CASE REPORT 
Annals of Nuclear Medicine Vol. 13, No. 6, 427-431, 1999 
Two cases of focal nodular hyperplasia of the liver: Value of scintigraphy with Tc-99m GSA and positron emission tomography with FDG 
Susumu SHIOMI,* Hiroko KUROOKA Yoshinon IWATA,*Nobumitsu SASAKI,* Kyoko MASAKI,* Hisato JOMURA,* Shuhei NISHIGUCHI,* Tetsuo KUROKJ* and Hironobu OCHl** 
*Third Department of Internal Medicine and **Division of Nuclear Medicine, Osaha City University Medical School 
Focal nodular hyperplasia (FNH) of the liver is relatively rare, and can be difficult to differentiate from other benign tumors arising in the liver. We describe a 23-year-old woman and a 25-year-old man with FNH. They were hospitalized for further evaluation of a space-occupying lesion in the liver. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) revealed increased radioactivity in the tumor in one patient and radioactivity similar to that in the normal part of liver in the other. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed uptake similar to that of the normal liver in both patients. FNH was diagnosed on the basis of angiographic findings and histological findings in liver biopsy specimens. Our results show that scintigraphy with Tc-99m GSA and FDG-PET may provide information helpful in the diagnosis of FNH. 
Key words: FDG, Tc-99m GSA, focal nodular hyperplasia, positron emission tomography 
INTRODUCTION 
FOCAL NODULAR HYPERPLASIA (FNH) is a benign hepatic tumor that characteristically occurs in women of reproductive age. It is often discovered incidentally.1 Since both hepatic adenoma and hepatocellular carcinoma (HCC) require surgical treatment,2 distinguishing FNH from these tumors is mandatory to avoid an unnecessary operation. To make a definite diagnosis of FNH, its characteristics must be confirmed by imaging studies. The characteristics of FNH have been described on the basis of 3,4 various image techniques, including ultrasonography, computed tomography (CT),3,5 and magnetic resonance imaging (MRI)6,7 but imaging studies do not always yield typical findings, and it is often difficult to make a definite diagnosis by such a method alone. Imaging with a radionuclide based on functional aspects of Kupffer cells and 
Received June 23, 1999, revision accepted September 9, 1999. 
For reprint contact: Susumu Shiomi, M.D., Third Department of Internal Medicine, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, JAPAN. 
E-mail: shiomis@med.osaka-cu.ac.jp 
hepatocytes offers valuable information not available with other imaging techniques. Such information may be useful for the diagnosis of FNH. We report two cases of FNH in which scintigraphy with Tc-99m diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) and positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET) were performed. 
CASE REPORT 
Case 1. 
A 23-year-old woman was referred to our hospital because of left hypochondrium pain. Abdominal ultrasonography showed a space-occupying lesion in the liver, and the patient was hospitalized. 
On admission, the patient was of moderate build and well-nourished. The red blood cell count was 495 x 104/ mm3, the platelet count was 9.5 x 104/mm3, the serum albumin concentration was 4.7 g/dL, the aspartate transferase activity was 24 IU/L, the alanine aminotransferase activity was 24 IU/L, the cholinesterase activity was 575 IU/L, the total bilirubin concentration was 1.0 mg/dL, the a-fetoprotein concentration was 4 ng/mL, the carcinoembryonic antigen was 1.1 ng/ml, the hepatitis B surface antigen was negative, and the hepatitis C virus antibody was negative. 
Contrast CT in the early phase revealed a tumor with uniform density in the liver (Fig. 1A); that in the late phase revealed an irregular high density area in the tumor (Fig. 1B). Color Doppler flow imaging showed a central color spot with a pulsatile wave in the mass (Fig. 2A). Celiac angiography showed a centrifugal vascular structure in the tumor (Fig. 2B). Scintigraphy with Tc-99m GSA revealed increased radioactivity in the tumor (Fig. 3A). FDG-PET showed uptake similar to that in the normal part of the liver (Fig. 3B). Hematoxylin-eosin staining of a specimen obtained by liver biopsy under ultrasonic guidance revealed no malignant lesion and extensive scar-like connective tissue, including abundant thick-walled arteries and proliferating bile ducts (Fig. 4). Case 2. 
A 25-year-old man was referred to our hospital because of abnormal results of liver blood tests. Abdominal ultra-sonography showed a space-occupying lesion in the liver, and the patient was hospitalized. 
On admission, the patient was of moderate build and well-nourished. The red blood cell count was 465 x 104/ mm3, the platelet count was 9.2 x 104/mm3, the serum albumin concentration was 4.2 g/dL, the aspartate transferase activity was 46 IU/L, the alanine aminotransferase activity was 42 IU/L, the gamma-glutamyl transpeptidase activity was 86 IU/L, the cholinesterase activity was 465 IU/L, the total bilirubin concentration was 0.8 mg/dL, the a-fetoprotein concentration was 3 ng/mL, the carcinoembryonic antigen was 1.0 ng/ml, the hepatitis B surface antigen was negative, and the hepatitis C virus antibody was negative. 
CT angiography in the artery phase revealed a tumor with high density (Fig. 5A), and that in the venous phase revealed low density in the liver (Fig. 5B). Celiac angiography showed a centrifugal vascular structure in the tumor (Fig. 6). Scintigraphy with Tc-99m GSA revealed uptake similar to that in the normal part of the liver (Fig. 7A). FDG-PET also showed uptake similar to that in the normal part of the liver (Fig. 7B). Hematoxylin-eosin staining of a specimen obtained by liver biopsy under ultrasonic guidance revealed no malignant lesion and extensive scar-like connective tissue, including abundant thick-walled arteries and proliferating bile ducts (Fig. 8). 
DISCUSSION 
Pathologically, FNH consists of hepatocytes and Kupffer cells and shows normal hepatic architecture. It often has a thin fibrous capsule. A central satellite-shaped collagenous scar with peripherally radiating septae is a typical finding.1,8 We used percutaneous fine-needle biopsy to confirm the diagnosis of FNH, but diagnosis may be difficult when a small biopsy specimen containing only normal hepatocytes is obtained, without the extensive scar-like connective tissue. Sampling errors may also occur. 
A central stellate scar is considered pathognomonic of FNH. In our patients, CT showed a hypodense area in the center of the tumor, suggesting a central scar, but this feature is detected in only a limited number of cases, with a central stellate scar being visualized in 18% to 26% of patients by ultrasonography,3,4 14% to 61% by CT,3,5 and 35% to 79% by MRI.6,7 Another feature of FNH is its specific vascular architecture, in which a large tortuous artery enters the center of the tumor and then supplies the nodules centrifugally.8 This anatomical feature appears as a wheel spike on angiograms and is unique to FNH. However, this feature was detected in only 44% of patients undergoing angiography.9 In recent years, angio CTIO and color Doppler ultrasonogrphy4,11,12 have been developed to evaluate the hemodynamics of liver tumors in detail. 
Normal or increased uptake of colloid scan has been suggested as pathognomonic of FNH, which contains functioning Kupffer cells.9 This finding is useful in discriminating between FNH and hepatic adenoma since the latter, which lacks Kupffer cells, shows a focal defect on colloid scintigraphy.13,14 Nevertheless, Welch et al.3 reported that among 10 tumors studied with Tc-99m sulfur colloid, 4 (40%) had increased uptake as compared with the normal liver; 3(30%) had uptake similar to that of the liver, and 3 (30%) had decreased uptake. Roger et al.9 reported that 4 (36%) of 11 cases showed decreased uptake on scintigraphy with Tc-99m sulfur colloid. 
Tc-99m GSA scintigraphy of the liver is based on visualization of the receptor binding of Tc-99m GSA to liver cells.15 In general, the accumulation of Tc-99m GSA is related to the functional activity and the number of functioning hepatocytes. A Iocalized area of decreased accumulation of Tc-99m GSA can be expected where a decreased number of asialoglycoprotein receptors are present. It is well known that the receptor-mediated binding with subsequent cellular endocytosis does not occur in HCC or metastatic tumors because surface asialoglycoprotein receptors are lost during malignant dedifferentiation.16,17 But, Saito et al.18 reported that scintigraphy with Tc-99m GSA showed increased uptake in 2(25%) of 8 patients with well differentiated HCC because some well differentiated HCCs have asialoglycoprotein receptor.19 
Kutaran et al.20 reported that scintigraphy with Tc-99m GSA showed increased uptake in 8 (67%) of 12 patients and normal uptake in the remaining 4 (33%) and, thus, the method was useful for the diagnosis of FNH. One of our patients showed an increased uptake and the other, a normal uptake. Hepatic tumors seldom show an increased uptake on scintigraphy with Tc-99m GSA, and this finding is characteristic of FNH and well differentiated HCC. The increased uptake on scintigraphy is likely to be caused by an increase in cell density, but there was no increase in cell density in our two cases, and the cause of the increased uptake could not be determined. 
We also performed FDG-PET in both cases. PET has been used recently to diagnose various types of tumors 21 and FDG-PET is considered particularly useful in the diagnosis of HCC and cholangiocellular carcinoma.22 Although the use of FDG-PET for the diagnosis of FNH has not been reported previously, the uptake was similar to that in the normal part of the liver in both of our patients. Torizuka et al.23 reported that glucose metabolism as assessed by FDG-PET closely reflects the enzymatic activity of glucose. This shows that glucose metabolism in FNH does not differ from that in the normal liver despite the presence of hyperplasia. 
In conclusion, imaging procedures such as ultrasonography. CT and MRI do not always yield typical finding, and it is often difficult to make a definite diagnosis of FNH by such a method alone. Our findings show that FDG-PET and scintigraphy with Tc-99m GSA may provide information helpful in the diagnosis of FNH. 
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