Conversion Surgery Following Durvalumab Plus Tremelimumab in Unresectable Hepatocellular Carcinoma with Para-Aortic Lymph Node Metastases: A Case of Complete Hepatic Response and Lymphatic Resistance.

INTRODUCTION: Recent advances in immune checkpoint inhibitor (ICI) therapy have made conversion surgery possible in selected patients with unresectable hepatocellular carcinoma (uHCC); however, outcomes in cases with extrahepatic spread remain unclear. CASE PRESENTATION: A 77-year-old man with hepatitis B-associated uHCC presented with a 60 mm tumor in the posterior section of the liver with several daughter nodules and multiple enlarged para-aortic lymph nodes (PALNs). Durvalumab plus tremelimumab was chosen over atezolizumab plus bevacizumab because of the patient's concurrent anticoagulant therapy for atrial fibrillation, which raised concerns about bleeding risk. Tumor markers (alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II) returned to normal after three cycles, and imaging demonstrated significant shrinkage of both the primary tumor and the lymph nodes. After nine treatment cycles, the primary tumor had further decreased to 25 mm without daughter nodules; however, two PALNs demonstrated regrowth. The patient subsequently underwent a subsegmentectomy of segment 6 and lymphadenectomy of the PALNs. Histopathological examination revealed a complete pathological response (pCR) in the liver tumor, with no viable tumor cells. However, metastatic lymph nodes contained viable undifferentiated carcinoma cells that were negative for hepatocellular markers (HepPar-1 and arginase-1) but positive for CAM5.2 and vimentin, indicating a treatment-resistant component. Twelve months postoperatively, the patient remained recurrence-free with preserved liver function and good general condition. CONCLUSIONS: This case demonstrates a discrepant therapeutic response, with a pCR in the liver contrasted with residual undifferentiated carcinoma in the PALNs. To our knowledge, this is the first reported HCC case demonstrating hepatic pCR after ICI therapy with residual undifferentiated carcinoma confined to the PALNs, highlighting immune-resistant extrahepatic clones and the diagnostic-therapeutic value of conversion surgery.