(Radiographics. 2001;21:877-892.)
© RSNA, 2001
Hepatic Adenomas: Imaging and Pathologic Findings1
Luigi Grazioli, MD,
Michael P. Federle, MD,
Giuseppe Brancatelli, MD,
Tomoaki Ichikawa, MD,
Lucio Olivetti, MD and
Arye Blachar, MD
1 From the Department of Radiology, University of Brescia, Brescia, Italy (L.G.); the Department of Radiology, University of Pittsburgh Medical Center, Presbyterian Hospital, 200 Lothrop St, Rm 4660 CHP MT, Pittsburgh, PA 15213 (M.P.F., G.B., A.B.); the Department of Radiology, Yamanashi Medical University, Nakakoma, Japan (T.I.); and the Department of Radiology, Istituti Ospitalieri di Cremona, Cremona, Italy (L.O.). Recipient of a Certificate of Merit award for a scientific exhibit at the 1999 RSNA scientific assembly. Received August 10, 2000; revision requested October 17 and final revision received December 4; accepted December 11. G.B. supported by the Nicholas Green Fulbright Grant. Address correspondence to M.P.F. (e-mail: federlemp@radserv.arad.upmc.edu).
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Abstract
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Hepatocellular adenoma is a rare benign lesion that is most often seen in young women with a history of oral contraceptive use. It is typically solitary, although multiple lesions have been reported, particularly in patients with glycogen storage disease and liver adenomatosis. Because of the risk of hemorrhage and malignant transformation, hepatocellular adenomas must be identified and treated promptly. At pathologic analysis, hepatocellular adenoma is usually a well-circumscribed, nonlobulated lesion, and at gross examination, resected adenomas frequently demonstrate areas of hemorrhage and infarction. Most adenomas are not specifically diagnosed at ultrasonography (US) and are usually further evaluated with computed tomography (CT) or other imaging modalities. Color Doppler US may help differentiate hepatocellular adenoma from focal nodular hyperplasia. Multiphasic helical CT allows more accurate detection and characterization of focal hepatic lesions. Hepatocellular adenomas are typically bright on T1-weighted magnetic resonance images and predominantly hyperintense relative to liver on T2-weighted images. The prognosis of hepatic adenoma is not well established. Criteria that guide treatment include the number and size of the lesions, the presence of symptoms, and the surgical risk incurred by the patient. Understanding the imaging appearance of hepatocellular adenoma can help avoid misdiagnosis and facilitate prompt, effective treatment.
Index Terms: Liver, calcification, 761.814 • Liver, hemorrhage • Liver neoplasms, 761.3192 • Liver neoplasms, CT, 761.1211 • Liver neoplasms, diagnosis, 761.1211, 761.1214 • Liver neoplasms, MR, 761.1214 • Liver neoplasms, US, 761.12983
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LEARNING OBJECTIVES FOR TEST 4
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After reading this article and taking the test, the reader will be able to:
- Describe the role of imaging in the evaluation and diagnosis of hepatic adenoma.
- Recognize the typical and atypical imaging features of hepatic adenoma.
- Recognize the specific and nonspecific pathologic features of hepatic adenoma.
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Introduction
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Hepatic adenoma is an uncommon benign neoplasm that is usually found in women with a history of oral contraceptive use. Modern cross-sectional imaging techniques can help detect these tumors, and recent studies suggest that differentiation from other benign and malignant neoplasms is possible in most cases (1). Optimization of imaging techniques is crucial because the key differential imaging features are usually not evident on "generic" ultrasonographic (US), computed tomographic (CT), or magnetic resonance (MR) imaging studies.
In this article, we discuss and illustrate the key clinical, histopathologic, and imaging features of hepatic adenomas as well as prognosis and treatment in the hope of facilitating more confident and cost-effective treatment of affected patients. Our findings are based on our recent experience with 50 patients, including those with single or multiple hepatocellular adenomas (n = 32), multiple hepatocellular adenomas and glycogen storage disease (n = 3), and liver adenomatosis (n = 15).
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Clinical and Epidemiologic Features
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Hepatic adenomas were virtually unknown prior to 1960, the year in which oral contraceptives were introduced (2). Although the precise pathogenic mechanism of hepatic adenomas is still unknown, the use of estrogen-containing (3) or androgen-containing (4) steroid medications clearly increases their prevalence, number, and size within the affected population and often within individual patients. Moreover, this causal relationship is related to dose and duration, with the greatest risk encountered in patients taking large doses of estrogen or androgen for prolonged periods of time (4). In women who have never used oral contraceptives, the annual incidence of hepatic adenoma is about 1 per million. This increases to 30–40 per million in long-term users of oral contraceptives (5).
Another risk group for hepatocellular adenoma are patients with type I glycogen storage disease (6). In these patients, the adenomas are also more likely to be multiple and to undergo malignant transformation, although the latter is still quite rare (7).
Hepatocellular adenomas occur sporadically in patients without known predisposing factors and rarely in children and adult males. A recently recognized association is that of congenital or acquired abnormalities of the hepatic vasculature. Portal vein absence or occlusion (8) or portohepatic venous shunts (9) have been noted, particularly in patients with "liver adenomatosis" (10), a term coined by Flejou et al (11) in 1985 to describe multiple (usually >10) adenomas in patients lacking other known risk factors for adenomas. Liver adenomatosis appears to be a distinct entity. Although the adenomas in liver adenomatosis are histologically similar to other adenomas, they are not steroid dependent, but are multiple, progressive, symptomatic, and more likely to lead to impaired liver function, hemorrhage, and perhaps malignant degeneration (10).
Many or most patients with no more than a few adenomas are asymptomatic and almost invariably have normal liver function and no elevation of serum "tumor markers" such as 
-fetoprotein. Large adenomas may cause a sensation of right upper quadrant fullness or discomfort. However, the classic clinical manifestation of hepatic adenoma is spontaneous rupture or hemorrhage, leading to acute abdominal pain and possibly progressing to hypotension and even death (12). Adenomas are increasingly being encountered as incidental findings in patients who undergo multiphasic CT or MR imaging for unrelated or nonspecific signs or symptoms.
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Histopathologic Features
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The histopathologic features of hepatic adenomas are now well established, although pathologists who are unfamiliar with primary hepatic neoplasms have used imprecise and confusing terminology and criteria that have blurred the distinction between these and other neoplasms, particularly focal nodular hyperplasia.
Hepatic adenomas are reported to be solitary in 70%–80% of cases, but it is not unusual to encounter two or three adenomas in one patient, particularly at multiphasic CT or MR imaging (13,14). Patients with glycogen storage disease or liver adenomatosis may have dozens of adenomas detected at imaging and even more at close examination of resected specimens (Fig 1) (10,11, 15). Individual adenomas vary in size from less than 1 cm to more than 15 cm. The typical steroid-related adenoma often comes to clinical attention when it reaches about 5 cm in diameter. Large and multiple adenomas are more prone to spontaneous hemorrhage (12).
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Figure 1a. Adenomatosis in a 35-year-old woman who presented with weight loss and ascites. (a) Portal venous-phase CT scan shows a markedly enlarged and diffusely heterogeneous liver due to the presence of multiple masses. Some of these masses are hyperattenuating (solid arrows), whereas others are isoattenuating and are suggested only by displacement of the vessels and distortion of the normal architecture (arrowheads). Note the areas of coarse calcification (open arrow). (b) Photograph of the explanted liver shows numerous green-brown adenomas that replaced over 90% of the liver parenchyma.
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Figure 1b. Adenomatosis in a 35-year-old woman who presented with weight loss and ascites. (a) Portal venous-phase CT scan shows a markedly enlarged and diffusely heterogeneous liver due to the presence of multiple masses. Some of these masses are hyperattenuating (solid arrows), whereas others are isoattenuating and are suggested only by displacement of the vessels and distortion of the normal architecture (arrowheads). Note the areas of coarse calcification (open arrow). (b) Photograph of the explanted liver shows numerous green-brown adenomas that replaced over 90% of the liver parenchyma.
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The propensity to hemorrhage reflects the histologic characteristics of adenomas, which consist of large plates or cords of cells closely resembling normal hepatocytes, with the plates separated by dilated sinusoids. These sinusoids are equivalent to thin-walled capillaries that are perfused by arterial pressure because adenomas lack a portal venous supply and are fed solely by peripheral arterial feeding vessels. The extensive sinusoids and feeding arteries constitute the hypervascular nature of hepatocellular adenoma, and poor connective tissue support, also predisposes to hemorrhage within the adenoma. Because a tumor capsule is usually absent or incomplete, hemorrhage may spread into the liver or abdominal cavity (16). Kupffer cells are often found in adenomas but in reduced numbers and with little or no function, as reflected by absent or diminished uptake of technetium (Tc)–99m sulfur colloid (17). Bile ductules are notably absent from adenomas, a key histologic feature that helps distinguish hepatocellular adenoma from focal nodular hyperplasia (18).
Adenoma cells are larger than normal hepatocytes and contain large amounts of glycogen and lipid (Fig 2). Intra- and intercellular lipid uncommonly manifests as macroscopic fat deposits within the tumor (13). Lipid accumulation is responsible for the characteristic yellow appearance of the cut surface of adenomas (Fig 3), and evidence of lipid at CT or MR imaging can be helpful in diagnosing hepatocellular adenoma.
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Figure 2. Adenoma. High-power photomicrograph (hematoxylin-eosin stain) of a core-needle biopsy specimen shows an adenoma composed of disorganized hepatocyte cords. The individual cells resemble normal hepatocytes but contain large amounts of lipid and glycogen, which accounts for the pale cytoplasm.
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Figure 3a. Single adenoma in a 49-year-old woman. The adenoma was discovered incidentally at laparoscopic surgery. (a) Unenhanced CT scan shows a 5-cm-diameter, exophytic, slightly hypoattenuating tumor in the right lower lobe of the liver (arrow). (b) On an arterial-phase CT scan, the tumor shows heterogeneous enhancement. Note the enhancing incomplete pseudocapsule (arrows). (c) Photograph of the resected specimen shows a well-circumscribed mass with extensive hemorrhage (open arrow), a partial capsule (curved arrow), and foci of yellow-tan tissue (straight solid arrow). These tissue foci demonstrated markedly increased cytoplasmic lipid content at histologic analysis.
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Figure 3b. Single adenoma in a 49-year-old woman. The adenoma was discovered incidentally at laparoscopic surgery. (a) Unenhanced CT scan shows a 5-cm-diameter, exophytic, slightly hypoattenuating tumor in the right lower lobe of the liver (arrow). (b) On an arterial-phase CT scan, the tumor shows heterogeneous enhancement. Note the enhancing incomplete pseudocapsule (arrows). (c) Photograph of the resected specimen shows a well-circumscribed mass with extensive hemorrhage (open arrow), a partial capsule (curved arrow), and foci of yellow-tan tissue (straight solid arrow). These tissue foci demonstrated markedly increased cytoplasmic lipid content at histologic analysis.
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Figure 3c. Single adenoma in a 49-year-old woman. The adenoma was discovered incidentally at laparoscopic surgery. (a) Unenhanced CT scan shows a 5-cm-diameter, exophytic, slightly hypoattenuating tumor in the right lower lobe of the liver (arrow). (b) On an arterial-phase CT scan, the tumor shows heterogeneous enhancement. Note the enhancing incomplete pseudocapsule (arrows). (c) Photograph of the resected specimen shows a well-circumscribed mass with extensive hemorrhage (open arrow), a partial capsule (curved arrow), and foci of yellow-tan tissue (straight solid arrow). These tissue foci demonstrated markedly increased cytoplasmic lipid content at histologic analysis.
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Adenomas rarely undergo malignant transformation to hepatocellular carcinoma (HCC), even after years of maintaining a stable appearance (Fig 4) (19–21). Moreover, adenomas and HCC may have similar imaging features and even histopathologic features, making differentiation difficult or impossible short of complete resection. Other criteria, such as interval growth of a mass or elevated serum -fetoprotein levels, favor a diagnosis of HCC.
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Figure 4a. Enlarging adenoma that degenerated into HCC in a 65-year-old woman. (a) Portal venous-phase CT scan of the liver shows a large, heterogeneous, lobulated mass with irregular regions of hypervascularity and small calcifications (arrow). (b) Photograph of the resected specimen shows a pink-yellow to hemorrhagic, multilobulated mass beneath the liver capsule. At histopathologic analysis, some areas were believed to represent "typical" hepatic adenoma, whereas others had frank malignant HCC.
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Figure 4b. Enlarging adenoma that degenerated into HCC in a 65-year-old woman. (a) Portal venous-phase CT scan of the liver shows a large, heterogeneous, lobulated mass with irregular regions of hypervascularity and small calcifications (arrow). (b) Photograph of the resected specimen shows a pink-yellow to hemorrhagic, multilobulated mass beneath the liver capsule. At histopathologic analysis, some areas were believed to represent "typical" hepatic adenoma, whereas others had frank malignant HCC.
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Imaging Features
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Ultrasonography
Adenomas are often detected first at US performed to evaluate right upper quadrant discomfort. The high lipid content of adenomas may contribute to the hyperechoic appearance of some of these lesions (Fig 5a). Intratumoral hemorrhage can also result in increased echogenicity and heterogeneity (Fig 6a), whereas other areas of hemorrhage may appear as hypoechoic or cystic areas. Calcifications may be present in association with areas of necrosis and manifest as hyperechoic foci with acoustic shadowing (Fig 7a). Color Doppler US may demonstrate peripheral peritumoral vessels and intratumoral vessels that typically have a flat continuous or, less commonly, triphasic waveform (Fig 8) (22,23). These Doppler US features are reported to be absent in the vessels within focal nodular hyperplasia and may be useful in distinguishing the two disease entities. Nevertheless, most adenomas are not specifically diagnosed at US and are usually further evaluated with CT or other imaging modalities.
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Figure 5a. Multiple adenomas in a 30-year-old woman who presented with increasing abdominal discomfort. Because of spontaneous hemorrhage, the patient underwent resection of the left lobe of the liver. (a) Sagittal US scan of the liver shows a well-defined, homogeneous, hyperechoic lesion in the right lobe (arrow). (b) Unenhanced CT scan shows multiple hypoattenuating lesions (arrows). (c) On a portal venous-phase CT scan, the lesions remain hypoattenuating relative to the liver parenchyma, although some enhancement is present. Note the penetrating vessels in the largest lesion (arrows). (d) Photograph of the resected specimen from the left lobe shows gross distortion by multiple nodules (arrows). The capsule of the liver appears focally hemorrhagic and expanded but is not penetrated by the nodules.
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Figure 5b. Multiple adenomas in a 30-year-old woman who presented with increasing abdominal discomfort. Because of spontaneous hemorrhage, the patient underwent resection of the left lobe of the liver. (a) Sagittal US scan of the liver shows a well-defined, homogeneous, hyperechoic lesion in the right lobe (arrow). (b) Unenhanced CT scan shows multiple hypoattenuating lesions (arrows). (c) On a portal venous-phase CT scan, the lesions remain hypoattenuating relative to the liver parenchyma, although some enhancement is present. Note the penetrating vessels in the largest lesion (arrows). (d) Photograph of the resected specimen from the left lobe shows gross distortion by multiple nodules (arrows). The capsule of the liver appears focally hemorrhagic and expanded but is not penetrated by the nodules.
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Figure 5c. Multiple adenomas in a 30-year-old woman who presented with increasing abdominal discomfort. Because of spontaneous hemorrhage, the patient underwent resection of the left lobe of the liver. (a) Sagittal US scan of the liver shows a well-defined, homogeneous, hyperechoic lesion in the right lobe (arrow). (b) Unenhanced CT scan shows multiple hypoattenuating lesions (arrows). (c) On a portal venous-phase CT scan, the lesions remain hypoattenuating relative to the liver parenchyma, although some enhancement is present. Note the penetrating vessels in the largest lesion (arrows). (d) Photograph of the resected specimen from the left lobe shows gross distortion by multiple nodules (arrows). The capsule of the liver appears focally hemorrhagic and expanded but is not penetrated by the nodules.
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Figure 5d. Multiple adenomas in a 30-year-old woman who presented with increasing abdominal discomfort. Because of spontaneous hemorrhage, the patient underwent resection of the left lobe of the liver. (a) Sagittal US scan of the liver shows a well-defined, homogeneous, hyperechoic lesion in the right lobe (arrow). (b) Unenhanced CT scan shows multiple hypoattenuating lesions (arrows). (c) On a portal venous-phase CT scan, the lesions remain hypoattenuating relative to the liver parenchyma, although some enhancement is present. Note the penetrating vessels in the largest lesion (arrows). (d) Photograph of the resected specimen from the left lobe shows gross distortion by multiple nodules (arrows). The capsule of the liver appears focally hemorrhagic and expanded but is not penetrated by the nodules.
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Figure 6a. Single adenoma in a 33-year-old woman who presented with abdominal pain. (a) Transverse US scan of the liver shows a hypoechoic lesion (cursors) with a hyperechoic center (arrow) due to recent hemorrhage. (b) Unenhanced CT scan shows a hypoattenuating lesion with high-attenuation blood centrally (arrow).
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Figure 6b. Single adenoma in a 33-year-old woman who presented with abdominal pain. (a) Transverse US scan of the liver shows a hypoechoic lesion (cursors) with a hyperechoic center (arrow) due to recent hemorrhage. (b) Unenhanced CT scan shows a hypoattenuating lesion with high-attenuation blood centrally (arrow).
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Figure 7a. Calcified adenoma in a 59-year-old man. (a) Transverse US scan of the right lobe of the liver shows hyperechoic lesions with acoustic shadowing (arrow). (b) Unenhanced CT scan shows a mass in the right lobe with a large central calcification (arrow). (c) Portal venous-phase CT scan shows heterogeneous enhancement of most of the adenoma. Calcifications are noted within hypoattenuating cystic areas. (d) Arterial-phase gadolinium-enhanced MR image shows heterogeneous enhancement of the adenoma and a signal void representing the central calcification. (e) Coronal MR image obtained following administration of superparamagnetic iron oxide shows the normal liver (L) with decreased signal intensity. The adenoma (A) remains unaffected.
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Figure 7b. Calcified adenoma in a 59-year-old man. (a) Transverse US scan of the right lobe of the liver shows hyperechoic lesions with acoustic shadowing (arrow). (b) Unenhanced CT scan shows a mass in the right lobe with a large central calcification (arrow). (c) Portal venous-phase CT scan shows heterogeneous enhancement of most of the adenoma. Calcifications are noted within hypoattenuating cystic areas. (d) Arterial-phase gadolinium-enhanced MR image shows heterogeneous enhancement of the adenoma and a signal void representing the central calcification. (e) Coronal MR image obtained following administration of superparamagnetic iron oxide shows the normal liver (L) with decreased signal intensity. The adenoma (A) remains unaffected.
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Figure 7c. Calcified adenoma in a 59-year-old man. (a) Transverse US scan of the right lobe of the liver shows hyperechoic lesions with acoustic shadowing (arrow). (b) Unenhanced CT scan shows a mass in the right lobe with a large central calcification (arrow). (c) Portal venous-phase CT scan shows heterogeneous enhancement of most of the adenoma. Calcifications are noted within hypoattenuating cystic areas. (d) Arterial-phase gadolinium-enhanced MR image shows heterogeneous enhancement of the adenoma and a signal void representing the central calcification. (e) Coronal MR image obtained following administration of superparamagnetic iron oxide shows the normal liver (L) with decreased signal intensity. The adenoma (A) remains unaffected.
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Figure 7d. Calcified adenoma in a 59-year-old man. (a) Transverse US scan of the right lobe of the liver shows hyperechoic lesions with acoustic shadowing (arrow). (b) Unenhanced CT scan shows a mass in the right lobe with a large central calcification (arrow). (c) Portal venous-phase CT scan shows heterogeneous enhancement of most of the adenoma. Calcifications are noted within hypoattenuating cystic areas. (d) Arterial-phase gadolinium-enhanced MR image shows heterogeneous enhancement of the adenoma and a signal void representing the central calcification. (e) Coronal MR image obtained following administration of superparamagnetic iron oxide shows the normal liver (L) with decreased signal intensity. The adenoma (A) remains unaffected.
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Figure 7e. Calcified adenoma in a 59-year-old man. (a) Transverse US scan of the right lobe of the liver shows hyperechoic lesions with acoustic shadowing (arrow). (b) Unenhanced CT scan shows a mass in the right lobe with a large central calcification (arrow). (c) Portal venous-phase CT scan shows heterogeneous enhancement of most of the adenoma. Calcifications are noted within hypoattenuating cystic areas. (d) Arterial-phase gadolinium-enhanced MR image shows heterogeneous enhancement of the adenoma and a signal void representing the central calcification. (e) Coronal MR image obtained following administration of superparamagnetic iron oxide shows the normal liver (L) with decreased signal intensity. The adenoma (A) remains unaffected.
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Figure 8. Single adenoma in a 37-year-old woman who presented with abdominal pain. The patient had been using oral contraceptives for the past 10 years. Color Doppler US image of peri- and intratumoral vessels shows a typically flat continuous waveform. (Courtesy of Riccardo Lencioni, MD, Division of Diagnostic and Interventional Radiology, University of Pisa, Italy.)
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Computed Tomography
Multiphasic helical CT allows more accurate detection and characterization of focal hepatic lesions. The ability to acquire separate series during the hepatic arterial-dominant and portal venous–dominant phases adds a temporal hemodynamic component to the morphologic depiction of tumors. Nevertheless, unenhanced and delayed-phase imaging may also provide important diagnostic clues. Fat or hemorrhage can easily be identified on unenhanced images, and delayed-phase images demonstrate the tendency for fibrotic components to enhance and retain contrast material.
The degree of attenuation of the adenoma relative to underlying liver depends on the composition of the tumor and of the liver as well as on the phase of contrast material enhancement. CT may demonstrate a hypoattenuating mass due to the presence of intratumoral fat (Figs 5, 9). However, because adenomas consist almost entirely of uniform hepatocytes and a variable number of Kupffer cells, it is not surprising that most of the adenomas in our experience are nearly isoattenuating relative to normal liver on unenhanced, portal venous–phase, and delayed-phase images (Fig 10). In patients with fatty liver, adenomas are hyperattenuating at all phases of contrast enhancement and on unenhanced images as well.
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Figure 9a. Multiple hepatic adenomas in a 50-year-old woman. (a) Unenhanced CT scan of the liver shows multiple hypoattenuating lesions (arrows) due to the presence of fat. (b) In-phase fast multiplanar spoiled gradient-echo MR image shows only the largest adenoma (arrow). (c) Out-of-phase fast multiplanar spoiled gradient-echo MR image shows decreased signal intensity in the lesions (arrows) due to suppression of signal from voxels containing both water and fat protons.
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Figure 9b. Multiple hepatic adenomas in a 50-year-old woman. (a) Unenhanced CT scan of the liver shows multiple hypoattenuating lesions (arrows) due to the presence of fat. (b) In-phase fast multiplanar spoiled gradient-echo MR image shows only the largest adenoma (arrow). (c) Out-of-phase fast multiplanar spoiled gradient-echo MR image shows decreased signal intensity in the lesions (arrows) due to suppression of signal from voxels containing both water and fat protons.
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Figure 9c. Multiple hepatic adenomas in a 50-year-old woman. (a) Unenhanced CT scan of the liver shows multiple hypoattenuating lesions (arrows) due to the presence of fat. (b) In-phase fast multiplanar spoiled gradient-echo MR image shows only the largest adenoma (arrow). (c) Out-of-phase fast multiplanar spoiled gradient-echo MR image shows decreased signal intensity in the lesions (arrows) due to suppression of signal from voxels containing both water and fat protons.
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Figure 10a. Multiple adenomas in a 39-year-old woman. The patient had approximately 10 adenomas ranging from 1 to 3 cm in diameter and had been using oral contraceptives for the past 8 years. Unenhanced CT revealed no discrete lesions. (a) Arterial-phase CT scan shows multiple hypervascular lesions (arrows). (b) On a portal venous-phase CT scan, the adenomas are isoattenuating relative to the surrounding parenchyma.
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Figure 10b. Multiple adenomas in a 39-year-old woman. The patient had approximately 10 adenomas ranging from 1 to 3 cm in diameter and had been using oral contraceptives for the past 8 years. Unenhanced CT revealed no discrete lesions. (a) Arterial-phase CT scan shows multiple hypervascular lesions (arrows). (b) On a portal venous-phase CT scan, the adenomas are isoattenuating relative to the surrounding parenchyma.
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In our experience, adenomas are sharply marginated (85% of cases), nonlobulated (95%), sometimes encapsulated (30%) (Fig 3), and rarely calcified (10%) (10,13). Calcifications are usually seen within cystic portions that represent areas of necrosis or old hemorrhage (Fig 7b, 7c). Hyperattenuating areas corresponding to recent hemorrhage can be noted in 25% of adenomas and in 40% of affected patients (Fig 6b). Old hemorrhage is seen as a heterogeneous, hypoattenuating area within the tumor (Fig 11a). The prevalence of hemorrhage is undoubtedly influenced by whether CT is being used to screen a patient population that is asymptomatic but at risk for adenoma (eg, patients with type I glycogen storage disease) or to evaluate patients with acute abdominal pain. CT evidence of fat within the adenoma is seen in only about 10% of cases.
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Figure 11a. Single adenoma in a 42-year-old woman. (a) Portal venous-phase CT scan shows a poorly enhancing, spheric mass without obvious hemorrhage. (b) On a T2-weighted MR image, the mass appears heterogeneously hyperintense. (c) T1-weighted MR image shows the mass with heterogeneous hyperintensity due to hemorrhage.
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Figure 11b. Single adenoma in a 42-year-old woman. (a) Portal venous-phase CT scan shows a poorly enhancing, spheric mass without obvious hemorrhage. (b) On a T2-weighted MR image, the mass appears heterogeneously hyperintense. (c) T1-weighted MR image shows the mass with heterogeneous hyperintensity due to hemorrhage.
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Figure 11c. Single adenoma in a 42-year-old woman. (a) Portal venous-phase CT scan shows a poorly enhancing, spheric mass without obvious hemorrhage. (b) On a T2-weighted MR image, the mass appears heterogeneously hyperintense. (c) T1-weighted MR image shows the mass with heterogeneous hyperintensity due to hemorrhage.
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At contrast material–enhanced CT, peripheral enhancement may be seen as reflecting the presence of the large subcapsular feeding vessels, with a centripetal pattern of enhancement (Fig 12). Small hepatocellular adenomas enhance rapidly and are hyperattenuating relative to the liver. Excluding lesions with acute or old tumor hemorrhage and fat deposition, hepatocellular adenoma demonstrated homogeneous or nearly homogeneous enhancement in 80% of cases in our patient population (Fig 9). The enhancementusually does not persist in adenomas because of arteriovenous shunting (Fig 13). Larger hepatocellular adenomas may be more heterogeneous than smaller lesions, and their CT appearance is less specific (Fig 14a). Multiple adenomas in adenomatosis or glycogen storage disease may have a wide variety of imaging appearances, but CT (and MR imaging) characteristics of individual lesions are similar to those reported for sporadic or solitary adenomas (Fig 1a).
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Figure 12a. Palpable epigastric mass in a 4-year-old girl. (a) Unenhanced CT scan shows a large mass with hemorrhage (H). (b) Arterial-phase CT scan shows the mass with large penetrating vessels (arrows).
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Figure 12b. Palpable epigastric mass in a 4-year-old girl. (a) Unenhanced CT scan shows a large mass with hemorrhage (H). (b) Arterial-phase CT scan shows the mass with large penetrating vessels (arrows).
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Figure 13a. Single adenoma in a 40-year-old woman. The adenoma was discovered at hysterectomy. (a) Axial portal venous-phase CT scan through the right lower lobe of the liver shows a large mass with large internal vessels (arrows). (b) Axial CT scan obtained at a higher level shows a portion of a large draining vein (arrow) that emptied into the right hepatic vein.
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Figure 13b. Single adenoma in a 40-year-old woman. The adenoma was discovered at hysterectomy. (a) Axial portal venous-phase CT scan through the right lower lobe of the liver shows a large mass with large internal vessels (arrows). (b) Axial CT scan obtained at a higher level shows a portion of a large draining vein (arrow) that emptied into the right hepatic vein.
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Figure 14a. Large single adenoma in a 45-year-old woman. (a) Axial portal venous-phase CT scan shows a large adenoma replacing the lateral segment of the left hepatic lobe. The mass is heterogeneously enhanced. (b) Axial fat-saturated T1-weighted MR image obtained following intravenous bolus injection of gadopentetate dimeglumine shows an enhancement pattern similar to that seen at CT. Note the peripheral hyperintense rim corresponding to the fibrous capsule (arrows). (c) On an axial MR image obtained 1 hour after intravenous administration of Gd-BOPTA, the liver and kidney show increased signal intensity. The adenoma fails to enhance due to decreased uptake and excretion of this hepatobiliary contrast agent. (d) Photograph of the resected specimen (cut section opened in a "bivalve" fashion) reveals that bands of different tumor constituents (mostly due to varying lipid content) account for the heterogeneity seen at imaging.
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Figure 14b. Large single adenoma in a 45-year-old woman. (a) Axial portal venous-phase CT scan shows a large adenoma replacing the lateral segment of the left hepatic lobe. The mass is heterogeneously enhanced. (b) Axial fat-saturated T1-weighted MR image obtained following intravenous bolus injection of gadopentetate dimeglumine shows an enhancement pattern similar to that seen at CT. Note the peripheral hyperintense rim corresponding to the fibrous capsule (arrows). (c) On an axial MR image obtained 1 hour after intravenous administration of Gd-BOPTA, the liver and kidney show increased signal intensity. The adenoma fails to enhance due to decreased uptake and excretion of this hepatobiliary contrast agent. (d) Photograph of the resected specimen (cut section opened in a "bivalve" fashion) reveals that bands of different tumor constituents (mostly due to varying lipid content) account for the heterogeneity seen at imaging.
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Figure 14c. Large single adenoma in a 45-year-old woman. (a) Axial portal venous-phase CT scan shows a large adenoma replacing the lateral segment of the left hepatic lobe. The mass is heterogeneously enhanced. (b) Axial fat-saturated T1-weighted MR image obtained following intravenous bolus injection of gadopentetate dimeglumine shows an enhancement pattern similar to that seen at CT. Note the peripheral hyperintense rim corresponding to the fibrous capsule (arrows). (c) On an axial MR image obtained 1 hour after intravenous administration of Gd-BOPTA, the liver and kidney show increased signal intensity. The adenoma fails to enhance due to decreased uptake and excretion of this hepatobiliary contrast agent. (d) Photograph of the resected specimen (cut section opened in a "bivalve" fashion) reveals that bands of different tumor constituents (mostly due to varying lipid content) account for the heterogeneity seen at imaging.
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Figure 14d. Large single adenoma in a 45-year-old woman. (a) Axial portal venous-phase CT scan shows a large adenoma replacing the lateral segment of the left hepatic lobe. The mass is heterogeneously enhanced. (b) Axial fat-saturated T1-weighted MR image obtained following intravenous bolus injection of gadopentetate dimeglumine shows an enhancement pattern similar to that seen at CT. Note the peripheral hyperintense rim corresponding to the fibrous capsule (arrows). (c) On an axial MR image obtained 1 hour after intravenous administration of Gd-BOPTA, the liver and kidney show increased signal intensity. The adenoma fails to enhance due to decreased uptake and excretion of this hepatobiliary contrast agent. (d) Photograph of the resected specimen (cut section opened in a "bivalve" fashion) reveals that bands of different tumor constituents (mostly due to varying lipid content) account for the heterogeneity seen at imaging.
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MR Imaging
On T1-weighted MR images, hepatocellular adenomas have been variously described as hyperintense, isointense, and hypointense lesions (24–26). More recent reports have suggested that most adenomas are bright on T1-weighted images (77% of cases in a study by Paulson et al [14] and 59% in a study by Arrivé et al [27]). However, Chung et al (28) observed that only 35% of the lesions were predominantly hyperintense on T1-weighted images. Adenomas are heterogeneous in appearance due to areas of increased signal intensity resulting from fat (36%–77% of cases in different series) and hemorrhage (52%–93%) (Fig 11b, 11c) (14,27,28) and low-signal-intensity areas corresponding to necrosis or old hemorrhage or calcifications (14).
It has been reported that 47%–74% of hepatocellular adenomas are predominantly hyperintense relative to liver on T2-weighted images; this is due to prolonged T2 and is consistent with findings in other hepatic tumors (27). Some lesions are hypointense and isointense on T2-weighted images. Most lesions are heterogeneous, demonstrating a combination of hyper- and hypointensity on T2-weighted images relative to hemorrhage and necrosis. However, in the study by Chung et al (28), no lesion was homogeneously isointense relative to surrounding liver on T2-weighted images, a finding that has been described in focal nodular hyperplasia (29). One-third of adenomas have a peripheral rim corresponding to a fibrous capsule (Fig 14b) (27).
Dynamic gadolinium-enhanced gradient-echo MR imaging, like dynamic CT, can be used to demonstrate early arterial enhancement that reflects the presence of subcapsular feeding vessels (Fig 7d) (28). Adenomas usually do not show uptake of superparamagnetic iron oxide particles (Fig 7e), resulting in decreased signal intensity on T2-weighted images. After injection of a hepatocellular-specific contrast agent such as gadolinium benzyloxypropionictetraacetate (Gd-BOPTA) there is usually no substantial uptake; in three of three cases in our series, there was no recognizable enhancement with Gd-BOPTA and the lesions appeared hypointense on delayed-phase images (Fig 14c).
Nuclear Scintigraphy
Findings at radionuclide scintigraphy are rarely diagnostic for hepatocellular adenoma. Compared with normal liver, adenomas usually show absent or decreased uptake of Tc-99m sulfur colloid, reflecting the decreased number or function of Kupffer cells (17). Whereas hepatobiliary scintigraphy (performed with Tc-99m HIDA or an analogue) is useful in diagnosing focal nodular hyperplasia, adenomas do not usually demonstrate the delayed clearance of radioactivity ("hot spots") (Fig 15); however, neither do other hepatic neoplasms (18).
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Figure 15a. Large, pedunculated hepatic adenoma in a 36-year-old woman who presented with right upper quadrant abdominal pain. (a) Tc-HIDA scan demonstrates faint activity below the inferior margin of the liver (arrow). (b) Coronal T1-weighted spin-echo MR image shows a pedunculated mass arising from the inferior margin of the liver (A). (c) Photograph of the resected specimen shows a well-circumscribed, brown, hemorrhagic mass, with some vessels cut in a transverse plane. The adenoma was almost completely extrahepatic.
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Figure 15b. Large, pedunculated hepatic adenoma in a 36-year-old woman who presented with right upper quadrant abdominal pain. (a) Tc-HIDA scan demonstrates faint activity below the inferior margin of the liver (arrow). (b) Coronal T1-weighted spin-echo MR image shows a pedunculated mass arising from the inferior margin of the liver (A). (c) Photograph of the resected specimen shows a well-circumscribed, brown, hemorrhagic mass, with some vessels cut in a transverse plane. The adenoma was almost completely extrahepatic.
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Figure 15c. Large, pedunculated hepatic adenoma in a 36-year-old woman who presented with right upper quadrant abdominal pain. (a) Tc-HIDA scan demonstrates faint activity below the inferior margin of the liver (arrow). (b) Coronal T1-weighted spin-echo MR image shows a pedunculated mass arising from the inferior margin of the liver (A). (c) Photograph of the resected specimen shows a well-circumscribed, brown, hemorrhagic mass, with some vessels cut in a transverse plane. The adenoma was almost completely extrahepatic.
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Angiography
Adenomas have a wide spectrum of angiographic appearances. Tumors may appear either hypovascular or hypervascular relative to focal nodular hyperplasia. The angiographic picture may be further complicated by areas of necrosis and hemorrhage. The vascularization of hepatocellular adenoma is not as fine and orderly as the pattern seen in focal nodular hyperplasia, nor are there septa within the tumor. Tumor staining also tends to be more heterogeneous than in focal nodular hyperplasia. Portal vein invasion, arteriovenous shunting, and other angiographic signs of malignancy are absent.
Transcatheter hepatic arterial embolization can be used in patients with hepatocellular adenoma to facilitate surgical resection of a neoplasm, control hemorrhage, or evaluate associated vascular abnormalities.
Differential Diagnosis
Because of the different therapeutic options (30), hepatocellular adenomas must be distinguished from other hypervascular lesions that occur in young adults without underlying cirrhosis (eg, fibrolamellar HCC, focal nodular hyperplasia, metastases) (24).
Fibrolamellar HCC is usually large, heterogeneous, and lobulated, with large, central, or eccentric scars and radiating fibrous septa (31). Calcifications are present in 40%–68% of tumors, and areas of hypervascularity are heterogeneous in all cases. In addition, abdominal lymphadenopathy is noted in 65% of patients with fibrolamellar HCC. Vascular and biliary invasion are other relatively common signs of the malignant nature of fibrolamellar HCC (31), distinguishing it from adenoma (Fig 16).
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Figure 16. Fibrolamellar HCC in a 15-year-old girl. Arterial-phase CT scan shows a large, well-marginated, hyperattenuating lesion in the dome of the liver, with stellate calcifications in the central hypoattenuating scar (straight arrow). Note the hyperattenuating cardiophrenic lymph node (curved arrow).
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Hepatocellular adenoma and focal nodular hyperplasia have several clinical and imaging similarities; however, focal nodular hyperplasia does not undergo malignant degeneration, nor is it likely to bleed. Therefore, unlike adenoma or other hypervascular masses, it rarely requires therapy. At multiphasic helical CT and dynamic MR imaging, focal nodular hyperplasia almost always appears as a homogeneous, markedly hypervascular mass on arterial-phase images with a central scar that is hypoattenuating or hypointense on early contrast-enhanced images and hyperattenuating or hyperintense on delayed-phase images. The scar typically appears hyperintense on T2-weighted MR images. On unenhanced, portal venous–phase, and delayed-phase images, focal nodular hyperplasia is usually nearly isoattenuating or isointense relative to liver (Fig 17) (32).
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Figure 17a. Focal nodular hyperplasia in a 31-year-old woman who presented with abdominal pain. (a) T1-weighted spin-echo (spoiled gradient-echo) MR image of the liver shows a large, isointense mass (arrows) almost completely replacing the lateral segment of the left hepatic lobe. (b) On a T1-weighted arterial-phase MR image obtained after intravenous bolus injection of gadopentetate dimeglumine, the lesion demonstrates homogeneous bright enhancement. (c) T1-weighted 5-minute delayed-phase MR image shows enhancement of the central scar (arrow). (d) On a T2-weighted MR image, the focal nodular hyperplasia shows mild hyperintensity relative to the background liver. The central scar appears hyperintense.
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Figure 17b. Focal nodular hyperplasia in a 31-year-old woman who presented with abdominal pain. (a) T1-weighted spin-echo (spoiled gradient-echo) MR image of the liver shows a large, isointense mass (arrows) almost completely replacing the lateral segment of the left hepatic lobe. (b) On a T1-weighted arterial-phase MR image obtained after intravenous bolus injection of gadopentetate dimeglumine, the lesion demonstrates homogeneous bright enhancement. (c) T1-weighted 5-minute delayed-phase MR image shows enhancement of the central scar (arrow). (d) On a T2-weighted MR image, the focal nodular hyperplasia shows mild hyperintensity relative to the background liver. The central scar appears hyperintense.
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Figure 17c. Focal nodular hyperplasia in a 31-year-old woman who presented with abdominal pain. (a) T1-weighted spin-echo (spoiled gradient-echo) MR image of the liver shows a large, isointense mass (arrows) almost completely replacing the lateral segment of the left hepatic lobe. (b) On a T1-weighted arterial-phase MR image obtained after intravenous bolus injection of gadopentetate dimeglumine, the lesion demonstrates homogeneous bright enhancement. (c) T1-weighted 5-minute delayed-phase MR image shows enhancement of the central scar (arrow). (d) On a T2-weighted MR image, the focal nodular hyperplasia shows mild hyperintensity relative to the background liver. The central scar appears hyperintense.
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Figure 17d. Focal nodular hyperplasia in a 31-year-old woman who presented with abdominal pain. (a) T1-weighted spin-echo (spoiled gradient-echo) MR image of the liver shows a large, isointense mass (arrows) almost completely replacing the lateral segment of the left hepatic lobe. (b) On a T1-weighted arterial-phase MR image obtained after intravenous bolus injection of gadopentetate dimeglumine, the lesion demonstrates homogeneous bright enhancement. (c) T1-weighted 5-minute delayed-phase MR image shows enhancement of the central scar (arrow). (d) On a T2-weighted MR image, the focal nodular hyperplasia shows mild hyperintensity relative to the background liver. The central scar appears hyperintense.
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The differentiation of adenoma from hypervascular metastases may be difficult or impossible. A careful search of other abdominal organs is warranted to detect a possible primary tumor such as a pancreatic islet cell tumor or renal carcinoma (Fig 18). Breast or thyroid carcinoma would probably be more likely in the age group of women most likely to have hepatocellular adenoma. Most hypervascular metastases are multiple and will manifest as lesions or portions of lesions that are hypoattenuating or hypointense relative to normal liver on unenhanced, portal venous–phase, and delayed-phase images (33). MR imaging characteristics are likely to be distinctive: Hypervascular metastases are usually hypointense on T1-weighted images and markedly hyperintense on T2-weighted images. Areas of fat and hemorrhage are commonly detected in adenomas with MR imaging but are rare in hypervascular metastases.
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Figure 18a. Renal carcinoma metastatic to the liver in a 70-year-old woman. (a) Arterial-phase CT scan shows a strongly enhancing, homogeneous lesion in the right posterior segment (arrow). (b) Portal venous-phase CT scan shows decreased lesion enhancement and conspicuity. Multiple simple hepatic cysts are seen incidentally.
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Figure 18b. Renal carcinoma metastatic to the liver in a 70-year-old woman. (a) Arterial-phase CT scan shows a strongly enhancing, homogeneous lesion in the right posterior segment (arrow). (b) Portal venous-phase CT scan shows decreased lesion enhancement and conspicuity. Multiple simple hepatic cysts are seen incidentally.
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Prognosis and Treatment
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The prognosis of hepatic adenoma is not well established. Some adenomas remain stable in size, others demonstrate slow but progressive enlargement, and still others regress after discontinuation of exogenous estrogen therapy. Nevertheless, the risks of hemorrhage and malignant transformation remain the primary clinical problems. Criteria that guide treatment include the number and size of the adenomas, the presence of symptoms, and the surgical risk incurred by the patient (34). Some clinicians have proposed nonsurgical management with cessation of hormone therapy, serial radiologic examinations, and screening for elevated -fetoprotein levels, especially in isolated small adenomas (30). Conversely, many surgeons have advocated resection of adenomas due to the recognized risk of rupture and hemorrhage (30). Others have concluded that resection should be performed only when it is possible to do so with minimal morbidity and mortality (34). Hepatic arterial embolization can be effective for controlling acute hemorrhage in an adenoma (35). Because of the increased potential for malignancy, adenomatosis may be considered an indication for liver transplantation (14,34).
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Conclusions
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Hepatic adenoma is a rare benign liver tumor but is encountered more frequently at modern cross-sectional imaging, especially in individuals who have glycogen storage disease or are taking oral contraceptives or anabolic androgenic steroids. In view of the risks of hemorrhage, rupture, and malignant transformation associated with hepatocellular adenoma, it is important to recognize this lesion and to differentiate it from other hypervascular lesions occurring in young adults without underlying cirrhosis (eg, focal nodular hyperplasia).
Hepatocellular adenoma is usually detected with US, but there is no pathognomonic echostructural pattern. Color Doppler US may help differentiate hepatocellular adenoma from focal nodular hyperplasia. Multiphasic helical CT can demonstrate findings that appear to be quite characteristic of hepatocellular adenoma. These include the presence of a single or multiple masses that may contain areas of fat or hemorrhage but are otherwise nearly isoattenuating relative to normal liver on unenhanced, portal venous–phase, and delayed-phase images. The lesions are moderately hyperattenuating relative to liver at hepatic arterial-phase imaging and enhance nearly homogeneously. They are also sharply marginated. Other features such as tumor encapsulation, early draining veins, and calcification are less common and overlap findings in other liver masses. Atypical features such as heterogeneous enhancement may require additional imaging—in particular, MR imaging with hepatocellular-specific contrast agents—or may require biopsy or even surgical resection to exclude a malignant neoplasm.
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Footnotes
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Abbreviations: Gd-BOPTA = gadolinium benzyloxypropionictetraacetate, HCC = hepatocellular carcinoma
See the commentary by Levy and Ros
following this article.
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Abstract
LEARNING OBJECTIVES FOR TEST...
