==== Front Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.39787 Gastroenterology Oncology Intrahepatic Cholangiocarcinoma With Lung Metastasis in a 29-Year-Old Male Patient: A Case Report Muacevic Alexander Adler John R Calle Prado Marco A 1 Casanova Rivera Maria F 1 Vasquez Cedeño Diego A 1 1 Faculty of Medicine, Universidad Católica de Santiago de Guayaquil, Guayaquil, ECU Marco A. Calle Prado marco.calle01@cu.ucsg.edu.ec 31 5 2023 5 2023 15 5 e3978731 5 2023 Copyright © 2023, Calle Prado et al. 2023 Calle Prado et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This article is available from https://www.cureus.com/articles/160269-intrahepatic-cholangiocarcinoma-with-lung-metastasis-in-a-29-year-old-male-patient-a-case-report Cholangiocarcinoma (CCA) is an uncommon biliary neoplasm that is more frequent in male patients. CCA is categorized into intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA) associated with the anatomical origin location. The clinical presentation is non-specific and varies depending on the origin, iCCA is generally asymptomatic until advanced disease is present therefore this neoplasm presents a poor prognosis with a survival rate of two years. We present a case of iCCA with lung metastasis in a 29-year-old male patient with no risk factors for this malignancy. cholangiocarcinoma aggressive neoplasm poor outcomes metastatic cholangiocarcinoma intrahepatic cholangiocarcinoma ==== Body pmcIntroduction Cholangiocarcinoma (CCA) is a rare malignancy of the biliary tree and represents 3% of gastrointestinal neoplasms [1,2]. CCAs have been classified according to their anatomical site of origin in intrahepatic (iCCA) and extrahepatic (eCCA), eCCAs have been sub-classified in perihilar and distal, 50% of CCAs arise in the perihilar region, 40% in the distal region, and 10% in the intrahepatic region [2,3]. The peak of incidence is the seventh decade of life with male predominance [4]. In most cases the cause leading to CCA can be traced to their chronic history of any of the risk factors including primary sclerosing cholangitis, choledochal cysts, chronic intrahepatic stone disease, chronic liver disease in the form of cirrhosis or chronic viral hepatitis are also being recognized; the strongest risk factors include non-alcoholic fatty liver disease and cholelithiasis associated with chronic inflammation. However, in most cases, no cause can be established [4-6]. The clinical manifestations of CCA are often subtle and depend if it is iCCA or eCCA. iCCA diagnosis is often incidental and occurs proximal to the second-order bile ducts which are the next largest branches or ducts of the biliary system which join to form or empty into the main hepatic bile duct, so symptoms of biliary obstruction are much less common compared with eCCA [7-9]. Jaundice is not frequent in iCCA, the symptoms are non-specific such as abdominal pain, fatigue, malaise, nausea, night sweats, and weight loss. Given these general and vague symptoms, iCCA is diagnosed at an advanced stage [8,10,11]. Conversely, eCCA most often present with jaundice, pruritus, clay-colored stools, tea-colored urine, and occasional right upper quadrant pain [7,8]. CCA has a poor prognosis with a median survival of two years [4,10]. Five-year survival remains low even with resection and ranges from 10 to 49% [7]. iCCA arising in non-cirrhotic livers has a poorer prognosis [11]. Case presentation A 29-year-old Ecuadorian man who had no previous medical history of diseases and denied family history of malignancies. The patient was admitted to the hospital for chief complaints of fatigue, malaise, and vomiting. Physical examination was unremarkable. Laboratory data are summarized in Table 1. His serum CA (carbohydrate antigen) 19-9, carcinoembryonic antigen (CEA), CA 72-4, liver kidney microsomal type 1 antibody (anti-LKM-1), antinuclear antibody (ANA), and soluble liver antigen (SLA) were within normal limits. He had negative serology for hepatitis B and C. Table 1 Initial laboratory investigation ALT: alanine aminotransferase AST: aspartate aminotransferase GGT: gamma-glutamyl transpeptidase ALP: alkaline phosphatase Laboratory test Normal range Result White blood cells 4.10-10.10 10x9/L 9.9 10x9/L Hemoglobin 12.9-16.7 g/dL 15.9 g/dL Mean corpuscular volume 80.8-94.1 fL 90 fL Platelet count 153-328 10x9/L 261 10x9/L ALT 21-72 U/L 62 U/L AST 17-59 U/L 67 U/L GGT 15-73 U/L 687 U/L ALP 38.0-126.0 U/L 225 U/L Albumin level 3.5-5.0 g/dL 5 g/dL Total bilirubin 0.2-1.3 mg/dL 1.10 mg/dL Abdominal computed tomography (CT) scan with and without intravenous contrast was obtained and showed irregular liver contours with a space-occupying lesion with indistinct borders, which has a low density in the portal phase with heterogeneous enhancements postcontrast, with a greater axial diameter of 19 cm, involves the entire left hepatic lobe and partially the medial segments of the right lobe associated with low-density nodular images in the portal phase with ring enhancement of 20 mm, 11 mm, 10 mm as well as adenopathies in the course of the celiac trunk (Figure 1). Figure 1 Abdominal CT demonstrated a low-density mass, involving the left hepatic lobe (green arrow) and medial segment of the right lobe (yellow arrow). B. The tumor exhibited celiac trunk adenopathies (red arrow). CT: computed tomography Abdominal magnetic resonance imaging (MRI) scan with and without contrast revealed a solid, expansive mass of approximately 20 x 12 cm that involves almost the entire left hepatic lobe and partially the medial segments of the right lobe, hyperintense on T2 with hypointense areas on T1 and a pseudocapsule on its periphery with peripheral enhancement in the early post-contrast phase, the mass causes irregularity of the hepatic contour associated with the presence of multiple nodular images inside, it is also associated with multiple multisegmented nodular lesions in the right lobe measuring 21 mm, 12 mm, 10 mm with ring enhancement in the early post-contrast phase, compatible with intrahepatic bile duct space-occupying mass. The lesion involves and infiltrates the left suprahepatic vein as well as the left branch of the portal vein and the left hepatic duct and its branches. Adenopathies in the course of the celiac trunk, measuring 17 mm, 16 mm (Figure 2). Figure 2 MRI demonstrated an irregular and heterogeneous mass (A). The mass showed multiple multisegmented nodular lesions in the right lobe (B). Biliary tree infiltration (C). MRI: magnetic resonance imaging The patient underwent a CT-guided liver biopsy. Pathologic analysis showed epithelial neoplastic proliferation with irregular and coalescent pseudoglandular structures with focal intraluminal necrosis, lined by cuboidal to columnar epithelium with nuclear atypia, mitotic figures, and some subnuclear vacuoles, immersed in the stroma with marked desmoplastic fibrosis consistent with iCCA (Figure 3). Figure 3 Microscopic findings of the resected liver mass exhibited rich stroma with fibrosis. Immunohistochemical staining of the mass revealed cytokeratin (CK7) 95% positive at the edges of the neoplastic glandular epithelium, CEA and CEA monoclonal (CEAm) were 90% positive at the apical luminal edges of the neoplastic glands, negative for CD10 and CDX2. Based on these histopathological and immunohistochemical the diagnosis was consistent with well-differentiated CCA (Figure 4). Figure 4 Immunohistochemical of the liver mass demonstrated that the tumor cells were positive for CK7 (A), CEA (B), and CEAm (C). CK7: cytokeratin; CEA: carcinoembryonic antigen; CEAm: carcinoembryonic antigen monoclonal A high-resolution chest CT scan with and without intravenous contrast was obtained and revealed multiple, bilateral pulmonary nodules of different sizes, randomly distributed, measuring between 13 mm, 12 mm, 11 mm, some of them with post-contrast enhancement, compatible with metastatic lesions. Medial supradiaphragmatic and right paracardiac lymph nodes of 17 mm and 13 mm, no pleural effusions were observed (Figure 5). Figure 5 Chest CT demonstrated multiple nodules bilaterally (A) and supradiaphragmatic and paracardiac lymph nodes (B). CT: computed tomography After determining that the patient was not a surgical candidate (due to metastasis), he was started on systemic therapy with gemcitabine and cisplatin for 21 cycles. Over the course of this regimen, slight dose adjustments were necessary due to weight variations and increase in metastatic lesions. Chemotherapy was changed to oxaliplatin, 5-fluorouracil (5-FU), and folinic acid due to persistent mass increase with a duration of four cycles after the patient presented a decompensation due to hematemesis, he underwent upper gastrointestinal endoscopy, which showed esophageal varices controlled by six-rubber-band ligation and red blood cell transfusion. Follow-up laboratories were performed while receiving gemcitabine + cisplatin and oxaliplatin, 5-fluorouracil (5-FU), and folinic acid. Results are summarized in Table 2. Table 2 Laboratories while receiving treatment with gemcitabine and cisplatin (column A) and oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (column B). ALT: alanine aminotransferase AST: aspartate aminotransferase GGT: gamma-glutamyl transpeptidase ALP: alkaline phosphatase Laboratory test Normal range Result Column A Result Column B White blood cells 4.10-10.10 10x9/L 8.9 10x9/L 8.29 10x9/L Hemoglobin 12.9-16.7 g/dL 12.5 g/dL 8.10 g/dL Platelet count 153-328 10x9/L 108 10x9/L 86 10x9/L ALT 21-72 U/L 27 U/L 15 U/L AST 17-59 U/L 48 U/L 50 U/L GGT 15-73 U/L 886 U/L 449 U/L ALP 38.0-126.0 U/L 186 U/L 197 U/L Albumin level 3.5-5.0 g/dL 3.8 g/dL 2.94 g/dL Total bilirubin 0.2-1.3 mg/dL 0.57 mg/dL 0.94 mg/dL The patient was stabilized and some days after he refused to continue with chemotherapy. He required frequent paracentesis for two months for nonmalignant ascites. The overall follow-up duration was 19 months, and the patient died 21 months after he was diagnosed. Discussion CCA is a rare neoplasm with an incidence rate of 0.3/100,000 habitants per year with a predominance in males between the fifth and seventh decade of life from Western countries with an annual incidence increase of 4% [2,11]. There are multiple risk factors with strong association with iCCA development such as cholelithiasis/choledocolithiasis, non-fatty liver disease, bile duct cysts, cholangitis, chronic pancreatitis, smoking, bile duct cysts, hepatitis, cirrhosis [2,4,5,12]. However, our patient developed iCCA at the unusual age of 29 years old, as well as the absence of both personal and family risk factors. Unfortunately, CCAs are generally diagnosed at advanced stages as a result of their non-specific clinical presentation. Signs and symptoms rely upon growth pattern, tumor location, and stage, due to this a large part of the cases are found incidentally. Although the clinical presentation, laboratory, and imaging studies serve as a guide, biopsy and immunohistochemistry are required to confirm the diagnosis [13,14]. The patient presented non-specific symptoms such as fatigue, malaise, and vomiting accompanied by altered liver tests which were complemented with CT and MRI scans which showed an occupying mass in the entirety of the left hepatic lobe and partially the right hepatic lobe these findings guided the diagnosis to neoplasm requiring biopsy and immunohistochemical staining to confirm the diagnosis. Serological tumor biomarkers such as CA 19-9 and CEA are usually elevated in CCA, however, the diagnostic accuracy is limited, since they can be elevated in benign conditions such as cholestasis, liver injury, and other cancers. Nevertheless, CA 19-9 values> 1000 U/mL have been associated with advanced-stage or metastatic iCCA [15,16]. Even though our patient was diagnosed with metastatic iCCA the tumor biomarkers remained within normal limits. Systemic chemotherapy is often the option for iCCA subjects with metastasis or unresectable tumor [8]. The ABC-02 study, in which patients with advanced biliary cancer were treated with the combination of gemcitabine-cisplatin and compared with patients treated with gemcitabine alone, demonstrated a higher median overall survival (11.7 vs 8.1 months, respectively; HR 0.64; 95% CI 0.52-0.8; p<0.001) in the first group, based on, it is considered the first-line chemotherapy regimen [6,8]. The ABC-06 study showed folinic acid, 5-fluorouracil, and oxaliplatin as a second line [1]. This was consistent with our patient who received a first-line regimen for 16 months but due to lack of response, it was changed to the second-line regimen. Conclusions iCCA is a very aggressive type of cancer with a high mortality rate that in most cases presents symptoms when it is in an advanced stage and surgery is often no longer an alternative treatment. Despite correct diagnosis and treatment, the disease is very aggressive and the patient was already in an advanced stage with metastases in both lungs, therefore, chemotherapy was administered to prolong the time and quality of life for several months until the patient stopped responding to treatment and ultimately succumbed to the disease. Human Ethics Consent was obtained or waived by all participants in this study The authors have declared that no competing interests exist. ==== Refs References 1 Cholangiocarcinoma Nat Rev Dis Primers Brindley PJ Bachini M Ilyas SI 65 7 2021 34504109 2 Cholangiocarcinoma: epidemiology and risk factors Liver Int Khan SA Tavolari S Brandi G 19 31 39 Suppl 1 2019 30851228 3 Current epidemiology of cholangiocarcinoma in Western countries J Hepatol Vithayathil M Khan SA 1690 1698 77 2022 35977611 4 Cholangiocarcinoma Surg Pathol Clin Krasinskas AM 403 429 11 2018 29751883 5 Examination on the risk factors of cholangiocarcinoma: a Mendelian randomization study Front Pharmacol Chen L Fan Z Sun X 900424 13 2022 36091764 6 Clinical treatment of cholangiocarcinoma: an updated comprehensive review Ann Hepatol Elvevi A Laffusa A Scaravaglio M 100737 27 2022 35809836 7 Cholangiocarcinoma Surg Clin North Am Khan AS Dageforde LA 315 335 99 2019 30846037 8 Intrahepatic cholangiocarcinoma Surg Oncol Clin N Am El-Diwany R Pawlik TM Ejaz A 587 599 28 2019 31472907 9 Cholangiocarcinoma: state of the art J Gastrointest Cancer Moazzami B Majidzadeh-A K Dooghaie-Moghadam A 774 781 51 2020 32157571 10 Cholangiocarcinoma 2020: the next horizon in mechanisms and management Nat Rev Gastroenterol Hepatol Banales JM Marin JJG Lamarca A 557 588 17 2020 32606456 11 Cholangiocarcinoma Pathologica Sarcognato S Sacchi D Fassan M 158 169 113 2021 34294934 12 Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a systematic review and meta-analysis J Hepatol Clements O Eliahoo J Kim JU Taylor-Robinson SD Khan SA 95 103 72 2020 31536748 13 Clinical presentation, diagnosis and staging of cholangiocarcinoma Liver Int Forner A Vidili G Rengo M Bujanda L Ponz-Sarvisé M Lamarca A 98 107 39 Suppl 1 2019 14 Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma Cancer Esnaola NF Meyer JE Karachristos A Maranki JL Camp ER Denlinger CS 1349 1369 122 2016 26799932 15 A metastatic intrahepatic cholangiocarcinoma treated with programmed cell death 1 inhibitor: a case report and literature review Immunotherapy Zhang J Wu L Liu J Lin M 555 561 12 2020 32372672 16 Pathogenesis, diagnosis, and management of cholangiocarcinoma Gastroenterology Rizvi S Gores GJ 1215 1229 145 2013 24140396