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Autosomal Recessive Polycystic Kidney Disease with Caroli Syndrome AN 8-year-old boy presented with persistent worsening abdominal pain for several days. The pain was described as intermittent and nocturnal without other associated symptoms or inciting factors. Medical history was significant for autosomal recessive polycystic kidney disease (ARPKD.) Ultrasound revealed mild dilatation of the common bile duct, hepatic cysts and enlarged kidneys with a hyperechoic renal sinus (fig. 1). Magnetic resonance imaging (MRI) performed for further evaluation of the biliary system showed innumerable tiny cysts enlarging each kidney consistent with ARPKD, and multifocal saccular and fusiform dilated intrahepatic bile ducts consistent with Caroli disease (fig. 2). ARPKD is a rare inherited form of polycystic kidney disease with significant mortality and morbidity. The disease has an incidence of 1 in 20,000 live births and clinically manifests at a mean age of 2.5 years without gender or ethnic predilection.1 It is characterized by nonobstructive cystic dilatation of the renal collecting ducts and concurrent renal parenchymal fibrosis. ARPKD is caused by a mutation in the PKHD1 gene, which expresses
a protein called fibrocystin-polyductin that is involved in maintaining the normal tubular architecture of epithelial cells in renal collecting ducts and intrahepatic ducts. The mutation leads to abnormal proliferation and differentiation of renal and biliary epithelial cells.2 Four types of ARPKD have been described. The perinatal type is most common and most severe, and presents during gestation with bilateral reniform enlargement, kidney failure, oligohydraminos and lung hypoplasia.3 The less severe neonatal, infantile and juvenile types may have no renal symptoms but present with hepatosplenomegaly, portal hypertension and recurrent cholangitis secondary to underlying progressive periportal hepatic fibrosis and abnormal intrahepatic duct ectasia, known as congenital hepatic fibrosis.3 Congenital hepatic fibrosis, Caroli disease and Caroli syndrome are considered a disease continuum of ductal plate malformation at different stages of severity.4 Ductal plate malformation is an abnormality that occurs during portal duct embryogenesis, resulting in excessive proliferation with abnormal branching of the intrahepatic ducts
Figure 1. Ultrasound in 8-year-old boy with ARPKD and Caroli syndrome. A, multiple cystic lesions of varying sizes in liver consistent with saccular dilated ducts (arrows). B, enlarged left kidney (arrows) with hyperechoic central renal sinus.
0022-5347/15/1932-0679/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
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RADIOLOGY PAGE
Figure 2. Coronal HASTE (half-Fourier acquisition single-shot turbo spin-echo) MRI in 8-year-old boy with ARPKD and Caroli syndrome shows enlarged hyperintense kidneys (open arrows) due to innumerable cysts. Also note saccular and fusiform intrahepatic biliary dilatation (white arrows) typical of Caroli disease.
associated with the PKHD1 mutation. Caroli disease, a rare congenital recessive disorder, is characterized by multiple, segmental and nonobstructive saccular intrahepatic bile duct dilatation without other abnormalities.4 Caroli syndrome is a combination of Caroli disease with histological evidence of congenital hepatic fibrosis and renal cystic disease, including ARPKD, renal tubular ectasia and autosomal dominant polycystic kidney disease.4 The literature shows a strong association between Caroli syndrome and ARPKD.5 The gold standards for diagnosing ARPKD and Caroli syndrome are genetic testing and liver biopsy, respectively. Ultrasound and MRI are used to diagnose and follow ARPKD and Caroli disease. Ultrasound findings of prenatal ARPKD are bilateral enlarged echogenic kidneys (fig. 1). The neonatal type of ARPKD is characterized by enlarged hyperechoic kidneys lacking corticomedullary differentiation and with cystic or tubular dilated ducts.6 The
infantile and juvenile types show normal-sized kidneys with less tubular or cystic dilatations than the neonatal type.6 MRI findings of prenatal type ARPKD are enlarged T2-hyperintense kidneys (fig. 2).6,7 The neonatal, infantile and juvenile types show normal to enlarged T2-hyperintense kidneys with microcysts or macrocysts. Findings of Caroli disease or syndrome are most specific on MRI. The central dot sign, which consists of small portal venous branches surrounded by saccular dilatations, is often seen on MRI. In addition, magnetic resonance cholangiopancreatography is specific in demonstrating direct communication of the segmental saccular ectasias with the intrahepatic biliary system.6,8 This latter feature is pathognomic for Caroli disease and differentiates it from other liver diseases with similar imaging appearances, such as primary sclerosing cholangitis, hepatic cysts of autosomal dominant polycystic kidney disease, biliary harmatomas and type IV choledochal cysts. The patient underwent percutaneous liver biopsy, which showed ductal plate malformation, liver cirrhosis, and numerous elongated lanceolate and anastomosing bile ducts, findings consistent with Caroli syndrome. Emmanuel C. Obusez and Unni Udayasankar Imaging Institute Cleveland Clinic Children’s Hospital Cleveland, Ohio 1. Zerres K, Rudnik-Schoneborn S and Mucher G: Autosomal recessive polycystic kidney disease: clinical features and genetics. Adv Nephrol Necker Hosp 1996; 25: 147. 2. Fedeles SV, Gallagher AR and Somlo S: Polycystin-1: a master regulator of intersecting cystic pathways. Trends Mol Med 2014; 20: 251. 3. Lonergan GJ, Rice RR and Suarez ES: Autosomal recessive polycystic kidney disease: radiologic-pathologic correlation. Radiographics 2000; 20: 837. 4. Desmet VJ: Ludwig symposium on biliary disordersdpart I. Pathogenesis of ductal plate abnormalities. Mayo Clin Proc 1998; 73: 80. 5. Waters K, Howman-Giles R, Rossleigh M et al: J. Intrahepatic bile duct dilatation and cholestasis in autosomal recessive polycystic kidney disease. Demonstration with hepatobiliary scintigraphy. Clin Nucl Med 1995; 20: 892. 6. Chung EM, Conrad RM, Schroeder JW et al: From the radiologic pathology archives: pediatric polycystic kidney disease and other ciliopathies: radiologicpathologic correlation. Radiographics 2014; 34: 155. 7. Nasu K, Yoshimatsu J, Anai T et al: Magnetic resonance imaging of fetal autosomal recessive polycystic kidney disease. J Obstet Gynaecol Res 1998; 24: 33. 8. Guy F, Cognet F, Dranssart M et al: Caroli’s disease: magnetic resonance imaging features. Eur Radiol 2002; 12: 2730.
Autosomal Recessive Polycystic Kidney Disease with Caroli Syndrome AN 8-year-old boy presented with persistent worsening abdominal pain for several days. The pain was described as intermittent and nocturnal without other associated symptoms or inciting factors. Medical history was significant for autosomal recessive polycystic kidney disease (ARPKD.) Ultrasound revealed mild dilatation of the common bile duct, hepatic cysts and enlarged kidneys with a hyperechoic renal sinus (fig. 1). Magnetic resonance imaging (MRI) performed for further evaluation of the biliary system showed innumerable tiny cysts enlarging each kidney consistent with ARPKD, and multifocal saccular and fusiform dilated intrahepatic bile ducts consistent with Caroli disease (fig. 2). ARPKD is a rare inherited form of polycystic kidney disease with significant mortality and morbidity. The disease has an incidence of 1 in 20,000 live births and clinically manifests at a mean age of 2.5 years without gender or ethnic predilection.1 It is characterized by nonobstructive cystic dilatation of the renal collecting ducts and concurrent renal parenchymal fibrosis. ARPKD is caused by a mutation in the PKHD1 gene, which expresses
a protein called fibrocystin-polyductin that is involved in maintaining the normal tubular architecture of epithelial cells in renal collecting ducts and intrahepatic ducts. The mutation leads to abnormal proliferation and differentiation of renal and biliary epithelial cells.2 Four types of ARPKD have been described. The perinatal type is most common and most severe, and presents during gestation with bilateral reniform enlargement, kidney failure, oligohydraminos and lung hypoplasia.3 The less severe neonatal, infantile and juvenile types may have no renal symptoms but present with hepatosplenomegaly, portal hypertension and recurrent cholangitis secondary to underlying progressive periportal hepatic fibrosis and abnormal intrahepatic duct ectasia, known as congenital hepatic fibrosis.3 Congenital hepatic fibrosis, Caroli disease and Caroli syndrome are considered a disease continuum of ductal plate malformation at different stages of severity.4 Ductal plate malformation is an abnormality that occurs during portal duct embryogenesis, resulting in excessive proliferation with abnormal branching of the intrahepatic ducts
Figure 1. Ultrasound in 8-year-old boy with ARPKD and Caroli syndrome. A, multiple cystic lesions of varying sizes in liver consistent with saccular dilated ducts (arrows). B, enlarged left kidney (arrows) with hyperechoic central renal sinus.
0022-5347/15/1932-0679/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2014.11.013 Vol. 193, 679-680, February 2015 Printed in U.S.A.
www.jurology.com
j
679
680
RADIOLOGY PAGE
Figure 2. Coronal HASTE (half-Fourier acquisition single-shot turbo spin-echo) MRI in 8-year-old boy with ARPKD and Caroli syndrome shows enlarged hyperintense kidneys (open arrows) due to innumerable cysts. Also note saccular and fusiform intrahepatic biliary dilatation (white arrows) typical of Caroli disease.
associated with the PKHD1 mutation. Caroli disease, a rare congenital recessive disorder, is characterized by multiple, segmental and nonobstructive saccular intrahepatic bile duct dilatation without other abnormalities.4 Caroli syndrome is a combination of Caroli disease with histological evidence of congenital hepatic fibrosis and renal cystic disease, including ARPKD, renal tubular ectasia and autosomal dominant polycystic kidney disease.4 The literature shows a strong association between Caroli syndrome and ARPKD.5 The gold standards for diagnosing ARPKD and Caroli syndrome are genetic testing and liver biopsy, respectively. Ultrasound and MRI are used to diagnose and follow ARPKD and Caroli disease. Ultrasound findings of prenatal ARPKD are bilateral enlarged echogenic kidneys (fig. 1). The neonatal type of ARPKD is characterized by enlarged hyperechoic kidneys lacking corticomedullary differentiation and with cystic or tubular dilated ducts.6 The
infantile and juvenile types show normal-sized kidneys with less tubular or cystic dilatations than the neonatal type.6 MRI findings of prenatal type ARPKD are enlarged T2-hyperintense kidneys (fig. 2).6,7 The neonatal, infantile and juvenile types show normal to enlarged T2-hyperintense kidneys with microcysts or macrocysts. Findings of Caroli disease or syndrome are most specific on MRI. The central dot sign, which consists of small portal venous branches surrounded by saccular dilatations, is often seen on MRI. In addition, magnetic resonance cholangiopancreatography is specific in demonstrating direct communication of the segmental saccular ectasias with the intrahepatic biliary system.6,8 This latter feature is pathognomic for Caroli disease and differentiates it from other liver diseases with similar imaging appearances, such as primary sclerosing cholangitis, hepatic cysts of autosomal dominant polycystic kidney disease, biliary harmatomas and type IV choledochal cysts. The patient underwent percutaneous liver biopsy, which showed ductal plate malformation, liver cirrhosis, and numerous elongated lanceolate and anastomosing bile ducts, findings consistent with Caroli syndrome. Emmanuel C. Obusez and Unni Udayasankar Imaging Institute Cleveland Clinic Children’s Hospital Cleveland, Ohio 1. Zerres K, Rudnik-Schoneborn S and Mucher G: Autosomal recessive polycystic kidney disease: clinical features and genetics. Adv Nephrol Necker Hosp 1996; 25: 147. 2. Fedeles SV, Gallagher AR and Somlo S: Polycystin-1: a master regulator of intersecting cystic pathways. Trends Mol Med 2014; 20: 251. 3. Lonergan GJ, Rice RR and Suarez ES: Autosomal recessive polycystic kidney disease: radiologic-pathologic correlation. Radiographics 2000; 20: 837. 4. Desmet VJ: Ludwig symposium on biliary disordersdpart I. Pathogenesis of ductal plate abnormalities. Mayo Clin Proc 1998; 73: 80. 5. Waters K, Howman-Giles R, Rossleigh M et al: J. Intrahepatic bile duct dilatation and cholestasis in autosomal recessive polycystic kidney disease. Demonstration with hepatobiliary scintigraphy. Clin Nucl Med 1995; 20: 892. 6. Chung EM, Conrad RM, Schroeder JW et al: From the radiologic pathology archives: pediatric polycystic kidney disease and other ciliopathies: radiologicpathologic correlation. Radiographics 2014; 34: 155. 7. Nasu K, Yoshimatsu J, Anai T et al: Magnetic resonance imaging of fetal autosomal recessive polycystic kidney disease. J Obstet Gynaecol Res 1998; 24: 33. 8. Guy F, Cognet F, Dranssart M et al: Caroli’s disease: magnetic resonance imaging features. Eur Radiol 2002; 12: 2730.
