Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous bile duct adenocarcinoma with a rising global incidence and a poor prognosis. This review aims to present a comprehensive overview of the most recent radiological research on iCCA, focusing on its histopathologic subclassification and the use of imaging findings to predict prognosis and inform treatment decisions. Histologically, iCCA is subclassified into small duct (SD-iCCA) and large duct (LD-iCCA) types. SD-iCCA typically arises in the peripheral small bile ducts and is often associated with chronic hepatitis or cirrhosis. It presents as a mass-forming lesion with a relatively favorable prognosis. LD-iCCA originates near the hepatic hilum, is linked to chronic bile duct diseases, and exhibits more aggressive behavior and poorer outcomes. Imaging is essential for differentiating these subtypes and assessing prognostic factors like tumor size, multiplicity, vascular invasion, lymph node metastasis, enhancement patterns, and intratumoral fibrosis. Imaging-based prognostic models have demonstrated predictive accuracy comparable to traditional pathological staging systems. Furthermore, imaging findings are instrumental in guiding treatment decisions, including those regarding surgical planning, lymphadenectomy, neoadjuvant therapy, and the selection of targeted therapies based on molecular profiling. Advancements in radiological research have improved our understanding of iCCA heterogeneity, facilitating prognosis prediction and treatment personalization. Imaging findings assist in subclassifying iCCA, predicting outcomes, and informing treatment decisions, thus optimizing patient management. Incorporating imaging-based approaches into clinical practice is crucial for advancing personalized medicine in the treatment of iCCA. However, further high-level evidence from international multicenter prospective studies is required to validate these findings and increase their clinical applicability.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, with poor clinical outcomes due to challenges in early detection and limited efficacy of current treatments such as receptor tyrosine kinase inhibitors and immunotherapy. HCC exhibits significant heterogeneity at both histopathological and molecular levels, complicating its management but offering potential for personalized therapeutic approaches. This review outlines the morpho-molecular heterogeneity of HCC and summarizes various histological subtypes, including steatohepatitic, clear cell, macrotrabecular-massive, scirrhous, lymphocyte-rich, and fibrolamellar HCCs. Each subtype possesses distinct clinical, histological, and molecular features; for instance, steatohepatitic HCC is associated with metabolic dysfunction and shows IL-6/JAK/STAT activation, while clear cell HCCs often have IDH1 mutations and favorable prognosis. The macrotrabecular-massive subtype is linked to poor outcomes and TP53 mutations, whereas scirrhous HCCs express stemness markers and have TSC1/TSC2 mutations. Lymphocyte-rich HCCs are characterized by immune cell infiltration and better prognosis. CTNNB1-mutated HCCs show specific morphological features and may benefit from targeted therapies. Understanding these subtypes and associated molecular alterations is crucial for developing effective diagnostic and therapeutic strategies, including potential predictive biomarkers and personalized treatments. Additionally, the identification of patterns like vessels-encapsulating-tumor-clusters offers prognostic implications and may guide therapeutic decisions. Recent molecular studies have enhanced our comprehension of HCC heterogeneity, laying the groundwork for more personalized approaches. Pathologists play a vital role in recognizing these subtypes, aiding in prognosis prediction and treatment planning. Advances in digital pathology and artificial intelligence may further facilitate biomarker research, ultimately improving patient outcomes in HCC management.