Isolated Metachronous Splenic Metastasis Following Discontinuation of PD-1 Inhibitor Therapy in Hepatocellular Carcinoma: A Rare Pattern of Late Recurrence — A Case Report

Xuheng Hu,1,* Junjie Chen,1,* Zhen Li,1 Qianlong Xie,1 Hengheng Long,1 Yongfei He,1 Jilong Wang,1 Tao Peng,1,2 Xinping Ye1,21Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinping Ye, Email yexinping@gxmu.edu.cn; Tao Peng, Email pengtaogmu@163.comBackground: Isolated splenic metastasis from hepatocellular carcinoma (HCC) is uncommon, with only a small number of well-characterised solitary cases reported in the English-language literature. Moreover, late extrahepatic recurrence after immune checkpoint inhibitor (ICI) discontinuation in patients achieving complete response remains poorly characterized, posing significant challenges for surveillance and management.Case Presentation: A 52-year-old woman with a 6-year history of HBV-related HCC underwent sequential treatments including hepatectomy, microwave ablation, repeat hepatectomy, and PD-1 inhibitor therapy (sintilimab), achieving a sustained complete radiological response. Approximately 18 months after ICI cessation, surveillance imaging revealed an isolated 3.0 × 2.6 cm splenic lesion with markedly elevated PIVKA-II (257.81 mAU/mL; reference < 40 mAU/mL) despite normal AFP. Following multidisciplinary evaluation and preoperative splenic artery embolization, open splenectomy was performed. Histopathology confirmed metastatic HCC (Glypican-3+, Arginase-1+, CK19 focal+, Ki-67 ~30%), and PIVKA-II normalized postoperatively. Maintenance lenvatinib (8 mg daily) was initiated 5 months postoperatively as a risk-adapted strategy based on high-risk pathological features. At 12-month follow-up, the patient remained without evidence of radiological or biochemical recurrence, with excellent performance status; longer follow-up is required to confirm durability of response.Conclusions: This case illustrates: (1) that the spleen may occasionally be a site of late oligometastatic recurrence in HCC sustained radiological complete response by mRECIST criteria; (2) the complementary value of PIVKA-II in detecting AFP-negative extrahepatic disease; and (3) that, in carefully selected patients, splenectomy combined with tailored systemic therapy may be a technically feasible option, though whether this approach constitutes a curative strategy remains unproven in the absence of prospective or large-cohort validation. The temporal association between ICI discontinuation and late relapse highlights critical knowledge gaps regarding immune-mediated tumor dormancy and optimal duration of immunotherapy, warranting prospective investigation.Keywords: hepatocellular carcinoma, isolated splenic metastasis, immune checkpoint inhibitor, tumor dormancy, oligometastasis, splenectomy