress correspondence to F. V. Coakley (Fergus.Coakley@ radiology.ucsf.edu). CME This article is available for CME credit. See for more information. JR 2010; 194: X/10/ merican Roentgen Ray Society Radiologic Mimics of Cirrhosis OJECTIVE. The objective of this article is to provide a practical review of the conditions other than cirrhosis that can result in diffuse surface nodularity of the liver or portal hypertension. CONCLUSION. Conditions that can mimic cirrhosis on imaging include pseudocirrhosis of treated breast cancer metastases to the liver, fulminant hepatic failure, miliary metastases, sarcoidosis, schistosomiasis, congenital hepatic fibrosis, idiopathic portal hypertension, early primary biliary cirrhosis, chronic udd-chiari syndrome, chronic portal vein thrombosis, and nodular regenerative hyperplasia. C T of patients with established cirrhosis shows diffuse surface nodularity of the liver and also may show decreased liver volume with relative hypertrophy of the left and caudate lobes or signs of portal hypertension. When seen at imaging, diffuse hepatic surface nodularity or signs of portal hypertension (i.e., splenomegaly, ascites, or portosystemic varices) are usually due to cirrhosis, but other conditions can also cause these findings. Knowledge of radiologic mimics of cirrhosis is increasingly important because some have been described only recently and because an erroneous diagnosis of cirrhosis in some settings could adversely impact contemporary treatment options. For example, underlying cirrhosis lowers the transplantation status of patients with acute hepatic failure. This article aims to provide a practical and current review of the conditions other than cirrhosis that can result in diffuse hepatic surface nodularity or signs of portal hypertension. Noncirrhotic Causes of Diffuse Hepatic Surface Nodularity General Comments Diffuse irregularity of the hepatic contour may be fine or coarse (ppendix 1). Causes of coarse lobulation include chronic udd- Chiari syndrome, chronic portal vein thrombosis, and pseudomyxoma peritonei [1]. The hepatic contour changes due to these conditions usually are easily distinguishable from cirrhosis because of characteristic features. The nodularity associated with cirrhosis is typically relatively fine and diffuse rather than coarse and lobulated [2]. However, noncirrhotic causes of fine, diffuse nodularity are occasionally encountered and include pseudocirrhosis of treated breast cancer metastases to the liver, fulminant hepatic failure, miliary metastases, and sarcoidosis [3 6]. Pseudocirrhosis of Treated reast Cancer Metastases to the Liver variety of hepatic contour changes can occur in breast cancer patients with metastases to the liver after chemotherapy including fine, diffuse nodularity that resembles cirrhosis (Fig. 1), which is commonly referred to as pseudocirrhosis [3]. Multifocal retraction of the liver capsule and enlargement of the caudate lobe also can be seen in this setting. The histopathologic or pathophysiologic basis of these changes is not well understood, and the prefix pseudo- may be a misnomer because these patients can develop features of portal hypertension such as portosystemic venous collaterals and bland ascites (Figs. 1 and 2). Why this phenomenon seems almost specific for breast cancer (Fig. 3) remains unclear, with only sporadic reports of these changes in other primary malignancies with liver metastases [7]. Fulminant Hepatic Failure Fulminant hepatic failure constitutes acute severe impairment of hepatic function in the absence of preexisting liver disease and receives higher priority for hepatic transplantation than JR:194, pril

2 Jha et al. hepatic failure developing in the setting of cirrhosis. The distinction of acute from acute-onchronic hepatic failure may be clinically difficult and hepatic surface nodularity might be considered indicative of underlying cirrhosis, adversely impacting transplantation status. Recently, fulminant hepatic failure alone was shown to result in diffuse surface nodularity because of a combination of alternating foci of confluent regenerative nodules and necrosis rather than cirrhosis [8] (Figs. 4 and 5). Miliary Metastases Diffuse surface nodularity due to miliary metastases is rare (Figs. 6 and 7) and is unlikely to mimic cirrhosis. In a large ultrasound study [4] of hepatic metastases (n = 225), surface irregularity was observed in 16 patients (7%); in only two patients, one with squamous cell carcinoma of the tonsil and one with ovarian carcinoma, was surface nodularity the only sign of metastatic disease [4]. Sarcoidosis Sarcoidosis of the liver is common pathologically but is rarely visible at imaging because the noncaseating granulomas are usually microscopic. Occasionally, hepatic sarcoidosis can be visible as diffuse granular heterogeneity with or without fine nodularity of the hepatic surface [5] (Figs. 8 and 9). Noncirrhotic Causes of Portal Hypertension General Comments Noncirrhotic causes of portal hypertension (ppendix 2) include chronic udd- Chiari syndrome, chronic portal vein thrombosis, sarcoidosis, schistosomiasis, nodular regenerative hyperplasia, congenital hepatic fibrosis, idiopathic portal hypertension, and early primary biliary cirrhosis [9]. Nodular Regenerative Hyperplasia Nodular regenerative hyperplasia is a rare but increasingly recognized condition characterized by widespread transformation of normal liver parenchyma into hyperplastic regenerative nodules that vary in size from microscopic to large and masslike [10]; the absence of fibrosis distinguishes nodular regenerative hyperplasia from cirrhosis. From a radiologic perspective, there appear to be two forms of the condition: a diffuse form in which the nodules are small and a widespread and a focal form in which the nodules are few in number, are scattered throughout the liver, and measure up to a few centimeters. The pathogenesis of diffuse nodular regenerative hyperplasia is unknown, but there are well-recognized associations (ppendix 3) with systemic cardiovascular, myeloproliferative, and autoimmune diseases, particularly systemic lupus erythematosus; the administration of certain drugs including chemotherapy; solid organ and bone marrow transplantation; and HIV infection [10]. Focal nodular regenerative hyperplasia has been primarily reported in long-standing udd-chiari syndrome, although similar masses have also been reported in autoimmune hepatitis [11, 12]. Diffuse nodular regenerative hyperplasia frequently results in noncirrhotic portal hypertension [10], and affected patients may present with variceal bleeding or hypersplenism. Imaging findings in patients with nodular hyperplasia can be subtle across all techniques, although parenchymal findings may be more obvious on ultrasound than on CT or MRI [13]. t ultrasound, widespread nodularity suggestive of cirrhosis or multiple masses may be seen (Fig. 10). t CT, the nodules may be hypodense with little enhancement. t MRI, diffuse nodular regenerative hyperplasia is usually of similar signal intensity to the liver on T1, T2, and gadolinium-enhanced sequences. Surface nodularity and features of portal hypertension may be seen across all techniques (Fig. 11). In focal nodular regenerative hyperplasia, CT or MRI typically shows multiple hypervascular masses in a patient with long-standing udd-chiari syndrome or autoimmune hepatitis. These masses may suggest metastases or hepatocellular carcinoma, although stability on follow-up studies or biopsy should help in making the correct diagnosis. Early Primary iliary Cirrhosis Investigators recently found that portal hypertension can develop early in primary biliary cirrhosis even before the onset of cirrhosis [14] possibly resulting from compression of the portal venous branches by granulomatous inflammation causing presinusoidal fibrosis and portal hypertension [14]. This condition has been described as the portal hypertensive variant of primary biliary cirrhosis and appears to carry a higher risk of hepatocellular carcinoma than the other variants of primary biliary cirrhosis. Congenital Hepatic Fibrosis Hepatic involvement in this multisystem autosomal recessive disorder consists of widespread periportal fibrosis leading to portal hypertension [15]. Portal vein thrombosis is common, and segmental biliary dilatation may also be observed (Fig. 12). Idiopathic Portal Hypertension Idiopathic portal hypertension is characterized by long-standing presinusoidal portal hypertension of unknown cause in adults and may reflect damage to the intrahepatic small portal veins or portal tracts by an immunologic disturbance, thromboembolism, or an infection. Imaging findings (Fig. 13) include subcapsular parenchymal atrophy, portal and parenchymal fibrosis, and portal venous thrombosis. Interestingly, cirrhosis does not develop even in the advanced stages of the disease [16]. Conclusion Diffuse surface nodularity of the liver or signs of portal hypertension usually reflect underlying cirrhosis, but noncirrhotic causes of these imaging findings include pseudocirrhosis of treated breast cancer metastases to the liver, fulminant hepatic failure, miliary metastases, sarcoidosis, schistosomiasis, congenital hepatic fibrosis, idiopathic portal hypertension, early primary biliary cirrhosis, chronic udd-chiari syndrome, chronic portal vein thrombosis, and nodular regenerative hyperplasia. Pseudocirrhosis of treated breast cancer metastases can be easily identified by reviewing the patient s medical history and prior imaging examinations. Pseudocirrhosis of fulminant hepatic failure should be considered in previously healthy patients with acute liver decompensation. Miliary metastases should be considered when fine hepatic surface nodularity is seen in a patient with a known primary malignancy and no signs of portal hypertension. raised serum angiotensin-converting enzyme level or mediastinal adenopathy suggests sarcoidosis. Congenital hepatic fibrosis should be considered in children with findings of portal hypertension, particularly if there are cysts in the kidneys. smooth liver of normal size with features of portal hypertension should raise suspicion for idiopathic portal hypertension, but biopsy may be required because this diagnosis is one of exclusion. Diffuse nodular regenerative hyperplasia should be considered when multiple small masses are seen in the liver of a patient with known risk factors, particularly if the clinical picture does not favor malignancy and if the lesions are more prominent at ultrasound than on other techniques. Focal nodular regenerative hyperplasia should be considered when multiple hypervascular hepatic masses are seen in a patient with long-standing udd- Chiari syndrome or autoimmune hepatitis. 994 JR:194, pril 2010

3 Radiologic Mimics of Cirrhosis lthough these distinguishing features may be helpful, histologic correlation will be required to diagnose some cases. Careful radiologic analysis and clinical correlation may be required to prevent an erroneous diagnosis that could potentially adversely impact management. References 1. Lipson J, Qayyum, vrin DE, Westphalen, Yeh M, Coakley FV. CT and MRI of hepatic contour abnormalities. JR 2005; 184:75 81 [Erratum in JR 2005; 184:1028] 2. Keedy, Westphalen C, Qayyum, et al. Diagnosis of cirrhosis by spiral computed tomography: a case-control study with feature analysis and assessment of interobserver agreement. J Comput ssist Tomogr 2008; 32: Qayyum, Lee GK, Yeh M, llen JN, Venook P, Coakley FV. Frequency of hepatic contour abnormalities and signs of portal hypertension at CT in patients receiving chemotherapy for breast cancer metastatic to the liver. Clin Imaging 2007; 31: Di Lelio, Cestari C, Lomazzi, eretta L. Cirrhosis: diagnosis with sonographic study of the liver surface. Radiology 1989; 172: Scott GC, erman JM, Higgins JL Jr. CT patterns of nodular hepatic and splenic sarcoidosis: a review of the literature. J Comput ssist Tomogr 1997; 21: rancatelli G, Federle MP, mbrosini R, et al. Cirrhosis: CT and MR imaging evaluation. Eur J Radiol 2007; 61: Kang SP, Taddei T, McLennan, Lacy J. Pseudocirrhosis in a pancreatic cancer patient with liver metastases: a case report of complete resolution of pseudocirrhosis with an early recognition and management. World J Gastroenterol 2008; 14: Poff J, Coakley FV, Qayyum, et al. Frequency and histopathologic basis of hepatic surface nodularity in patients with fulminant hepatic failure. Radiology 2008; 249: Kumar V, bbas K, Fausto N, Robbins SL, Cotran RS, eds. Robbins and Cotran pathologic basis of disease, 7th ed. Philadelphia, P: Elsevier Saunders, Dachman H, Ros PR, Goodman ZD, Olmsted WW, Ishak KG. Nodular regenerative hyperplasia PPENDIX 1: Noncirrhotic Causes of Diffuse Hepatic Contour Irregularity Coarse lobulation Chronic udd-chiari syndrome Chronic portal vein thrombosis Pseudomyxoma peritonei Fine nodularity Pseudocirrhosis of treated breast cancer metastases to the liver Fulminant hepatic failure Miliary metastases Sarcoidosis PPENDIX 2: Noncirrhotic Causes of Portal Hypertension 1. Chronic udd-chiari syndrome 2. Chronic portal vein thrombosis 3. Sarcoidosis 4. Schistosomiasis 5. Nodular regenerative hyperplasia 6. Congenital hepatic fibrosis 7. Idiopathic portal hypertension 8. Early primary biliary cirrhosis PPENDIX 3: ssociations of Diffuse and Focal Forms of Nodular Regenerative Hyperplasia Diffuse form Cardiovascular diseases Myeloproliferative diseases utoimmune diseases, particularly systemic lupus erythematosus Certain drugs including chemotherapy Solid organ and bone marrow transplantation HIV infection Focal form Chronic udd-chiari syndrome utoimmune hepatitis of the liver: clinical and radiologic observations. JR 1987; 148: Qayyum, Graser, Westphalen, et al. CT of benign hypervascular liver nodules in autoimmune hepatitis. JR 2004; 183: Rha SE, Lee MG, Lee YS, et al. Nodular regenerative hyperplasia of the liver in udd-chiari syndrome: CT and MR features. bdom Imaging 2000; 25: Casillas C, Marti-onmati L, Galant J. Pseudotumoral presentation of nodular regenerative hyperplasia of the liver: imaging in five patients including MR imaging. Eur Radiol 1997; 7: Murata Y, be M, Furukawa S, et al. Clinical features of symptomatic primary biliary cirrhosis initially complicated with esophageal varices. J Gastroenterol 2006; 41: khan O, Karaosmanoglu D, Ergen. Imaging findings in congenital hepatic fibrosis. Eur J Radiol 2007; 61: Nakanuma Y, Tsuneyama K, Ohbu M, Katayanagi K. Pathology and pathogenesis of idiopathic portal hypertension with an emphasis on the liver. Pathol Res Pract 2001; 197:65 76 JR:194, pril

4 Jha et al. Fig year-old woman with breast cancer treated with chemotherapy., xial contrast-enhanced CT image obtained after patient had received chemotherapy treatment shows diffuse surface nodularity in liver and recanalized umbilical vein (arrow); these findings are suggestive of cirrhosis., xial contrast-enhanced CT image obtained 6 months before, which was before patient started chemotherapy, shows multiple hepatic metastases. Liver is otherwise normal. Setting of breast cancer metastases treated with chemotherapy indicates rapid development of diffuse changes seen in likely represents pseudocirrhosis of treated breast cancer. Fig year-old woman with multiple hypodense biopsy-proven hepatic metastases from invasive ductal carcinoma of breast., xial contrast-enhanced CT image obtained before patient started chemotherapy., xial contrast-enhanced CT image obtained 6 months after that is, after patient had started chemotherapy shows diffuse hepatic nodularity, bland ascites (asterisk), esophageal varices (arrow), and partial regression of hepatic metastases. Findings are of pseudocirrhosis of treated breast cancer metastases; however, without prior studies and clinical history, these findings could suggest diagnosis of cirrhosis. 996 JR:194, pril 2010

5 Radiologic Mimics of Cirrhosis Fig year-old woman who presented for imaging after receiving two cycles of chemotherapy for hepatic metastases thought to be from primary pancreatic carcinoma., xial contrast-enhanced CT image shows liver surface is coarsely lobulated with several irregular hypodense parenchymal lesions. ppearance was considered suggestive of pseudocirrhosis, casting doubt on diagnosis of pancreatic cancer., xial contrast-enhanced image obtained at more superior level than shows small hypervascular lesion (arrow) in right breast. Further workup including resection of breast mass confirmed diagnosis of metastatic breast cancer. Fig year-old man with fulminant hepatic failure and history of chronic hepatitis infection., Contrast-enhanced CT image shows nodularity (arrow) of liver surface outlined by ascites; there findings are suggestive of cirrhosis. Histopathologic examination of explanted liver 5 days later showed confluent regenerative nodules surrounded by large areas of necrosis, but no cirrhosis. Hepatic surface nodularity is not a reliable sign of underlying cirrhosis in fulminant hepatic failure and should not be used to diagnose cirrhosis in this setting., Photomicrograph of explanted hepatic surface from transplant surgery performed 5 days after shows that irregularity of liver surface reflects combination of confluent regenerative nodules (R) and alternating bands of necrosis (N). (H and E, 200) Fig year-old woman with fulminant hepatic failure that developed 6 weeks after commencement of methyldopa therapy for hypertension. Sagittal ultrasound image of right hepatic lobe shows nodularity (arrow) of liver surface outlined by ascites; there findings are suggestive of cirrhosis. Histopathologic examination of explanted liver 3 days later showed confluent regenerative nodules surrounded by large areas of subacute necrosis but no cirrhosis. JR:194, pril

6 Jha et al. Fig year-old woman with metastatic lobular breast cancer. xial contrastenhanced CT image shows fine nodularity of hepatic surface. Liver biopsy revealed metastatic breast cancer without cirrhosis. Fig year-old man with sarcoidosis. xial contrast-enhanced CT image shows widespread diffuse parenchymal and surface hepatic nodularity (arrow). ppearance of liver on CT alone could be interpreted as cirrhosis, but note multiple hypodense nodules in spleen. Retroperitoneal adenopathy (not shown) was also present. Nodal biopsy confirmed diagnosis of sarcoidosis. Fig year-old woman with bilateral lobular breast cancer. xial contrastenhanced CT image shows widespread diffuse parenchymal and surface hepatic nodularity. iopsy revealed metastatic disease without cirrhosis. Fig year-old man with sarcoidosis. xial unenhanced CT image shows splenomegaly (asterisk) and recanalized umbilical vein (arrow) arising from somewhat shrunken and irregular liver. Liver biopsy revealed sarcoidosis without cirrhosis. Sarcoidosis is one cause of noncirrhotic portal hypertension. 998 JR:194, pril 2010

7 Radiologic Mimics of Cirrhosis Fig year-old man with history of renal transplantation for HIV nephropathy who presented with sepsis 1 day after right hemicolectomy for colonic volvulus., Sagittal ultrasound image of right hepatic lobe shows subtle echogenic nodularity of liver that could be considered suggestive of cirrhosis. Representative nodule (arrow) is visible anteriorly., xial contrast-enhanced CT image shows subtle parenchymal heterogeneity consisting of small hypodense nodules. Representative nodule (arrow) is visible posteriorly. Subsequent liver biopsy confirmed diagnosis of nodular regenerative hyperplasia. Fig year-old man with portal hypertension leading to gastrointestinal bleeding, ascites, and thrombocytopenia due to biopsy-proven nodular regenerative hyperplasia in liver transplant; transplantation was performed 18 years earlier for primary sclerosing cholangitis. xial contrast-enhanced CT image shows liver surface (arrow) is irregular and shows relative hypertrophy of left hepatic lobe (asterisk). These findings mimic those of cirrhosis. Fig year-old man with idiopathic portal hypertension. xial contrast-enhanced CT image shows splenomegaly (S), gastroesophageal varices (white arrow), and ascites (black arrow), but liver appears normal in size and contour. Liver biopsy confirmed absence of cirrhosis; final diagnosis was idiopathic portal hypertension. Fig year-old girl with renal failure due to autosomal recessive polycystic kidney disease. Coronal T2-weighted MR image shows kidneys (K) are replaced by innumerable relatively small cysts. Focal segmental biliary dilatation (arrow) in liver reflects coexistent congenital hepatic fibrosis, which can occur in association with autosomal recessive polycystic kidney disease and is cause of noncirrhotic portal hypertension. Note spleen (asterisk) is enlarged. FOR YOUR INFORMTION This article is available for CME credit. See for more information. JR:194, pril