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Gastrointestinal Imaging |
1 From the Department of Diagnostic Imaging and Nuclear Medicine, School of Medicine, Kyoto University, Japan (T.K.); Departments of Radiology (J.G.F., C.D.J.) and Anatomic Pathology (K.N., L.J.B.), Mayo Clinic, 200 First St SW, Mayo East 2B, Rochester, MN 55905; and Department of Radiology, Scottsdale Medical Imaging, Ariz (M.S.K.). Received May 2, 2001; revision requested June 8; revision received and accepted September 7. Address correspondence to J.G.F. (e-mail: fletcher.joel@mayo.edu).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Findings from imaging examinations in 13 patients with pathologically confirmed primary hepatic angiosarcoma were retrospectively reviewed (computed tomographic [CT] images obtained in 10 patients and magnetic resonance [MR] images obtained in five patients were available for review). Two gastrointestinal radiologists evaluated lesion number, size, attenuation and signal intensity characteristics, and the pattern and degree of contrast material enhancement. Medical records were reviewed for clinical features associated with angiosarcoma.
RESULTS: Angiosarcoma appeared as multiple nodules (n = 6), as dominant masses (n = 6), or as a diffusely infiltrating lesion (n = 1). Multiple nodules were hypoattenuating at unenhanced and contrast material–enhanced CT (six of six patients). When dominant masses were encountered at MR imaging, T2-weighted MR imaging demonstrated heterogeneous internal architecture (four of four patients) similar to that of hepatocellular carcinoma. Multiphase contrast-enhanced CT and MR images showed dominant masses to have heterogeneous and progressive enhancement (three of three patients). Clinical features associated with angiosarcoma included splenic metastases (six of 13 patients), thrombocytopenia (seven of 13 patients), disseminated intravascular coagulation (four of 13 patients), and hemolytic anemia (three of 13 patients).
CONCLUSION: Primary hepatic angiosarcoma exhibits a spectrum of appearances that reflect its varied pathologic features.
© RSNA, 2002
Index terms: Liver neoplasms, 761.322 • Liver, nodules, 761.322 • Sarcoma, 761.322
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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Early reports of hepatic angiosarcoma focused on its association with environmental carcinogens, such as thorium dioxide (Thorotrast), arsenic, and vinyl chloride, but exposure to these agents is now rare. Most of these tumors occur either in the absence of known risk factors or with cirrhosis (2).
Various appearances of hepatic angiosarcoma on computed tomographic (CT) images have been described in case reports and in a few small series (5–11). On CT images, angiosarcoma has been known to simulate benign hemangioma or metastases (7,11). The appearance of this tumor at magnetic resonance (MR) imaging is described in only a few sporadic case reports in the English-language literature, so its MR features have not been clearly delineated (11–13). The purpose of our study was to evaluate and describe cross-sectional imaging findings in patients with pathologically confirmed primary hepatic angiosarcoma.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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All patients had biopsy-proven hepatic angiosarcoma (nine patients underwent CT-guided biopsy, two underwent surgical resection, and four underwent exploratory laparotomy). CT-guided biopsy was unsuccessful in two patients (requiring subsequent exploratory laparotomy), and substantial bleeding was not observed in the immediate postprocedure period in any of the patients who underwent percutaneous biopsy.
Unenhanced CT images were obtained in six patients, and contrast material–enhanced CT images were obtained in eight patients with the use of intravenous iodinated contrast material. Six patients received 140–150 mL of iopamidol (Isovue 300; Bracco Diagnostics, Princeton, NJ), and two patients received 150 mL of iothalamate meglumine (Conray 60; Mallinckrodt Medical, St Louis, Mo). Regarding the contrast-enhanced examinations, one patient underwent imaging in the arterial phase, seven underwent imaging in the portal venous phase, and two underwent delayed imaging. Section thickness ranged between 5 and 10 mm.
Transverse T1- and T2-weighted MR images were obtained in five patients. A conventional spin-echo technique was used to obtain T1-weighted images (repetition time msec/echo time msec, 250–660/14–20). Regarding T2-weighted images, a fast spin-echo technique (4,000–8,571/105–140) was used in two patients, and a conventional spin-echo technique (2,000–2,500/100–120) was used in three patients. Dynamic T1-weighted three-dimensional fast spoiled gradient-echo images were obtained in two patients after intravenous administration of 10 mL of gadopentetate dimeglumine (Magnevist; Berlex Laboratories, Wayne, NJ) or 16 mL of gadoteridol (ProHance; Bracco Diagnostics), respectively.
Two gastrointestinal radiologists (T.K., J.G.F., C.D.J.) examined lesion size (diameter in centimeters), number, and location, as well as characteristics such as hemorrhage, necrosis, and sites of metastasis, and formed a consensus interpretation. Tumor attenuation (for the entire tumor and for the foci of enhancement within the tumor) was visually graded as greater than, less than, or equal to the attenuation of the surrounding hepatic parenchyma and the aorta. Enhancement patterns within tumors were characterized as focal regions of enhancement, irregularly shaped regions of enhancement, or rim enhancement. On MR images, the signal intensity characteristics of the lesion were compared with those of the surrounding liver parenchyma and the muscles, and the pattern of enhancement was also characterized, as described above. Pathologic findings in surgical specimens were compared with imaging findings (T.K., K.N., L.J.B.). Point-to-point comparison was not possible, however, since only two patients underwent complete surgical resection.
Clinical records of patients were reviewed (T.K., J.G.F.) regarding clinical presentation, preexisting diseases, abnormal findings of laboratory tests, and history of exposure to environmental carcinogens. Clinical histories were reviewed for history of exposure to Thorotrast, vinyl chloride, anabolic steroids, or arsenic, and for history of hemochromatosis, chronic hematoma, or pyothorax. The following values were obtained from laboratory tests and recorded at diagnosis of angiosarcoma (n = 12) or at presentation to our institution (n = 1), when applicable: hemoglobin (n = 13), hematocrit (n = 11), platelets (n = 13), D-dimer (n = 4), and fibrinogen (n = 4).
Clinical records of patients were also reviewed for sites of metastasis. All 13 patients underwent either chest CT (n = 9) or chest radiography (n = 13) to document pulmonary metastases. Splenic metastases were assessed either with surgical specimens (n = 2) or with CT or MR imaging of the abdomen (n = 11), as previously described. Bone metastases were noted when present on any image (CT, MR, or plain radiographic). All patients underwent MR imaging or CT of the abdomen, nine underwent CT of the chest, seven underwent CT of the pelvis, and one underwent a radiographic, metastatic bone survey.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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Imaging Findings
The number and size of hepatic tumors were based on CT and MR imaging findings. Six patients had multiple small nodules, usually measuring less than 3 cm in diameter, scattered within both lobes of the liver. Five patients had a large dominant mass measuring 8–14 cm (three in the right lobe, one in the left lobe, and one in both lobes). Four of these five patients had other intrahepatic lesions that measured less than 3 cm. One patient had two large focal lesions (one in each lobe) measuring 7–9 cm, and one patient had a diffusely infiltrating tumor throughout the liver.
Seven patients (54%) had metastatic lesions. Six (46%) had splenic metastases, while three (23%) had lung metastases. Three (23%) also had bone metastases, but only eight patients underwent either a metastatic bone survey or CT of the entire chest, abdomen, and pelvis. On unenhanced CT images, all lesions were hypoattenuating compared with normal liver parenchyma. The lesions had attenuation similar to that of the aorta, but they exhibited a heterogeneous appearance because of the presence of focal areas of hyperattenuation. In two patients with a history of Thorotrast exposure, multiple lesions displaced the linear network of residual Thorotrast, and the spleen was atrophic and hyperattenuating due to prior Thorotrast exposure.
Contrast-enhanced CT images (n = 8) showed multiple tumor nodules in five patients. In these patients, tumor nodules were hypoattenuating. In three patients, most lesions contained focal areas of enhancement (Fig 1a). The attenuation of many foci of enhancement was less than that of the aorta but greater than that of the hepatic parenchyma. A few foci of enhancement were isointense with the aorta. Some areas of enhancement had irregular shapes, and others were ring shaped. Focal regions of enhancement were located predominantly in the central portion of each lesion, with a few located peripherally. Two of these three patients had innumerable nodular masses.
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Pathologic Findings
All tumors were characterized microscopically by spindle-shaped cells, which demonstrated vascular formation in various patterns. In specimens of substantial size, necrosis was present in 10 of 12 (83%) specimens, and hemorrhage was present in nine of 11 (82%) specimens (one was too small to evaluate). The presence of necrosis and hemorrhage in the examined samples correlated with high T1-weighted signal intensity at MR imaging in four of five tumors. Heterogeneous attenuation on unenhanced CT scans correlated with the presence of necrosis in four of six patients and hemorrhage in three of five patients. Cavernous spaces lined with neoplastic cells were present in six of eight (75%) cases with sufficiently large sample volume. For example, one patient with hemochromatosis and a dominant mass with satellite tumors at imaging had a tumor that contained numerous, blood-filled cystic spaces (Fig 3). In another patient with a multifocal tumor, images showed abundant cavernous spaces lined with tumor cells (Fig 1). These cavernous vascular spaces simulated those seen with cavernous hemangioma; interestingly, these tumors demonstrated focal enhancement at contrast-enhanced CT (Fig 1). Another lesion, which arose at the site of a chronic hematoma, was predominantly solid and demonstrated neoplastic cells (forming freely anastomosing vascular channels with few dilated vascular spaces), central fibrosis, and hyalinization (Fig 2).
Some tumors did have unique features. MR images of one patient showed little heterogeneity of signal intensity in the liver. This patient had undergone splenectomy and wedge resection in the lateral segment 10 months prior to the imaging study. At the time of resection, the surgeon noted that the liver "contained a diffuse process, appearing vascular in nature, characterized by small, less-than-1-cm, reddish-purple spots." At histologic analysis, the spleen and entire wedge resection were diffusely involved with angiosarcoma, with hyperchromatic tumor cells diffusely spreading along the portal tracts and sinusoidal spaces without forming macronodular lesions (Fig 5).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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Angiosarcoma has received attention in recent decades because of its frequent association with several environmental carcinogens, such as Thorotrast, vinyl chloride, and arsenic compounds (5,6). Both hemochromatosis and anabolic steroids have been associated with angiosarcoma (14,15), as seen in one patient with aplastic anemia in our series. Chronic inflammation has also been implicated as a potential cause of the development of pleural angiosarcoma in patients with pyothorax (16). In one of our patients, angiosarcoma originated in or adjacent to a chronic organized hematoma. However, in most patients with primary hepatic angiosarcoma, cause is not apparent (2,3).
Patients usually present with nonspecific symptoms, including abdominal pain, weakness, fatigue, anorexia, and weight loss. Hematologic abnormalities, including microangiopathic hemolytic anemia and thrombocytopenia, are frequently associated (3). Most patients in our series were anemic (62%) and thrombocytopenic (54%), with microangiopathic hemolytic anemia in 23%. Erythrocytes are thought to be traumatized in the poorly organized neoplastic vessels, and platelets may be trapped. Occasionally, this localized coagulopathy results in the development of systemic disseminated intravascular coagulation, which was seen in 31% of our patients.
Most patients have metastatic lesions at the time of presentation. The most common site of metastases is the lung, followed by the spleen (3). In our series, 23% of patients had pulmonary metastases, but 46% had splenic metastases. The high frequency of splenic metastases is notable, but in some instances it is difficult to determine whether the liver or the spleen is the site of the primary neoplasm. It may be speculated that splenic lesions represent simultaneous occurrence, which may be related to known or unknown environmental carcinogens.
Diagnosis by means of liver biopsy has been reported as treacherous and nondiagnostic (17). Our experience differs in that seven of nine (78%) percutaneous biopsies in our series yielded diagnostic specimens without substantial bleeding. Nevertheless, recent reports of lethal complications following image-guided percutaneous biopsy remain (17). Therefore, surgical backup may be prudent if percutaneous biopsy is attempted.
The gross appearance of angiosarcoma at pathologic evaluation is characterized by the presence of remarkable necrosis and hemorrhage and can show four types of growth patterns: multiple nodules, a large dominant mass, mixed patterns of a dominant mass with nodules, and, rarely, a diffusely infiltrating micronodular tumor (18,19). Angiosarcoma is characterized microscopically by spindle-shaped cells that form vascular channels. These channels show a wide spectrum of patterns, ranging from excessively dilated sinusoidal or cavernous spaces that simulate cavernous hemangioma to slitlike, freely anastomosing vascular channels (2,18,19). These various vascular patterns are usually intermingled with each other, with the predominant pattern differing in each patient. Fibrosis and deposition of hemosiderin are frequently encountered in solid portions of the tumor (18,19).
There have been several reports on CT findings of angiosarcoma. In the case of Thorotrast exposure, which is well documented, tumors are hypoattenuating on unenhanced CT scans and are inferred by the displacement of the hyperattenuating linear network of residual Thorotrast (4–6). Even in patients without Thorotrast exposure, unenhanced CT images demonstrate the tumor to be predominantly hypoattenuating compared with the surrounding hepatic parenchyma. On contrast-enhanced images, most lesions are hypoattenuating compared with normal liver tissue, but some lesions can be hyperattenuating (8). While White et al have reported progressive centripetal enhancement similar to that of cavernous hemangioma (10), recent reports have demonstrated that angiosarcoma does not resemble benign cavernous hemangioma at biphasic imaging (8,9,12). Peterson et al found only one tumor nodule in six patients that had the typical nodular enhancement of a hemangioma (8). We observed focal areas of enhancement in three of five (60%) patients with multiple tumor nodules. These lesions were different from multiple cavernous hemangiomas for several reasons: Focal areas of enhancement showed less attenuation than the aorta, with bizarre shapes, central enhancement, or peripheral ring-shaped enhancement. Innumerable hepatic lesions indicated that a malignancy was present. Unlike the patient group of Peterson et al, three patients in our series had large dominant masses. None of these patients demonstrated foci of enhancement similar to those of hemangioma.
Although there have been several reports on the CT appearances of angiosarcoma, little has been discussed on the MR imaging features of angiosarcoma and the role of MR imaging in preoperative diagnosis. We found that MR imaging demonstrated the hemorrhagic, heterogeneous, and hypervascular nature of all the dominant masses in our series.
On T1-weighted MR images, all four dominant mass lesions contained irregular areas of high signal intensity, suggesting hemorrhage. The high frequency of hemorrhage in the lesions demonstrated on T1-weighted images is in good accordance with gross pathologic features. The presence of fluid-fluid levels on T2-weighted images is another finding that reflects the hemorrhagic nature of angiosarcoma, but this finding is also often seen with hypervascular metastases.
All four dominant mass lesions that underwent T2-weighted MR imaging also showed a markedly heterogeneous architecture, with focal areas of high intensity along with septumlike or rounded areas of low intensity on T2-weighted images. This appearance suggests compartmentalization within the tumor, and it is similar to that observed with hepatocellular carcinoma. Areas of low signal intensity on T2-weighted images may reflect hemosiderin, fibrous solid portions, or fresh hemorrhage, on occasion, while areas of high intensity may represent hemorrhage or necrosis. Unlike results in earlier case reports, no tumors in our series showed a central area of low intensity or a few internal septa that could have been confused with hemangioma (11,20,21).
On dynamic contrast-enhanced MR images, each lesion showed heterogeneous enhancement on the arterial- and portal-phase images. At delayed imaging, however, there was progressive enhancement of the lesion compared with that of early-phase images. The heterogeneous enhancement pattern on contrast-enhanced images was similar to that observed with CT and likely represents the heterogeneity of microscopic vascular patterns within each tumor. The areas with abundant, freely anastomosing vascular channels may enhance quickly, while dilated cavernous vascular spaces may show slowly progressive enhancement.
In one patient with diffuse signal heterogeneity throughout the liver on T1-weighted MR images, pathologic findings were surprising, as tumor cells diffusely infiltrated the liver parenchyma along the portal tracts. This micronodular pattern is an unusual feature of angiosarcoma (18).
Since angiosarcoma commonly appears as multiple masses or as a heterogeneous dominant mass, it often cannot be readily distinguished from hypervascular metastases (such as neuroendocrine tumors) and hepatocellular carcinoma. All of these tumors may demonstrate internal hemorrhage and heterogeneity, in addition to early and heterogeneous enhancement (22,23). In contrast to hepatocellular carcinoma, however, angiosarcoma demonstrates continuing, progressive enhancement on delayed-phase images. Splenic metastases and lack of cirrhosis may also suggest angiosarcoma instead of hepatocellular carcinoma.
Clinical findings may also help to distinguish angiosarcoma from other hypervascular lesions. Hepatocellular carcinoma is usually associated with chronic hepatitis or liver cirrhosis caused by chronic virus infections, and it may be associated with elevated 
-fetoprotein levels. Hematologic abnormalities, including thrombocytopenia, disseminated intravascular coagulation, and hemolytic anemia, are more frequently associated with angiosarcoma.
Our study had several weaknesses—predominantly, small sample size and lack of consistent imaging parameters, due to the rarity of the tumor and the length of time in which cases were collected. Not all patients received intravenous contrast material or underwent dynamic imaging. Only two patients underwent complete surgical resection, which prohibited point-to-point radiologic-pathologic correlation. Nevertheless, we believe that some important and consistent patterns emerged.
Angiosarcoma has various appearances at CT or MR imaging that reflect its varied histologic composition. When an angiosarcoma appears as a massive lesion, MR images can demonstrate its hemorrhagic and heterogeneous appearance. Dynamic enhancement of a dominant mass at CT or MR imaging may show heterogeneous enhancement on the early-phase images and progressive enhancement on delayed images. T2-weighted MR images demonstrate a corresponding heterogeneous or compartmentalized appearance of the dominant mass. When angiosarcoma appears as multiple nodular lesions at CT, most lesions are hypoattenuating, and foci of enhancement may be present, but they are clearly distinguishable from the nodular enhancement in benign hemangiomas. Such nodular enhancement may be less than that of the aorta. It is often bizarre in shape, with ring enhancement seen in some nodules. Splenic metastases are also common with angiosarcoma. In a patient with a hypervascular and hemorrhagic dominant mass or multiple liver lesions, characteristic hematologic abnormalities may suggest a diagnosis of primary hepatic angiosarcoma.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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This article has been cited by other articles:
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  T. Maeda, U. Tateishi, T. Hasegawa, H. Ojima, Y. Arai, and K. Sugimura Primary Hepatic Angiosarcoma on Coregistered FDG PET and CT Images Am. J. Roentgenol., June 1, 2007; 188(6): 1615 - 1617. [Full Text] [PDF]
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 W. T. Yang, B. T. J. Hennessy, M. J. Dryden, V. Valero, K. K. Hunt, and S. Krishnamurthy Mammary Angiosarcomas: Imaging Findings in 24 Patients Radiology, March 1, 2007; 242(3): 725 - 734. [Abstract] [Full Text] [PDF]
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K. A. Kim, K. W. Kim, S. H. Park, S. J. Jang, M.-S. Park, P. N. Kim, M.-G. Lee, and H. K. Ha Unusual mesenchymal liver tumors in adults: radiologic-pathologic correlation. Am. J. Roentgenol., November 1, 2006; 187(5): W481 - W489. [Abstract] [Full Text] [PDF]
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