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1 Case Report The Korean Journal of Pancreas and Biliary Tract 2016;21: pissn eissn 간농양과감별이어려웠던간내육종양담관암 1 예 성균관대학교의과대학삼성창원병원내과 공성민 김광민 이재진 홍웅표 최익성 정계화 권병수 이동규 A Case of Intrahepatic Sarcomatoid Cholangiocarcinoma Mimicking Liver Abscess Sung Min Kong, Kwang Min Kim, Jae Jin Lee, Woong Pyo Hong, Ik Sung Choi, Kye Hwa Jeong, Byung Soo Kwan, Dong Gyu Lee Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea Sarcomatoid transformation of intrahepatic cholangiocarcinoma is rarely found but usually has very poor prognosis due to the lack of effective approaches for early detection and its aggressive nature. We report a case of this tumor type, in a 60-year-old man who was referred to our hospital for further evaluation of screeningdetected, asymptomatic hepatic lesion. Clinical diagnosis was elusive despite performance of different imaging modalities and a transcutaneous liver biopsy. Pathology of the surgically resected tumor demonstrated intrahepatic sarcomatoid cholangiocarcinoma. In our case, tumor cells expressed strong immunoreactivity to both cytokeratin-19 and vimentin. We assume the relatively good prognosis of this patient would be expected because surgery played a critical role at an early stage of the tumor. Keywords: Cholangiocarcinoma, Sarcomatoid, Spindle cell, Cytokeratin, Vimentin Received Mar. 6, 2016 Revised Apr. 10, 2016 Accepted Apr. 28, 2016 Corresponding author : Kwang Min Kim Department of Internal Medicine, Samsung Changwon Medical Center, Sungkyunkwan University School of Medicine, 158 Paryong-ro, Masanhoewon-gu, Changwon 51353, Korea Tel Fax ; kwmin.kim@samsung.com This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2016 by The Korean Journal of Pancreas and Biliary Tract 서론 10-15%. 1, 4.5%. 2 (intrahepatic sarcomatoid cholangiocarcinoma),. 3,4.,,, Copyright 2016 by Korean Pancreatobiliary Association

2 Sung Min Kong, et al.. 증례 60 장경 3.0 cm (computed tomography, CT). 6,. 120/80 mmhg, 36.4, 74 /, 20 /.,.,,,,.,,. 5,000/mm 3, 14.2 g/dl, 182,000/mm 3 C- 5 mg/dl. (AST) 34 IU/L, (ALT) 42 IU/L, (total bilirubin) 1.0 mg/dl, (ALP) 55 IU/L, (BUN) 16.5 mg/dl, 0.73 mg/ dl. B A B C Fig. 1. Selected images of this case from various preoperative image modalities. (A) Ultrasound image of a low-level echo collection with a relatively well-defined mass in the right lobe of the liver. (B) Portal venous-phase contrast-enhanced computed tomography (CT) scan showing approximately 3 2 cm of a heterogeneously low density lesion with peripheral enhancement on segment 8 of the right hepatic lobe. (C) Axial T-weighted magnetic resonance imaging (MRI) revealing a central aspect with high signal intensity and internal septa, which is surrounded by an inflamed area slightly hypointense to the liver. (D) Positron emission tomography/computed tomography (PET/CT) scan showing no definite FDG uptake in the position where the lesion was confirmed in other image modalities. D 175

3 Intrahepatic Sarcomatoid Cholangiocarcinoma Mimicking Liver Abscess A B C Fig. 2. (A) Photomicrograph of percutaneous liver biopsy shows only a mild atypical epithelial proliferation without evidence of definite tumor cells (H&E, 200). (B) Immunohistochemistry using pan-cytokeratin reveals reactivity with the epithelial component (pan-cytokeratin, 200), but (C) negative for vimentin due to an absence of a sarcomatous component (vimentin, 200). A liver biopsy failed to elucidate the diagnosis in this patient. C. (AFP), proteins induced by vitamin K absence or antagonist-ii (PIVKA-II) 2.93 ng/ml, 18 mau/ml cabohydrate antigen 19-9 (CA 19-9) U/mL. CT (Fig. 1) (magnetic resonance imaging, MRI) (Fig. 1) 8 3 cm. MRI T1 T2.. (positron emission tomography/ct, FDG-PET/CT) 8 FDG., CT 2 (mild dysplastic changes) (Fig. 2). CT (hypoattenuating)., CA cm, (well differentiated adenocarcinoma), (spindle cell). (mitosis) 10 HPF (high power field) 1 mitosis (pleomorphism). - (angiolymphatic invasion).. cytokeratin-19 (CK-19) vimentin (Fig. 3). 7 AJCC TNM 6 T1N0M0. 12, 4, CT

4 Sung Min Kong, et al. 고 찰 병인 중 하나로 제시하기도 하였다. 간내 육종양 담관암과 일 반적인 간내 담관암을 조직학적 확진 전에 미리 구별하는 것 육종양 암종은 방추세포암(spindle cell carcinoma)이나 가 은 매우 어렵다. 일반적인 간내 담관암은 우상복부 동통이나 육종(pseudosarcoma) 등으로 불리우는데 이러한 상피암종의 황달 등의 다양한 증상을 주소로 내원하게 되며 조직학적으로 육종형 변화는 폐, 식도, 피부 등과 같이 편평상피가 분포하는 는 잘 분화된 선암종이 대부분을 차지한다. 혈청 CA 19-9는 곳에서 주로 발생하나 신장, 유방, 위 등에서 발생한 예가 드물 85% 이상에서 증가한다고 알려져 있으며 항암화학요법이나 7,8 게 보고되고 있다. 원발성 간암에서의 육종양 변화는 간세포 방사선치료에 잘 듣지 않는 경우가 흔해 전반적인 예후는 불 암에서 가장 흔하며, 특히 항암치료나 경동맥 화학 색전술 량하지만 병의 진행 속도는 느릴 수 있다. 에에 반해 간내 육종 9 (transarterial chemoembolization, TACE) 후에 잘 관찰된다. 양 담관암은 일반적인 간내 담관암에서 보이는 우상복부 동 하지만, 간내 담관의 육종양 변화는 간세포암에 비해 드물며 통, 황달 등의 일반적인 증상에 비해 열감을 자주 호소하고 CA 항암치료와의 연관성도 알려진 바가 없고 발병 기전도 명확하 19-9 등의 종양 표지자가 음성인 경우가 많으며 조직학적으로 10 게 밝혀지지 않았다. Yoo 등 은 유전학적 형질 발현에 의한 담 대부분에서 중증도 혹은 분화가 나쁜 선암 세포 및 방추 세포 관 상피세포의 미분화 시기에 육종양 세포로의 변화 가능성을 등의 다양한 세포들이 혼합된 형태를 보인다 CT 검사에서 A B C D Fig. 3. Microscopic findings from a resected specimen. (A) Tumor cells reveal a malignant biphasic neoplasm consisting of well differentiated carcinomatous and sarcomatous components with a loosely textured arrangement of spindle cells (H&E, 40). (B) The glandular structures show moderate nuclear pleomorphisms with prominent nucleoli and frequent mitosis (H&E, 200). (C) Immunohistochemistry with the antibody to cytokeratin-19 (CK-19) shows strong reactivity with the epithelial component (CK-19, 200). (D) The tumor cells are strongly immunoreactive to vimentin (vimentin, 200). 09증례 indd 오전 9:15:42

5 Intrahepatic Sarcomatoid Cholangiocarcinoma Mimicking Liver Abscess Table 1. Summary of cases of intrahepatic sarcomatoid cholangiocarcinoma in the literature Outcome Recurrence after surgery/ second-line treatment Reference Age / Sex Sarcomatoid component IHC Initial Treatment Malhotra, et al. 60/F Pleomorphic and spindle cells CK 19 (+) / Vimentin (+) Surgery (+)/Gemcitabine plus Cisplatin CTX Alive beyond 29 months after diagnosis CK 7 (+) / Vimentin (+) CTX NA Died within 1month after diagnosis Kim, et al. 68/F Spindle cells with rhabdoid transformation (+)/Gemcitabine plus Cisplatin CTX Alive beyond 8 months after diagnosis Surgery with adjuvant CTX Jung, et al. 59/M Undifferentiated spindle cells PAN-CK (+)/ Vimentin (+) Lost to follow-up Hong, et al. 69/F Pleomorphic and spindle cells CK 19 (+) / Vimentin (+) None NA Inoue, et al. 61/M Undifferentiated spindle cells CK 7 (+) / Vimentin (+) Surgery (+)/(-) Died within 2 months after diagnosis Sato, et al. 87/M Round cell variant CK 19 (+) / Vimentin (+) None NA Died within 3month after diagnosis F, female; M, male; IHC, Immunohistochemistry; CTX, Chemotherapy; CK; cytokeratin NA; not applicable. MRI T1, T2.. CA CT,,,,,,. (gas bubbles). CT 3,, (double target sign). (satellite nodule) CT. CT,,.., (cancer navel). MRI T1, T2. T2,., cytokeratin vimentin. 7,13 CK-19 vimentin

6 Sung Min Kong, et al.,. 12 (gemcitabine), (cisplatin),. 14., (Table 1). 8,13,15, AJCC/UICC stage I.,.,. 요약...,. 국문색인 : 담관암, 육종양, 간농양 Conflicts of Interest The authors declare that they have no conflicts of interest. REFERENCES 1. Parkin DM, Ohshima H, Srivatanakul P, Vatanasapt V. Cholangiocarcinoma: epidemiology, mechanisms of carcinogenesis and prevention. Cancer Epidemiol Biomarkers Prev 1993;2: Sato K, Murai H, Ueda Y, Katsuda S. Intrahepatic sarcomatoid cholangiocarcinoma of round cell variant: a case report and immunohistochemical studies. Virchows Arch 2006;449: Watanabe G, Uchinami H, Yoshioka M, Nanjo H, Yamamoto Y. Prognosis analysis of sarcomatous intrahepatic cholangiocarcinoma from a review of the literature. Int J Clin Oncol 2014;19: Aishima S, Kuroda Y, Asayama Y, et al. Prognostic impact of cholangiocellular and sarcomatous components in combined hepatocellular and cholangiocarcinoma. Hum Pathol 2006;37: Kakizoe S, Kojiro M, Nakashima T. Hepatocellular carcinoma with sarcomatous change. Clinicopathologic and immunohistochemical studies of 14 autopsy cases. Cancer 1987;59: Sobin LH, Compton CC. TNM seventh edition: what s new, what s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer 2010;116: Haratake J, Horie A. An immunohistochemical study of sarcomatoid liver carcinomas. Cancer 1991;68: Wi JH, Ahn MS, Chung SO, et al. A case of sarcomatoid carcinoma in the gallbladder. Korean J Med 1999;57: Kojiro M, Sugihara S, Kakizoe S, Nakashima O, Kiyomatsu K. Hepatocellular carcinoma with sarcomatous change: a special reference to the relationship with anticancer therapy. Cancer Chemother Pharmacol 1989;23(Suppl): Yoo HJ, Yun BR, Kwon JH, et al. Genetic and expression alterations in association with the sarcomatous change of cholangiocarcinoma cells. Exp Mol Med 2009;41: Shimada M, Takenaka K, Rikimaru T, et al. Characteristics of sarcomatous cholangiocarcinoma of the liver. Hepatogastroenterology 2000;47: Kaibori M, Kawaguchi Y, Yokoigawa N, et al. Intrahepatic sarcomatoid cholangiocarcinoma. J Gastroenterol 2003;38: Kim WS, Kim TH, Hwang JJ, et al. A case of intrahepatic sarcomatoid cholangiocarcinoma with rhabdoid transformation. Korean J Med 2011;80: Malhotra S, Wood J, Mansy T, Singh R, Zaitoun A, Madhusudan S. Intrahepatic sarcomatoid cholangiocarcinoma. J Oncol 2010;2010: Inoue Y, Lefor AT, Yasuda Y. Intrahepatic cholangiocarcinoma with sarcomatous changes. Case Rep Gastroenterol 2012;6:

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