SPONTANEOUS INTRACRANIAL TUMOR BLEEDING FROM METASTATIC HEPATOCELLULAR CARCINOMA: A CASE OF REPORT

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1 tjj "i:'liuwj~ ( J. Chinese Oncal. Soc. ) 20(2), 10-21, 2004 SPONTANEOUS INTRACRANIAL TUMOR BLEEDING FROM METASTATIC HEPATOCELLULAR CARCINOMA: A CASE OF REPORT Wen-Chi Chou', Shih-Ming lun g', Jen-Shi Chen' ABSTRACT The most common metastatic sites of hepatocellular carcinoma (HCC) include intra-abdominal lymph nodes, lung and bones. Extremely rare cases present as intracranial metastases, which almost have precluded pulmonary metastases. Due to the tendency of spontaneous tumor bleeding, these patients frequently presented with symptoms and signs which were similar to the presentations of intracranial hemorrhage, such as sudden onset consciousness change, hemiplegia, and headache. We report a typical case of HCC with pulmonary metastases followed by intracranial metastasis with spontaneous tumor bleeding, and review the literature. Key Words: Hepatocellular carcinoma, brain metastasis, intracranial hemorrhage INTRODUCTION Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in Taiwan and ranks the first leadin g cancer-related death annually'. Most patients present with advanced disease because of the lack of early symptoms. The median surv ival of patient with advanced HCC is around three to six months z- However, rece nt advance in local ablation therapy have resulted in a better clinical outco me" 4, distant metastasis of HCC is observed more frequently in the group of patients who have longer survival. Extrahepatic spreads of HCC are often found in lungs (34-70%) and lymph nodes (16-45%) (5-7). So me patients even have br ain metast ases. Though HCC with brain metastasis is a rare 'Division of Hemato logy and Oncology, Department of Internal Medicine; ' Department of Patho logy, Chang Gung Memorial Hospital, Linkou, Taiwan. Correspondence to: Dr. Jen-Shi Chen, Divisio n of Hematology-Oncology, Departmen t of Internal Medicine, Chang Gung Memorial Hospital, 199 Tung Hwa North Road, Taipei, Taiwan TEL: ext 2114 FAX: Received for publication: October 26,

2 11 event, metastatic intracranial tumor frequently presented as spontaneous hemorrhage" 9 We presented one patient diagnosed with HCC with multiple lung metastasis, and developed metastatic brain tumor with hemorrhage during the course of palliative chemotherapy. CASE PRESENTATION A 65 years old male patient was diagnosed multifocal HCCs and hepatitis C virus carrier one and a half year ago documented by liver biopsy. He received three courses of transhepatic artery embolization (TAE) therapy in six months. Multiple lung metastases and progressive elevation of alpha-fetoprotein were noted after the third course TAE. The treatment method was shift to palliative chemotherapy with fluorouracil, mitoxantrone and cisplatin regimen". Sudden onset left limb weakness and disturbed consciousness developed during hospitalization before chemotherapy. An emergent non-enhanced brain CT scan revealed intracranial hemorrhage, size around 4.3x 3.4x3cm, in right parietal lobe with significant perifocal edema (Figure I). His AFP was ng/mL, aspartate aminotransferase was 93u/L, alanine aminotransferase was 36u/L, total bilirubin was 1.2mg/dL, alkaline phosphatase was 71 u/l, hemoglobin was 10.7g/dL, platelet count was Fig 2. Microscopic appearance of the HCC in the brain. Tumor nest is present in the right field. The tumor con sisted of epithelioid cells with eosinophilic cytoplasm that grew as trabecular pattern. A large hemorrhagic area is present between normal brain tissue and tumor nest. x ,000/uL, prothrombin time was l2.9sec (controlell.zsec, INR=1.l4), and activated partial thromboplastin time was 27. 8sec (control=29.8sec). He received surgical decompression for intracranial hemorrhage in the next day. The pathology was compatible with metastatic HCC with hematoma (Figure 2). Postoperative whole brain irradiation was planned, but was disrupted due to rapid progression of multiple lung metastases with presentation of orthopnea. We gave supportive care for the patient. He was discharged one month after intracranial hemorrhage and was referred to local hospital for supportive care. DISCUSSION Fig 1. in the right parietal lobe, compatible with hemorrhage. Extensive peri-focal edema is present. HCC is a highly prevalent tumor in Taiwan, mainly related to chronic inflammation of viral infection of hepatitis B or C. The prognosis is grave due to advanced disease status and ineffective therapies. The systemic chemotherapy also reveals poor result in this patient group. The response rate is around 0-19% in metastatic HCC, with median survival around 3-6 months "'''. Most patients die of hepatic failure and complications of concomitant cirrhosis. In past two decades, the 35

3 12 effective therapeutic modalities with TAE, percutaneous alcohol injection or cry otherapy improve the survival of HCC patients. Distant metastasis of HCC is observed more frequently in the group of patients who have longer survival. Lung, lymph node and bone are the most frequent metastasis sites of HCC 5. '. Brain metastasis of HCC has been observed, but is relatively unusual with incidence around % in sev era l autopsy series'". The metastatic route to brain is via hematogenous spread after lung metastasis. Yen FS et al reported around 77% patients had preceded lung metastases". Some cases of brain metastases via meninges with subsequent spread to the ce rebra l parenchyma have also been described1".20. It has been reported th at the med ian duration from HCC diagnosis to brain metastasis is around 19.8 months, and the median duration from lung metastasis to brain metastasis is around fo ur months'. Mo st clinical sy mpto ms of metastatic brain tumor are consciousness change, sudden onset hemiplegia and brain herniation, resulting from tumor bleeding. Typical image of brain CT reveal parench ymal hemorrhage. Rim enha nce ment or adjacent homog eneousl y enhancing, hematoma location (mai nly lobar) suggested intraneoplastic hemorrhage rather than hypertensive hemorrhage" IS. The precise mechanism of easy tumor bleeding was unknown. Hypervascularity of tumor itself and coagulopathy associated with liver cirrhosis are the possible mechanisms. The incidence of tumor bleeding is strongly related to tumor size. One study rep orted th at the incidence of tumor bleeding larger than 50% while tumor size greater than 2 em, and almost 100% if tumor larger than 4 ern". The histological picture of HCC with brain metastasis is usually consistent with primary liver pathol ogy. Some immunohistochemistry stains such as alpha l- chymotrypsin, PSA-diastase and Alcian blue stain, also help for further supports of the diagnosis". Due to the catastrophic result of brain tumor bleedin g, the prognosis was grave. The median survival ranges from days to months according to treatment modality. Yen FS et al had been reported median survival was 15 days if patient was tre ated with dexameth asone onl y and 94 days if was treated with surg ical resection or radioth erapy". Multi variate survival analysis in their study revealed only treatment mod ality (surgery versus steroid or supportive care) of brain metast asi s from HCC had significant implication (p=o.ooi), while other variables including age, cirr hotic score, tumor gr ade, neurological deficit, liver function test, and alphafetoprotein we re ins ig nificant. The role of surgery in patient s with brain meta sta sis is to provide immediate relief of symptoms resulting from the mass effect of the tumor, to establish a hi stological di agn osis, and to improve local control of the tumor". Most patients die due to systemic organs failure or intracranial herniation " CONCLUSION HCC with brain metastasis is a rare event and frequently pre sents as intracranial tum or bleeding. Surgical resection or radiotherapy may prolong survival in some cases, but the result is disappointing. REFERENCES I. Cancer Registry Annual Report, 2000, Republic of China. Bureau of h ealth promotion department of health. The exective yuan, December R epublic of China, 2. Okuda K, Obata H, Nakajima Y, Ohtsuki T, Okazaki N, Ohnishi K. : Prognosis of primary hepatocellular carcinoma. 36

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5 14 Cancer, 15: , Taylor C. :Immunomicroscopy : A Di agnostic Tool fo r the Surgical Pathol ogi st. : Sa unde rs, pp , D e vi 間, Vin cen t T; Hellman, Samuel; Ro senb 巴 rg, Steven A.; Cancer: Principle and pr acti ce of On col ogy.; Lippincott Williams & Wilkins, pp2685, 病例報告 : 顱內轉移性肝痞產生白發性腫瘤出血 周文其 榮世明 i 來仁熙 肝癌為臺灣常見之惡性腫瘤, 大多數腫瘤在診斷初期仍侷限在肝臟內部, 以局部侵犯所造成的臨床症狀為主要表現 肝癌的追處轉移通常以局部淋巴結 肺臟及骨酪? 為主 顱內轉移並不常見, 但此類病患常常以顱內出血為初始臨床表現, 常見症狀包括突發性意識變化 半身偏癱或急性頭痛 腦部電腦斷層於未顯影相與一般自發性腦血管出血的影像類似, 但出血病兆周圍伴有明顯的腦組織水腫為其特色, 於顯影後, 顱內腫瘤會有明顯顯影, 表示此類腫瘤富含血管 肝癌顱內轉移容易出血可能與 的凝血功能不良有關 肝癌發生腦部轉移可能 透過血行, 性轉移, 因為此類病患先前多數已診 斷有肺部轉移 此類病患預後非常不佳, 即使 接受腦部放射線治療或手術切除顱內腫瘤, 病 患大多死於顱內壓過高導致的腦幹壓迫或腫瘤 全身侵犯導致之器官衰竭 本篇病例報告乙例 典型肝癌患者併發顱內轉移的臨床病程及處置 經過, 同時回顧以往前人發表的相關文獻報 主 t 三 t=l Key Words: Hepatocellular carcinoma, br ain metastasis, intracranial hemorrhage 腫瘤本身富含血管及病患本身原本肝硬化導致 林口長庚紀念醫院血液腫瘤科 受理日期 : 民國 9 4 年 10 月 2 6 日 14 39