Serkan Sucu, Brian Longbottom, Hassan Aziz
Liver transplantation (LT) is the definitive treatment for early hepatocellular carcinoma (HCC), based on established criteria. Pre-transplant imaging occasionally underestimates the tumor burden or biological aggressiveness, leading to explant pathology that exceeds the projection criteria, such as Milan. This paper aims to review the incidence, prognostic implications, post-transplant management, and outcomes of explant pathology in patients with HCC beyond Milan. We conducted a narrative review of the literature focusing on imaging-pathology discrepancies, recurrence risk stratification, immunosuppression strategies, surveillance, and adjuvant therapeutic considerations. A significant proportion of LT recipients had explant findings that exceeded the predicted criteria. These patients are at higher risk of recurrence, particularly those with microvascular invasion and poor differentiation. Currently, no standard adjuvant therapy exists; however, individualized surveillance and immunosuppression optimization, including sirolimus-based regimens, are reasonable strategies. Prospective studies are needed to define the optimal post-transplant pathways. Explant-beyond-criteria HCC represents a distinct high-risk population that requires individualized post-transplant management. While no validated adjuvant therapy exists, risk stratification using tools such as the RETREAT score, immunosuppression optimization with mammalian target of rapamycin (mTOR) inhibitors, and intensified surveillance may improve outcomes. Prospective studies are needed to define the optimal management strategies for this challenging population.