Clear Cell Carcinoma: A Rare Variant of Cholangiocarcinoma Case Report and Systematic Review

<b>Background:</b> Cholangiocarcinoma (CCA) is a rare malignancy of the biliary epithelium, accounting for approximately 3% of gastrointestinal cancers. The clear-cell variant of CCA is rare, with only nine documented cases worldwide. This case report describes a unique presentation of clear-cell intrahepatic (or peripheral) cholangiocarcinoma (ICC), highlighting its clinical course, histopathological features, and management. <b>Case Presentation:</b> A 56-year-old female with no significant medical history presented with postprandial right upper quadrant and epigastric pain. Following an initial diagnosis of gallbladder stones, laparoscopic cholecystectomy was performed. However, persistent epigastric pain, nausea, and vomiting led to further evaluation, revealing a 2.7 × 2.5 cm mass in the gallbladder bed compressing the common bile duct with associated intrahepatic biliary dilation. Endoscopic retrograde cholangiopancreatography confirmed the findings, and the patient underwent a left hemihepatectomy with radical choledectomy and biliary reconstruction. Histopathology demonstrated clear-cell ICC. Postoperatively, the patient received adjuvant chemotherapy and remained disease free at 14 months' follow-up. <b>Methods:</b> A systematic review and meta-analysis were conducted according to PRISMA guidelines and the Cochrane Handbook. A comprehensive search of PubMed and SCOPUS was performed without restrictions until December 2024 to identify case reports and case series of clear-cell CCA. Data on clinical presentation, diagnostic findings, treatment modalities, and outcomes were extracted and analyzed. The quality of included studies was assessed using the Joanna Briggs Institute critical appraisal tools. <b>Results:</b> The systematic review included 7 studies reporting 9 cases of clear-cell CCA. The mean patient age was 59.7 years, and 77.8% of the cases underwent surgical intervention. Outcomes varied, with disease-free survival ranging from 7 to 30 months in the reported cases. Factors such as tumor size and the presence of metastasis influenced prognosis. <b>Conclusion:</b> Clear-cell CCA, though rare, should be considered in the differential diagnosis of biliary masses. Early surgical intervention is pivotal for improved outcomes, but further studies are needed to develop consensus treatment guidelines. Reporting additional cases is essential to enhance understanding and optimize management of this rare malignancy.