(Radiographics. 2001;21:892-894.)
© RSNA, 2001
Invited Commentary
Angela D. Levy, LTC, MC, USA and
Pablo R. Ros, MD, MPH
Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC, Department of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, Department of Radiology, Brigham and Women’s Hospital and, Harvard Medical School, Boston, Massachusetts, Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC
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Commentary
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The imaging characterization of hepatic masses continues to be challenging because clinical and surgical management of hepatic lesions has expanded over the last several decades to include a wide range of therapeutic options. The imaging diagnosis of hepatocellular adenomas has remained difficult despite the advent of new imaging modalities and contrast agents. The imaging findings in hepatocellular adenoma and hepatocellular carcinoma and in some cases of focal nodular hyperplasia overlap such that the diagnosis of hepatocellular adenoma cannot be made on the basis of imaging criteria alone. Grazioli et al (1) have provided an excellent review of the imaging features of hepatocellular adenomas based on their recently published experience (2,3). The pathologic correlation they provide is essential for understanding the spectrum of radiologic appearances manifested by hepatocellular adenomas.
Hepatocellular adenomas are treated with surgical resection because they have a propensity to hemorrhage and carry a risk of malignant transformation. Grazioli et al (1) describe this risk as "rare." However, the true prevalence of malignancy is difficult to ascertain from the literature. Two studies reported its prevalence as 8% (4) and 13% (5). If these studies are valid, the risk of malignancy is not truly rare. However, both of these studies looked at a relatively small number of patients. Given the rarity of hepatocellular adenomas and the lack of understanding of their true natural history (we know that some spontaneously regress, yet an unknown percentage may harbor malignancy), it is difficult at this time to know the true risk of malignant transformation.
It is useful to divide the imaging appearances of hepatic adenomas into three categories: hemorrhagic, nonhemorrhagic, and multifocal. The multifocal pattern of hepatocellular adenomas seen in patients with glycogen storage disease, multiple adenomas, or adenomatosis is indistinguishable from metastatic disease on the basis of imaging criteria alone. In the absence of a clinical history of glycogen storage disease, the diagnosis of multifocal adenomas or hepatocellular adenomatosis can be made only with biopsy.
A solitary, hemorrhagic mass in a noncirrhotic liver in the correct clinical setting (ie, a young woman on oral contraceptives) is most likely an adenoma. As noted by Grazioli et al (1), hepatocellular adenomas have a hepatic arterial blood supply and an extensive sinusoidal network. However, we would like to dissent from the opinion of the authors regarding the mechanism of spontaneous hemorrhage in hepatocellular adenomas. To our knowledge, there is no evidence to support the notion that adenomas hemorrhage due to arterial pressure within the sinusoids. Hepatocellular adenomas (especially large adenomas) demonstrate degenerative changes centrally that are characterized by necrosis, hemorrhage, and vascular ectasia (6). Senior pathologists at the Armed Forces Institute of Pathology (AFIP) agree that hemorrhage within an adenoma is related to infarction, which occurs as the tumor outgrows its blood supply. It has also been our experience at the AFIP that most tumors have a fibrous capsule (6). The capsule may be thin and incomplete (Fig 1) or may be a prominent feature of the tumor (Fig 2). Although the tumor is typically well circumscribed at cross-sectional imaging, the capsule may not be apparent.
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Figure 1a. Hepatocellular adenoma in a 29-year-old woman who presented with right upper quadrant pain. The patient underwent right hepatectomy. (a) Cut surface of the resected specimen shows a large adenoma with a thin, incomplete capsule (arrow). There is central hemorrhage within the tumor. (b) Contrast-enhanced portal venous-phase CT scan shows a low-attenuation mass containing central hemorrhage. The thin capsule is imperceptible.
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Figure 1b. Hepatocellular adenoma in a 29-year-old woman who presented with right upper quadrant pain. The patient underwent right hepatectomy. (a) Cut surface of the resected specimen shows a large adenoma with a thin, incomplete capsule (arrow). There is central hemorrhage within the tumor. (b) Contrast-enhanced portal venous-phase CT scan shows a low-attenuation mass containing central hemorrhage. The thin capsule is imperceptible.
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Figure 2a. Hepatocellular adenoma in a 33-year-old woman. The patient underwent partial right hepatectomy. (a) Cut surface of the resected specimen shows a thick, fibrous capsule surrounding portions of the tumor (arrow). The tumor is bile stained and contains foci of fat. (b) Contrast-enhanced delayed-phase CT scan shows the adenoma occupying the majority of the right lobe of the liver. The fibrous capsule is not clearly apparent on this image. The fat within the tumor demonstrates low attenuation (arrow).
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Figure 2b. Hepatocellular adenoma in a 33-year-old woman. The patient underwent partial right hepatectomy. (a) Cut surface of the resected specimen shows a thick, fibrous capsule surrounding portions of the tumor (arrow). The tumor is bile stained and contains foci of fat. (b) Contrast-enhanced delayed-phase CT scan shows the adenoma occupying the majority of the right lobe of the liver. The fibrous capsule is not clearly apparent on this image. The fat within the tumor demonstrates low attenuation (arrow).
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There are no specific imaging features of a solitary, nonhemorrhagic adenoma that permit definitive diagnosis, particularly differentiation of hepatocellular adenoma from hepatocellular carcinoma. Both lesions may contain macroscopic fat that is visible as low-attenuation areas at CT. Both hepatocellular adenoma and hepatocellular carcinoma may have areas of high signal intensity at T1-weighted MR imaging as a result of fat or hemorrhage. On T2-weighted MR images, both lesions have heterogeneous signal intensity. The differentiation of hepatocellular adenoma from fibrolamellar carcinoma is typically not a dilemma from an imaging standpoint. In the majority of cases, fibrolamellar carcinoma contains a central low-attenuation scar at CT that distinguishes it from hepatocellular adenoma.
On the other hand, the features of focal nodular hyperplasia may overlap with those of hepato-cellular adenoma and hepatocellular carcinoma. Kupffer cell–specific MR imaging agents may help distinguish focal nodular hyperplasia from hepatocellular adenoma and hepatocellular carcinoma. Ferumoxide (superparamagnetic iron oxide) particles are taken up by Kupffer cells that occur in normal liver and in some primary hepatic neoplasms such as focal nodular hyperplasia, hepatocellular adenoma (7), and hepatocellular carcinoma. It has recently been shown that only focal nodular hyperplasia demonstrates significant signal intensity loss on ferumoxide-enhanced T2-weighted images (8). Hepatocyte-specific MR imaging agents such as Gd-BOPTA and mangafodipir trisodium have been reported to be taken up by all three of these primary liver neoplasms (9,10).
In conclusion, we believe that the only subset of hepatocellular adenomas that can be confidently diagnosed with imaging in the proper clinical setting are those with acute hemorrhage. Hemorrhage within an adenoma is the sequela of infarction. Solitary nonhemorrhagic adenomas and multifocal adenomas require biopsy for definitive diagnosis.
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Footnotes
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The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
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References
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Grazioli L, Federle MP, Brancatelli G, Ichikawa T, Olivetti L, Blachar A. Hepatic adenomas: imaging and pathologic findings. RadioGraphics 2001; 21:877-892.[Abstract/Free Full Text]
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Grazioli L, Federle MP, Ichikawa T, Balzano E, Nalesnik M, Madariaga J. Liver adenomatosis: clinical, histopathologic, and imaging findings in 15 patients. Radiology 2000; 216:395-402.[Abstract/Free Full Text]
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Ichikawa T, Federle MP, Grazioli L, Nalesnik M. Hepatocellular adenoma: multiphasic CT and histopathologic findings in 25 patients. Radiology 2000; 214:861-868.[Abstract/Free Full Text]
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Kerlin P, Davis GL, McGill DB, Weiland LH, Adson MA, Sheedy PF. Hepatic adenoma and focal nodular hyperplasia: clinical, pathologic, and radiologic features. Gastroenterology 1983; 84(5 pt 1):994-1002.[Medline]
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Foster JH, Berman MM. The malignant transformation of liver cell adenomas. Arch Surg 1994; 129:712-717.[Abstract/Free Full Text]
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Craig JR, Peters RL, Edmondson HA. Atlas of tumor pathology: tumors of the liver and intrahepatic bile ducts, fasc 27, ser 2 Washington, DC: Armed Forces Institute of Pathology, 1989; 19-41.
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Goodman ZD, Mikel UV, Lubbers PR, Ros PR, Langloss JM, Ishak KG. Kupffer cells in hepatocellular adenomas. Am J Surg Pathol 1987; 11:191-196.[Medline]
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Paley MR, Mergo PJ, Torres GM, Ros PR. Characterization of focal hepatic lesions with ferumoxides-enhanced T2-weighted MR imaging. AJR Am J Roentgenol 2000; 175:159-163.[Abstract/Free Full Text]
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Coffin CM, Diche T, Mahfouz A, et al. Benign and malignant hepatocellular tumors: evaluation of tumoral enhancement after mangafodipir trisodium injection on MR imaging. Eur Radiol 1999; 9:444-449.[Medline]
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Grazioli L, Kirchin M, Pirovano G, Spinazzi A. MultiHance in the dynamic phase of contrast enhancement: a pictorial assessment. J Comput Assist Tomogr 1999; 23(suppl 1):61-64.
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