A case of multiple hepatic angiomyolipomas with high 18 F-fluorodeoxyglucose uptake

Background Hepatic angiomyolipoma is a rare benign mesenchymal tumor. We report an unusual case of a patient with multiple hepatic angiomyolipomas exhibiting high 18 F-fluorodeoxyglucose (FDG) uptake. Case presentation A 29-year-old man with a medical history of tuberous sclerosis was admitted to our hospital for fever, vomiting, and weight loss. Abdominal dynamic computed tomography revealed faint hypervascular hepatic tumors in segments 5 (67 mm) and 6 (10 mm), with rapid washout and clear borders; however, the tumors exhibited no definite fatty density. Abdominal magnetic resonance imaging revealed that the hepatic lesions were slightly hypointense on T1-weighted imaging, slightly hyperintense on T2-weighted imaging, and hyperintense with no apparent fat component on diffusion-weighted imaging. FDG-positron emission tomography (PET) imaging revealed high maximum standardized uptake values (SUVmax) of 6.27 (Segment 5) and 3.22 (Segment 6) in the hepatic tumors. A right hepatic lobectomy was performed, and part of the middle hepatic vein was also excised. Histological examination revealed that these tumors were characterized by the background infiltration of numerous inflammatory cells, including spindle-shaped cells, and a resemblance to an inflammatory pseudotumor. Immunohistochemical evaluation revealed that the tumor stained positively for human melanoma black-45. The tumor was therefore considered an inflammatory pseudotumor-like angiomyolipoma. Although several case reports of hepatic angiomyolipoma have been described or reviewed in the literature, only 3 have exhibited high 18 F-FDG uptake on PET imaging with SUVmax ranging from 3.3–4.0. In this case, increased 18 F-FDG uptake is more likely to appear, particularly if the inflammation is predominant. Conclusion Although literature regarding the role of 18 F-FDG-PET in hepatic angiomyolipoma diagnosis is limited and the diagnostic value of 18 F-FDG-PET has not yet been clearly defined, the possibility that hepatic angiomyolipoma might exhibit high 18 F-FDG uptake should be considered.


Background
Angiomyolipoma (AML) of the liver is a rare benign mesenchymal tumor with positive human melanoma black-45 (HMB-45) expression and a heterogeneous composition of blood vessels, and smooth muscle cells, and adipose tissue cells, which account for the tumors varying morphological features [1]. Most AMLs contain various amount of fat that enable detection via computed tomography (CT) or magnetic resonance imaging (MRI) [2][3][4][5]. However, some hepatic AMLs have low fat contents, posing difficulties for establishing a definitive preoperative diagnosis [6,7]. Diagnostic functional positron emission tomography (PET) imaging using an 18 F-fluorodeoxyglucose (FDG) tracer is a useful technique for detecting and differentiating benign and malignant tumors. Similar to benign tumors, which tend to exhibit low FDG uptake, hepatic AMLs have been reported to exhibit similarly low uptake levels in the absence of hemorrhage [8]. However, we encountered a distinct case with multiple AMLs with high FDG uptake in the liver of a 29-year-old man.

Case presentation
A 29-year-old man with a medical history of tuberous sclerosis was admitted to our hospital for fever, vomiting, and weight loss (4 kg/month). His serum C-reactive protein and hepatic enzyme levels were increased. Tests for all evaluated markers of hepatic viruses and tumors such as alpha-fetoprotein, carcinoembryonic antigen, protein induced by vitamin K absence-2, and cancer antigen 19-9 were negative.
Abdominal dynamic CT revealed faint hypervascular hepatic tumors in segments 5 (S5; 67 mm) and 6 (S6; 10 mm), with rapid washout and clear borders but without definite fatty densities. CT also revealed multiple tumors with fat components in both kidneys, but these did not show definite enhancements ( Figure 1).
Abdominal MR imaging (1.5 T Magnetom Symphony; Siemens Medical Solutions, Erlangen, Germany) revealed that the hepatic lesions were slightly hypointense on T1-weighted imaging (T1WI), slightly hyperintense on T2-weighted imaging (T2WI), and hyperintense on diffusion-weighted imaging (DWI) with no apparent fat component ( Figure 2). The tumors in both kidneys were mildly hypointense on both T1WI and T2WI and mildly hyperintense with fat components on DWI. 18 F-FDG PET/CT (Biograph 16; Siemens Medical Solutions, Erlangen, Germany) imaging revealed that the hepatic tumors exhibited high maximum standard uptake values (SUVmax) of 6.27 (S5) and 3.22 (S6; Figure 3). No definite FDG-uptake was observed in the renal AMLs.
Although a preoperative percutaneous biopsy was performed and a histological examination of the specimens suggested the diagnosis of angiomyolipoma, the high FDG uptake and increasing tumor sizes made it difficult to exclude a malignant transformation of angiomyolipoma. A right hepatic lobectomy was performed and a part of the middle hepatic vein was also excised. The patient recovered well after surgery. His initial symptoms resolved completely, and his serological parameters of inflammation returned to normal by the time of release from hospital. Currently, the patient remains in a healthy condition and has exhibited no signs of recurrence at 4 years after surgery.
Histological examination revealed that these tumors were characterized by the background infiltration of numerous inflammatory cells, including spindle-shaped cells, and an absence of fat ( Figure 4) and thus resembled inflammatory pseudotumors. On immunohistochemical analysis, the tumors stained positively for HMB-45, CD31, vimentin, and α-smooth muscle actin. However, the tumor cells were negative for keratin, epithelial membrane antigen, hepatocyte paraffin1, c-kit, CD34, CD56, and S-100. The tumor was hence diagnosed as an inflammatory pseudotumor-like AML.

Discussion
AML is a benign mesenchymal tumor that has reportedly occurred frequently in the kidney but rarely in the liver. Approximately 5%-10% of hepatic AML are associated with renal AML and tuberous sclerosis (Bourneville's disease), and this was true for our patient. The first case of hepatic AML was described by Ishak in 1976 [9]. Although fatty tissue is a characteristic of AML, the fat content within the tumor can range from 5% to 90% of the tumor volume, thus resulting in varying radiological appearances [2,5,6,10]. Preoperative diagnosis relies on imaging studies, which include CT and MRI. However, it is often difficult to distinguish these lesions from other hepatic fatty tumors such as fat-containing hepatic adenomas or hepatocellular carcinomas with fatty metamorphosis.
Although AMLs are considered benign, malignant transformation is not a rare complication associated with renal AML [11]. In recent years, the malignant transformation of hepatic AML has also been reported in the literature [12,13]. 18 F-FDG PET/CT is useful for detecting malignant transformation [14]. Moreover, because hepatic AML has been reported to exhibit low 18 F-FDG-uptake [8], 18 F-FDG PET/CT might be highly valuable for excluding malignancies among hepatic lesions suspected to be AML.
We performed a Medline search using the search terms "liver", "angiomyolipoma", and "FDG". Although several case reports of hepatic AML have been described or reviewed in the literature, only 3 cases exhibited high 18 F-FDG uptake on PET imaging, with SUVmax ranging from 3.3-4.0 [8,13,[15][16][17][18][19][20] (Table 1).  Kinugasa et al. [17] suggested that glucose hypermetabolism in smooth muscle cells and a high cell density due to the lack of a fat component might increase the 18 F-FDG uptake. Takanami et al. [8] suggested that hepatic AMLs might exhibit increased 18 F-FDG uptake in the presence of hemorrhage or an inflammatory response. In such cases, increased 18 F-FDG uptake is more likely to appear, particularly if the inflammatory tissue is predominant. Because the average mean SUV of the normal liver is approximately 3.5 ± 3.1 and the malignant lesion-to-liver SUV ratio is approximately 1.9 ± 1.4 [21], the FDG uptakes of the angiolipomas described in Table 1 were easily obscured by the FDG uptake of the normal liver tissue. In our case, the angiolipomas exhibited apparently high levels of FDG uptake.
Recently, some hepatic epithelioid AMLs have been reported to have features similar to those of renal AMLs reported previously. Epithelioid AMLs either lack or contain only a minimal amount of adipose tissue and are thus more difficult to distinguish from other hypervascular tumors. The imaging features of epithelioid AMLs include an absent capsule and hypervascularity with central punctiform or filiform vessels that exhibit characteristic enhancement [22,23]. No literature reports have described the FDG-PET imaging features of epithelioid AMLs. In our case, although the CT and MRI imaging features were similar to those of epithelioid AML, no epithelial cells were observed in a histopathological examination.
The presence of HMB-45-positive smooth muscle cells in an immunostaining analysis is the definitive criterion for diagnosing hepatic AML [24]. Although AML was already suggested by the findings the preoperative percutaneous biopsy, we could not completely rule out the possibility of malignancy because of the atypical MRI findings and high 18 F-FDG uptake in the lesions.

Conclusion
We report herein a case of multiple hepatic angiomyolipomas with high 18 F-FDG uptake. Although the literature reports on the role of 18 F-FDG PET/CT in hepatic