Japanese Journal of Clinical Oncology 30:440-445 (2000)
© 2000 Foundation for Promotion of Cancer Research
Highly Enhanced Hepatic Masses Seen on CT During Arterial Portography: Early Hepatocellular Carcinoma and Adenomatous Hyperplasia
1Diagnostic Radiology Division, National Cancer Center Hospital East, Kashiwa, Chiba, 2Department of Radiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, 3Pathology Division, National Cancer Center Hospital Research Institute, Kashiwa, Chiba and 4Diagnostic Radiology Division, National Cancer Center Hospital, Tokyo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
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Background: To describe computed tomographic (CT) features of highly enhanced hepatic masses as seen on CT during arterial portography (CTAP) and to survey the varieties of hepatic lesions associated with such findings.
Methods: CTAP files for 400 patients were reviewed, on the basis of which six patients with highly enhanced hepatic masses were selected. These six patients also subsequently underwent CT during hepatic arteriography (CTHA) on the same day. All the patients had chronic liver damage, which was cirrhotic in five cases. Five had a current diagnosis and one had a history of hepatocellular carcinoma (HCC).
Results: Solitary highly enhanced masses were observed on CTAP in three patients, three masses were seen in one patient and multiple (10–12) masses in the other two patients. All the CTAP-enhanced masses except one were round in shape and homogeneous in attenuation. The size of the mass ranged from 6 to 25 mm in diameter. In all except two nodules in one patient, the masses were hypoattenuated on CTHA. On histopathological examination of five nodules in three patients, the nodular lesions were consistent with so-called early HCC (well-differentiated HCC of Edmondson I) in four nodules and adenomatous hyperplasia in the other nodule.
Conclusions: Highly enhanced hepatic masses relative to the surrounding liver parenchyma have been sporadically noted on CTAP, especially in patients with liver cirrhosis. When present, such nodules are typically hypoattenuated on CTHA and histological features are consistent with early HCC and adenomatous hyperplasia.
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INTRODUCTION |
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Except for well-differentiated hepatocellular carcinoma (HCC), the blood supply for hepatic tumors is almost always provided entirely systemically via the hepatic arteries. For this reason, computed tomography (CT) during arterial portography (CTAP) is one of the most sensitive methods for detecting hepatic tumors of any vascularity (1,2). Early HCC and precancerous hepatocellular nodules in cirrhotic liver receive a variable amount of portal blood flow in addition to hepatic arterial blood flow. Thus, on CTAP, such lesions may appear to be isoattenuated or hypoattenuated to varying degrees.
Positive application of CTAP and CT during hepatic arteriography (CTHA) in patients with liver cirrhosis increases the detection of dysplastic nodules (3), regenerating nodules, as well as small lesions consistent with overt HCC. Based on a retrospective study of the CTAP files of 400 patients, we found that highly enhanced masses might also be present on CTAP, a finding which has not been reported in the English radiological literature. The purpose of this paper is to describe the CT features of highly enhanced hepatic masses as seen on CTAP and to describe the varieties of hepatic lesions associated with such findings.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
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CTAP files for 400 patients with or suspected of having HCCs at two institutions obtained over a 3-year period were reviewed to identify cases of highly enhanced hepatic masses. At one institution a unified helical CT and angiography unit (IVR-CT/Angiography System, Toshiba Medical System, Tokyo) was used to perform CTAP in 290 patients. All of these patients also underwent CTHA through the proper hepatic artery and/or one of its branches following CTAP during the same examination. At the other institution, a conventional CT unit (CT/T 9800 Advantage, General Electric, Milwaukee, WI) was used to perform CTAP in 110 patients, about a quarter of whom also underwent CTHA on the same day. All the patients had chronic hepatitis or liver cirrhosis, mostly induced by the hepatitis C virus.
For the CTAP examination, a catheter was introduced into the superior mesenteric artery beyond the pancreatic arcade so as to avoid injection of contrast agent into the arterial supply to the liver. Identification of the catheter tip position was done by introducing as small an amount of contrast agent as possible. For IVR-CT, 105 ml of contrast agent (60 mg of iodine/ml diluted with physiological saline) were injected at a rate of 3.5 ml/s and scanning was started 20 s after the initiation of injection. For the conventional CT unit, 150 ml of contrast agent (100 mg of iodine/ml) were injected at a rate of 3 ml/s and scanning was likewise performed 20 s after the initiation of injection. At both institutions, nicardipine (5 mg) or papaverine (40 mg) was injected through the catheter as a vasodilator within 1 min prior to the injection of contrast agent in order to increase portal blood flow. CTAP was always performed prior to any other angiographic studies, including CTHA, which was performed via the proper hepatic artery at an injection rate of 2–2.5 ml/s (60 mg of iodine/ml) for IVR-CT and at 2 ml/s (100 mg of iodine/ml) for conventional CT. The dose and injection rate of contrast agent were reduced when CTHA was performed through a more distal hepatic artery. A highly enhanced hepatic mass as seen on CTAP was defined as a spherical or approximately spherical hyperattenuated mass that showed higher attenuation relative to that of any portion of the liver parenchyma. Wedged or irregularly shaped hyperattenuated masses were not included.
Out of the 400 patients, six had at least one highly enhanced hepatic mass seen on CTAP; all of these were male with ages ranging from 38 to 75 years (mean 60 years). All six patients had chronic liver damage, one with chronic hepatitis and five with liver cirrhosis, induced by the hepatitis C virus. Each of these underwent CTHA on the same day. Five of the six patients were suspected to have primary liver cancer and one had a history of treatment for HCC. Surgical resection was performed in one patient with three enhanced nodules. Biopsies were performed on three nodules in three patients.
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RESULTS |
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The pathologically correlated nodular lesions from the six patients are summarized in Table 1. The number of enhanced masses was one in three patients (Fig. 1), three in one patient (Fig. 2) and multiple in two patients (10 in one and 12 in the other; Fig. 3). The masses ranged from 6 to 25 mm in diameter. All hepatic nodules showed homogeneous high enhancement on CTAP except for one that was partly isoattenuated. Most nodules were unenhanced or markedly and homogeneously hypoattenuated on CTHA. Two lesions, however, showed heterogeneous enhancement on CTHA: one was a heterogeneously enhanced mass with slight hypoattenuation (Fig. 1b) and the other a markedly hypoattenuated mass with an area of slight enhancement at the center.
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The size and shape of the 10 multiple masses in one patient were almost the same on CTAP and CTHA, although two of these lesions demonstrated slightly differing cross-sectional areas between CTAP and CTHA (Fig. 3a and 3b) and another had ill-defined margins and an irregular shape as seen on CTHA, whereas the same lesion appeared well-defined and spherical on CTAP.
Histopathological examination was consistent with so-called early HCC (well-differentiated HCC of Edmondson I; Fig. 2a and 2d) in four nodules from three patients. Three samples were obtained by resection in one patient and single samples were obtained by needle biopsy in the other two. Adenomatous hyperplasia was observed in one of the three nodules obtained by resection (Fig. 2b and 2e). Instead of tumor cells, non-tumorous hepatic parenchyma was identified in one patient from whom the sample was obtained by needle biopsy (presumably due to a technical problem).
The incidence of enhanced masses on CTAP was 1.4% (4/290) at the institution using a unified helical CT and angiography unit and 1.8% (2/110) at the institution using a conventional CT unit.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
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CTAP was developed by Matsui (1) and is regarded as one of the best imaging modalities for detecting liver tumors, especially hypovascular tumors. With advances in pathological studies, multi-step carcinogenesis in cirrhotic liver induced by hepatitis virus leading to hepatocellular carcinoma has been identified as a pathological process in addition to the de novo process. The progression of multi-step carcinogenesis has been described (2,4) as follows: from a large regenerating nodule to adenomatous hyperplasia (adenomatous hyperplastic nodule) to early HCC (well-differentiated HCC) to early advanced HCC (overt HCC focus within a region of early HCC), finally leading to overt HCC (moderately or poorly differentiated HCC).
From the viewpoint of imaging, the evaluation of both portal and arterial blood flows is an essential point for differentiating nodular hepatocellular lesions from other types. Portal flow and arterial flow to a mass can be separately assessed using CTAP and CTHA (1,2,5). While the early phase of intravenous dynamic CT can be used as a substitute for CTHA, this technique is of lower sensitivity. Over the course of multi-step carcinogenesis, portal blood flow gradually diminishes and finally disappears entirely by the stage of overt HCC. Although the arterial blood supply likewise diminishes over the progression to varying degrees, it eventually increases sharply during the stage of well-differentiated HCC. Thus, whereas a small, well-differentiated HCC lesion may be hypovascular or hypervascular as seen on angiography, when arterial hypovascularity is present, portal blood flow is often evident to varying degrees as seen on CTAP (5,6).
In striking contrast to the high frequency of highly enhanced hepatocellular nodules seen on CTHA, highly enhanced masses seen on CTAP have not been reported in the English language literature (7,8). Generally, the finding of a hyperattenuated hepatocellular nodule on CTAP can be related to one or both of two factors: (a) the nodule receives increased portal blood flow relative to the hepatic parenchyma as a whole (absolute increase in blood flow to the nodule) and (b) the surrounding parenchyma adjacent to the nodule receives decreased portal blood flow relative to the nodule and other regions of parenchyma (relative increase in blood flow to the nodule).
In the case of advanced liver cirrhosis with widening of the portal tract area, large regenerating nodules show stronger enhancement as they receive increased portal flow relative to the portal tract area which consists of widened loose connective tissue and a narrowed portal vein. Any mass lesion receiving portal blood flow, such as a regenerating nodule or dysplastic nodule, appears as a hyperattenuated lesion on CTAP owing to this mechanism. Large regenerating nodules situated in post-necrotic liver scar tissue or in the liver in fulminant hepatic failure may likewise show this phenomenon due to decreased portal flow to the affected or collapsed surrounding parenchyma (8,9). On the other hand, some nodules appear hyperattenuated on CTAP even though the liver parenchyma shows ordinary homogeneous enhancement and lacks prominent, hypoattenuated portal tract areas or confluent fibrosis (9,10), as in the case of the subjects in the present study.
Most subjects who had undergone CTAP in the current series were patients at high risk for HCC and had chronic liver disease, most often cirrhosis of the liver. At another institution, where chemoinfusion therapy was performed for metastatic liver tumors (unpublished data), a CTAP review of 100 non-cirrhotic patients with known primary malignant tumors other than primary liver tumors (mostly colorectal cancer) failed to demonstrate any case with enhanced masses.
There are only a few case reports of highly enhanced masses as seen in CTAP studies (7,11). Matsui’s group reported such a case with a highly enhanced adenomatous hyperplastic nodule. Histopathologically, enlarged portal veins were noted within the nodule (11). They also reported another unusual case with multiple cavernous hemangiomas that mainly received portal flow and appeared as highly enhanced nodules on CTAP (7). The endothelium-lined vascular spaces within these nodules were markedly larger than those seen in conventional cavernous hemangiomas.
Regarding the differential diagnosis of highly enhanced masses seen on CTAP, a portal aneurysm with or without a porto-hepatic venous shunt can mimic such findings, although color Doppler ultrasound and highly enhanced helical CT (especially late enhanced CT) are useful for identifying such vascular abnormalities (12). Mass lesions showing delayed and prolonged enhancement (13), such as cholangiocellular carcinoma, metastatic liver cancer, especially of adenocarcinoma, sclerosing HCC, epithelioid hemangioendothelioma and any mass lesion associated with prominent fibrosis, including liver scar tissue, may appear as hyperattenuated on CTAP when the examination is performed after the administration of large amounts of the contrast agent (angiographic examinations and/or CTHA). To avoid this phenomenon, CTAP is performed as the first in a series of CT–angiographic examinations at most institutions. Even so, peripheral areas of a mass do not exhibit delayed enhancement in most cases of malignant tumors, and this is a useful differentiating factor for CTAP-enhanced early HCC and adenomatous hyperplasia.
In conclusion, highly enhanced hepatic masses relative to the surrounding liver parenchyma have been sporadically noted on CTAP, especially in patients with liver cirrhosis. Such nodules have often been found to be early HCC and adenomatous hyperplasia on histopathological examination in our experience and should be carefully followed up as potentially malignant lesions.
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Acknowledgments |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
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This work was supported in part by the 2nd Term Comprehensive 10-year Strategy for Cancer Control and a Grant-in-Aid for Cancer Research (10–16) from the Ministry of Health and Welfare, Japan.
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FOOTNOTES |
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+ For reprints and all correspondence: Hiroaki Onaya, Diagnostic Radiology Division, National Cancer Center Hospital East, 5–1 Kashiwanoha 6-chome, Kashiwa, Chiba 277–8577, Japan. E-mail: honaya@east.ncc.go.jp
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REFERENCES |
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Received March 21, 2000; accepted July 31, 2000.
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