Intrahepatic cholangiocarcinoma initially diagnosed as adenocarcinoma of unknown primary with hepatoduodenal ligament lymph node metastases: A case report

Noh,Sangik; Ham,Ahrong; Gil,Je Ryung; Lee,Miji; Lim,Taekyu

doi:10.3892/ol.2023.14140

Intrahepatic cholangiocarcinoma initially diagnosed as adenocarcinoma of unknown primary with hepatoduodenal ligament lymph node metastases: A case report

Authors:
- Sangik Noh
- Ahrong Ham
- Je Ryung Gil
- Miji Lee
- Taekyu Lim
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Affiliations: Division of Hepato‑Pancreato‑Biliary Surgery, Department of Surgery, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea, Division of Hematology‑Oncology, Department of Internal Medicine, Ewha Womans University Medical Center, Ewha Womans University College of Medicine, Seoul 07985, Republic of Korea, Division of Radiology, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea, Department of Pathology, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea, Division of Hematology‑Oncology, Department of Internal Medicine, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea
Published online on: November 8, 2023 https://doi.org/10.3892/ol.2023.14140
Article Number: 7
Copyright: © Noh et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intrahepatic cholangiocarcinoma (iCCA) with regional lymph node metastases, which lacks a well‑delineated liver mass, may be misdiagnosed as a carcinoma of unknown primary (CUP) origin. The present study reports the case of a 69‑year‑old man initially diagnosed with CUP, who was incidentally found to have abdominal lymphadenopathy during ultrasonography (US). The clinical course from the time of lymphadenectomy and CUP diagnosis to iCCA detection after long‑term follow‑up is reported. A patient with a history of hypertensive renal disease presented with an incidental finding of enlarged abdominal lymph nodes in the perihepatic region on US. Abdominal contrast‑enhanced computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed two enlarged lymph nodes in the hepatoduodenal ligament. Exploratory laparotomy and lymphadenectomy were performed for diagnostic and therapeutic purposes, respectively. Poorly differentiated metastatic adenocarcinoma positive for cytokeratin 7 and negative for cytokeratin 20 was identified in two of the 22 lymph nodes. Postoperatively, a positron emission tomography/CT (PET/CT) scan was performed, which failed to locate the primary site. The diagnosis of CUP was confirmed based on clinical, radiological and histopathological characteristics. A sequential abdominal CT scan 48 months after lymphadenectomy revealed a faintly enhancing, intraductal polypoid mass with localized ductal dilatation in liver segment 3. MRI and PET/CT confirmed a mass in the left lobe of the liver. US‑guided percutaneous needle biopsy confirmed the presence of moderately differentiated adenocarcinoma. The patient refused surgical treatment because of general weakness caused by Coronavirus disease 2019 infection. The patient received radical radiotherapy and underwent left hepatectomy after recovery of their performance status. Histopathological examination of the surgical specimen demonstrated prevailing fibrosis and mucin accumulation, with scattered cancer cells observed focally in the resected liver specimen owing to the effect of the radiotherapy. Consequently, a definitive diagnosis of primary adenocarcinoma of the intrahepatic bile duct was confirmed. The present report may improve understanding of the pathophysiology and clinical progression of iCCA, with a specific focus on the intraductal growth subtype.

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1	Sigel CS, Drill E, Zhou Y, Basturk O, Askan G, Pak LM, Vakiani E, Wang T, Boerner T, Do RKG, et al: Intrahepatic cholangiocarcinomas have histologically and immunophenotypically distinct small and large duct patterns. Am J Surg Pathol. 42:1334–1345. 2018. View Article : Google Scholar : PubMed/NCBI
2	Banales JM, Marin JJG, Lamarca A, Rodrigues PM, Khan SA, Roberts LR, Cardinale V, Carpino G, Andersen JB, Braconi C, et al: Cholangiocarcinoma 2020: The next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 17:557–588. 2020. View Article : Google Scholar : PubMed/NCBI
3	Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T, Pawlik TM and Gores GJ: Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 60:1268–1289. 2014. View Article : Google Scholar : PubMed/NCBI
4	Conway AM, Morris GC, Smith S, Vekeria M, Manoharan P, Mitchell C, Backen A, Oliveira P, Hubner RA, Lamarca A, et al: Intrahepatic cholangiocarcinoma hidden within cancer of unknown primary. Br J Cancer. 127:531–540. 2022. View Article : Google Scholar : PubMed/NCBI
5	Sirica AE, Gores GJ, Groopman JD, Selaru FM, Strazzabosco M, Wei Wang X and Zhu AX: Intrahepatic cholangiocarcinoma: Continuing challenges and translational advances. Hepatology. 69:1803–1815. 2019. View Article : Google Scholar : PubMed/NCBI
6	Raoof M and Singh G: Rising trends in intrahepatic cholangiocarcinoma incidence and mortality: Getting at the root cause. Hepatobiliary Surg Nutr. 8:301–303. 2019. View Article : Google Scholar : PubMed/NCBI
7	Florio AA, Ferlay J, Znaor A, Ruggieri D, Alvarez CS, Laversanne M, Bray F, McGlynn KA and Petrick JL: Global trends in intrahepatic and extrahepatic cholangiocarcinoma incidence from 1993 to 2012. Cancer. 126:2666–2678. 2020. View Article : Google Scholar : PubMed/NCBI
8	Varadhachary GR: Carcinoma of unknown primary origin. Gastrointest Cancer Res. 1:229–235. 2007.PubMed/NCBI
9	Oda E, Hashimoto D, Shiomi Y, Ohnishi K, Hayashi H, Chikamoto A, Takeya M and Baba H: A case of occult intrahepatic cholangiocarcinoma diagnosed by autopsy. Surg Case Rep. 1:1012015. View Article : Google Scholar : PubMed/NCBI
10	Nozaki Y, Yamamoto M, Ikai I, Yamamoto Y, Ozaki N, Fujii H, Nagahori K, Matsumoto Y and Yamaoka Y: Reconsideration of the lymph node metastasis pattern (N factor) from intrahepatic cholangiocarcinoma using the International Union Against Cancer TNM staging system for primary liver carcinoma. Cancer. 83:1923–1929. 1998. View Article : Google Scholar : PubMed/NCBI
11	Chung YE, Kim MJ, Park YN, Choi JY, Pyo JY, Kim YC, Cho HJ, Kim KA and Choi SY: Varying appearances of cholangiocarcinoma: Radiologic-pathologic correlation. RadioGraphics. 29:683–700. 2009. View Article : Google Scholar : PubMed/NCBI
12	Martin SP, Drake J, Wach MM, Ruff SM, Diggs LP, Wan JY, Good ML, Dominguez DA, Ayabe RI, Glazer ES, et al: Resection and chemotherapy is the optimal treatment approach for patients with clinically node positive intrahepatic cholangiocarcinoma. HPB (Oxford). 22:129–135. 2020. View Article : Google Scholar : PubMed/NCBI
13	Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR and Winchester DP: American Joint Committee on Cancer, American Cancer Society: AJCC cancer staging manual. 8th edition. American Joint Committee on Cancer; Chicago, IL: 2017
14	Yamamoto M, Takasaki K and Yoshikawa T: Lymph node metastasis in intrahepatic cholangiocarcinoma. Jpn J Clin Oncol. 29:147–150. 1999. View Article : Google Scholar : PubMed/NCBI
15	Martin SP, Ruff S, Diggs LP, Drake J, Ayabe RI, Brown ZJ, Wach MM, Steinberg SM, Davis JL and Hernandez JM: Tumor grade and sex should influence the utilization of portal lymphadenectomy for early stage intrahepatic cholangiocarcinoma. HPB (Oxford). 21:419–424. 2019. View Article : Google Scholar : PubMed/NCBI
16	de Jong MC, Nathan H, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H, Pulitano C, Barroso E, Clary BM, Aldrighetti L, et al: Intrahepatic cholangiocarcinoma: An international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol. 29:3140–3145. 2011. View Article : Google Scholar : PubMed/NCBI
17	Jutric Z, Johnston WC, Hoen HM, Newell PH, Cassera MA, Hammill CW, Wolf RF and Hansen PD: Impact of lymph node status in patients with intrahepatic cholangiocarcinoma treated by major hepatectomy: A review of the National Cancer Database. HPB (Oxford). 18:79–87. 2016. View Article : Google Scholar : PubMed/NCBI
18	Zhang XF, Xue F, Dong DH, Weiss M, Popescu I, Marques HP, Aldrighetti L, Maithel SK, Pulitano C, Bauer TW, et al: Number and station of lymph node metastasis after curative-intent resection of intrahepatic cholangiocarcinoma impact prognosis. Ann Surg. 274:e1187–e1195. 2021. View Article : Google Scholar : PubMed/NCBI
19	Jolissaint JS, Soares KC, Seier KP, Kundra R, Gönen M, Shin PJ, Boerner T, Sigel C, Madupuri R, Vakiani E, et al: Intrahepatic cholangiocarcinoma with lymph node metastasis: Treatment-Related outcomes and the role of tumor genomics in patient selection. Clin Cancer Res. 27:4101–4108. 2021. View Article : Google Scholar : PubMed/NCBI
20	Yamamoto M, Takasaki K, Yoshikawa T, Ueno K and Nakano M: Does gross appearance indicate prognosis in intrahepatic cholangiocarcinoma? J Surg Oncol. 69:162–167. 1998. View Article : Google Scholar : PubMed/NCBI
21	Ohtsuka M, Ito H, Kimura F, Shimizu H, Togawa A, Yoshidome H and Miyazaki M: Results of surgical treatment for intrahepatic cholangiocarcinoma and clinicopathological factors influencing survival. Br J Surg. 89:1525–1531. 2002. View Article : Google Scholar : PubMed/NCBI
22	Shimada K, Sano T, Sakamoto Y, Esaki M, Kosuge T and Ojima H: Surgical outcomes of the mass-forming plus periductal infiltrating types of intrahepatic cholangiocarcinoma: A comparative study with the typical mass-forming type of intrahepatic cholangiocarcinoma. World J Surg. 31:2016–2022. 2007. View Article : Google Scholar : PubMed/NCBI
23	Wang Y, Li J, Xia Y, Gong R, Wang K, Yan Z, Wan X, Liu G, Wu D, Shi L, et al: Prognostic nomogram for intrahepatic cholangiocarcinoma after partial hepatectomy. J Clin Oncol. 31:1188–1195. 2013. View Article : Google Scholar : PubMed/NCBI
24	Utada M, Ohno Y, Tamaki T, Sobue T and Endo G: Long-term trends in incidence and mortality of intrahepatic and extrahepatic bile duct cancer in Japan. J Epidemiol. 24:193–199. 2014. View Article : Google Scholar : PubMed/NCBI
25	Kubo S, Shinkawa H, Asaoka Y, Ioka T, Igaki H, Izumi N, Itoi T, Unno M, Ohtsuka M, Okusaka T, et al: Liver Cancer Study Group of Japan Clinical Practice Guidelines for Intrahepatic Cholangiocarcinoma. Liver Cancer. 11:290–314. 2022. View Article : Google Scholar : PubMed/NCBI