Clinicopathological Features of Intrahepatic Cholangiocarcinoma with Assessment of IDH1 Mutation: A Two-Center...

Background/Objective: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with limited therapeutic options and poor survival outcomes. Recent advances in molecular oncology have highlighted the significance of isocitrate dehydrogenase 1 (IDH1) mutations as potential therapeutic targets. However, data on the prevalence and prognostic implications of IDH1 mutations in patients with iCCA are scarce. This study aimed to retrospectively investigate the IDH1 mutation rate, histopathological features, and survival outcomes of patients with iCCA. Methods: We retrospectively analyzed 88 patients diagnosed and treated between 2005 and 2025 at two tertiary oncology centers. Clinical, pathological, and survival data were obtained from the institutional oncology archives and national population databases. IDH1 mutation status was evaluated using polymerase chain reaction and next-generation sequencing of paraffin-embedded tissue samples. Results: A total of 88 patients with iCCA were included, with a median age of 62 years, and 62.5% were male. Abdominal pain was the most common presenting symptom (67%). The most frequent stages at diagnosis were stage IB and stage IIIB (22.7% each). Histopathologically, the small-duct subtype (55.7%), nodular morphology (67.0%), and solitary tumors (79.5%) predominated. IDH1 mutation was detected in 2.3% of patients. Curative surgery was performed in 78.2% of cases and was more common in early-stage disease. Gemcitabine-capecitabine was the most frequently used adjuvant regimen, whereas gemcitabine-cisplatin was the most common palliative treatment regimen. Median overall survival differed significantly by albumin-bilirubin (ALBI) grade, with 40.1, 11.1, and 4.4 months for grades 1, 2, and 3, respectively (p < 0.001). Conclusions: In this multicenter cohort, iCCA was characterized by diverse clinicopathological features and treatment approaches. Surgical resection remains the main treatment modality for patients with localized disease, whereas systemic therapies are more frequently used in advanced stages. The findings highlight the prognostic relevance of baseline clinical and biochemical characteristics and may improve risk stratification in patients with iCCA.