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Gastrointestinal Imaging |
1 Departments of Radiology (C.B.W., L.H.S., D.M.P.)
2 Surgery (Y.F., L.H.B.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.
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Abstract |
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MATERIALS AND METHODS: MR images in 36 patients with HCC (30 men and six women aged 42–84 years [mean age, 65 years]) were retrospectively reviewed. The number and size of hepatic lesions were assessed. Lesion margins were categorized as well circumscribed or ill defined. The presence of a capsule, intratumoral high signal intensity on T1-weighted MR images, and a stellate scar were determined.
RESULTS: Eleven (31%) patients had MR imaging evidence of cirrhosis, and 25 (69%) did not. Lesions in cirrhotic livers differed significantly from those in noncirrhotic livers in terms of size (22 cm2 vs 99 cm2, P < .05), frequency of a solitary lesion (27% vs 72%, P < .05), and frequency of a central scar (6% vs 50%, P < .05). There was no difference between the cirrhotic and noncirrhotic livers with regard to tumor margin, intratumoral high signal intensity on T1-weighted images, or tumor capsule.
CONCLUSION: Differences exist in the MR imaging appearance of HCC between patients with and those without cirrhosis, although there is overlap of imaging findings.
Index terms: Liver, cirrhosis, 761.794 • Liver, MR, 761.121411, 761.121412, 761.12143 • Liver neoplasms, 761.323
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Introduction |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Magnetic resonance (MR) imaging plays an important role in the evaluation of pathologic conditions of the liver, not only for lesion detection and characterization but also for treatment planning. The appearance of HCC at MR imaging has been extensively described (3–6). Most studies, however, have been of HCC in Asian populations, in whom hepatitis B is the major cause of HCC, usually in the presence of cirrhosis. Although the applicability of the Asian data to the non-Asian population has recently been challenged (7), most studies performed to evaluate HCC in the non-Asian population included predominantly patients with cirrhosis (8–11). To our knowledge, there has been no report of the MR imaging appearance of HCC in patients without cirrhosis. The purpose of our study was to compare the MR imaging findings of primary HCC in cirrhotic and noncirrhotic livers.
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MATERIALS AND METHODS |
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MR Imaging Technique
MR imaging was performed with a 1.5-T MR imaging system (Signa; GE Medical Systems, Milwaukee, Wis). Twenty-nine patients underwent MR imaging with the body coil, and seven underwent imaging with the torso phased-array coil.
Spin-echo T1-weighted images were obtained in 35 patients by using the following parameters: 500–600/9–16 (repetition time msec/echo time msec), two to four signals acquired, 256 x 128–192 matrix, 8-mm-thick sections with a 2-mm intersection gap, and respiratory compensation. In-phase T1-weighted fast multiplanar spoiled gradient-recalled-echo images were acquired in one patient with use of the following parameters: 100/4.2, 70° flip angle, two signals acquired, 256 x 128 matrix, and 8-mm-thick sections with a 2-mm intersection gap.
Fast spin-echo T2-weighted images with frequency-selective fat saturation were obtained in 29 patients with use of the following parameters: 4,000–5,000/92–105 (repetition time msec/effective echo time msec), echo train length of eight, two to four signals acquired, 256 x 192–256 matrix, 8-mm-thick sections with a 2-mm intersection gap, and flow compensation. Fast spin-echo T2-weighted images were obtained in 19 patients with use of the following parameters: 5,000–6,000/165–180 (effective), echo train length of 12, four signals acquired, 256 x 192 matrix, 8-mm-thick sections with a 2-mm intersection gap, and flow compensation. Single-shot fast spin-echo T2-weighted images with fat saturation in seven patients and without fat saturation in three patients were obtained by using the following parameters: effective echo time of 106 msec, one-half signal acquired, 256 x 256 matrix, and flow compensation.
Fast multiplanar spoiled gradient-recalled-echo breath-hold images were obtained in 25 patients by using the following parameters: 90/2.3, 70° flip angle, 256 x 128 matrix, and one to two signals acquired both before and after dynamic intravenous administration of 0.1 mmol of gadopentetate dimeglumine (Magnevist; Berlex Laboratories, Wayne, NJ) per kilogram of body weight. All patients underwent T1-weighted and T2-weighted imaging with fat saturation at least once.
Histopathologic Confirmation
Histopathologic confirmation was performed by examining biopsy specimens in seven patients (open biopsy in four, percutaneous biopsy in two; in one patient, the pathology slides from another institution were provided for review, but the method of biopsy was not recorded), percutaneous fine-needle aspiration specimens in 10 patients, and surgical resection specimens in 14 patients. One patient underwent both percutaneous biopsy and fine-needle aspiration. The remaining six patients had a serum 
-fetoprotein level of greater than 500 ng/mL (500 µg/L), which, in conjunction with a focal hepatic mass, was considered to be diagnostic of HCC (13). Four of these six patients had evidence of cirrhosis at MR imaging. Review of medical charts was performed to assess for a history of alcohol abuse, hepatitis, and other known liver disease. Retrospective review of pathology reports was performed to determine the presence of cirrhosis in those patients who underwent surgical resection.
Qualitative Evaluation
Each MR imaging study was retrospectively reviewed by two of three experienced radiologists (C.B.W., L.H.S., D.M.P.), with decisions made by consensus. Criteria for the diagnosis of cirrhosis on MR images included regenerative nodules (defined as lesions with very low signal intensity on T2-weighted and spoiled gradient-recalled-echo images [14]), linear high signal intensity on T2-weighted images (15), and surface nodularity (16,17). The presence of cirrhosis as determined on MR images was correlated with the findings at pathologic examination of the surgical specimens in those cases in which resection was performed (n = 14).
The number and size of focal liver lesions compatible with HCC were determined. Lesions considered to be cysts or hemangiomata on the basis of homogeneous high signal intensity on heavily T2-weighted images—that is, images obtained with an echo time of 160–180 msec—and no enhancement (cyst) or peripheral nodular enhancement on the postgadolinium images (hemangioma) were excluded (18,19). The product of two perpendicular diameters of each lesion obtained from an axial image was calculated. The Student t test was used to determine if there existed statistically significant differences in the size of lesions between cirrhotic livers and noncirrhotic livers.
Lesion margins were categorized as well circumscribed or ill defined. Lesions were evaluated for the presence of intratumoral high signal intensity on T1-weighted images. The presence of a capsule, defined as a thin rim of low signal intensity on T1-weighted images that surrounded at least 25% of the lesion, was noted. The presence of a scar, defined as a focal area of high signal intensity with a stellate or cleft configuration on the T2-weighted images, was assessed. The statistical significance of differences among these features was assessed with the 
2 test.
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RESULTS |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Review of medical records revealed that cirrhosis was due to infection with hepatitis B (n = 6), hemochromatosis (n = 2), or 1-antitrypsin deficiency (n = 1). In two patients, the cause of cirrhosis was not discernible. Of the 25 patients without MR imaging evidence of cirrhosis, four had a history of alcohol abuse, 11 had a history of hepatitis B infection, one had a history of hepatitis A infection, and five had no known liver disease. No clinical history was available for four patients, who were seen only in consultation at our institution.
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DISCUSSION |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Classic MR imaging findings of HCC, including intratumoral fat, tumor encapsulation, portal or hepatic vein invasion, and arterial–portal venous shunting, have predominantly been described in patients with cirrhosis (3–6) and in Asian populations (3,4), in whom hepatitis B is endemic. In both Asia and the United States, HCC is most commonly seen in the presence of underlying cirrhosis. In Western countries, it has been estimated that 60%–70% of patients with cirrhosis are chronic alcoholics (20). Viral hepatitis and other identifiable causes such as hepatotoxins, hemochromatosis, and Wilson disease account for cirrhosis in 15%–30% of patients. In the remaining 10%–15% of patients, the cause is not known (ie, cryptogenic). Some patients with primary HCC have no underlying evidence of cirrhosis. A transient hepatitis B infection may play a role in hepatocarcinogenesis without causing cirrhosis (2). Also, HCC may occur de novo in the absence of any underlying liver disease (2).
Researchers who have challenged the relevance of the Asian data to that of the non-Asian population have assessed the differences between the two populations (7), but those studies included mainly patients with cirrhosis in the non-Asian study groups (8–11). Yamashita et al (21) demonstrated that the association between HCC and cirrhosis in the United States was less than that in Japan (56.2% vs 91.0%).
The only option for cure in HCC is surgical resection. The most favorable indication for surgery is a small, solitary, encapsulated nodule without vascular invasion, although multicentric tumor confined to one lobe is not an absolute contraindication to resection (13). Patients with multinodular lesions have a worse long-term prognosis after hepatic resection than do those with a solitary nodule (22).
Our finding that HCC in noncirrhotic patients is more likely to be unifocal than it is in patients with cirrhosis (72% vs 27%) corroborates the pathologic results of Smalley et al (23), who noted that at gross pathologic examination of specimens from noncirrhotic livers HCC was a well-circumscribed mass in 57% of cases and a dominant mass with smaller satellite lesions in 6% of cases. Thirty-three percent of cases of HCC manifested as multiple intrahepatic tumors, and none could be clearly defined as a dominant lesion. In 3% of patients in the study by Smalley et al, HCC had a diffuse infiltrative pattern.
It has been suggested (2) that the pathogenesis of HCC in patients with cirrhosis may differ from that in patients without cirrhosis. HCC may arise de novo in an otherwise normal liver, whereas a multistep sequence of carcinogenesis has been described in cirrhotic livers. This process includes a spectrum of disease progression from regenerating nodules to dysplastic nodules to early HCC (24). Because patients with cirrhosis have diffuse liver disease with multiple regenerating nodules, it is not surprising that HCC tends to be multifocal. Another explanation for the presence of multifocal tumors in patients with cirrhosis is metastatic spread through the hepatic and portal veins (20). It has been demonstrated (23) that venous invasion is substantially more common in patients with cirrhosis (41%) than in patients without underlying liver disease (15%) and thus potentially promotes hematogenous tumor spread throughout the hepatic parenchyma.
The size of a lesion is an important variable for both treatment planning and patient outcome. Lesions larger than 5 cm in diameter have been shown (11,25,26) to be associated with a poorer prognosis after hepatic resection. Those patients who are not surgical candidates, with small lesions, may benefit from percutaneous ethanol ablation (27).
Our results show that lesions in a noncirrhotic liver were significantly larger than those in a cirrhotic liver. These results are in accordance with computed tomographic (CT) and angiographic results evaluated by Yamashita et al (21), who demonstrated that HCC lesions in noncirrhotic livers tend to be larger than those in cirrhotic livers in both Asian and non-Asian populations. HCC in cirrhotic livers often manifests as relatively small lesions (25). A possible explanation for this finding may be that patients with cirrhosis undergo imaging more frequently, thus allowing for earlier lesion detection. Conversely, patients with an otherwise normal liver have a larger percentage of functional hepatic reserve, which results in a longer interval before presentation and thus more extensive tumor growth (2,25).
Encapsulated lesions are associated with a better prognosis than are unencapsulated lesions (10,26,28) after surgical resection. In patients who are not candidates for surgery, it has been suggested (29,30) that encapsulated lesions are more amenable to percutaneous ethanol ablation than are unencapsulated lesions, possibly because encapsulated lesions can retain the injected ethanol longer. The identification of a tumor capsule, therefore, not only is important in the differential diagnosis but also has therapeutic implications. In our study, there was no statistical difference between cirrhotic and noncirrhotic livers with regard to the presence of a capsule.
HCC in noncirrhotic livers more commonly had a scar visible on MR images than did HCC in cirrhotic livers (50% vs 6%, P < .05). In the noncirrhotic livers, the larger lesions were more likely to contain a scar than were the smaller lesions (P < .05). Although a central scar has been described in fibrolamellar HCC (12), focal nodular hyperplasia, hepatic adenomas, and large hemangiomata, we found, as did other investigators (25,31), that HCC also may contain a central scar.
The MR imaging technique was not standardized in this retrospective study. Not all of the MR imaging examinations were performed with gadolinium enhancement or with flow-sensitive gradient-recalled-echo sequences. Thus, we were not able to assess for the presence of hypervascularity, a mosaic pattern of enhancement, or an arteriovenous shunt, all of which are MR imaging findings that have been described (3–6) in HCC in patients with cirrhosis. In addition, because not all MR studies included fat-saturated or opposed-phase images, we could not further characterize intratumoral high signal intensity seen on T1-weighted images as being due to fat or hemorrhage. Because this was a retrospective study and detailed pathologic evaluation of the scars was not routinely available, we did not aim to further characterize the size, morphology, or signal intensity of the scars. It is likely the causes of the scars varied and included necrosis, edema, fibrosis, and hemorrhage.
Our criteria for the diagnosis of cirrhosis included regenerative nodules, linear high signal intensity on T2-weighted images (15), and surface nodularity (16,17). Because tumor extension into portal veins and the biliary tree may cause atrophy (32), segmental hypertrophy was not used as a criterion to assess for cirrhosis. In addition, the presence of portal hypertension was not evaluated, because tumor thrombus within the main portal vein or arteriovenous shunts within a tumor may cause portal hypertension in the absence of cirrhosis.
The presence or absence of cirrhosis determined on MR images was confirmed only in the 14 patients who underwent surgical resection. A specimen obtained by means of biopsy or fine-needle aspiration was not considered an adequate sample to assess for the presence of underlying cirrhosis, due to the possibility of sampling error. In the 14 patients who underwent surgical resection, MR images were accurate with regard to the presence (n = 1) or absence (n = 13) of cirrhosis. In this study, neither the sensitivity nor the specificity of MR images for the detection of cirrhosis were assessed. Some patients with no MR imaging evidence of cirrhosis may have had early cirrhosis that would have been diagnosed if surgical resection were performed. The radiologist, however, typically does not have the results of histopathologic examination of the background liver tissue at the time of the initial evaluation of a hepatic lesion. Thus, the radiologist's impression of the MR imaging appearance of the liver with regard to the presence of cirrhosis is clinically relevant when initially characterizing a focal hepatic lesion.
Of the 36 patients in our study group, 11 (31%) had MR imaging evidence of cirrhosis, whereas 25 (69%) did not. Although HCC is more common in patients with cirrhosis in both the United States and Asia, the relatively high percentage of patients without cirrhosis in our study probably reflects a bias in referrals to our institution. Of the 25 patients without MR imaging evidence of cirrhosis, 16 had underlying liver disease (12 with a history of hepatitis infection and four with a history of alcohol abuse). This finding supports the assumption that hepatitis and toxins may cause HCC in the absence of cirrhosis (2).
In patients with multiple lesions, biopsy was performed in only a single mass. Thus, we do not have pathologic proof for all of the lesions considered to represent HCC at MR imaging. It is possible, especially in patients with cirrhosis, that the additional lesions may actually have represented dysplastic nodules, which are considered (24) to be premalignant. In addition, it theoretically is possible that some of the patients without histopathologic proof of HCC had fibrolamellar HCC. Criteria used for HCC in the absence of histopathologic confirmation included a serum -fetoprotein level of greater than 500 µg/L and the presence of a focal hepatic mass. The serum -fetoprotein level is, however, elevated in less than 10% of cases of fibrolamellar HCC (12). In addition, fibrolamellar HCC usually is seen in the absence of cirrhosis (12). Four of the six patients with -fetoprotein levels greater than 500 µg/L had MR imaging evidence of cirrhosis. Although we cannot confirm the absence of fibrolamellar HCC in these patients, we consider this to be unlikely.
Patients with HCC in whom CT or ultrasonographic studies were obtained and considered to be adequate for treatment planning were not referred for MR imaging; our results might have been different if those patients had undergone MR imaging. The patients in this study were, however, selected for MR imaging on the basis of actual clinical practice. Also, we compared two patient groups (patients with cirrhosis and patients without cirrhosis) who were referred for the same imaging study because of clinical grounds. An additional bias is that our study group consisted of only those patients referred to a tertiary care center; these patients may represent particularly challenging or technically difficult cases to treat. Our study was designed not to assess the overall sensitivity or specificity of the MR imaging findings but rather to describe the differences and similarities of the MR imaging features in the two patient groups.
In conclusion, we found that differences exist between cirrhotic and noncirrhotic livers in terms of the MR imaging appearance of primary HCC. HCC in the cirrhotic liver commonly appears as multifocal small lesions, whereas HCC in the noncirrhotic liver is more typically a large, solitary mass with a stellate scar. Recognition of the MR imaging appearance of HCC is important in the differential diagnosis of a solitary mass in an otherwise normal-appearing liver and may provide valuable information for disease management.
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Footnotes |
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Abbreviation: HCC = hepatocellular carcinoma
Author contributions: Guarantors of integrity of entire study, C.B.W., D.M.P.; study concepts and design, C.B.W., L.H.S., D.M.P.; definition of intellectual content, C.B.W., L.H.S., Y.F., L.H.B., D.M.P.; literature research, C.B.W.; clinical studies, C.B.W., L.H.S., Y.F., L.H.B., D.M.P.; data acquisition, C.B.W., L.H.S., D.M.P.; data analysis, C.B.W.; statistical analysis, C.B.W., L.H.S.; manuscript preparation, C.B.W.; manuscript editing and review, C.B.W., L.H.S., Y.F., L.H.B., D.M.P.
Received January 9, 1998;
revision requested February 23, 1998; revision received May 27, 1998;
accepted August 4, 1998.
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References |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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