Focal Hepatic Masses in Pediatric Patients

Residents Section Pattern of the Month deyiga et al. Focal Hepatic Masses in Pediatric Patients Residents Section Pattern of the Month Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved Residents inradiology debunmi O. deyiga 1 Edward Y. Lee 1 Ronald L. Eisenberg 2 deyiga O, Lee EY, Eisenberg RL Keywords: focal hepatic masses, pediatrics DOI:10.2214/JR.11.7581 Received July 15, 2011; accepted after revision November 22, 2011. 1 Department of Radiology, Children s Hospital oston, Harvard Medical School, oston, M. 2 Department of Radiology, eth Israel Deaconess Medical Center, Harvard Medical School, 330 rookline ve, oston, M 02215. ddress correspondence to R. L. Eisenberg (rleisenb@bidmc.harvard.edu). WE This is a Web exclusive article. JR 2012; 199:W422 W440 0361 803X/12/1994 W422 merican Roentgen Ray Society Focal Hepatic Masses in Pediatric Patients wide variety of focal hepatic masses can be seen in the pediatric population. For generating a differential diagnosis, focal hepatic masses in pediatric patients can be categorized into congenital, neoplastic, and infectious masses (Table 1). dditionally, it is important to be aware of the spectrum of lesions that can mimic focal hepatic masses in the pediatric population (Table 1). lthough some of these may be discovered incidentally, the majority of pediatric patients with focal hepatic masses usually present with abdominal pain or abnormal physical findings, such as a palpable abdominal mass or distention. fter physical examination, imaging evaluation is the next step in managing pediatric patients with suspected focal hepatic masses. lthough abdominal radiographs may provide helpful imaging findings that can suggest the presence of focal hepatic masses such as hepatomegaly, displacement of bowel or other solid organs, or calcification, ultrasound is the initial imaging modality of choice because it can detect, characterize, and provide TLE 1: Focal Hepatic Masses in an extent of focal hepatic masses. However, Pediatric Patients CT or MRI is often subsequently performed for further characterization, assessment of a precise extent, and detection of associated metastatic disease in cases of malignant hepatic neoplasm. Therefore, understanding the characteristic imaging appearances of various focal hepatic masses is essential for making a prompt and accurate diagnosis, which in turn can lead to optimal patient management. Congenital Masses Hepatic Cyst hepatic cyst is a benign congenital lesion that results from abnormal development of intrahepatic biliary ducts and does not communicate with the biliary tree. Congenital hepatic cysts occur in approximately 2.5% of the general population. lthough most of those discovered in pediatric patients are incidental, infants and children with large hepatic cysts may present with abdominal pain and distention. Common complications of hepatic cysts include intracystic infection and bleeding. When there are multiple hepatic cysts (> 10), polycystic liver disease should be considered. Polycystic liver disease most commonly occurs in association with autosomal-dominant polycystic kidney disease (DPKD), and is referred to as a ciliopathy because the pathogenesis is thought to be related to defective Congenital masses Hepatic cyst Choledochal cyst Primary neoplasm Infantile hepatic hemangioma Hepatic adenoma Focal nodular hyperplasia Mesenchymal hamartoma Regenerative nodule Hepatoblastoma Hepatocellular carcinoma Fibrolamellar hepatocellular carcinoma Undifferentiated (embryonal) sarcoma ngiosarcoma Lymphoma Metastatic disease Infection acterial infection Fungal infection Parasitic infection Conditions that can mimic focal hepatic masses Focal fatty proliferation Hepatic infarction Extrahepatic masses W422 JR:199, October 2012

Focal Hepatic Masses in Pediatric Patients Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved ciliary proteins. Otherwise, polycystic liver disease less commonly occurs in patients with autosomal-dominant polycystic liver disease, which is not typically associated with renal cysts and is not thought to represent a celiopathy because the disease process involves nonciliary proteins. Simple hepatic cysts are typically unilocular, thin-walled, anechoic masses without septation, mural nodules, or internal vascularity on ultrasound (Fig. 1). On CT and MRI, they appear as round nonenhancing masses with an imperceptible wall and follow the attenuation and signal intensity of water (Figs. 2 and 3). Symptomatic hepatic cysts in pediatric patients are surgically resected because of their large size or recurrent superimposed infection. Small simple hepatic cysts in asymptomatic pediatric patients do not require treatment or follow-up imaging assessment. Choledochal Cyst Choledochal cysts are rare congenital malformations of the intrahepatic or extrahepatic biliary ductal systems. These lesions are more common in girls than boys and are more prevalent in Eastern countries, particularly Japan. ffected pediatric patients usually present with a triad of abdominal pain, palpable right upper quadrant mass, and jaundice. Choledochal cysts are thought to be risk factors for the later development of cholangiocarcinoma. The current imaging modalities of choice in pediatric patients are ultrasound and MRCP, which show focal cystic dilations that communicate with the intrahepatic and extrahepatic bile ducts (Figs. 4 and 5). The Todani classification system categorizes choledochal cysts into five types on the basis of the pattern of ductal involvement: Type I: saccular or fusiform dilation of the extrahepatic bile duct Type II: true diverticulum of the extrahepatic bile duct Type III: Choledochocele or dilation of intraduodenal segment of the common bile duct Type IVa: Multiple dilations of both intrahepatic and extrahepatic bile ducts Type IVb: Multiple dilations involving only extrahepatic bile ducts Type V: Multiple dilations of intrahepatic bile ducts (Caroli disease) Todani types IV and V fall under the category of focal hepatic masses. Caroli disease (type V choledochal cyst) is a rare, autosomal-recessive disorder that is thought to result from derangement of the normal embryologic ductal remodeling process. lthough the Todani classification of choledochal cysts includes Caroli disease as a type V choledochal cyst, the current understanding of the pathogenesis of Caroli disease (autosomal-recessive and often associated with renal disorders) and choledochal cysts (congenital and not associated with renal disorders) makes it unlikely that these entities are related. Of note, many fibrocystic hepatic disease processes are thought to be related to defective ciliary proteins and are therefore often referred to as ciliopathies as mentioned in the previous section. Included within this group of pathologies are ductal plate malformations, such as Caroli disease, as well as the aforementioned polycystic liver disease associated with DPKD. Pediatric patients with choledochal Fig. 1 Simple hepatic cyst in 4-year-old boy who presented with palpable abdominal mass. Transverse ultrasound image shows large unilocular, thinwalled, anechoic mass (M) without septation or mural nodules in right hepatic lobe. Serial follow-up ultrasound examinations showed interval stability. Fig. 2 utosomal-dominant polycystic kidney disease with simple hepatic cyst in 15-year-old boy. Enhanced axial CT image shows round nonenhancing lesion (curved arrow) with imperceptible wall in right hepatic lobe. lso noted are renal cysts (straight arrows). JR:199, October 2012 W423

deyiga et al. Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved Fig. 3 Simple hepatic cyst in 14-year-old girl with chronic abdominal pain. Hepatic cyst was incidental finding., xial T2-weighted image shows oval cystic mass (arrow) with imperceptible wall., xial contrast-enhanced T1-weighted image shows no contrast enhancement in cystic mass (arrow). cysts typically present with recurrent cholangitis. Caroli disease produces multiple intrahepatic cystic lesions, many of which may contain a characteristic central dot representing a portal vein branch surrounded by the dilated biliary duct. Neoplasms Infantile Hepatic Hemangioma Infantile hepatic hemangioma, formerly referred to as infantile hemangioendothelioma, is a benign vascular tumor of the liver that is lined by endothelium. The most common benign hepatic tumor in infants, it is divided into focal, multifocal, and diffuse subtypes. Focal infantile hepatic hemangioma is thought to be the hepatic form of cutaneous rapidly involuting congenital hemangioma (RICH) (Fig. 6). RICH is a vascular mass that is fully formed at birth, does not increase in size postnatally, and usually involutes completely by 12 14 months. There is typically no association with cutaneous hemangiomas and no known sex predilection. Histopathologic antibody staining of the endothelial cells in Fig. 4 Choledochal cyst in 9-year-old boy who presented with abdominal pain, right upper quadrant mass, and jaundice. Transverse color Doppler ultrasound image shows focal cystic dilation of bile duct (D). G = gallbladder. Fig. 5 Choledochal cyst in 11-year-old girl who presented with chronic nausea, vomiting, and abdominal pain., xial T2-weighted image shows focal cystic dilation of bile duct (D)., Coronal MRCP image shows both intrahepatic (asterisk) and extrahepatic (arrow) bile duct dilation. W424 JR:199, October 2012

Focal Hepatic Masses in Pediatric Patients Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved C D Fig. 6 Rapidly involuting congenital hemangioma in 3-day-old girl who presented with hepatomegaly, abnormal liver function tests, and coagulopathy., Longitudinal ultrasound image shows heterogeneous liver mass with anechoic vascular spaces., Longitudinal Doppler ultrasound image shows markedly increased vascularity of hepatic mass. C, Coronal contrast-enhanced CT image obtained during arterial phase shows large hepatic mass with early peripheral enhancement. D, Coronal contrast-enhanced CT image obtained during delayed phase shows large hepatic mass with delayed partial central enhancement (arrow). RICH is negative for glucose transporter protein-1 (GLUT1). RICH is usually symptomatic because of arteriovenous shunting. The multifocal subtype of infantile hepatic hemangioma is thought to be the hepatic form of simple cutaneous infantile hemangioma and is often associated with cutaneous hemangiomas in the same patient (Fig. 7). The majority of affected patients present before the age of 6 months, and these masses have a female predilection. Histopathologic antibody staining of the endothelial cells in this subtype of infantile hepatic hemangioma is positive for GLUT1, similar to cutaneous infantile hemangioma. Most of these lesions eventually involute, and the overall survival rate is approximately 90%. ffected infants may present with a palpable abdominal mass and bruit as well as high-output heart failure if they are especially large. The diffuse subtype of infantile hepatic hemangioma is characterized by almost complete replacement of hepatic parenchyma by infantile hemangiomas. These patients may present with a large palpable abdominal mass and develop high-output heart failure because of arteriovenous shunting. On ultrasound, infantile hepatic hemangiomas are usually heterogeneous but predominately hypoechoic solid masses (Figs. 6 and 7). nechoic areas within the mass may represent JR:199, October 2012 W425

deyiga et al. Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved C E Fig. 7 Multifocal subtype of infantile hemangioma in 2-month-old girl who presented with hepatomegaly and multiple cutaneous hemangiomas., Transverse ultrasound image shows multiple hypoechoic masses (arrows)., xial unenhanced CT image shows multiple low-attenuation lesions throughout liver. C, xial contrast-enhanced CT image obtained during arterial phase shows peripheral enhancement of hepatic lesions. D, xial contrast-enhanced CT image obtained during delayed phase shows enhancement of hepatic lesions. E, xial T2-weighted image shows multiple hepatic lesions with increased signal intensity. F, xial contrast-enhanced T1-weighted image shows contrast enhancement within hepatic lesions. underlying vascular channels or central necrosis. Infantile hepatic hemangiomas typically appear on CT as low-attenuation masses that may contain calcification. fter IV contrast administration, there is usually early peripheral and nodular enhancement with variable delayed central enhancement (Figs. 6 and 7). On MRI, infantile hepatic hemangiomas typically are hypointense on T1-weighted images and hyperintense on T2-weighted images (Fig. 7). The contrast enhancement pattern on MRI is similar to that seen on CT. D F W426 JR:199, October 2012

Focal Hepatic Masses in Pediatric Patients Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved Fig. 8 Hepatic adenoma in 13-year-old girl with underlying glycogen storage disease. xial contrastenhanced CT image obtained during portal venous phase shows hyperattenuating lesion (arrow) in left hepatic lobe, which stands out against background of diffuse steatosis. Hepatic denoma Hepatic adenoma is a rare benign tumor derived from hepatocytes. More commonly seen in females, hepatic adenomas are prone to hemorrhage, necrosis, and fatty change. Risk factors for developing hepatic adenomas include oral contraceptive or anabolic steroid use in adolescent or older children as well as underlying diabetes mellitus and glycogen storage disease. Hepatic adenomas may be found incidentally or present with abdominal pain due to hemorrhage. lthough the appearance on ultrasound is nonspecific, hepatic adenomas typically are heterogeneous solid masses that show internal vascularity with Doppler imaging. ecause of their lipid content, hepatic adenomas are usually hypodense on unenhanced CT. They show a variable pattern of enhancement with washout of contrast material on delayed images (Fig. 8). The MRI characteristics of hepatic adenomas depend on the amount of fat, hemorrhage, and necrosis within the lesion. ecause of their variable underlying composition, hepatic adenomas may appear heterogeneous on both T1- and T2-weighted images. Heterogeneous early enhancement is usually seen after gadolinium administration, with subsequent washout but delayed pseudocapsule enhancement. MRI with chemical shift or fat-suppression techniques is particularly useful in detecting adenomas with high lipid content. Focal Nodular Hyperplasia Focal nodular hyperplasia (FNH) is a benign hepatic mass consisting of hyperplastic parenchymal nodules with abundant abnormal vessels. ccounting for approximately 4% of all primary hepatic tumors in the pediatric population, most are found incidentally. FNH has been recognized as a late complication seen in patients with a history of previously treated malignancy, with the pathogenesis possibly linked to treatment-related vascular damage. In such cases, it is particularly important to be aware of the typical imaging features of FNH, allowing more accurate restaging examinations and reducing the number of unnecessary biopsies. FNH typically appears on ultrasound as a well-circumscribed solid hepatic mass with a central hypoechoic scar. There may be a spoked wheel pattern of vascularity. On CT, FNH is similar in density to normal hepatic parenchyma on unenhanced images. fter contrast administration, there is avid enhancement of FNH, with delayed enhancement of the central scar. On MRI, FNH is isointense to normal liver and the central scar is hypointense on T1-weighted images and mildly hyperintense on T2-weighted images (Fig. 9). fter contrast administration, there is usually early arterial enhancement of the mass with delayed enhancement of the central scar. Technetium-99 cu m sulfur colloid scanning can also be used to identify FNH, which shows normal or increased uptake because of the presence of Kupffer cells. Mesenchymal Hamartoma Mesenchymal hamartoma is a cystic hepatic tumor that is the second most common benign hepatic liver mass in the pediatric population. Usually detected in patients under the age of 2 years, mesenchymal hamartoma occurs twice as often in boys than in girls. ffected pediatric patients typically present with an enlarging abdominal mass but are otherwise asymptomatic. s the mass enlarges, patients may develop vomiting, diarrhea, or constipation. resultant mass effect on the diaphragm may cause respiratory distress. On ultrasound, mesenchymal hamartoma presents as a multiseptated cystic mass with little or no internal vascularity (Fig. 10). On CT and MRI, there is a multiseptated mass of water attenuation and signal intensity, respectively (Fig. 10). The thin internal septations may show contrast enhancement. Mesenchymal hamartoma most commonly involves the right hepatic lobe and is not typically associated with calcification or hemorrhage. JR:199, October 2012 W427

deyiga et al. Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved C Fig. 9 Focal nodular hyperplasia in 23-year-old man with portal hypertension., xial unenhanced CT image shows subtle liver contour abnormality (arrow) in left hepatic lobe., xial T1-weighted image with fat saturation obtained during early contrast-enhancement phase shows enhancing masses (arrows) with hypoenhancing central areas (i.e., scars). C, xial T1-weighted image with fat saturation obtained during delayed contrast-enhancement phase shows partial enhancement of central scars (arrows). Regenerative Hepatic Nodule Regenerative hepatic nodule, also referred to as nodular regenerative hyperplasia, is a rare disorder consisting of diffuse micronodular transformation of hepatic parenchyma without intervening fibrous septa. Rarely seen in pediatric patients, a regenerative hepatic nodule is thought to represent a hyperplastic response of hepatocytes to small-vessel disease and ischemia. If regenerative hepatic nodules are small ( 0.5 cm), CT and MRI may show a normal appearance of the liver. However, larger regenerative hepatic nodules (0.5 4.0 cm) may appear on CT as focal nodules that are isodense to normal hepatic parenchyma and show diffuse Fig. 10 Mesenchymal hamartoma in 15-month-old boy who presented with palpable abdominal mass., Transverse color Doppler ultrasound image shows cystic mass (M) with septations (arrows). lood flow within septations is also seen., xial contrast-enhanced CT image shows large multiseptated mass (CM). Note solid component of mass (SM). W428 JR:199, October 2012

Focal Hepatic Masses in Pediatric Patients Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved C Fig. 11 Regenerative hepatic nodules in 20-year-old woman with hepatic cirrhosis and portal hypertension after surgical resection of hepatoblastoma and radiation treatment., Transverse ultrasound image shows coarse heterogeneous echotexture of liver., xial contrast-enhanced CT image shows heterogeneous hepatic parenchyma and enhancement. C, xial T1-weighted image with fat saturation and without contrast administration shows heterogeneous hepatic parenchymal signal intensity. D, xial contrast-enhanced T1-weighted image with fat saturation obtained during arterial phase shows heterogeneously enhancing hepatic parenchyma. contrast enhancement (Fig. 11). On MRI, regenerative hepatic nodules are isointense on T1- weighted images and iso- to hypointense on T2-weighted images. s with CT, they usually show diffuse contrast enhancement (Fig. 11). Hepatoblastoma Hepatoblastoma is a malignant hepatic tumor of epithelial and mesenchymal cell origin. The most common hepatic malignancy in the pediatric population, it affects boys twice as often as girls. The vast majority of patients with hepatoblastoma have an elevated serum α-fetoprotein level. Metastatic disease is common, with the lung being the most common site for metastases. ffected pediatric patients typically present with a large, painless abdominal mass. Imaging by ultrasound, CT, and MRI usually shows a well-circumscribed heterogeneous mass that is generally located in the right lobe of the liver (Fig. 12). Calcifications are present in approximately 50% of cases (Fig. 13), and there may be areas of hemorrhage or necrosis. Tumor vascularity may be identified on ultrasound. On CT, hepatoblastoma is usually hypodense on unenhanced images and typically is heterogeneous after contrast administration, although to a lesser degree than normal hepatic parenchyma (Fig. 12). On MRI, a D JR:199, October 2012 W429

deyiga et al. hepatoblastoma is predominantly hypointense on T1-weighted images and hyperintense on T2-weighted images. However, the MRI signal characteristics of hepatoblastoma may vary if there is associated hemorrhage and necrosis. The tumor typically shows heterogeneous contrast enhancement (Fig. 12). Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved C Fig. 12 Hepatoblastoma in 15-month-old boy who presented with large palpable abdominal mass and markedly elevated serum α-fetoprotein level., Longitudinal ultrasound image shows heterogeneous hepatic mass (M)., Coronal unenhanced CT image shows heterogeneous enhancement of right hepatic mass to lesser degree than adjacent normal hepatic parenchyma. C, Coronal contrast-enhanced T1-weighted image with fat saturation shows heterogeneously enhancing, multilobulated mass predominantly located within right hepatic lobe. Fig. 13 Hepatoblastoma in 10-month-old girl who presented with irritability, weight loss, and abdominal distention., bdominal radiograph shows large calcified mass (M)., xial contrast-enhanced CT image shows heterogeneously enhancing mass (M) containing areas of calcification. W430 JR:199, October 2012

Focal Hepatic Masses in Pediatric Patients Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved Fig. 14 Hepatocellular carcinoma in 15-year-old boy who presented with abdominal pain, abnormal liver function tests, and elevated serum α-fetoprotein level., Transverse ultrasound image shows large hepatic mass with heterogeneous echotexture., xial T1-weighted image with fat saturation shows large well-circumscribed right hepatic mass (M) with decreased signal intensity compared with adjacent normal hepatic parenchyma. C, xial contrast-enhanced T1-weighted image with fat saturation shows heterogeneously enhancing right hepatic mass (M). Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy in adults but is rarely seen in the pediatric population. ffected children are usually older than 13 years. When occurring in the pediatric population, HCC is likely to be more extensive and the prognosis is poor. HCC is commonly associated with an elevated serum α-fetoprotein level and most patients have underlying cirrhosis of the liver. Contrast-enhanced CT and MRI are the current imaging modalities of choice for evaluation of HCC (Fig. 14). The characteristic imaging appearance of HCC is early arterial enhancement followed by washout during C Fig. 15 Fibrolamellar hepatocellular carcinoma in 16-year-old boy who presented with abdominal pain., xial unenhanced CT image shows hypoattenuating mass with several central calcifications (arrow)., xial contrast-enhanced CT image shows enhancing mass (arrows). JR:199, October 2012 W431

deyiga et al. delayed imaging. Doppler ultrasound can also assess the vascularity of the tumor, but it is less sensitive than CT or MRI (Fig. 14). Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved Fibrolamellar Hepatocellular Carcinoma Fibrolamellar HCC, or fibrolamellar carcinoma, is a rare malignant tumor of the liver that differs clinically and radiologically from conventional HCC. It accounts for less than 10% of all HCCs. Unlike conventional HCC, fibrolamellar carcinoma typically arises within normal liver parenchyma and there are no specific risk factors or elevated α-fetoprotein levels. Patients with fibrolamellar carcinoma present at a younger age (second or third decade of life) than those with conventional HCC. The prognosis of fibrolamellar carcinoma is more favorable, with a 5-year survival rate of approximately 67%. Fibrolamellar carcinoma typically appears as a large solitary well-defined mass that is hypodense and heterogeneous on CT. The central scar, when present, is usually hypodense, and there may be associated calcification and necrosis (Fig. 15). Most lesions show heterogeneous contrast enhancement (Fig. 15). On MRI, fibrolamellar carcinoma is slightly hypointense on T1- weighted images and hyperintense on T2-weighted images and usually shows intense heterogeneous enhancement. The central scar appears hypointense on both T1-weighted images and T2-weighted images. There is usually no enhancement of the central scar on arterial or portal venous phases, but the central scar may partially enhance on delayed phase images. Undifferentiated (Embryonal) Sarcoma Undifferentiated (embryonal) sarcoma is a rare malignant hepatic neoplasm that occurs primarily in children between 6 10 years old. ffected pediatric patients typically present with abdominal pain, fever, and weight loss. Undifferentiated (embryonal) sarcoma is not associated with elevated serum α-fetoprotein levels, and the prognosis is typically poor, with median survival of less than 1 year. On ultrasound, undifferentiated (embryonal) sarcoma usually presents as a heterogeneous solid hepatic mass with borders that are often ill defined. The tumor is typically hypodense on CT (Fig. 16) and heterogeneously hyperintense on T2- weighted MR images (Fig. 16). fter contrast administration, there is usually delayed enhancement of undifferentiated (embryonal) sarcoma on both CT and MRI. ngiosarcoma ngiosarcoma is a malignant spindle cell tumor of the liver derived from endothelial cells. lthough more commonly seen in older adult patients, it can also rarely occur in pediatric patients. Early metastases are common and the prognosis is poor, with a median survival of 6 months. Risk factors for developing angiosarcoma include exposure to environmental carcinogens, cyclophosphamide, anabolic steroids, and prior radiation. ngiosarcoma is prone to rupture and Fig. 16 Undifferentiated (embryonal) sarcoma in 9-year-old boy who presented with weight loss, fever, and abdominal pain., xial contrast-enhanced CT image shows large hypoattenuating mass (M)., xial T2-weighted image shows heterogeneously hyperintense mass (arrows). W432 JR:199, October 2012

Focal Hepatic Masses in Pediatric Patients Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved Fig. 17 ngiosarcoma in 3-year-old boy who presented with right upper quadrant mass detected on physical examination during annual check-up., Transverse ultrasound image shows large heterogeneous mass with increased internal vascularity (arrow)., xial contrast-enhanced CT image shows nodular pattern of heterogeneous contrast enhancement within large hepatic mass. hemorrhage. On ultrasound, angiosarcoma is a heterogeneous mass with marked internal vascularity (Fig. 17). On CT, angiosarcoma typically presents as a solitary lesion or as multiple hypodense masses. reas of increased density on CT typically represent underlying hemorrhage. There is usually heterogeneous early contrast enhancement and progressively homogeneous enhancement during the delayed phase (Fig. 17). On MRI, angiosarcoma usually appears hypointense on T1- weighted images and heterogeneous but predominantly hyperintense on T2-weighted images. reas of T1 hyperintensity or T2 hypointensity of the tumor are related to underlying hemorrhage or hemosiderin. There is heterogeneous contrast enhancement during the arterial phase, with progressive enhancement on delayed images. Less commonly, there may be early peripheral nodular enhancement on CT or MRI, with delayed washin of contrast material in the central portion. Lymphoma oth Hodgkin disease and non-hodgkin lymphoma (NHL) involve the liver in more than one half of patients. Primary hepatic lymphoma is rare (Fig. 18), and secondary lymphomatous involvement of the liver is more common in both pediatric and adult patients. Secondary hepatic lymphoma is seen in over half of patients with Hodgkin disease or NHL. Risk factors for developing primary hepatic lymphoma include immunosuppressed states due to prior transplantation or an infectious process, such as IDS. On CT, primary hepatic lymphoma may appear isodense to hypodense compared with normal hepatic parenchyma (Fig. 18). Secondary hepatic lymphoma typically appears as multiple hypodense lobulated masses (Fig. 19). However, the infiltrative type of hepatic lymphoma may present as a diffusely hypodense liver. Hepatic lymphoma does not show substantial contrast enhancement. On MRI, lymphoma is hypointense on T1-weighted images and hyperintense on T2-weighted images and usually shows only minimal contrast enhancement. Metastatic Disease The liver is a common site for malignant spread of neoplasms. Hepatic metastatic disease is much more common than primary hepatic Fig. 18 Primary hepatic lymphoma in 17-yearold boy who presented with weight loss, fatigue, abnormal liver function tests, and abdominal pain. xial contrast-enhanced CT image shows predominantly hypoattenuating mass (arrows) in left hepatic lobe. JR:199, October 2012 W433

deyiga et al. Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved Fig. 19 Metastatic hepatic lymphoma in 15-year-old girl with underlying primary cell lymphoma who presented with abdominal pain., xial contrast-enhanced CT image shows numerous hypoenhancing liver masses (arrows)., xial fused PET/CT image shows increased metabolic activity (arrows) corresponding with hepatic metastases. Fig. 20 Hypervascular hepatic metastasis from adrenocortical carcinoma in 17-year-old girl., xial contrast-enhanced CT image shows large hepatic mass with area of contrast enhancement (arrow)., Coronal contrast-enhanced CT image shows large enhancing hepatic metastasis (M). lso noted is primary right adrenocortical carcinoma (arrows). malignancy in the pediatric population. Hypovascular liver metastases usually originate from lung, gastrointestinal tract, and pancreatic tumors, whereas hypervascular metastases arise from endocrine, renal, and sarcomatous tumors (Fig. 20). In the pediatric population, the most common primary tumors that metastasize to the liver are neuroblastoma and Wilms tumor. On abdominal radiographs, an enlarged liver may suggest possible hepatic metastatic disease in pediatric oncology patients. On CT, metastases usually produce multiple focal hypodense or hyperdense masses of varying size that are distributed randomly throughout the liver parenchyma (Fig. 21). On MRI, hepatic metastases are generally hypointense on T1-weighted images. On T2-weighted images, there is variable signal intensity (usually ranging from intermediate to high signal intensity) depending on the primary tumor. Hypovascular metastases may show peripheral contrast enhancement with a nonenhancing or necrotic center on both CT and MRI, whereas hypervascular metastases show early arterial phase enhancement. Infection acterial Infection acterial infection of the liver can lead to the development of a hepatic pyogenic abscess, which results from destruction of hepatic parenchyma and formation of localized collections W434 JR:199, October 2012

Focal Hepatic Masses in Pediatric Patients Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved of pus. Hepatic pyogenic abscess is rare in pediatric patients and is more typically seen in adults. The most common bacterial organism causing hepatic pyogenic abscess in the pediatric population is Staphylococcus aureus, whereas Escherichia coli is the most frequent offending bacterial organism in adults. Hepatic pyogenic abscess can occur via several different pathways, such as hematogenous spread of infection via the hepatic artery, portal venous spread from intestinal infectious processes, biliary spread related to cholangitis, direct extension from other intraabdominal infectious processes, and secondary infection after blunt or penetrating trauma. On ultrasound, a hepatic pyogenic abscess typically has variable echogenicity, with approximately one half appearing anechoic (Fig. Fig. 21 Hepatic metastases from melanoma in 16-year-old girl who presented with weight loss and abdominal pain. xial contrast-enhanced CT image shows multiple hypodense lesions throughout liver. 22). The lesion is usually spherical or ovoid and may be surrounded by an irregular hypoechoic or echogenic wall. On unenhanced CT, a hepatic pyogenic abscess appears as a welldefined single hypodense mass. lternatively, it may appear as a hypodense mass with multiple septations, representing a cluster of multiple small abscesses (Fig. 22). Internal gas is present in about 20% of hepatic pyogenic abscesses. Contrast enhancement usually occurs along the periphery of an abscess and may involve internal septa. On MRI, a hepatic pyogenic abscess is hypointense to normal liver parenchyma on T1-weighted images and hyperintense on T2- weighted images. There may be increased T2-weighted signal in the adjacent hepatic parenchyma, representing edema or inflammatory changes, and a pyogenic hepatic abscess generally shows peripheral rim and septal contrast enhancement. Fungal Infection Hepatic fungal infection is typically the result of dissemination from systemic disease. Pediatric patients at increased risk for developing hepatic fungal infection are generally immunocompromised due to neutropenia after treatment of hematologic malignancies, transplantation, IDS, and chronic granulomatous diseases of childhood. The most common fungi causing hepatic infection are Candida species, specifically C. albicans. The most frequent route of infection is via intestinal seeding of the portal venous circulation. On ultrasound, CT, and MRI, hepatic fungal infection appears as numerous microabscesses (< 1 cm) that are distributed diffusely throughout the liver (Fig. 23). The appearance of fungal infection on ultrasound depends on the phase of infection and treatment. During the Fig. 22 acterial pyogenic hepatic abscess in 13-year-old boy who presented with fever and abdominal pain., Transverse ultrasound image shows relatively anechoic spherical mass (arrows) in right hepatic lobe., xial contrast-enhanced CT image shows relatively hypodense mass (arrows) with multiple septations. JR:199, October 2012 W435

deyiga et al. Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved Fig. 23 Fungal hepatic infection in 5-year-old boy who presented with fever, abdominal pain, and leukocytosis after induction chemotherapy for underlying acute lymphoblastic leukemia. lood culture was positive for Candida infection., Transverse ultrasound image shows multiple anechoic (short arrows) and targetlike (long arrow) lesions., xial T2-weighted image shows multiple small hyperintense lesions throughout liver and spleen. early phase of infection, there are focal hypoechoic lesions with alternating echogenic and hypoechoic peripheral zones. s the infection progresses, the lesions are usually hypoechoic with echogenic centers, producing a targetlike configuration. fter the institution of antifungal therapy, the lesions become smaller and echogenic and may resolve completely. Unenhanced CT of pediatric patients with hepatic fungal infection shows multiple small hypodense lesions that often show scattered calcifications during the healing phase. The central portion of lesions is typically nonenhancing with variable degrees of peripheral enhancement. The presence of central or eccentric enhancement is thought to represent hyphae. MRI is the current imaging modality of choice when evaluating pediatric patients suspected of hepatic involvement with disseminated fungal infection because of its high sensitivity for detecting small hepatic lesions and the lack of exposure to ionizing radiation (Fig. 23). Hepatic fungal lesions are hypointense on T1-weighted images, hyperintense on T2-weighted images, and do not show substantial contrast enhancement. Parasitic Infection Hepatic amebic abscess n amebic abscess is a parasitic infection that results in destruction of hepatic parenchyma and formation of localized collections of pus. The most common causative organism is Entamoeba histolytica. Hepatic amebic abscess is rare in the pediatric population and is more commonly seen in adults. mebic abscesses are more common in developing countries, although they may be detected in recent immigrants to Western countries. The clinical presentation of pediatric patients with hepatic amebic abscess is similar to that of hepatic pyogenic abscess, most commonly tender hepatomegaly and diarrhea with mucus. Initial infection with the cystic form of E. histolytica is by contaminated water. fter cysts enter the gastrointestinal tract and their cystic walls become digested, trophozoites Fig. 24 mebic hepatic abscess in 6-year-old boy who presented with right upper quadrant pain, fever, and leukocytosis. xial contrast-enhanced CT image shows hypodense hepatic mass with peripheral enhancement and edema in adjacent liver parenchyma. (Courtesy of Ricardo Restrepo) are released into the intestines. Hepatic involvement occurs by portal venous and lymphatic spread; rarely, it may develop by direct extension from the colon. spiration of an amebic abscess shows the classic appearance W436 JR:199, October 2012

Focal Hepatic Masses in Pediatric Patients Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved of material that is dark reddish brown with fluid consistency and has been likened to anchovy paste. On ultrasound, hepatic amebic abscess appears as a well-defined hypoechoic mass with through-transmission. CT usually shows a unilocular or multilocular peripheral hypodense mass with a thick enhancing capsule (Fig. 24). On MRI, the lesions are hypointense on T1- weighted images and hyperintense on T2- weighted images, often with evidence of edema in the surrounding hepatic parenchyma. s with CT, enhancement of a thick peripheral capsule is often seen on MRI. Hepatic echinococcal disease Hepatic echinococcal or hydatid disease is liver infection due to the larval stage of an Echinococcus tapeworm. The causative organism may be the more common E. granulosus, Fig. 25 Hepatic echinococcal disease in 9-yearold boy. xial contrast-enhanced CT image shows hypodense hepatic mass with thick peripheral rimlike calcification. (Courtesy of li Yikilmaz) which results in hydatid disease, or E. multilocularis, which produces a diffuse infiltrative process. Humans serve as an intermediate host, with the tapeworm larvae infecting the liver via the portal venous system. Hydatid cysts in the liver develop within 4 to 5 days of infection with E. granulosus, typically reach a diameter of 1 cm after 6 months, and grow approximately 2 3 cm per year. Infection with E. multilocularis results in proliferation of larvae and subsequent penetration of surrounding tissues, leading to infiltrative hepatic disease. Hydatid disease is usually acquired in childhood but often goes undiagnosed until adulthood. ffected pediatric patients are usually asymptomatic but may become symptomatic with progressive infection and cyst rupture. They typically present with abdominal pain, fever, jaundice, hepatomegaly, and allergic reaction with peripheral eosinophilia. spiration of a hydatid cyst is associated with a risk of anaphylactic reaction if there is spillage of cyst contents into the peritoneal cavity. The hydatid form of hepatic echinococcosis typically presents as a dominant cystic lesion that contains multiple peripheral daughter cysts. On ultrasound, hydatid cysts are well defined and predominantly anechoic, with some echogenic contents present between daughter cysts. The water lily sign refers to a cyst containing a floating membrane with a detached endocyst that develops after cyst rupture. On CT, the mother cyst is hypodense, with the daughter cysts even more hypodense relative to the dominant cyst. Peripheral rim calcifications are often seen, particularly during the healing phase of the disease (Fig. 25). The fibrous cyst wall and internal septa typically show contrast enhancement. On T1- weighted images, the mother cyst has intermediate signal intensity and daughter cysts are hypointense. The rim and any internal floating membranes are hypointense. On T2-weighted images, both the mother and daughter cysts have variable hyperintensity, although the rim and floating membranes are hypointense. oth the cyst wall and septa enhance after contrast administration. The infiltrative form of hepatic echinococcosis presents on ultrasound as single or multiple echogenic lesions, usually confined to the right hepatic lobe. The lesions are heterogeneous, with poorly defined borders, and they may be associated with dilatation of intrahepatic biliary ducts. On CT, they usually are multiple cystic and solid masses with irregular margins and amorphous calcifications. The noncalcified portions of the lesion show mild contrast enhancement. On MRI, infiltrative echinococcal lesions are heterogeneous and show mild contrast enhancement. Calcifications are difficult to detect on MRI. Transdiaphragmatic spread to the thoracic cavity is more common with the infiltrative form of hepatic echinococcosis. Conditions That Can Mimic Focal Hepatic Masses Hepatic Fatty Proliferation Hepatic fatty proliferation, or hepatic steatosis, is a metabolic complication resulting from toxic, ischemic, or infectious liver insults. It more commonly occurs in the adult population and may be associated with underlying diabetes and obesity. ffected patients are typically asymptomatic. Hepatic steatosis may be focal or diffuse. In the diffuse type, there may be areas of focal sparing that can often be confused with true hepatic lesions. Focal sparing usually occurs in JR:199, October 2012 W437

deyiga et al. Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved Fig. 26 Focal fatty infiltration in 17-year-old girl who presented with epigastric abdominal pain. xial contrast-enhanced CT image shows focal fatty infiltration in medial segment of left hepatic lobe (arrow). Fig. 27 Focal sparing in setting of underlying hepatic steatosis in 14-year-old boy who presented with abdominal pain. xial contrast-enhanced CT image shows diffusely fatty liver with focal sparing (arrows) in lateral segment of left hepatic lobe, mimicking hyperdense liver lesion. hepatic segment IV and often borders the gallbladder fossa (Fig. 26). On ultrasound, areas of steatosis are hyperechoic, with poor visualization of portal and hepatic veins in the involved segments. Focal sparring is seen as a relatively hypoechoic lesion in an otherwise echogenic liver. On CT, areas of fatty liver involvement are hypodense relative to the spleen. The most common location for focal fatty infiltration is the watershed zone adjacent to the falciform ligament. Diffuse steatosis with focal sparing presents as a relatively hyperdense focus within an otherwise hypodense liver (Fig. 27). fter contrast administration, normal vessels can be seen coursing through areas of steatosis. MRI with chemical-shift imaging is helpful in the evaluation of hepatic steatosis. Involved areas have increased signal intensity relative to the spleen on T1-weighted in-phase gradientecho sequences and show loss of signal on opposed-phase sequences. There is no enhancement with gadolinium. Hepatic Infarction Hepatic infarction represents areas of necrosis due to ischemia caused by disrupted hepatic perfusion. It is relatively rare because of the presence of a dual blood supply via the Fig. 28 Hepatic infarction in 6-year-old boy who presented with abdominal pain after being hit by car., xial contrast-enhanced CT image shows hypodense hepatic laceration (arrow) emanating from hepatic hilum, with hypoenhancement of devascularized left hepatic lobe (asterisk)., Coronal contrast-enhanced CT image shows hepatic laceration (straight arrow) with devascularized liver (asterisk) and spleen (curved arrow). W438 JR:199, October 2012

Focal Hepatic Masses in Pediatric Patients Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved Fig. 29 Wilms tumor of right kidney mimicking hepatic mass in 7-year-old girl who presented with right-sided abdominal pain., xial contrast-enhanced CT image shows round predominantly low-attenuation lesion that appears to be hepatic mass., Coronal contrast-enhanced CT image shows large right renal mass with its superior aspect (arrow) displacing liver and mimicking focal hepatic mass seen on. Fig. 30 Porta hepatis lymphadenopathy mimicking hepatic mass in 14-year-old boy who presented with recent diagnosis of Hodgkin disease., xial contrast-enhanced CT image shows hypodense mass (arrow) in region of porta hepatis., xial fused PET/CT image shows hypermetabolic activity (arrow) corresponding to mass in, which proved to be extrahepatic lymphadenopathy. hepatic arterial and portal venous systems. Hepatic infarction may be secondary to thrombus or embolus. In particular, hepatic infarction due to arterial thrombus is a relatively common (up to 12%) complication of liver transplantation in the pediatric population. Other causes of hepatic infarction include trauma, infection, vasculitis, hypercoagulable states, and iatrogenic postsurgical complications. n area of hepatic infarction typically appears hypoechoic on ultrasound. Color Doppler imaging may show absence of normal hepatic arterial blood flow; less commonly, findings of portal vein thrombosis may be identified. On CT, hepatic infarction appears as a hypodense area with sharply defined margins (Fig. 28). ecause of perfusion defects, lesions are often more conspicuous after contrast administration and remain hypodense on all phases of contrast-enhanced imaging. The MRI signal characteristics of hepatic infarction reflect edema within the lesion, which appears hypointense relative to normal hepatic parenchyma on T1- weighted images and hyperintense on T2-weighted images. s with CT, there is lack of enhancement because of perfusion defects and necrosis. JR:199, October 2012 W439

deyiga et al. Downloaded from www.ajronline.org by 148.251.232.83 on 04/27/18 from IP address 148.251.232.83. Copyright RRS. For personal use only; all rights reserved Extrahepatic Masses Various other lesions in the right upper abdominal quadrant may be confused with focal hepatic masses. These include masses arising from the right adrenal gland (neuroblastoma) and right kidney (Wilms tumor or other primary renal masses) (Fig. 29). Lymphadenopathy in the porta hepatic related to metastatic disease or lymphoma also may mimic an exophytic hepatic lesion (Fig. 30). On CT and MRI, careful 2D imaging correlated with clinical data can permit these types of lesions to be appropriately identified, thus leading to timely and accurate diagnoses. Conclusion wide spectrum of congenital, neoplastic, and infectious conditions may present as focal hepatic masses in pediatric patients. The specific imaging characteristics of various focal hepatic masses are often distinctive. Recognition of these patterns, combined with correlative clinical data, is imperative for accurate diagnosis and proper patient management. dditionally, it is important to recognize that intraabdominal right upper quadrant lesions not arising in the liver may mimic focal hepatic masses. Suggested Reading 1. nderson SW, Kruskal J, Kane R. enign hepatic tumors and iatrogenic pseudotumors. Radio- Graphics 2009; 29:211 229 2. aron PW, Majlessipour F, edros, et al. Undifferentiated embryonal sarcoma of the liver successfully treated with chemotherapy and liver resection. J Gastrointest Surg 2007; 11:73 75 3. rancatelli G, Federle MP, Vullierme MP, et al. CT and MR imaging evaluation of hepatic adenoma. J Comput ssist Tomogr 2006; 30:745 750 4. Christison-Lagay ER, urrows PE, lomari, et al. Hepatic hemangiomas: subtype classification and development of a clinical practice algorithm and registry. J Pediatr Surg 2007; 42:62 68 5. Chung EM, Cube R, Lewis R, et al. Pediatric liver masses: radiologic-pathologic correlation. Part 1. enign tumors. RadioGraphics 2010; 30:801 826 6. Crider MH, Hoggard E, Manivel JC. Undifferentiated (embryonal) sarcoma of the liver. Radio- Graphics 2009; 29:1665 1668 7. Elsayes KM, Narra VR, Yin Y, et al. Focal hepatic lesions: diagnostic value of enhancement pattern approach with contrast-enhanced 3D gradient-echo MR imaging. RadioGraphics 2005; 25:1299 1320 8. Gunay-ygun M. Liver and kidney disease in ciliopathies. m J Med Genet C Semin Med Genet 2009; 151C:296 306 9. Kawamoto S, Soyer P, Fishman EK, et al. Nonneoplastic liver disease: evaluation with CT and MR imaging. RadioGraphics 1998; 18:827 848 10. Kim OH, Chung HJ, Choi G. Imaging of the choledochal cyst. RadioGraphics 1995; 15:69 88 11. Levy D, Rohrmann C, Murakata L, et al. Caroli s disease: radiologic spectrum with pathologic correlation. JR 2002; 179:1053 1057 12. Mortelé KJ, Segatto E, Ros PR. The infected liver: radiologic-pathologic correlation. Radio- Graphics 2004; 24:937 955 13. Regier TS, Ramji FG. Pediatric hepatic hemangiomas. RadioGraphics 2004; 24:1719 1724 14. Shi L, Peng SY, Meng XK, et al. Diagnosis and treatment of congenital choledochal cyst: 20 years experience in China. World J Gastroenterol 2001; 7:732 734 W440 JR:199, October 2012