A rare case of unresectable, microsatellite instability-high hepatocellular carcinoma and an examination of the tumor microenvironment

Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide, and the mortality rate of patients with unresectable HCC is very high. Microsatellite instability (MSI) is an essential biomarker for response to immune checkpoint inhibitors (ICI) in various tumors. However, the frequency of MSI in HCC is low (1.11%). There is only one case report of MSI-high HCC, and it is not well understood how high MSI affects the tumor microenvironment of HCC. Hence, we describe an interesting patient with unresectable MSI-high HCC, including the evaluation of immune status in the tumor microenvironment. A 68-year-old man presented to our department with HCC in liver segment 1. Contrast-enhanced CT revealed a liver tumor of 6.0 cm in maximum size. The patient underwent extended left and caudate lobectomy of the liver for HCC. Four months after surgical resection, contrast-enhanced computed tomography (CECT) detected 13 recurrent nodules. The patient was diagnosed with unresectable hepatocellular carcinoma recurrence, and we decided to administer systematic chemotherapy. Lenvatinib was administered over approximately 2 years as a first-line treatment, which resulted in intrahepatic tumor shrinkage. However, follow-up CECT showed new lesions, hepatogastric mesentery lymph node swelling, and peritoneal dissemination. After MSI-high status was identified, the patient began to receive pembrolizumab (200 mg, every 3 weeks). Eleven cycles of pembrolizumab therapy were administered over approximately 8 months, during which the diameter of the hepatogastric mesentery lymph node swelling and peritoneal dissemination showed shrinkage but later re-increased. As the third- and fourth-line therapy has been administered, the tumors and lymph nodes have shrunk. We report a rare case in which multikinase inhibitors were effectively used to treat MSI-high HCC.