Published online before print September 11, 2006, 10.1148/radiol.2412051243
(Radiology 2006;241:433-440.)
© RSNA, 2006
Liver Adenomatosis: Classification of MR Imaging Features and Comparison with Pathologic Findings1
Maïté Lewin, MD, PhD,
Adriana Handra-Luca, MD, PhD,
Lionel Arrivé, MD,
Dominique Wendum, MD, PhD,
Valérie Paradis, MD, PhD,
Etienne Bridel, MD,
Jean-François Fléjou, MD, PhD,
Jacques Belghiti, MD,
Jean-Michel Tubiana, MD and
Valérie Vilgrain, MD
1 From the Departments of Radiology (M.L., L.A., E.B., J.M.T.) and Pathology (D.W., J.F.F.), Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 184 rue du Faubourg Saint-Antoine, 75012 Paris, France; and Departments of Pathology (A.H., V.P.), Hepatic Surgery (J.B.), and Radiology (V.V.), Hôpital Beaujon, Assistance Publique des Hôpitaux de Paris, Clichy, France. From the 2003 RSNA Annual Meeting. Received July 25, 2005; revision requested September 27; revision received October 27; accepted November 17; final version accepted February 1, 2006.
Address correspondence to M.L. (e-mail: maite.lewin{at}sat.ap-hop-paris.fr).
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ABSTRACT
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Purpose: To retrospectively compare the clinical manifestation and magnetic resonance (MR) imaging features of liver adenomatosis with pathologic findings.
Materials and Methods: This study had institutional review board approval, and informed consent was waived. Twenty patients were classified on the basis of pathologic findings into three groups: those with a steatotic, those with a peliotic, and those with a mixed (steatotic and peliotic) form of liver adenomatosis. MR images were reviewed in consensus by two abdominal radiologists, and findings were compared with the pathologic classification. Statistical evaluation was performed with the Student t test.
Results: All patients were women (mean age, 39 years ± 10 [standard deviation]). Lesions of the steatotic form (n = 7) showed (a) a mean diameter of 6.3 cm ± 1.7, (b) slightly hyperintense signal on T2-weighted images, (c) hyper- or isointense signal on T1-weighted images with a signal dropout with fat suppression sequences, and (d) moderate enhancement at the arterial phase with no delayed enhancement. Lesions of the peliotic form (n = 7) showed (a) a somewhat larger size (8.3 cm ± 3.6), (b) markedly hyperintense signal on T2-weighted images, (c) iso- or hyperintensity on T1-weighted images with no signal dropout with fat suppression sequences, and (d) strong arterial enhancement and persistent enhancement at the portal and delayed phase. Lesions of the mixed form (n = 6) included a combination of imaging features of the steatotic and peliotic forms. Lesions, however, were significantly larger in the mixed form than in the steatotic form (10.3 cm ± 4, P < .05).
Conclusion: There are three patterns of MR imaging features of liver adenomatosis that are associated with three pathologic forms (steatotic, peliotic, and mixed).
© RSNA, 2006
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INTRODUCTION
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Adenomas are uncommon and benign neoplasms of the liver that occur in young women in whom an association with estrogen therapy has been established (1,2). Hepatic adenomas are solitary in most cases; however, patients with two or three adenomas have been reported (3–6).
In 1985, Fléjou et al (7) described liver adenomatosis as a separate clinical entity characterized by the presence of multiple adenomas (arbitrarily, more than 10) in an otherwise normal liver parenchyma; thus patients with glycogen storage disease and those with a history of steroid intake are not considered to have liver adenomatosis. These authors did not find any correlation between liver adenomatosis and oral contraceptive use and noted abnormal increases in serum alkaline phosphatase and 
-glutamyltransferase levels (7).
This clinical entity is rare—to our knowledge, only 70 cases have been reported to date—although its real frequency could be underestimated because many patients are asymptomatic (8). Surgery is usually considered because of a risk of intratumoral or intraperitoneal bleeding and of potential malignant transformation. To our knowledge, there is no consensus in this respect, however, and recommendations have ranged from conservative monitoring to resection or even orthotopic liver transplantation (9,10). The magnetic resonance (MR) imaging features of this entity have been documented in a few reports, which are mainly case reports (11–15).
MR imaging findings include a variety of appearances but are mainly fatty, necrotic, or hemorrhagic tumors. We hypothesized that these different imaging findings could reflect different pathologic patterns for the disease. Thus, the aim of our study was to retrospectively compare the clinical manifestation and MR imaging features with pathologic findings in 20 adult patients with liver adenomatosis.
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MATERIALS AND METHODS
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Patients
Medical and surgical records of 20 patients with liver adenomatosis who were seen from 1995 to 2004 at two university hospitals were reviewed (M.L., E.B.). This retrospective study was approved by the institutional review boards, and informed consent was waived. Inclusion criteria were the presence of more than 10 adenomas on the resected liver specimen at pathologic examination, the presence of more than 10 adenomas at MR imaging with at least one pathologically confirmed lesion, or both (7). Patients with a history of glycogen storage disease or steroid intake or with congenital portocaval shunts were excluded as suggested by Fléjou et al (7). Clinical information collected included sex, age, medical and family history, oral contraceptive use, presence of diabetes, symptoms, and body mass index. Biochemical findings, including results of liver function tests and serum 
-fetoprotein levels, were noted. In addition, follow-up imaging (ultrasonography [US], computed tomography [CT], or MR imaging) was performed in all patients (mean follow-up duration, 3.2 years ± 2 [standard deviation]; range, 1–9 years).
MR Imaging
MR imaging examinations were performed in 20 patients with a 1.5-T system (Magnetom, Siemens Medical Systems, Erlangen, Germany; Gyroscan Intera, Philips Medical Systems, Best, the Netherlands) by using a phased-array torso coil for signal reception. A breath-hold T1-weighted fast field-echo pulse sequence was performed. (Siemens acquisition parameters were as follows: repetition time msec/echo time msec, 174/4; flip angle, 75°; field of view, 38 cm; matrix, 256 x 256; number of sections, 20; section thickness, 8 mm; and one signal acquired. Philips acquisition parameters were as follows: 212/4; flip angle, 80°; field of view, 34 cm; matrix, 200 x 256; number of sections, 24; section thickness, 8 mm; and one signal acquired.) A respiratory-triggered T2-weighted fast spin-echo pulse sequence was also performed. (Siemens acquisition parameters were as follows: 1900/96; flip angle, 80°; field of view, 38 cm; matrix, 256 x 256; number of sections, 20; section thickness, 8 mm; and one signal acquired. Philips acquisition parameters were as follows: 1600/70; flip angle, 90°; field of view, 34 cm; reconstruction matrix, 512 x 512; number of sections, 24; section thickness, 8 mm; and two signals acquired.)
In all patients, a T1-weighted gradient-echo MR sequence was performed during the hepatic late arterial, portal venous, and delayed phases after manual administration of gadolinium-based contrast medium (Dotarem; Guerbet, Villepinte, France) at a dose of 0.1 mmol/kg. Fat imaging was performed in 15 patients prior to administration of contrast medium with a chemical shift technique (also called in-phase and opposed-phase imaging) (n = 8), with fat-suppressed T1-weighted MR sequences (n = 13), or both (n = 6).
Image Evaluation
All MR imaging studies were reviewed retrospectively and in consensus by two experienced abdominal radiologists (M.L. and V.V., with 6 and 17 years of experience, respectively) with knowledge of the diagnosis of liver adenomatosis but without knowledge of the pathologic features. MR images were reviewed on hard-copy film for (a) lesion location according to the hepatic segment numbering system of Couinaud; (b) lesion diameter (measurements made with calipers); (c) signal intensity of the lesions on unenhanced T1- and T2-weighted images and contrast medium–enhanced T1-weighted MR images when compared with that of the surrounding liver parenchyma; (d) presence of tumor fat (ie, lipid) when the tumor components showed signal dropout on opposed-phase or fat-suppressed MR images; (e) presence of acute hemorrhage when there was fluid in or around the tumor that was hyperintense on both T1- and T2-weighted MR images, presence of necrosis when there were focal areas in the tumor that were hypointense on T1-weighted images before and after injection of contrast medium, or both; (f) homogeneous or heterogeneous appearance; and (g) presence of a peripheral rim, defined as an enhanced rim that defines the tumor from the normal liver parenchyma on delayed-phase MR images. Hyperintensity on T2-weighted MR images was defined as slight if the signal intensity was between that of the liver and that of the spleen; hyperintensity was defined as strong if the signal intensity was equal to or greater than that of the spleen. Imaging evidence of vascular liver abnormalities or associated liver lesions was also recorded.
Pathologic Examination
All tissue specimens (17 surgical specimens and three biopsy specimens) were retrospectively reviewed by one pathologist (A.H., 8 years of experience in hepatic pathologic examination). The following gross features, retrieved from pathologic reports and macroscopic figures, were analyzed: number, location, size of tumors, presence of hemorrhage, and necrosis. Microscopic examination was performed on paraffin-embedded representative sections of the lesions, which were routinely processed and stained with hematoxylin-eosin staining, as well as with Masson trichrome, Sirius red, and Perls stainings. Hepatocyte dysplasia, steatosis, necrosis, hemorrhage, and peliosis were noted. The presence of a capsule and of adenomas smaller than 1 cm in diameter were assessed. The extratumoral liver parenchyma was assessed for fibrosis, steatosis, and associated tumoral lesions. Patients were classified into the following three groups according to the presence of intratumoral steatosis, peliosis, or both: those with a steatotic form of adenomatosis (if all tumors showed more than 20%–30% steatosis), those with a peliotic form of adenomatosis (if all tumors showed more than 20%–30% peliosis), and those with a mixed form of adenomatosis (if tumors were either steatotic or peliotic). Finally, after the retrospective imaging was performed and pathologic reviews were noted, a direct comparison between imaging findings and pathologic findings was performed in consensus for each patient and for each tumor by one pathologist (A.H.) and one radiologist (M.L.).
Statistical Analysis
The mean sizes of the largest tumors in the three forms (steatotic, peliotic, and mixed) of adenomatosis were compared by using the Student t test. A P value of less than .05 indicated a statistically significant difference.
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RESULTS
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Clinical Findings
All patients (Table 1) were women (mean age ± standard deviation, 39 years ± 10; age range, 19–54 years). Nine patients were asymptomatic, 10 had acute abdominal pain due to intratumoral bleeding, and one had chronic fever. Eleven patients had used oral contraceptives for various periods (1–28 years). No familial form of liver adenomatosis or familial diabetes was found. Four patients, however, were obese (body mass index >30). Serum -fetoprotein levels were normal in all patients; however, results of liver tests were abnormal in 17 patients.
Follow-up imaging depicted an increase in the size of adenoma, number of adenomas, or both in three (15%) patients. One patient with liver adenomatosis proved with a biopsy specimen died of multivisceral complications after severe pulmonary sepsis.
Pathologic Findings
There were more than 20 adenomas in each patient, including small adenomas (diameter less than 1 cm), which were diagnosed only at pathologic examination. Each patient had at least one and up to eight tumors larger than 1 cm in diameter, and a total of 51 tumors larger than 1 cm in diameter were analyzed. Tumor diameter ranged from 0.3 to 19 cm. At gross examination, the tumors were well defined and had a firm to soft consistency. None of the adenomas were encapsulated. Three tumors had a pseudocapsule defined as an incomplete rim with fibrotic tissue, atrophic liver parenchyma (related to tumor compression), or both. Seven of 20 patients had intratumoral necrosis, and 14 had hemorrhagic zones. At microscopy, all lesions included sheets and cords of benign hepatocytes without dysplasia. Zones of hepatocellular carcinoma (HCC) were observed within the largest adenoma in one patient (patient 4). Mitosis was rare. Various degrees of intratumoral macro- and microvesicular steatosis were observed in 16 of 20 patients, which involved 5%–80% of the intratumoral hepatocytes. Intratumoral peliosis was observed in 13 of 20 patients. Seven (35%) patients had a steatotic form of adenomatosis (Fig 1), seven (35%) patients had a peliotic form (Fig 2), and six (30%) patients had a mixed form (Fig 3). None of the patients with the steatotic form of adenomatosis had peliosis; three patients with the peliotic form had discrete steatosis (5% of the intratumoral hepatocytes).
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Figure 1a: Patient 3. Steatotic form of liver adenomatosis in 30-year-old woman. (a) On transverse T2-weighted MR image (1900/96, 80° flip angle), multiple adenomas (arrows) are slightly hyperintense relative to liver parenchyma. (b) On transverse T1-weighted MR image (174/4, 75° flip angle), adenomas are isointense relative to liver parenchyma. (c) After fat-suppressed imaging (174/4, 75° flip angle), adenomas have signal dropout, which indicates lipid content. (d) Contrast-enhanced T1-weighted image (174/4, 75° flip angle) at portal venous phase shows no enhancement of multiple adenomas. (e) Surgical specimen (one square = 1 x 1 cm) was almost entirely occupied by nonencapsulated tumor that contained several yellow zones. (f) At pathologic examination, these zones consisted of proliferation of hepatocytes showing extensive macro- and microvesicular steatosis. (Hematoxylin-eosin stain; original magnification, x100.)
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Figure 1b: Patient 3. Steatotic form of liver adenomatosis in 30-year-old woman. (a) On transverse T2-weighted MR image (1900/96, 80° flip angle), multiple adenomas (arrows) are slightly hyperintense relative to liver parenchyma. (b) On transverse T1-weighted MR image (174/4, 75° flip angle), adenomas are isointense relative to liver parenchyma. (c) After fat-suppressed imaging (174/4, 75° flip angle), adenomas have signal dropout, which indicates lipid content. (d) Contrast-enhanced T1-weighted image (174/4, 75° flip angle) at portal venous phase shows no enhancement of multiple adenomas. (e) Surgical specimen (one square = 1 x 1 cm) was almost entirely occupied by nonencapsulated tumor that contained several yellow zones. (f) At pathologic examination, these zones consisted of proliferation of hepatocytes showing extensive macro- and microvesicular steatosis. (Hematoxylin-eosin stain; original magnification, x100.)
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Figure 1c: Patient 3. Steatotic form of liver adenomatosis in 30-year-old woman. (a) On transverse T2-weighted MR image (1900/96, 80° flip angle), multiple adenomas (arrows) are slightly hyperintense relative to liver parenchyma. (b) On transverse T1-weighted MR image (174/4, 75° flip angle), adenomas are isointense relative to liver parenchyma. (c) After fat-suppressed imaging (174/4, 75° flip angle), adenomas have signal dropout, which indicates lipid content. (d) Contrast-enhanced T1-weighted image (174/4, 75° flip angle) at portal venous phase shows no enhancement of multiple adenomas. (e) Surgical specimen (one square = 1 x 1 cm) was almost entirely occupied by nonencapsulated tumor that contained several yellow zones. (f) At pathologic examination, these zones consisted of proliferation of hepatocytes showing extensive macro- and microvesicular steatosis. (Hematoxylin-eosin stain; original magnification, x100.)
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Figure 1d: Patient 3. Steatotic form of liver adenomatosis in 30-year-old woman. (a) On transverse T2-weighted MR image (1900/96, 80° flip angle), multiple adenomas (arrows) are slightly hyperintense relative to liver parenchyma. (b) On transverse T1-weighted MR image (174/4, 75° flip angle), adenomas are isointense relative to liver parenchyma. (c) After fat-suppressed imaging (174/4, 75° flip angle), adenomas have signal dropout, which indicates lipid content. (d) Contrast-enhanced T1-weighted image (174/4, 75° flip angle) at portal venous phase shows no enhancement of multiple adenomas. (e) Surgical specimen (one square = 1 x 1 cm) was almost entirely occupied by nonencapsulated tumor that contained several yellow zones. (f) At pathologic examination, these zones consisted of proliferation of hepatocytes showing extensive macro- and microvesicular steatosis. (Hematoxylin-eosin stain; original magnification, x100.)
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Figure 1e: Patient 3. Steatotic form of liver adenomatosis in 30-year-old woman. (a) On transverse T2-weighted MR image (1900/96, 80° flip angle), multiple adenomas (arrows) are slightly hyperintense relative to liver parenchyma. (b) On transverse T1-weighted MR image (174/4, 75° flip angle), adenomas are isointense relative to liver parenchyma. (c) After fat-suppressed imaging (174/4, 75° flip angle), adenomas have signal dropout, which indicates lipid content. (d) Contrast-enhanced T1-weighted image (174/4, 75° flip angle) at portal venous phase shows no enhancement of multiple adenomas. (e) Surgical specimen (one square = 1 x 1 cm) was almost entirely occupied by nonencapsulated tumor that contained several yellow zones. (f) At pathologic examination, these zones consisted of proliferation of hepatocytes showing extensive macro- and microvesicular steatosis. (Hematoxylin-eosin stain; original magnification, x100.)
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Figure 1f: Patient 3. Steatotic form of liver adenomatosis in 30-year-old woman. (a) On transverse T2-weighted MR image (1900/96, 80° flip angle), multiple adenomas (arrows) are slightly hyperintense relative to liver parenchyma. (b) On transverse T1-weighted MR image (174/4, 75° flip angle), adenomas are isointense relative to liver parenchyma. (c) After fat-suppressed imaging (174/4, 75° flip angle), adenomas have signal dropout, which indicates lipid content. (d) Contrast-enhanced T1-weighted image (174/4, 75° flip angle) at portal venous phase shows no enhancement of multiple adenomas. (e) Surgical specimen (one square = 1 x 1 cm) was almost entirely occupied by nonencapsulated tumor that contained several yellow zones. (f) At pathologic examination, these zones consisted of proliferation of hepatocytes showing extensive macro- and microvesicular steatosis. (Hematoxylin-eosin stain; original magnification, x100.)
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Figure 2a: Patient 17. Peliotic form of liver adenomatosis in 47-year-old woman. (a) On transverse T2-weighted MR image (1600/70, 90° flip angle), multiple adenomas (arrows) are markedly hyperintense relative to liver parenchyma. (b) On T1-weighted MR image (212/4, 80° flip angle), there was no signal dropout after fat-suppressed imaging. (c, d) MR image from combination of (c) in-phase (148/4.6, 80° flip angle) and (d) opposed-phase (148/2.3, 80° flip angle) sequences show no signal dropout of adenomas. (e, f) Contrast-enhanced T1-weighted MR images (212/4, 80° flip angle) show enhancement of adenomas at (e) arterial phase and (f) portal phase. (g) Resected liver specimen (one square = 1 x 1 cm) shows adenoma in left lobe that measures 5 cm in diameter. Tumor was well delimited, was nonencapsulated (arrows), and contained several hemorrhagic areas. (h) At pathologic examination, these areas corresponded to multifocal peliosis. (Hematoxylin-eosin stain; original magnification, x200.)
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Figure 2b: Patient 17. Peliotic form of liver adenomatosis in 47-year-old woman. (a) On transverse T2-weighted MR image (1600/70, 90° flip angle), multiple adenomas (arrows) are markedly hyperintense relative to liver parenchyma. (b) On T1-weighted MR image (212/4, 80° flip angle), there was no signal dropout after fat-suppressed imaging. (c, d) MR image from combination of (c) in-phase (148/4.6, 80° flip angle) and (d) opposed-phase (148/2.3, 80° flip angle) sequences show no signal dropout of adenomas. (e, f) Contrast-enhanced T1-weighted MR images (212/4, 80° flip angle) show enhancement of adenomas at (e) arterial phase and (f) portal phase. (g) Resected liver specimen (one square = 1 x 1 cm) shows adenoma in left lobe that measures 5 cm in diameter. Tumor was well delimited, was nonencapsulated (arrows), and contained several hemorrhagic areas. (h) At pathologic examination, these areas corresponded to multifocal peliosis. (Hematoxylin-eosin stain; original magnification, x200.)
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Figure 2c: Patient 17. Peliotic form of liver adenomatosis in 47-year-old woman. (a) On transverse T2-weighted MR image (1600/70, 90° flip angle), multiple adenomas (arrows) are markedly hyperintense relative to liver parenchyma. (b) On T1-weighted MR image (212/4, 80° flip angle), there was no signal dropout after fat-suppressed imaging. (c, d) MR image from combination of (c) in-phase (148/4.6, 80° flip angle) and (d) opposed-phase (148/2.3, 80° flip angle) sequences show no signal dropout of adenomas. (e, f) Contrast-enhanced T1-weighted MR images (212/4, 80° flip angle) show enhancement of adenomas at (e) arterial phase and (f) portal phase. (g) Resected liver specimen (one square = 1 x 1 cm) shows adenoma in left lobe that measures 5 cm in diameter. Tumor was well delimited, was nonencapsulated (arrows), and contained several hemorrhagic areas. (h) At pathologic examination, these areas corresponded to multifocal peliosis. (Hematoxylin-eosin stain; original magnification, x200.)
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Figure 2d: Patient 17. Peliotic form of liver adenomatosis in 47-year-old woman. (a) On transverse T2-weighted MR image (1600/70, 90° flip angle), multiple adenomas (arrows) are markedly hyperintense relative to liver parenchyma. (b) On T1-weighted MR image (212/4, 80° flip angle), there was no signal dropout after fat-suppressed imaging. (c, d) MR image from combination of (c) in-phase (148/4.6, 80° flip angle) and (d) opposed-phase (148/2.3, 80° flip angle) sequences show no signal dropout of adenomas. (e, f) Contrast-enhanced T1-weighted MR images (212/4, 80° flip angle) show enhancement of adenomas at (e) arterial phase and (f) portal phase. (g) Resected liver specimen (one square = 1 x 1 cm) shows adenoma in left lobe that measures 5 cm in diameter. Tumor was well delimited, was nonencapsulated (arrows), and contained several hemorrhagic areas. (h) At pathologic examination, these areas corresponded to multifocal peliosis. (Hematoxylin-eosin stain; original magnification, x200.)
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Figure 2e: Patient 17. Peliotic form of liver adenomatosis in 47-year-old woman. (a) On transverse T2-weighted MR image (1600/70, 90° flip angle), multiple adenomas (arrows) are markedly hyperintense relative to liver parenchyma. (b) On T1-weighted MR image (212/4, 80° flip angle), there was no signal dropout after fat-suppressed imaging. (c, d) MR image from combination of (c) in-phase (148/4.6, 80° flip angle) and (d) opposed-phase (148/2.3, 80° flip angle) sequences show no signal dropout of adenomas. (e, f) Contrast-enhanced T1-weighted MR images (212/4, 80° flip angle) show enhancement of adenomas at (e) arterial phase and (f) portal phase. (g) Resected liver specimen (one square = 1 x 1 cm) shows adenoma in left lobe that measures 5 cm in diameter. Tumor was well delimited, was nonencapsulated (arrows), and contained several hemorrhagic areas. (h) At pathologic examination, these areas corresponded to multifocal peliosis. (Hematoxylin-eosin stain; original magnification, x200.)
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Figure 2f: Patient 17. Peliotic form of liver adenomatosis in 47-year-old woman. (a) On transverse T2-weighted MR image (1600/70, 90° flip angle), multiple adenomas (arrows) are markedly hyperintense relative to liver parenchyma. (b) On T1-weighted MR image (212/4, 80° flip angle), there was no signal dropout after fat-suppressed imaging. (c, d) MR image from combination of (c) in-phase (148/4.6, 80° flip angle) and (d) opposed-phase (148/2.3, 80° flip angle) sequences show no signal dropout of adenomas. (e, f) Contrast-enhanced T1-weighted MR images (212/4, 80° flip angle) show enhancement of adenomas at (e) arterial phase and (f) portal phase. (g) Resected liver specimen (one square = 1 x 1 cm) shows adenoma in left lobe that measures 5 cm in diameter. Tumor was well delimited, was nonencapsulated (arrows), and contained several hemorrhagic areas. (h) At pathologic examination, these areas corresponded to multifocal peliosis. (Hematoxylin-eosin stain; original magnification, x200.)
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Figure 2g: Patient 17. Peliotic form of liver adenomatosis in 47-year-old woman. (a) On transverse T2-weighted MR image (1600/70, 90° flip angle), multiple adenomas (arrows) are markedly hyperintense relative to liver parenchyma. (b) On T1-weighted MR image (212/4, 80° flip angle), there was no signal dropout after fat-suppressed imaging. (c, d) MR image from combination of (c) in-phase (148/4.6, 80° flip angle) and (d) opposed-phase (148/2.3, 80° flip angle) sequences show no signal dropout of adenomas. (e, f) Contrast-enhanced T1-weighted MR images (212/4, 80° flip angle) show enhancement of adenomas at (e) arterial phase and (f) portal phase. (g) Resected liver specimen (one square = 1 x 1 cm) shows adenoma in left lobe that measures 5 cm in diameter. Tumor was well delimited, was nonencapsulated (arrows), and contained several hemorrhagic areas. (h) At pathologic examination, these areas corresponded to multifocal peliosis. (Hematoxylin-eosin stain; original magnification, x200.)
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Figure 2h: Patient 17. Peliotic form of liver adenomatosis in 47-year-old woman. (a) On transverse T2-weighted MR image (1600/70, 90° flip angle), multiple adenomas (arrows) are markedly hyperintense relative to liver parenchyma. (b) On T1-weighted MR image (212/4, 80° flip angle), there was no signal dropout after fat-suppressed imaging. (c, d) MR image from combination of (c) in-phase (148/4.6, 80° flip angle) and (d) opposed-phase (148/2.3, 80° flip angle) sequences show no signal dropout of adenomas. (e, f) Contrast-enhanced T1-weighted MR images (212/4, 80° flip angle) show enhancement of adenomas at (e) arterial phase and (f) portal phase. (g) Resected liver specimen (one square = 1 x 1 cm) shows adenoma in left lobe that measures 5 cm in diameter. Tumor was well delimited, was nonencapsulated (arrows), and contained several hemorrhagic areas. (h) At pathologic examination, these areas corresponded to multifocal peliosis. (Hematoxylin-eosin stain; original magnification, x200.)
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Figure 3a: Patient 1. Mixed form of liver adenomatosis in 22-year-old woman. On (a) T2-weighted MR image (1900/96, 80° flip angle) and (b) T1-weighted MR image (174/4, 75° flip angle), large adenoma (arrow) with intratumoral hemorrhage appears heterogeneously hyperintense. (c, d) Contrast-enhanced T1-weighted MR images (174/4, 75° flip angle) at portal phase show (c) tumor enhancement in large adenoma and (d) multiple adenomas (arrows) with no enhancement at distance from largest nodule. (e) Resected liver specimen (after formol fixation) shows nodule measuring 8 cm in diameter and hemorrhagic and necrotic areas. (f) Several small nodules (white arrows) were observed at distance from largest nodule (black arrow).
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Figure 3b: Patient 1. Mixed form of liver adenomatosis in 22-year-old woman. On (a) T2-weighted MR image (1900/96, 80° flip angle) and (b) T1-weighted MR image (174/4, 75° flip angle), large adenoma (arrow) with intratumoral hemorrhage appears heterogeneously hyperintense. (c, d) Contrast-enhanced T1-weighted MR images (174/4, 75° flip angle) at portal phase show (c) tumor enhancement in large adenoma and (d) multiple adenomas (arrows) with no enhancement at distance from largest nodule. (e) Resected liver specimen (after formol fixation) shows nodule measuring 8 cm in diameter and hemorrhagic and necrotic areas. (f) Several small nodules (white arrows) were observed at distance from largest nodule (black arrow).
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Figure 3c: Patient 1. Mixed form of liver adenomatosis in 22-year-old woman. On (a) T2-weighted MR image (1900/96, 80° flip angle) and (b) T1-weighted MR image (174/4, 75° flip angle), large adenoma (arrow) with intratumoral hemorrhage appears heterogeneously hyperintense. (c, d) Contrast-enhanced T1-weighted MR images (174/4, 75° flip angle) at portal phase show (c) tumor enhancement in large adenoma and (d) multiple adenomas (arrows) with no enhancement at distance from largest nodule. (e) Resected liver specimen (after formol fixation) shows nodule measuring 8 cm in diameter and hemorrhagic and necrotic areas. (f) Several small nodules (white arrows) were observed at distance from largest nodule (black arrow).
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Figure 3d: Patient 1. Mixed form of liver adenomatosis in 22-year-old woman. On (a) T2-weighted MR image (1900/96, 80° flip angle) and (b) T1-weighted MR image (174/4, 75° flip angle), large adenoma (arrow) with intratumoral hemorrhage appears heterogeneously hyperintense. (c, d) Contrast-enhanced T1-weighted MR images (174/4, 75° flip angle) at portal phase show (c) tumor enhancement in large adenoma and (d) multiple adenomas (arrows) with no enhancement at distance from largest nodule. (e) Resected liver specimen (after formol fixation) shows nodule measuring 8 cm in diameter and hemorrhagic and necrotic areas. (f) Several small nodules (white arrows) were observed at distance from largest nodule (black arrow).
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Figure 3e: Patient 1. Mixed form of liver adenomatosis in 22-year-old woman. On (a) T2-weighted MR image (1900/96, 80° flip angle) and (b) T1-weighted MR image (174/4, 75° flip angle), large adenoma (arrow) with intratumoral hemorrhage appears heterogeneously hyperintense. (c, d) Contrast-enhanced T1-weighted MR images (174/4, 75° flip angle) at portal phase show (c) tumor enhancement in large adenoma and (d) multiple adenomas (arrows) with no enhancement at distance from largest nodule. (e) Resected liver specimen (after formol fixation) shows nodule measuring 8 cm in diameter and hemorrhagic and necrotic areas. (f) Several small nodules (white arrows) were observed at distance from largest nodule (black arrow).
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Figure 3f: Patient 1. Mixed form of liver adenomatosis in 22-year-old woman. On (a) T2-weighted MR image (1900/96, 80° flip angle) and (b) T1-weighted MR image (174/4, 75° flip angle), large adenoma (arrow) with intratumoral hemorrhage appears heterogeneously hyperintense. (c, d) Contrast-enhanced T1-weighted MR images (174/4, 75° flip angle) at portal phase show (c) tumor enhancement in large adenoma and (d) multiple adenomas (arrows) with no enhancement at distance from largest nodule. (e) Resected liver specimen (after formol fixation) shows nodule measuring 8 cm in diameter and hemorrhagic and necrotic areas. (f) Several small nodules (white arrows) were observed at distance from largest nodule (black arrow).
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There was steatosis, which was evaluated at more than 10%, in the nontumoral liver in five patients, including three patients with a peliotic form of adenomatosis and two patients with a mixed form of adenomatosis. There was no evidence of hepatic fibrosis or steatohepatitic (alcoholic or nonalcoholic) lesions.
Imaging Findings
In the three groups of patients with different MR features of liver adenomatosis, liver adenomatosis involved multiple hepatic segments with no right or left lobe predominance (Table 2).
In the steatotic form (n = 7) (Fig 1), signal dropout on the opposed-phase or fat-suppressed MR image was found in all patients. We did not observe any association with a steatotic liver or diabetes. In the peliotic form (n = 7) (Fig 2), an absence of signal dropout on the opposed-phase or fat-suppressed MR image was found in all patients. In the mixed steatotic-peliotic form of adenomatosis (n = 6) (Fig 3), the mean size of the largest tumor was larger than that of the largest tumor in the steatotic form (P < .05). A fatty liver was found in all obese patients (body mass index > 30) in the peliotic and mixed forms. Necrosis or subacute hemorrhage was identified in adenomas in 10 patients and only in adenomas larger than 4 cm in diameter. This was observed whatever the pattern of MR features: three patients with the steatotic form, three with the peliotic form, and four with the mixed form. The adenomas with necrosis or subacute hemorrhage had a heterogeneous appearance. In contrast, adenomas without these features had a homogeneous appearance.
A tumor with a peripheral rim was found in only eight patients, and the largest adenomas contained a hemorrhagic area. At pathologic analysis, however, a tumor pseudocapsule was found in adenomas from only three patients. In the five remaining patients, the peripheral rim depicted at MR imaging might have corresponded to abnormal compression of the adjacent hepatic parenchyma.
In one patient with a mixed form of adenomatosis, zones of HCC within an adenoma of 15 cm in diameter were not detected at MR imaging but were identified at pathologic examination (patient 4). Other liver lesions were observed at MR imaging in six patients: hepatic cysts in four patients, biliary hamartomas in one patient, and a hemangioma in one patient. No signs of chronic liver disease or cirrhosis were found. No vascular abnormalities were detected.
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DISCUSSION
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Our study, based mainly on surgical specimens, suggests that there are three MR imaging patterns of liver adenomatosis that correlate to three pathologic forms having the following characteristics.
In the steatotic form (a) the lesions have a mean diameter of 6.3 cm ± 1.7, (b) the signal intensity on T2-weighted images is slightly hyperintense, (c) the signal intensity of most lesions on T1-weighted images is hyper- or isointense, and signal dropout occurs when fat suppression sequences are used, and (d) most lesions display moderate enhancement at the arterial phase with no delayed enhancement.
In the peliotic form (a) the lesions are somewhat larger than those of the steatotic form (although not significantly), (b) the signal intensity on T2-weighted images is markedly hyperintense, (c) the signal intensity of most lesions on T1-weighted images is iso- or hyperintense and signal dropout does not occur when fat suppression sequences are used, and (d) the lesions have a strong arterial enhancement and a persistent enhancement at the portal and delayed phases. This contrast enhancement is due probably to sinusoidal dilatation or peliosis and is clearly distinct from that of the steatotic form.
In the mixed form with steatotic and peliotic lesions (a) the lesions are larger than those of the two other forms (a significant difference between the steatotic form and mixed form), (b) the signal intensity on T2-weighted images is hyperintense, (c) the signal intensity of the lesions on T1-weighted images is variable, which combines the imaging characteristics of the steatotic and peliotic forms, and (d) the lesions had an enhancement at the arterial, portal, and delayed phases in all patients except one.
The hemorrhagic complication, which usually leads to surgical resection, was observed only in large lesions (more than 4 cm in diameter) whatever the pathologic form. Previous results and those from our study suggest that the risk of bleeding is more dependent on tumor size than on the gross pattern (10). Intratumoral bleeding may explain the abdominal pain of 10 (50%) patients in our study.
HCC within an adenoma was found in the resected liver specimen of one patient. There are few published cases of malignant transformation in liver adenomatosis (3,11,16). According to the literature, patients with liver adenomatosis have an increased risk of developing HCC and should be closely monitored with CT or MR imaging and serum -fetoprotein markers (increased in only 50% of malignant tumors). Resection of large (
5 cm) or symptomatic adenomas and monitoring of smaller lesions (
3 cm) is recommended because of the risk of bleeding or underlying malignancy (10,17).
There is little information on the MR imaging features of liver adenomatosis. Previous case reports have shown that almost all patients with liver adenomatosis have hyperintense adenomas on T2-weighted images (8,11,12,14,15). In one case report, however, adenomas were isointense on T2-weighted images (13). On T1-weighted images, adenomas were mainly hyperintense (11,12,13,15), but they could also be isointense (11) or hypointense (8,14) to the liver. In reported studies, gadolinium-enhanced MR images show an enhancement of most adenomas (8,11,14,15). Our results are consistent with results of these previous studies. Furthermore, current results clearly show that different pathologic forms of liver adenomatosis correspond to different MR imaging features. In particular, the peliotic form is characterized by a delayed enhancement at MR imaging.
Except for the number of lesions, no difference was observed between imaging features of adenomatosis and those of solitary adenomas. In the literature, solitary adenomas are hyperintense (47%–74%), isointense (18%–39%), or hypointense (4%–8%) on T2-weighted images (4,6). Depending on the presence and duration of the hemorrhage, fat, and peliotic content, lesions on T1-weighted MR images can be hyperintense (59%–77%), isointense (6%–33%), or hypointense (8%–17%) to the liver (4,6). Contrast-enhanced T1-weighted images show early (67%) and delayed enhancement (45%) of the adenomas (4).
Differential diagnosis varies according to the imaging features. Differential diagnosis of the steatotic form of liver adenomatosis includes the presence of multifocal nodular fatty infiltration, and there is usually enhancement of the adenomas after injection of a gadolinium-based contrast agent (18). Fatty changes can also be seen in up to 35% of small (<1.5 cm), well-differentiated HCCs, but, unlike the uniform fat deposits found in adenomas, fat deposition in HCCs is usually patchy (19). On the other hand, distinguishing the peliotic and mixed forms of liver adenomatosis from multifocal HCC may be difficult with imaging criteria alone, but in most instances cirrhosis or clinical evidence of chronic liver disease is evident and serum tumor marker levels are elevated (20). Multiple telangiectatic focal nodular hyperplasia may share imaging features with the peliotic form of liver adenomatosis (21). However, telangiectatic focal nodular hyperplasia displays a molecular pattern closer to that of hepatocellular adenomas than to that of focal nodular hyperplasia and should now be considered "telangiectatic hepatocellular adenomas" (22).
Our study may have potential benefit for the management of liver adenomatosis. The suggested classification of the MR imaging features into three pathologic forms could help predict the potential complications of the adenomas. The mixed form with lesions that are larger than those in the steatotic form has a higher risk of complications and requires close follow-up with a surgical option.
Interestingly, no change in the MR imaging findings of adenomas was found at follow-up. The conditions that may cause predisposal to a form of liver adenomatosis are poorly understood. Although 45% of our patients used oral contraceptives, no direct link between the use of oral contraceptives and liver adenomatosis has been firmly proved. All patients in the study were women, although liver adenomatosis is reported to affect both men and women (7). Grazioli et al (11) also found a clear female preponderance in their study (14 female patients and one male patient).
Our study has two main limitations. First, each form was observed in approximately one-third of the cases. Although this could reflect the true proportion of liver adenomatosis, there could be a bias due to the types of patients seen in the liver surgery centers involved in this study. Second, biopsy specimens (instead of surgical specimens) were used in three patients.
In conclusion, liver adenomatosis is an uncommon entity that occurs most often in young women and has three MR imaging patterns that are associated with three pathologic forms. The steatotic form (35%) appears as multifocal lesions with fat components. The peliotic form (35%) also appears as multifocal lesions but with a peliotic component. The mixed form includes steatotic and peliotic lesions (30%). More data are needed to evaluate the variants of the progression of liver adenomatosis that could require different treatments.
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ADVANCE IN KNOWLEDGE
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- There are three patterns of MR features of liver adenomatosis associated with three pathologic forms: steatotic, peliotic, and mixed.
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FOOTNOTES
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Abbreviations: HCC = hepatocellular carcinoma
Authors stated no financial relationship to disclose.
Author contributions: Guarantor of integrity of entire study, M.L.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, all authors; clinical studies, all authors; statistical analysis, M.L.; and manuscript editing, all authors
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ABSTRACT
INTRODUCTION
