Zhineng Xie, Jie Huang, Kailong Fu
BACKGROUND Hepatocellular carcinoma (HCC) is an aggressive malignancy. Peritoneal metastasis is uncommon but carries a poor prognosis. Diagnosis of HCC with peritoneal metastasis is particularly challenging when alpha-fetoprotein (AFP) levels are normal. This report highlights diagnostic difficulties and the critical role of histopathological confirmation in such atypical presentations. CASE REPORT A 65-year-old man with chronic hepatitis B and a history of lung adenocarcinoma, who had previously undergone radiofrequency ablation and partial hepatectomy for HCC (the primary tumor was histologically confirmed as moderately differentiated HCC with negative AFP immunostaining), presented with recurrent left lower abdominal pain. Laboratory tests showed normal serum AFP but elevated carbohydrate antigen 125 (CA125). Imaging revealed a solitary peritoneal mass without evidence of intrahepatic recurrence. The patient underwent surgical resection. Immunohistochemistry confirmed hepatocellular origin (hepatocyte paraffin 1-positive, arginase-1-positive) and excluded lung adenocarcinoma (thyroid transcription factor-1-negative, napsin A-negative). Importantly, AFP immunohistochemistry findings were negative in the metastatic tumor, consistent with the primary tumor. The Ki-67 proliferation index was 50%. Postoperative recovery was uneventful, and no recurrence was observed at the 3-month follow-up. CONCLUSIONS Normal AFP levels do not exclude recurrent or metastatic HCC. In patients with multiple primary malignancies, diagnosis of new lesions requires careful integration of clinical history, imaging findings, and histopathological evaluation. Surgery may offer both diagnostic and therapeutic value in selected patients, although its long-term benefit remains uncertain.