Metastatic Hepatocellular Carcinoma Mimicking a Solitary Mediastinal Tumor

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台灣癌症醫誌 (J. Cancer Res. Pract.) 26(6),257-262, 200 Case Report journal homepage:www.cos.org.tw/web/index.asp Metastatic Hepatocellular Carcinoma Mimicking a Solitary Mediastinal Tumor Shiau-Ru Chiou, Ting-Lung Lin, Dibyajyoti Bora, Hung-I Lu 2, Chao-Long Chen, Shih-Ho Wang, Chih-Che Lin, Yueh-Wei Liu, Chee-Chien Yong, Wei-Feng Li, Chun-Yi Liu, Chih-Chi Wang * Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Department of Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan Abstract. A 47-year-old woman who had undergone extended right hepatectomy for hepatocellular carcinoma 6 years ago presented with gradual onset of dyspnea for 2 months. Imaging studies revealed a mass involving the right paratracheal region. Bronchoscopy showed a mass effect at the anterior wall of the lower trachea. She underwent thoracoscopic right paratracheal tumor excision and high mediastinal lymph node dissection. The final histopathology revealed metastatic hepatocellular carcinoma. The patient s symptoms improved after surgery, and there was no recurrence during 4 months of follow-up. 病例報告 Keywords : mediastinum, metastasis, hepatocellular carcinoma 轉移性肝細胞癌神似單一縱膈腔腫瘤 邱筱茹李韋鋒 林廷龍劉俊毅 Dibyajyoti Bora 王植熙 * 呂宏益 2 陳肇隆 王世和 林志哲 劉約維 楊志權 高雄長庚紀念醫院一般外科 2 高雄長庚紀念醫院胸腔外科 中文摘要一位 47 歲女性於 6 年前因為肝細胞癌接受擴大右肝切除手術 最近兩個月逐漸感覺到呼吸困難 影像學檢查發現一個腫瘤位於氣管右側 支氣管鏡發現氣管下段的前側有腫塊壓迫效應 她接受胸腔鏡切除氣管右側腫瘤及清除縱膈腔淋巴結 病理化驗證實腫瘤為轉移性肝細胞癌 這個病人的症狀於手術後改善了 而且在追蹤了 4 個月之後, 並未發現有腫瘤復發 關鍵字 : 縱膈腔 轉移性腫瘤 肝細胞癌 INTRODUCTION Hepatocellular carcinoma (HCC) represents the sixth most common malignancy and the third most common cause of cancer-related death worldwide [].

258 S. R. Chiou et al./jcrp 26(200) 257-262 The most common sites of extrahepatic metastasis are the lungs, bones, abdominal lymph nodes, and adrenal glands [2]. Mediastinal lymph node involvement occurs in approximately 4% to 5% of patients with HCC and solitary paratracheal lymphadenopathy occurs in less than % [3-7]. Patients with distant metastasis usually have viable intrahepatic tumors and carry a poor prognosis. We report on a patient with good survival after removal of a solitary mediastinal lymph node metastasis discovered 6 years after resection of the primary liver tumor. CASE REPORT A 47-year-old woman without chronic viral hepatitis (B or C) and with normal alpha-fetoprotein (AFP) had a 8.6-cm pedunculated HCC at segment 4 of liver treated with transcatheter arterial embolization followed by extended right hepatectomy with cholecystectomy in 2003. The histopathology showed moderately differentiated, partially encapsulated HCC with focally infiltrative borders. The resection margin and lymph nodes were free of involvement (Stage, AJCC-7th edition). She was on regular follow-up from the time of surgery till 2009, with detailed physical examination, serum AFP measurement, chest radiography (CXR) and computed tomography (CT) of liver, and there was no evidence of recurrence. However, since August 2009, the patient had progressive dyspnea for two months. Her symptoms aggravated while lying down in the dorsal recumbent position and were relieved while lying down in the lateral decubitus position. In addition, she had chest tightness and occasional cough with scanty sputum. There was no hemoptysis, body weight loss, fever, chills, night *Corresponding author: Chih-Chi Wang M.D. * 通訊作者 : 王植熙醫師 Tel: +886-7-73723 ext.8093 Fax: +886-7-7354309 E-mail: ufel4996@ms26.hinet.net sweats, or back pain. The patient denied travel and smoking history. Physical examination showed clear breathing sounds. There was no palpable lymphadenopathy at the axillary and neck regions. Her hemogram, biochemistry and AFP were within normal range. CXR showed widened mediastinum (Figure ), and chest CT disclosed a 4 cm necrotic mediastinal lymph node at the right paratracheal region (Figure 2). Bronchoscopy showed bulging of the anterior tracheal wall (Figure 3). The lesion was highly suspected to be malignant by F-8 FDG PET scan (Figure 4). Under the impression of right paratracheal tumor, she underwent thoracoscopic paratracheal tumor excision and high mediastinal lymph node dissection. A 6x4 cm well-defined tumor, rubbery in consistency, was found surrounding the lower trachea, superior vena cava, azygous vein, and ascending aorta. The inferior part of the tumor was adjacent to the superior vena cava and azygous vein (Figure 5). The final histopathology revealed metastatic HCC. The patient recovered uneventfully after the surgery, and no recurrence was found 4 months after surgery. DISCUSSION When encountering a mediastinal mass, the mass location, patient s age, and the presence or absence of symptoms may be associated with the possibility of malignancy. In a study of 400 patients, 59%, 29%, and 6% of anterior, middle, and posterior mediastinal masses, respectively, were malignant. In this patient, the tumor located in the right anterior mediastinum was symptomatic and was likely to be malignant in nature. In HCC patients with mediastinal metastases, metastatic lesions were mostly diagnosed simultaneously with the viable intrahepatic tumor. Our patient was diagnosed with mediastinal metastasis 6 years after resection of primary HCC. However, when did the mediastinal metastasis originate is not known. It might have derived from the primary tumor and existed before extended right hepatectomy or from an-

S. R. Chiou et al./jcrp 26(200) 257-262 259 A B Figure. A. Supine chest antero-posterior view showed widening of the upper mediastinum. Bulging in the right upper mediastinum was seen (arrow). B. The lateral view showed white out of the right anterior chest cavity (arrow) A B Figure 2. A. Coronal view and B. axial view of enhanced chest CT showed a 4-cm necrotic lymph node at the right paratracheal region compressing the lower trachea (arrow)

260 S. R. Chiou et al./jcrp 26(200) 257-262 A B Figure 3. Bronchoscopy revealed posterior tracheal wall bulging during expiratory phase, right main bronchus collapse, and anterior wall of lower trachea bulging with submucosal infiltration Figure 4. A. Sagital view and B. Coronal view of PET scan showed increased FDG uptake in the right paratracheal lymph node with central necrosis, highly suspicious of malignancy (arrow) other new undetected tumor that metastasized to the mediastinal region. The later hypothesis is less likely as no recurrence was seen 4 months after resection of mediastinal metastasis. The most common route of distant metastasis is hematogenous, which occurs via the invasion of the hepatic venous system. Mediastinal metastasis may occur through 3 routes of hepatic lymphatic drainage [8]. The first route is from the left hepatic lobe via the anterior phrenic lymph nodes to the parasternal or subcarinal lymph nodes, the second one runs from the liver through the hepatic falciform ligament to the parasternal or paratracheal lymph nodes, and the third one runs from the right hepatic lobe through the right triangular ligament to the paratracheal lymph nodes. Our patient s primary tumor was located at segment 4, so the second route was more likely. Some mediastinal metastases are asymptomatic and are discovered incidentally [3], while others may cause superior vena cava syndrome, pancoast syndrome, or dysphagia [4,9,0]. To our knowledge, this is the first case presenting initially with dyspnea and chest tightness caused by lower airway compression. This tumor, located anterior to the trachea, directly compressed on the airway when the patient was in supine position. Partial hepatectomy of the resectable HCC in non-cirrhotic, and even in cirrhotic patients, is the definite treatment of HCC. Median survival rate after operation is 50% (7 69%) at 5 years [,2]. In this patient, the primary HCC was single, vascular invasion was absent, and therefore was classified as stage I. After resection of primary HCC, the patient had 6 years of disease-free survival before she was proven to have solitary mediastinal metastasis.

S. R. Chiou et al./jcrp 26(200) 257-262 26 be taken into consideration. Patients with symptomatic solitary mediastinal metastasis from HCC may have better life quality and survival if surgical removal of the tumor is feasible. REFERENCES. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin 55: 74-08, 2005. 2. Katyal S, Oliver JH 3rd, Peterson MS, et al. Extrahepatic metastases of hepatocellular carcinoma. Radiology 26: 698-703, 2000. 3. Hurwitz MA, Taylor HG. Hepatoma seen as an asymptomatic mediastinal mass. Arch Intern Med 42: 964-5, 982. 4. Kew MC. Hepatocellular carcinoma presenting with the superior mediastinal syndrome. Am J Gastroenterol 84: 092-4, 989. 5. Byrd RP Jr, Roy TM, Korfhage LG, et al. Hepatocellular carcinoma presenting as a mediastinal mass. J Ky Med Assoc 92: 260-2, 994. 6. Huang CC, Ng WW, Chiang JH, et al. Hepatocellular carcinoma with mediastinal and pericardial invasion: report of two cases. Zhonghua Yi Xue Za Zhi (Taipei) 62: 89-5, 999. Figure 5. A. A 6x4 cm well defined elastic tumor (ar- 7. Seki S, Kitada T, Sakaguchi H, et al. Cardiac row) was located between the lower trachea, tamponade caused by spontaneous rupture of superior vena cava, azygous vein and as- mediastinal lymph node metastasis of hepatocel- cending aorta. The inferior part of the tumor lular carcinoma. J Gastroenterol Hepatol 6: was adjacent to the superior vena cava and 702-4, 200. azygous vein. B. Gross appearance of the excised lymph node 8. Tanaka O, Kanematsu M, Kondo H, et al. Solitary mediastinal lymph node metastasis of hepatocellular carcinoma: MR imaging findings. Magn Reson Imaging 23: -4, 2005. CONCLUSIONS 9. Hung JJ, Lin SC, Hsu WH. Pancoast syndrome While most HCCs are traditionally thought to be caused by metastasis to the superior mediastinum cured after 5 years of disease-free survival, this case of hepatocellular carcinoma. Thorac Cardiovasc showed that a metastatic HCC might still be indolent Surg 55: 463-5, 2007. for more than 5 years. Therefore, if a patient with his- 0. Yamashita R, Takahashi M, Kosugi M, et al. [A tory of resected HCC presents with breathlessness due case of metastatic hepatocellular carcinoma of the to a mediastinal mass, metastatic HCC still needs to superior mediastinum]. Nippon Kyobu Geka

262 S. R. Chiou et al./jcrp 26(200) 257-262 Gakkai Zasshi 4: 709-3, 993.. Takayama T. Surgical treatment for hepatocellular carcinoma. Jpn J Clin Oncol 4: 447-54, 20. 2. Wang CC, Iyer SG, Low JK, et al. Perioperative factors affecting long-term outcomes of 473 consecutive patients undergoing hepatectomy for hepatocellular carcinoma. Ann Surg Oncol 6: 832-42, 2009.