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Life sciences · Journal article
Frontiers in Oncology · October 15, 2026
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Background Immune checkpoint inhibitors (ICIs) are associated with a wide spectrum of immune-related adverse events (irAEs), reflecting enhanced immune activation. Pancreatic involvement is rare and typically presents as asymptomatic hyperlipasemia or diffuse inflammatory changes. Focal or multifocal mass-like presentations are uncommon and may mimic pancreatic malignancy, posing a significant diagnostic challenge. Case presentation We report the case of a 48-year-old woman treated with Pembrolizumab and Paclitaxel for axillary recurrence of triple-negative breast cancer. After four cycles, FDG PET/CT demonstrated a complete metabolic response at the initial tumor site but revealed new multifocal hypermetabolic pancreatic lesions. Magnetic resonance imaging confirmed multiple pancreatic masses, raising suspicion of metastatic disease or dissociated response. Endoscopic ultrasound-guided fine-needle aspiration at two concordant pancreatic sites showed neutrophil-predominant inflammatory infiltration without malignant cells, consistent with immune-related pancreatic injury. The patient subsequently developed symptoms of exocrine pancreatic insufficiency, which improved after concomitant initiation of pancreatic enzyme replacement therapy and corticosteroid tapering, with the relative contribution of each not clearly distinguishable. Follow-up imaging demonstrated complete resolution of pancreatic lesions. Discussion This case highlights a rare mass-forming (pseudotumoral) phenotype of ICI-related pancreatic injury (ICI-PI), presenting as multifocal FDG-avid pancreatic pseudomasses. Such findings may represent a major pitfall in PET/CT interpretation under immunotherapy, particularly in the context of otherwise favorable oncologic response. Histopathological confirmation is critical to distinguish immune-mediated inflammation from metastatic disease. This observation supports the concept of organ-specific immune dysregulation driven by ICIs and expands the radiological spectrum of pancreatic irAEs. Conclusion Multifocal FDG-avid pancreatic lesions occurring during immunotherapy should raise suspicion for immune-related pancreatic injury (ICI-PI), especially in the absence of systemic progression. Early recognition is essential to avoid misdiagnosis and inappropriate treatment decisions.