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<p>Primary hepatic undifferentiated carcinoma is an extremely rare and aggressive malignancy with no established systemic therapy, and the efficacy of immune checkpoint inhibitors (ICIs) remains unknown. We report a 67-year-old man with compensated hepatitis C–related cirrhosis who presented with a 27&#xa0;mm segment 8 liver lesion and lymph node and bone metastases. Liver biopsy revealed undifferentiated carcinoma with high programmed death-ligand 1 (PD-L1) expression, and combination therapy with durvalumab and tremelimumab (Dur/Tre) was initiated. Shortly after treatment, the patient developed cranial nerve palsies (III, VII, VIII), suspected to represent either an immune-related adverse event or Ramsay Hunt syndrome; his symptoms improved with prednisolone and valaciclovir, allowing Dur/Tre to be resumed. After four courses, partial tumor shrinkage was achieved, and after 17 courses the primary tumor had decreased to 10&#xa0;mm with complete resolution of nodal metastases, without further significant adverse events. To our knowledge, this is the first report of primary hepatic undifferentiated carcinoma with high PD-L1 expression demonstrating a sustained response to Dur/Tre. This case suggests that PD-L1 expression may serve as a potential biomarker for predicting ICI responsiveness in this rare and aggressive tumor.</p>

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Durvalumab and tremelimumab combination therapy achieved remarkable response in primary hepatic undifferentiated carcinoma with high PD-L1 expression

  • 期刊论文

  • 发表日期：

    2026年5月4日

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  • Michihiko Kawahara,
  • Hatsue Fujino,
  • Yasutoshi Fujii,
  • Atsushi Ono,
  • Tomokazu Kawaoka,
  • C. Nelson Hayes,
  • Masataka Tsuge,
  • Tetsuya Nakagiri,
  • Koji Arihiro,
  • Shiro Oka

摘要

Primary hepatic undifferentiated carcinoma is an extremely rare and aggressive malignancy with no established systemic therapy, and the efficacy of immune checkpoint inhibitors (ICIs) remains unknown. We report a 67-year-old man with compensated hepatitis C–related cirrhosis who presented with a 27 mm segment 8 liver lesion and lymph node and bone metastases. Liver biopsy revealed undifferentiated carcinoma with high programmed death-ligand 1 (PD-L1) expression, and combination therapy with durvalumab and tremelimumab (Dur/Tre) was initiated. Shortly after treatment, the patient developed cranial nerve palsies (III, VII, VIII), suspected to represent either an immune-related adverse event or Ramsay Hunt syndrome; his symptoms improved with prednisolone and valaciclovir, allowing Dur/Tre to be resumed. After four courses, partial tumor shrinkage was achieved, and after 17 courses the primary tumor had decreased to 10 mm with complete resolution of nodal metastases, without further significant adverse events. To our knowledge, this is the first report of primary hepatic undifferentiated carcinoma with high PD-L1 expression demonstrating a sustained response to Dur/Tre. This case suggests that PD-L1 expression may serve as a potential biomarker for predicting ICI responsiveness in this rare and aggressive tumor.