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Remarkable Response to Pembrolizumab in Metastatic Cancer of Unknown Primary
Background:
Cancer of unknown primary (CUP) is aggressive, with limited options and poor prognosis. Mismatch repair-deficient (dMMR) CUP is rare, and reports of its response to immunotherapy are scarce.
Case Presentation:
A 52-year-old man presented with extensive liver metastases and severe hepatic dysfunction (bilirubin 14 mg/dL, ECOG 3). The primary site could not be identified; biopsy showed poorly differentiated carcinoma. Immunohistochemistry showed loss of MSH2, MLH1, and PMS2 (dMMR). Pembrolizumab produced rapid improvement, with bilirubin normalizing within three months and complete response by six months, sustained beyond 30 months.
Conclusions:
Pembrolizumab can achieve durable responses in dMMR CUP despite advanced disease and poor performance.
