Clinical Radiology (2009) 64, 779e785
Primary hepatic angiosarcoma: imaging findings and palliative treatment with transcatheter arterial chemoembolization or embolization Y.S. Park, J.H. Kim*, K.W. Kim, I.S. Lee, H.-K. Yoon, G.-Y. Ko, K.-B. Sung Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea Received 12 November 2008; received in revised form 11 February 2009; accepted 16 February 2009
AIM: To describe the image findings and results of transcatheter arterial chemoembolization (TACE) or transcatheter arterial embolization (TAE) for treating primary hepatic angiosarcoma. MATERIALS AND METHODS: A retrospective review of the electronic medical database from 2002 to 2007, revealed six patients with primary hepatic angiosarcoma confirmed by percutaneous liver biopsy. The computed tomography (CT) and angiography imaging findings, the TACE or TAE results, and the post-procedure course were evaluated in all patients. RESULTS: On CT and angiography, each tumour appeared as a solitary mass or as multiple nodules or masses with heterogeneously early and progressive enhancement. One of the two patients with tumour response to TACE died 8 months after initial presentation, and the remaining patient was still alive at the last follow-up 12 months after initial presentation. However, two patients with no response to TACE and two patients who underwent emergent TAE for tumour rupture died 1 week to 5 months (mean 2.1 months) after initial presentation. CONCLUSIONS: Primary hepatic angiosarcoma appears as a solitary or multiple, hypervascular lesions with heterogeneously early and progressive enhancement on CT and angiography. Although TAE may be the primary procedure for achieving emergent bleeding control caused by the rupture of hepatic angiosarcomas, TACE may be effective for treating patients with a dominant hepatic angiosarcoma with or without intrahepatic metastases. ª 2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Although primary hepatic angiosarcoma is rare and accounts for 2% of primary hepatic tumours, it is the most common malignant mesenchymal tumour of the liver.1e4 It is usually seen in older male patients.2,5 Because it occurs so rarely, its natural history, prognostic factors, and optimal management are still poorly understood.3 Various appearances of primary hepatic angiosarcoma on computed tomographic (CT) and magnetic resonance imaging (MRI), have been indicated * Guarantor and correspondent: J. H. Kim, Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap-2dong, Songpa-gu, Seoul 138-736, Republic of Korea. Tel.: þ82 2 3010 4384; fax: þ82 2 476 0090. E-mail address:
[email protected] (J.H. Kim).
in case reports and in a few small series1e6; however, few studies have described the angiographic findings of primary hepatic angiosarcoma.1 Transcatheter arterial chemoembolization (TACE) is indicated in patients with unresectable hepatocellular carcinoma of intermediate stage and without extrahepatic spread, and has been proven to increase the survival rates in these patients.7e10 In cases of hepatic tumour rupture with haemoperitoneum, transcatheter arterial embolization (TAE) has been the primary procedure used to control bleeding.11 TACE has recently shown promising results for the palliative treatment of patients with hepatic metastasis from neuroendocrine neoplasm, colorectal cancer, ocular melanoma, or cholangiocarcinoma.12e15 However, to the authors’ knowledge, there have been no studies reporting the efficacy of TACE for treating
0009-9260/$ - see front matter ª 2009 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2009.02.019
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primary hepatic angiosarcoma. Because hepatic angiosarcoma is a hypervascular tumour, TACE can be hypothesized to be an effective palliative treatment. The purpose of the present study was to describe the CT and angiographic findings and the results of TACE or TAE treatment for primary hepatic angiosarcoma.
was infused into the feeding arteries until arterial flow stasis was achieved or iodized oil appeared in the portal branches. Embolization of the feeding arteries was then performed using 1-mm diameter absorbable gelatin sponge particles (Gelfoam; Upjohn, Kalamazoo, MI, USA). The technique of TAE was identical to that of TACE except for the infusion of cisplatin. Four of the six patients underwent TACE once, and the remaining two patients underwent emergent TAE one and three times, respectively, for bleeding control. CT images, including unenhanced, arterial, and portal venous phases, were obtained ca. 0e20 days before the procedures in all patients. Follow-up CT was obtained in five patients 1 month after the procedures. The CT and angiography imaging findings, results of TACE or TAE, and the post-procedure course were evaluated in all patients.
Materials and methods The study protocol was approved by the institutional review board, and informed consent was obtained for the intervention (TACE or TAE). Retrospective review of the electronic medical database from August 2002 to March 2007, revealed six patients with primary hepatic angiosarcoma confirmed by percutaneous liver biopsy. The patient characteristics are summarized in Table 1. Alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9 levels were within normal ranges in all patients. The hepatic angiosarcoma was unresectable in all six patients due to extrahepatic tumour spread (n ¼ 3), diffuse and multiple tumours making the patient an unsuitable candidate for complete tumour removal (n ¼ 2), and impaired liver function precluding the planned hepatic resection (n ¼ 1). Therefore, palliative treatment was indicated in all of these patients. The TACE technique was as follows: superior mesenteric and coeliac arteriography was initially performed in order to assess the anatomy, tumour burden, vascularity, and portal vein patency. Cisplatin was then infused into the hepatic artery for 15 min without embolic particle administration. The infused dose of cisplatin was 2 mg/kg of the patient’s weight. After selective catheterization of the feeding artery using a microcatheter, an emulsion of iodized oil (Lipiodol, Laboratoire Guerbet, Roissy CdG CEDEX, France) and cisplatin
Table 1
Results CT and angiographic findings The number and size of the hepatic tumours were based on the CT imaging findings. Three patients had multiple small nodules or masses measuring ca. 1e5 cm in diameter, and these nodules or masses were scattered within both lobes of the liver (Table 1). One patient had a large, dominant mass measuring 17 cm with multiple intrahepatic lesions measuring less than 3 cm. Two patients each had one large, dominant mass measuring 6 and 10 cm, respectively, with or without several intrahepatic lesions. Tumour rupture with haemoperitoneum occurred in three patients (50%). Splenic metastasis occurred in one patient (patient 6; 17%). On the unenhanced CT images, all lesions were hypoattenuating compared with normal liver
Characteristics of patient population
Patient no./age (y)/sex
Clinical symptoms
1/76/F
4/55/M 5/64/M
Fever, chill, None No abdominal pain Abdominal distension Alcoholic LC No Abdominal pain, None Yes palpable mass, haematuria, anaemia Incidentally detected mass Alcoholic LC No Sudden onset abd.pain None Yes
6/45/M
Sudden onset abd.pain
2/80/M 3/29/M
Underlying disease
None
Tumour rupture
Yes
Tumour characteristics
Palliative treatment
Survival period (months)
DM with 3 IHN
TACE
8
Inumerable IHN Inumerable IHN and IHM
TACE TAE
5 0.25
DM TACE DM with TACE Inumerable IHN Inumerable IHN TAE and IHM
12 2 1.3
LC, liver cirrhosis; DM, dominant mass; IHL, intrahepatic lesion; IHN, intrahepatic nodule; IHM, intrahepatic mass.
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parenchyma (Figs. 1a, 2a, 3a). In three patients (50%), hyperattenuating foci (caused by fresh internal haemorrhage) were mixed with the hypoattenuating lesions (Fig. 2a). On contrast-enhanced CT, most of the nodular lesions were hypoattenuating with enhanced foci (Fig. 1b). Enhancement in most nodular lesions was less than that of the aorta; however, some nodular lesions were isoattenuating with the aorta. Some nodular lesions showed irregular or ring enhancement. Foci of enhancement were predominantly located in the central portion of lesions, although a few were located peripherally. Large, dominant, mass lesions showed heterogeneous enhancement (hypoattenuating and enhancing foci), suggesting central necrosis and fibrotic change (Figs. 2bec, 3bec). In all six cases, the lesions showed more
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progressive enhancement on delayed images compared with early-phase images. Regarding the angiographic findings, multiple nodular or mass lesions (Fig. 1ced) presented with multiple areas of fluffy staining and early pooling of contrast medium that increased and persisted over time. Large, dominant, mass lesions (Figs. 2dee, 3dee) showed ill-defined, irregular tumour blush containing an unstained area. The large dominant masses also showed early contrast medium pooling that increased and persisted over time.
TACE or TAE Among the four patients who underwent TACE, the size of the dominant, large mass decreased from 10 to 6 cm (Fig. 2f), and from 6 to 4 cm (Fig. 3f),
Figure 1 A 45-year-old man (patient 6) with angiosarcoma who presented with sudden onset abdominal pain. (a) Unenhanced CT image after TAE shows multiple nodules and masses both with and without lipiodol uptake; they are predominantly hypoattenuating compared with the surrounding hepatic parenchyma. (b) On contrastenhanced CT during the portal venous phase, most lesions are hypoattenuating and foci of enhancement (arrows and arrowheads) are present. (ced) Common hepatic angiography during the early (c) and late phase (d), shows multiple areas of fluffy staining and early pooling of contrast medium that increased and persisted over time.
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Figure 2 A 76-year-old woman (patient 1) with angiosarcoma presented with fever, chills, and abdominal pain. (a) Unenhanced CT image before TACE shows a large, dominant mass in the left lobe of the liver; it is predominantly hypoattenuating compared with the surrounding hepatic parenchyma. (bec) Contrast-enhanced CT images taken during the arterial (b) and portal venous (c) phases, show heterogeneous, delayed, progressive enhancement (arrows and arrowheads). (dee) Common hepatic angiography during the early (d) and late (e) phases, shows an ill-defined, irregular, tumour-blush-containing area with no staining and with delayed progressive enhancement (arrowheads). (f) Contrast-enhanced CT image obtained 1 month after TACE shows the decreased size of the mass (arrowheads) as well as the partial lipiodol uptake.
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Figure 3 A 55-year-old man (patient 4) with angiosarcoma, presented with an incidentally detected mass. (a) Unenhanced CT image before TACE shows a dominant mass (arrowheads) in the right lobe of the liver; it is predominantly hypoattenuating with hyperattenuating foci (arrow). (bec) Contrast-enhanced CT images obtained during the arterial (b) and portal venous (c) phases, show a hypoattenuating mass (arrowheads) with central, enhancing foci (arrow). (dee) Common hepatic angiography obtained during the early (d) and late (e) phases, shows an ill-defined, irregular, tumour-blush-containing area with no staining and with delayed, progressive enhancement (arrowheads). (f) Contrast-enhanced CT image obtained 1 month after TACE, shows the decreased size of the mass (arrowheads) as well as the partial lipiodol uptake.
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respectively, in two patients. After TACE in the remaining two patients, follow-up CT showed tumour aggravation. One patient developed a hepatic abscess 10 days after TACE. The abscess was successfully drained using a percutaneous approach. Emergent TAE was successful for acute bleeding control in two patients with tumour rupture. However, one of these patients died 1 day after TAE due to acute renal failure, and the other patient showed aggravation of the tumour on CT 1 month after TAE.
Follow-up One of the two patients with tumour response to TACE died 8 months after initial presentation, and the remaining patient was still alive at the last follow-up (12 months) after initial presentation. However, two patients with no response to TACE and two patients who underwent emergent TAE for tumour rupture died 1 week to 5 months (mean 2.1 months) after their initial presentation.
Discussion Hepatic angiosarcoma is a malignant mesenchymal tumour consisting of spindle or pleomorphic cells that are vasoformative and form poorly organized vessels or a line or that grow into preformed vascular spaces, such as sinusoids and small veins.16 Hepatic angiosarcoma can be induced by exposure to chemical carcinogens including Thorotrast (thorium oxide, a previously used contrast agent), vinyl chloride monomer, arsenic, and androgenic anabolic steroids.17 However, hepatic angiosarcoma occurs more commonly in the absence of the known risk factors.2 None of the six patients in the current study had any of the aforementioned risk factors. Hepatic angiosarcoma can be classified into four types according to their growth pattern, i.e., multiple nodules, a large solitary mass, a mixed pattern of a dominant mass with nodules, and, rarely, a diffuse infiltrating micronodular tumour.2 In the current study, the first three types were observed. The CT findings of hepatic angiosarcoma in the present study were similar to those of previous studies.2 On unenhanced CT images, all lesions were hypoattenuating with or without hyperattenuating foci. On contrast-enhanced CT, most nodular lesions were hypoattenuating and had enhanced foci. The enhancement was less than that of the aorta, and some nodular lesions showed irregular or ring enhancement. Large, dominant, mass lesions showed heterogeneous enhancement
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suggesting central necrosis and fibrotic change. There was a delayed progressive enhancement pattern in all of the enhanced lesions. The heterogeneous enhancement pattern likely represents the heterogeneity of the microscopic vascular patterns within each tumour2 as areas with abundant, freely anastomosing vascular channels may enhance quickly, whereas dilated cavernous vascular spaces may show slowly progressing enhancement. Major differential diagnoses include hypervascular metastasis, hepatocellular carcinoma, and haemangioma. In contrast to hepatocellular carcinoma, angiosarcoma presents continuing progressive enhancement on delayed-phase images. Splenic metastases and the absence of cirrhosis or elevated alpha-fetoprotein levels may also indicate angiosarcoma rather than hepatocellular carcinoma.2 Most patients with hepatic metastases have a primary lesion in the lung, pancreas, stomach, breast, or other site.18 The most important differential diagnosis may be hepatic haemangioma. In particular, the angiographic findings of hepatic angiosarcoma in the present study were very similar to those of hepatic haemangioma. However, rapid growth or rupture of the tumour or increasing pain may suggest angiosarcoma rather than haemangioma.19 Given the rarity of primary hepatic angiosarcomas, their natural history, prognostic factors, and optimal management are poorly understood, and the prognosis of these patients has been reported to be particularly poor.2,3 Even with complete tumour resection to treat primary hepatic angiosarcoma, recurrence was common and patients died within 11 months.3 Of the four patients who received TACE in the current study, two demonstrated a decrease in tumour size. These two patients had a dominant, large mass with or without a few intrahepatic small metastases, while the remaining two patients with innumerable hepatic nodules or masses showed tumour aggravation after TACE. Compared to the survival period (8 and 12 months) of the two patients who showed tumour response to TACE, that of the two patients with no response to TACE and of the two patients who underwent emergent TAE for tumour rupture, was very low (range, 1 week to 5 months; mean, 2.1 months). From these results, it was noted that patients with a dominant, large mass with or without a few intrahepatic metastases, may benefit from TACE. Multiple tumours and the presence of tumour rupture seem to be important prognostic factors affecting the survival rate of patients with hepatic angiosarcomas. However, due to the small number of study patients in the present study, a larger study would be required in order to be
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able to draw definite conclusions regarding the efficacy of TACE or to determine the prognostic factors regarding the survival of patients with hepatic angiosarcomas. In summary, primary hepatic angiosarcoma presents with solitary or multiple hypervascular lesions showing heterogeneous enhancement on early-phase images and continuing progressive enhancement on delayed-phase CT and angiography images. Although TAE may be the primary procedure used to control emergent bleeding caused by the rupture of hepatic angiosarcomas, TACE may be effective for treating patients with a dominant hepatic angiosarcoma with or without a few intrahepatic metastases.
Acknowlegements The authors thank Bonnie Hami, (MA, USA) for her editorial assistance in the preparation of this manuscript.
References 1. Ikeda K, Maehara M, Ohmura N, et al. Spontaneous rupture of a necrotic hepatic angiosarcoma: findings on dual-phase computed tomography and angiography. Radiat Med 2006; 24:369e72. 2. Koyama T, Fletcher JG, Johnson CD, et al. Primary hepatic angiosarcoma: findings at CT and MR imaging. Radiology 2002;222:667e73. 3. Weitz J, Klimstra DS, Cymes K, et al. Management of primary liver sarcomas. Cancer 2007;109:1391e6. 4. Maeda T, Tateishi U, Hasegawa T, et al. Primary hepatic angiosarcoma on coregistered FDG PET and CT images. AJR Am J Roentgenol 2007;188:1615e7. 5. Locker GY, Doroshow JH, Zwelling LA, et al. The clinical features of hepatic angiosarcoma: a report of four cases and a review of the English literature. Medicine 1979;58:48e64. 6. Kitami M, Yamada T, Sato A, et al. Diffuse hepatic angiosarcoma with a portal venous supply mimicking hemangiomatosis. J Comput Assist Tomogr 2003;27:626e9.
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7. Brown DB, Cardella JF, Sacks D, et al. Quality improvement guidelines for transhepatic arterial chemoembolization, embolization, and chemotherapeutic infusion for hepatic malignancy. J Vasc Interv Radiol 2006;17:225e32. 8. Shen H, Agarwal D, Qi R, et al. Predictors of outcome in patients with unresectable hepatocellular carcinoma receiving transcatheter arterial chemoembolization. Aliment Pharmacol Ther 2007;26:393e400. 9. Liapi E, Geschwind JF. Transcatheter and ablative therapeutic approaches for solid malignancies. J Clin Oncol 2007;25:978e86. 10. Takayasu K, Arii S, Ikai I, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology 2006;131:461e9. 11. Kim PT, Su JC, Buczkowski AK, et al. Computed tomography and angiographic interventional features of ruptured hepatocellular carcinoma: pictorial essay. Can Assoc Radiol J 2006;57:159e68. 12. Ho AS, Picus J, Darcy MD, et al. Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors. AJR Am J Roentgenol 2007;188:1201e7. 13. Sharma KV, Gould JE, Harbour JW, et al. Hepatic arterial chemoembolization for management of metastatic melanoma. AJR Am J Roentgenol 2008;190:99e104. 14. Kim JH, Yoon HK, Sung KB, et al. Transcatheter arterial chemoembolization or chemoinfusion for unresectable intrahepatic cholangiocarcinoma: clinical efficacy and factors influencing outcomes. Cancer 2008;113:1614e22. 15. Vogl TJ, Zangos S, Eichler K, et al. Colorectal liver metastases: regional chemotherapy via transarterial chemoembolization (TACE) and hepatic chemoperfusion: an update. Eur Radiol 2007;17:1025e34. 16. Buetow PC, Buck JL, Ros PR, et al. Malignant vascular tumors of the liver: radiologicepathologic correlation. RadioGraphics 1994;14:153e66. 17. Kim KA, Kim KW, Park SH, et al. Unusual mesenchymal liver tumors in adults: radiologicepathologic correlation. AJR Am J Roentgenol 2006;187:W481e9. 18. Melia WM, Wilkinson ML, Portmann BC, et al. Hepatocellular carcinoma in the non-cirrhotic liver: a comparison with that complicating cirrhosis. Q J Med 1984;53:391e400. 19. Peterson MS, Baron RL, Rankin SC. Hepatic angiosarcoma: findings on multiphasic contrast-enhanced helical CT do not mimic hepatic hemangioma. AJR Am J Roentgenol 2000;175:165e70.
