Clinical journal of gastroenterology · 2026
Paradoxical hyperprogressive disease in MSI-high intrahepatic cholangiocarcinoma treated with pembrolizumab.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
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Tanaka Takayuki, Sumida Yorihisa, Ikeda Takahiro, Fukuda Akiko, Hisanaga Makoto, Wakata Kohki, Araki Masato, Hayashi Hiroko, Nakamura Kosuke, Hidaka Masaaki
Аннотация
BACKGROUND: Cholangiocarcinoma carries a poor prognosis, and surgical resection remains the only curative option. Microsatellite instability-high (MSI-H) is a rare molecular subtype in intrahepatic cholangiocarcinoma (ICC). Although immune checkpoint inhibitors (ICIs) are effective in MSI-H malignancies, responses are variable. We report a rare case of MSI-H ICC that developed hyperprogressive disease (HPD) following pembrolizumab.
CASE PRESENTATION: An 81-year-old man with a history of endoscopic submucosal dissection for esophageal cancer underwent surveillance computed tomography (CT), which revealed a liver mass with intrahepatic bile duct dilation. Tumor markers were elevated (CA19-9: 214.9 U/mL). Suspecting ICC, liver resection was performed, achieving R0 resection. However, recurrence in the liver and hilar lymph nodes occurred within months. Systemic chemotherapy was ineffective. Genomic profiling (FoundationOne® CDx) revealed MSI-H, and pembrolizumab was initiated. After two cycles, rapid tumor progression was observed, with a ≥ twofold increase in tumor growth rate, consistent with HPD, along with new liver, bone, and peritoneal metastases. The patient died shortly thereafter.
CONCLUSION: This case highlights the paradoxical response to ICIs in ICC, demonstrating that MSI-H status does not preclude HPD. Further investigation of the tumor immune microenvironment is warranted.
CASE PRESENTATION: An 81-year-old man with a history of endoscopic submucosal dissection for esophageal cancer underwent surveillance computed tomography (CT), which revealed a liver mass with intrahepatic bile duct dilation. Tumor markers were elevated (CA19-9: 214.9 U/mL). Suspecting ICC, liver resection was performed, achieving R0 resection. However, recurrence in the liver and hilar lymph nodes occurred within months. Systemic chemotherapy was ineffective. Genomic profiling (FoundationOne® CDx) revealed MSI-H, and pembrolizumab was initiated. After two cycles, rapid tumor progression was observed, with a ≥ twofold increase in tumor growth rate, consistent with HPD, along with new liver, bone, and peritoneal metastases. The patient died shortly thereafter.
CONCLUSION: This case highlights the paradoxical response to ICIs in ICC, demonstrating that MSI-H status does not preclude HPD. Further investigation of the tumor immune microenvironment is warranted.