Published online before print August 27, 2003, 10.1148/radiol.2291021284
(Radiology 2003;229:75-79.)
© RSNA, 2003
Prevalence of Hepatic Hemangioma in Patients with Focal Nodular Hyperplasia: MR Imaging Analysis1
Valérie Vilgrain, MD,
Florence Uzan, MD,
Giuseppe Brancatelli, MD,
Michael P. Federle, MD,
Magali Zappa, MD and
Yves Menu, MD
1 From the Department of Radiology, Hôpital Beaujon, Clichy, France (V.V., F.U., G.B., M.Z., Y.M.); and Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (M.P.F.). Received October 4, 2002; revision requested December 12; revision received January 10, 2003; accepted February 28. Address correspondence to G.B., Department of Radiology, University of Palermo, Via Villaermosa 29, Palermo 90139, Italy (e-mail: gbranca@yahoo.com).
 |
ABSTRACT
|
|---|
PURPOSE: To evaluate the prevalence of hepatic hemangioma in a large population of patients with focal nodular hyperplasia (FNH) and to determine if the prevalence is higher than that in patients with other hepatic masses.
MATERIALS AND METHODS: Over a period of 40 months, 247 patients with one or more hepatic masses underwent magnetic resonance (MR) imaging at our institution and met the inclusion criteria for this study. One hundred forty-eight patients received a diagnosis of FNH (study group). Ninety-nine patients had a lesion other than FNH and had no history of chronic liver disease (control group). Imaging findings of the main lesion and presence of associated hemangioma were investigated. 
2 analysis was used to determine if there was a statistically significant difference in the two groups regarding the number of patients with associated masses.
RESULTS: Twenty-nine of 148 patients (20%) in the study group had FNH with one or more associated hepatic hemangiomas. Among the 99 patients in the control group, nine (9%) had an associated hemangioma. The prevalence of hemangioma was significantly higher (P < .02) in the study group than in the control group. The prevalence of hemangioma in patients with a solitary FNH lesion compared with that in patients with multiple FNH lesions was not significantly different.
CONCLUSION: Patients with FNH are more likely to have an associated hepatic hemangioma than are those with another type of focal hepatic mass.
© RSNA, 2003
Index terms: Liver, focal nodular hyperplasia, 761.3198 • Liver, hemangioma, 761.3194 • Liver, MR, 761.121411, 761.121412, 761.121415, 761.12143 • Liver neoplasms, diagnosis • Liver neoplasms, MR, 761.121411, 761.121412, 761.121415, 761.12143
|
INTRODUCTION
|
|---|
Focal nodular hyperplasia (FNH) and hemangioma are benign and generally asymptomatic hepatic tumors that are increasingly being discovered as incidental findings with the use of imaging tests. In our clinical practice, we have noted that these two types of lesions sometimes coexist in the same liver. Knowledge and recognition of this association is important, because in our experience, the presence of multiple hypervascular masses with variable imaging characteristics is likely to be interpreted as suggestive of hepatic malignancy, which may potentially lead to inappropriate further evaluation and therapy.
While several authors (1–3) have speculated that in patients with FNH, the prevalence of hemangioma is higher than that in the general population, this has not been documented in a study involving a large population and appropriate imaging evaluation. Thus, the purpose of our retrospective study was to evaluate the prevalence of hepatic hemangioma in a large number of patients with FNH and determine if the prevalence is higher than that in patients with other hepatic masses.
|
MATERIALS AND METHODS
|
|---|
Institutional review board approval was obtained for this study. Our review board did not require patient consent. One investigator reviewed the reports of all consecutive patients who underwent magnetic resonance (MR) imaging of the liver during a 40-month period at our institution. Patients with a diagnosis of FNH or a hepatic lesion other than FNH were included, while exclusion criteria were (a) normal MR imaging findings, (b) cirrhosis or chronic hepatitis, (c) a diagnosis of hepatic hemangioma or biliary cyst only, (d) unobtainable diagnosis of certainty, and (e) MR images obtained with contrast media other than gadolinium (eg, ferrite or manganese chelates). A total of 247 patients were selected to constitute our study population.
MR Imaging
MR imaging was performed with a 2.0-T Gyrex (Elscint, Haifa, Israel) superconducting system with a body coil. Sequences included T2-weighted fast spin echo (repetition time msec/echo time msec, 3,250/110; matrix, 200 x 256; echo train length, 20; field of view, 350 mm; section thickness, 10 mm; gap, 3 mm; four signals acquired) and T1-weighted breath-hold gradient echo (160/4.9 [in phase]; matrix, 100 x 200; flip angle, 80°; field of view, 34 cm; section thickness, 10 mm; gap, 2–3 mm; two signals acquired), with or without fat suppression. The time required to perform this sequence was 16 seconds times two. A T1-weighted gradient-echo MR sequence was performed in all patients during the hepatic arterial and portal venous phases (at 20 and 50 seconds, respectively) after manual administration of 0.1 mmol per kilogram of body weight of gadoterate meglumine (Dotarem; Laboratoire Guerbet, Roissy, France), followed by a 20-mL saline flush. Delayed-phase imaging was performed 5 minutes after contrast medium injection in all patients as part of our routine MR imaging protocol in patients with hepatic lesions.
Qualitative Analysis
For every patient, two authors (V.V., F.U.) performed qualitative analysis by means of consensus. Parameters included patient age and sex; type, size, number, and location of hepatic lesion(s) (in cases of multiple lesions, the largest lesion was considered); and proof of diagnosis.
Proof of Diagnosis
For 148 patients with FNH in the study group, proof of diagnosis of FNH was established with MR imaging in 126 patients when all established criteria (4) were met (isointensity or slight hypointensity to adjacent liver parenchyma on T1-weighted MR images obtained before injection of gadolinium chelates and on portal venous and delayed-phase MR images; strong and homogeneous hyperintensity on T1-weighted MR images obtained in the arterial phase; isointensity or slight hyperintensity to adjacent liver parenchyma on T2-weighted MR images; and hyperintense central scar on T1- or T2-weighted delayed-phase MR images).
In patients whose focal lesion did not meet all established MR imaging features of FNH, histologic confirmation was available by means of biopsy (n = 14) or surgery (n = 6). In two patients, the diagnosis was corroborated by means of computed tomographic (CT) criteria (isoattenuation or slight hypoattenuation to adjacent liver parenchyma before contrast material injection and on CT portal venous and delayed-phase images; strong homogeneous hyperattenuation on arterial phase CT images; hypoattenuating central scar on unenhanced arterial or portal venous phase CT images; and hyperattenuating central scar on delayed-phase CT images).
For the 99 patients in the control group with focal hepatic masses other than those of FNH, proof of diagnosis of the focal mass was obtained as follows. All patients with hepatic adenoma (n = 19), intrahepatic cholangiocarcinoma (n = 7), or fibrolamellar hepatocellular carcinoma (n = 5) underwent percutaneous biopsy (18-gauge needle, n = 20) or surgical resection of the entire specimen (n = 11) for histologic confirmation. The diagnosis of hepatic metastasis (n = 55) was confirmed by means of percutaneous core biopsy (n = 11) or surgical resection (n = 12), while the "proof" in 32 patients constituted a combination of clinical examination and imaging findings, including known extrahepatic primary malignancy and evolution of hepatic lesions on follow-up images.
Additional focal lesions in the control group included abscess (n = 4), angiomyolipoma (n = 2), lymphoma (n = 2), and one patient each with a primary hepatic carcinoid tumor, adenocarcinoma (related to thorium dioxide), inflammatory pseudotumor, hydatid cyst, and histiocytic fibroma. All seven patients with neoplastic lesions had histologic confirmation, while patients with inflammatory masses had needle aspiration biopsy (n = 2) and/or characteristic imaging findings during therapy and follow-up.
The diagnosis of hepatic hemangioma was based on widely accepted (5,6) MR imaging criteria, including marked hyperintensity on T2-weighted MR images, hypointensity on T1-weighted MR images, and nodular peripheral and centripetal contrast material enhancement on dynamic bolus T1-weighted MR images.
Statistical Analysis
To determine if there was a significant difference in the prevalence of hemangioma in the study and control groups, we used 2 analysis with the number of patients as the unit of measure, the percentage of cases in each group as the variable, and a P value of less than .05 as indicative of a statistically significant difference.
|
RESULTS
|
|---|
Study Group
Of the 148 patients with FNH, 139 (94%) were women and nine (6%) were men, with a mean age of 38.2 years (range, 20–74 years). FNH lesions were solitary in 114 patients (77%) and multiple in 34 patients (23%); there were two lesions in 21 patients, three lesions in two patients, four lesions in five patients, and five or more lesions in six patients. Lesions were in the right anterior or posterior hepatic segments in 103 patients, in the left lateral or medial hepatic segments in 34 patients, and in the caudate lobe in 11 patients. In patients with multiple FNH lesions, only the site of the largest lesion (mean size, 5.2 cm ± 3.8 [SD]) was considered.
Twenty-nine of these 148 patients (20%) also had one or more hepatic hemangiomas (Figs 1, 2). Among the 114 patients with one FNH lesion, 22 (19%) had one or more hemangiomas. Among the 34 patients with multiple FNH lesions, seven (20%) had one or more hemangiomas. This difference was not significant.
View larger version (145K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1a. Transverse MR images show hemangioma associated with FNH in a 49-year-old woman. (a) T2-weighted fast spin-echo MR image (3,250/110) shows mildly hyperintense FNH lesion (long arrow) in the right hepatic lobe. Hemangioma (short arrow) with signal intensity almost as strong as that of the gallbladder (g) is seen posteriorly. (b) T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows hepatic hemangioma (arrow) to be hypointense to surrounding liver parenchyma. FNH lesion is isointense to adjacent liver parenchyma and is not easily seen. (c) Gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during arterial phase shows strong hyperintensity of FNH lesion (long arrow) to normal liver. Hemangioma (short arrow) shows nodular peripheral enhancement. (d) Gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during portal venous phase shows centripetal filling of hemangioma (short arrow) except for the central region, while FNH lesion (long arrow) is isointense to normal liver. (e) Delayed-phase (5 minutes) gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows isointensity of FNH lesion (long arrow) with enhancement of central scar (arrowhead) and pseudocapsule. Hemangioma (short arrow) is now almost completely filled with contrast material.
|
|
View larger version (136K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1b. Transverse MR images show hemangioma associated with FNH in a 49-year-old woman. (a) T2-weighted fast spin-echo MR image (3,250/110) shows mildly hyperintense FNH lesion (long arrow) in the right hepatic lobe. Hemangioma (short arrow) with signal intensity almost as strong as that of the gallbladder (g) is seen posteriorly. (b) T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows hepatic hemangioma (arrow) to be hypointense to surrounding liver parenchyma. FNH lesion is isointense to adjacent liver parenchyma and is not easily seen. (c) Gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during arterial phase shows strong hyperintensity of FNH lesion (long arrow) to normal liver. Hemangioma (short arrow) shows nodular peripheral enhancement. (d) Gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during portal venous phase shows centripetal filling of hemangioma (short arrow) except for the central region, while FNH lesion (long arrow) is isointense to normal liver. (e) Delayed-phase (5 minutes) gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows isointensity of FNH lesion (long arrow) with enhancement of central scar (arrowhead) and pseudocapsule. Hemangioma (short arrow) is now almost completely filled with contrast material.
|
|
View larger version (143K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1c. Transverse MR images show hemangioma associated with FNH in a 49-year-old woman. (a) T2-weighted fast spin-echo MR image (3,250/110) shows mildly hyperintense FNH lesion (long arrow) in the right hepatic lobe. Hemangioma (short arrow) with signal intensity almost as strong as that of the gallbladder (g) is seen posteriorly. (b) T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows hepatic hemangioma (arrow) to be hypointense to surrounding liver parenchyma. FNH lesion is isointense to adjacent liver parenchyma and is not easily seen. (c) Gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during arterial phase shows strong hyperintensity of FNH lesion (long arrow) to normal liver. Hemangioma (short arrow) shows nodular peripheral enhancement. (d) Gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during portal venous phase shows centripetal filling of hemangioma (short arrow) except for the central region, while FNH lesion (long arrow) is isointense to normal liver. (e) Delayed-phase (5 minutes) gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows isointensity of FNH lesion (long arrow) with enhancement of central scar (arrowhead) and pseudocapsule. Hemangioma (short arrow) is now almost completely filled with contrast material.
|
|
View larger version (140K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1d. Transverse MR images show hemangioma associated with FNH in a 49-year-old woman. (a) T2-weighted fast spin-echo MR image (3,250/110) shows mildly hyperintense FNH lesion (long arrow) in the right hepatic lobe. Hemangioma (short arrow) with signal intensity almost as strong as that of the gallbladder (g) is seen posteriorly. (b) T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows hepatic hemangioma (arrow) to be hypointense to surrounding liver parenchyma. FNH lesion is isointense to adjacent liver parenchyma and is not easily seen. (c) Gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during arterial phase shows strong hyperintensity of FNH lesion (long arrow) to normal liver. Hemangioma (short arrow) shows nodular peripheral enhancement. (d) Gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during portal venous phase shows centripetal filling of hemangioma (short arrow) except for the central region, while FNH lesion (long arrow) is isointense to normal liver. (e) Delayed-phase (5 minutes) gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows isointensity of FNH lesion (long arrow) with enhancement of central scar (arrowhead) and pseudocapsule. Hemangioma (short arrow) is now almost completely filled with contrast material.
|
|
View larger version (136K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 1e. Transverse MR images show hemangioma associated with FNH in a 49-year-old woman. (a) T2-weighted fast spin-echo MR image (3,250/110) shows mildly hyperintense FNH lesion (long arrow) in the right hepatic lobe. Hemangioma (short arrow) with signal intensity almost as strong as that of the gallbladder (g) is seen posteriorly. (b) T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows hepatic hemangioma (arrow) to be hypointense to surrounding liver parenchyma. FNH lesion is isointense to adjacent liver parenchyma and is not easily seen. (c) Gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during arterial phase shows strong hyperintensity of FNH lesion (long arrow) to normal liver. Hemangioma (short arrow) shows nodular peripheral enhancement. (d) Gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during portal venous phase shows centripetal filling of hemangioma (short arrow) except for the central region, while FNH lesion (long arrow) is isointense to normal liver. (e) Delayed-phase (5 minutes) gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows isointensity of FNH lesion (long arrow) with enhancement of central scar (arrowhead) and pseudocapsule. Hemangioma (short arrow) is now almost completely filled with contrast material.
|
|
View larger version (154K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2a. Transverse MR images show hemangioma associated with FNH in a 34-year-old woman. (a) Fat-suppressed T2-weighted fast spin-echo MR image (3,250/110) shows mildly hyperintense FNH lesion (long arrow). Hemangioma (short arrow) with signal intensity as strong as that of cerebrospinal fluid is seen posteriorly. (b) Fat-suppressed T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows hepatic hemangioma (short arrow) to be hypointense to surrounding liver parenchyma. FNH lesion (long arrow) is isointense to liver parenchyma. (c) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during arterial phase shows enhancement of FNH lesion (long arrow) to normal liver. Hemangioma (short arrow) shows nodular peripheral enhancement. (d) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during portal venous phase shows centripetal filling of hemangioma (short arrow), while FNH lesion (long arrow) is almost isointense to normal liver. Note numerous draining veins around FNH lesion. (e) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during delayed-phase (5 minutes) imaging shows isointensity of FNH lesion to liver parenchyma. Hemangioma (short arrow) is partially filled with contrast material.
|
|
View larger version (134K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2b. Transverse MR images show hemangioma associated with FNH in a 34-year-old woman. (a) Fat-suppressed T2-weighted fast spin-echo MR image (3,250/110) shows mildly hyperintense FNH lesion (long arrow). Hemangioma (short arrow) with signal intensity as strong as that of cerebrospinal fluid is seen posteriorly. (b) Fat-suppressed T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows hepatic hemangioma (short arrow) to be hypointense to surrounding liver parenchyma. FNH lesion (long arrow) is isointense to liver parenchyma. (c) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during arterial phase shows enhancement of FNH lesion (long arrow) to normal liver. Hemangioma (short arrow) shows nodular peripheral enhancement. (d) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during portal venous phase shows centripetal filling of hemangioma (short arrow), while FNH lesion (long arrow) is almost isointense to normal liver. Note numerous draining veins around FNH lesion. (e) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during delayed-phase (5 minutes) imaging shows isointensity of FNH lesion to liver parenchyma. Hemangioma (short arrow) is partially filled with contrast material.
|
|
View larger version (142K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2c. Transverse MR images show hemangioma associated with FNH in a 34-year-old woman. (a) Fat-suppressed T2-weighted fast spin-echo MR image (3,250/110) shows mildly hyperintense FNH lesion (long arrow). Hemangioma (short arrow) with signal intensity as strong as that of cerebrospinal fluid is seen posteriorly. (b) Fat-suppressed T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows hepatic hemangioma (short arrow) to be hypointense to surrounding liver parenchyma. FNH lesion (long arrow) is isointense to liver parenchyma. (c) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during arterial phase shows enhancement of FNH lesion (long arrow) to normal liver. Hemangioma (short arrow) shows nodular peripheral enhancement. (d) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during portal venous phase shows centripetal filling of hemangioma (short arrow), while FNH lesion (long arrow) is almost isointense to normal liver. Note numerous draining veins around FNH lesion. (e) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during delayed-phase (5 minutes) imaging shows isointensity of FNH lesion to liver parenchyma. Hemangioma (short arrow) is partially filled with contrast material.
|
|
View larger version (142K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2d. Transverse MR images show hemangioma associated with FNH in a 34-year-old woman. (a) Fat-suppressed T2-weighted fast spin-echo MR image (3,250/110) shows mildly hyperintense FNH lesion (long arrow). Hemangioma (short arrow) with signal intensity as strong as that of cerebrospinal fluid is seen posteriorly. (b) Fat-suppressed T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows hepatic hemangioma (short arrow) to be hypointense to surrounding liver parenchyma. FNH lesion (long arrow) is isointense to liver parenchyma. (c) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during arterial phase shows enhancement of FNH lesion (long arrow) to normal liver. Hemangioma (short arrow) shows nodular peripheral enhancement. (d) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during portal venous phase shows centripetal filling of hemangioma (short arrow), while FNH lesion (long arrow) is almost isointense to normal liver. Note numerous draining veins around FNH lesion. (e) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during delayed-phase (5 minutes) imaging shows isointensity of FNH lesion to liver parenchyma. Hemangioma (short arrow) is partially filled with contrast material.
|
|
View larger version (143K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 2e. Transverse MR images show hemangioma associated with FNH in a 34-year-old woman. (a) Fat-suppressed T2-weighted fast spin-echo MR image (3,250/110) shows mildly hyperintense FNH lesion (long arrow). Hemangioma (short arrow) with signal intensity as strong as that of cerebrospinal fluid is seen posteriorly. (b) Fat-suppressed T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) shows hepatic hemangioma (short arrow) to be hypointense to surrounding liver parenchyma. FNH lesion (long arrow) is isointense to liver parenchyma. (c) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during arterial phase shows enhancement of FNH lesion (long arrow) to normal liver. Hemangioma (short arrow) shows nodular peripheral enhancement. (d) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during portal venous phase shows centripetal filling of hemangioma (short arrow), while FNH lesion (long arrow) is almost isointense to normal liver. Note numerous draining veins around FNH lesion. (e) Fat-suppressed gadolinium-enhanced T1-weighted gradient-echo MR image (160/4.9, 80° flip angle) obtained during delayed-phase (5 minutes) imaging shows isointensity of FNH lesion to liver parenchyma. Hemangioma (short arrow) is partially filled with contrast material.
|
|
FNH and hemangioma were located in the same hepatic lobe (the right lobe) in 14 of 29 patients (48%) and in different lobes in 15 patients (52%). Lesions were located in the same hepatic segment (according to Couinaud classification) in four patients (14%). In 16 of the 29 patients (55%), the hemangioma was solitary. There were two hemangiomas in four patients, three hemangiomas in three patients, and five or more hemangiomas in six patients. The 29 patients with an associated hemangioma had a mean age of 39 years (range, 24–74 years). There were 27 women (93%) and two men (7%). In these patients, the median size of the FNH lesions (or of the largest lesion in patients with multiple lesions) was 5.1 cm.
The 119 patients without associated hemangioma had a median age of 37.2 years (range, 20–68 years). There were 112 women (94%) and seven men (6%). In this subgroup of patients, the mean size of FNH lesions was 4.9 cm. There were no significant differences in patient age, sex, or lesion size between the patients who had and those who did not have a hemangioma in association with FNH.
Control Group
The group of patients with a lesion other than FNH comprised 99 patients (63 women [64%] and 36 men [36%]; median age, 51 years; age range, 20–82 years). Of the 99 patients, nine (9%) had an associated hemangioma (eight women and one man). These nine patients had hepatic adenoma (n = 3), metastases (n = 4), inflammatory pseudotumor (n = 1), and histiocytic fibroma (n = 1). The prevalence of hemangioma was higher in the 19 patients with hepatic adenoma (16%) than that in other subgroups. If we exclude the 19 patients with adenoma, 80 patients would then form the control group, six of whom had an associated hemangioma, with a resulting prevalence of 7.5%. In this subgroup of patients, the prevalence of associated hemangioma was 13% in women and 3% in men.
Study and Control Groups
There was a higher prevalence of hepatic hemangioma among the 148 patients with FNH (20%) than in the control group (9%) of 99 patients. This difference was statistically significant (P < .02). If we exclude patients with adenoma, the prevalence of hemangioma in the control group was 7.5%, and the difference between the two percentages is still significant (P < .02).
|
DISCUSSION
|
|---|
Our results indicate that there is a significant nonrandom association between FNH and cavernous hemangioma in the liver. While each of these lesions is found commonly as an isolated hepatic mass, the presence of both lesions in the same patient is common: 20% in our study group. Hemangiomas have been reported in 0.4%–20% of the general adult population (7,8), and FNH has been reported in 0.6%–3.0% (2,8). If there were no common associated causes for FNH and hemangioma, by multiplying the respective lowest and highest ranges encountered for these two lesions in unselected autopsy series, we would expect to find them together in 0.0024%–0.6% of patients.
Among patients who had primary hepatic masses other than FNH, the prevalence of hemangioma was significantly lower (9%). By excluding patients with hepatic adenoma, only 7.5% of patients with other hepatic masses had associated hemangioma, which may represent the "background" prevalence of hemangioma in the general population.
Our results are in accord with those of Mathieu and colleagues (3), who found hemangiomas in six of 23 patients (26%) with FNH. Several authors have speculated that both lesions may have causative factors in common, including focal disturbance of the hepatic blood supply that somehow facilitates the hyperplastic development of these benign lesions. Benz and Baggenstoss (1) found hemangiomas in seven of 34 patients (20%) with FNH. Wanless et al (9) analyzed the liver in 2,500 consecutive autopsies and found 23 cases of FNH, four of which (17%) occurred with associated hemangioma (9).
While hepatic adenoma is much less common than hemangioma or FNH, reports of the clinicopathologic findings in patients with adenomas also provide some intriguing insights into potential pathophysiology among these benign lesions. In a series of 168 patients with 305 FNH lesions, the association of FNH with hepatocellular adenoma was observed in 3.6% of cases (10). Other investigators (11,12) have noted that FNH and hepatic adenomas occur more often in patients who have coexisting vascular tumors, portal venous absence or occlusion, or portohepatic venous shunts. Both FNH and adenoma occur almost exclusively (>90%) in women of childbearing age. In our patients with FNH, 94% were women. Hemangioma also has a female predominance over males, reported as approximately 5:1. We report that three of our 19 patients with adenoma (16%) also had hemangioma. This finding is a further clue to the hypothesis that the development of FNH is due to altered blood flow as a result of the coexistence of other hypervascularized lesions, such as hepatocellular adenoma or adenomatosis.
We decided to exclude patients with chronic liver disease or cirrhosis for several reasons. Hemangiomas are difficult to diagnose by means of imaging because the progressive fibrosis that occurs in cirrhosis alters the blood supply of the liver, causes loss of characteristic imaging features of hemangiomas, and ultimately results in obliteration of the hemangioma (13). In addition, lesions that are indistinguishable from FNH on the basis of imaging and even histologic criteria are commonly encountered within the damaged liver, including various forms of hyperplastic nodules (14).
After excluding patients with chronic liver disease and those with only MR imaging evidence of a solitary hepatic cyst or hemangioma as the only type of focal hepatic mass, we tried to avoid other sources of selection bias. Because our institution is a referral center for patients with liver disease and because this is a retrospective study, some bias may be unavoidable; however, we did include all consecutive patients with hepatic masses who met the inclusion criteria and who were all studied at a single institution by using a similar MR imaging protocol within a relatively short time period. The MR imaging technique we used might not be considered optimal with the equipment available today because of the relatively thick (10-mm) sections that might limit detection of very small hemangiomas. However, whatever decreased sensitivity for diagnosing hemangioma that might have resulted from this technique would be reflected in the study and control groups alike and would probably not affect the results or conclusions. Moreover, the MR imaging criteria for diagnosis of both FNH and hemangioma are based on both signal intensity of the lesions at T2-weighted MR imaging and dynamic contrast enhancement patterns, features that were available with our equipment. Another limitation of our study is the absence of pathologic proof in many of our cases. Nevertheless, we used strict and widely accepted criteria whenever surgical or biopsy results were not available. By using the combination of MR imaging features that we did, others have reported 100% specificity for the diagnosis of FNH at MR imaging (15).
In conclusion, the prevalence of hepatic hemangioma is higher in patients who also have FNH. Radiologists must be aware of this association to avoid mistaking these two common benign hepatic lesions for metastatic disease.
|
FOOTNOTES
|
|---|
Abbreviation: FNH = focal nodular hyperplasia
Author contributions: Guarantors of integrity of entire study, V.V., F.U., G.B.; study concepts, V.V., M.P.F.; study design, V.V.; literature research, V.V., F.U.; clinical studies, V.V., F.U., Y.M.; data acquisition, F.U., V.V.; data analysis/interpretation, F.U., V.V., G.B.; statistical analysis, F.U., G.B.; manuscript preparation, V.V., G.B., F.U., M.P.F.; manuscript definition of intellectual content, V.V.; manuscript editing and revision/review, V.V., G.B., M.P.F.; manuscript final version approval, all authors
|
REFERENCES
|
|---|
- Benz EJ, Baggenstoss AH. Focal cirrhosis of the liver: its relation to the so-called hamartoma (adenoma, benign hepatoma). Cancer 1953; 6:743-755.
- Wanless IR. Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules. Hepatology 1990; 11:787-797.[Medline]
- Mathieu D, Zafrani ES, Anglade MC, Dhumeaux D. Association of focal nodular hyperplasia and hepatic hemangioma. Gastroenterology 1989; 97:154-157.[Medline]
- Vilgrain V, Flejou JF, Arrive L, et al. Focal nodular hyperplasia of the liver: MR imaging and pathologic correlation in 37 patients. Radiology 1992; 184:699-703.[Abstract/Free Full Text]
- Quinn SF, Benjamin GG. Hepatic cavernous hemangiomas: simple diagnostic sign with dynamic bolus CT. Radiology 1992; 182:545-548.[Abstract/Free Full Text]
- Leslie DF, Johnson CD, Johnson CM, Ilstrup DM, Harmsen WS. Distinction between cavernous hemangiomas of the liver and hepatic metastases on CT: value of contrast enhancement patterns. AJR Am J Roentgenol 1995; 164:625-629.[Abstract/Free Full Text]
- Edmondson HA. Tumors of the liver and intrahepatic bile ducts In: Atlas of tumor pathology. First series. Washington, DC: Armed Forces Institute of Pathology, 1958.
- Karhunen PJ. Benign hepatic tumors and tumor-like conditions in men. J Clin Pathol 1986; 39:183-188.[Abstract/Free Full Text]
- Wanless IR, Albrecht S, Bilbao J, et al. Multiple focal nodular hyperplasia of the liver associated with vascular malformations of various organs and neoplasia of the brain: a new syndrome. Mod Pathol 1989; 2:456-462.[Medline]
- Nguyen BN, Flejou JF, Terris B, Belghiti J, Degott C. Focal nodular hyperplasia of the liver: a comprehensive pathologic study of 305 lesions and recognition of new histologic forms. Am J Surg Pathol 1999; 23:1441-1454.[CrossRef][Medline]
- Ishak KG, Rabin L. Benign tumors of the liver. Med Clin North Am 1975; 995-1013.
- 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]
- Brancatelli G, Federle MP, Blachar A, Grazioli L. Hemangioma in the cirrhotic liver: diagnosis and natural history. Radiology 2001; 219:69-74.[Abstract/Free Full Text]
- Bioulac-Sage P, Balabaud C, Wanless IR. Diagnosis of focal nodular hyperplasia: not so easy. Am J Surg Pathol 2001; 25:1322-1325.[CrossRef][Medline]
- Belghiti J, Pateron D, Panis Y, et al. Resection of presumed benign liver tumours. Br J Surg 1993; 80:380-383.[Medline]
This article has been cited by other articles:
|
|
|
|
 
I. R. Kamel, E. Liapi, and E. K. Fishman
Focal nodular hyperplasia: lesion evaluation using 16-MDCT and 3D CT angiography.
Am. J. Roentgenol.,
June 1, 2006;
186(6):
1587 - 1596.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V Glinkova, O Shevah, M Boaz, A Levine, and H Shirin
Hepatic haemangiomas: possible association with female sex hormones
Gut,
September 1, 2004;
53(9):
1352 - 1355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Ragozzino, G. Brancatelli, V. Vilgrain, M. P. Federle, F. Uzan, M. Zappa, and Y. Menu
Biases Likely Invalidate the Conclusions [letter] * Dr Brancatelli and colleagues respond:
Radiology,
June 1, 2004;
231(3):
926 - 927.
[Full Text]
[PDF]
|
|
|
TOP
ABSTRACT
INTRODUCTION
