Pleural effusion in GIST: Imatinib, an unforeseen culprit

Abstract Pleural effusion is a common clinical scenario, typically linked to cardiac failure, infections, or malignancies. Imatinib, a tyrosine kinase inhibitor (TKI) widely used for GIST and chronic myeloid leukemia, is known to cause fluid retention; however, significant serosal effusions are uncommon and poorly characterized. This case report highlights a rare instance of imatinib-induced pleural effusion in a 73-year-old female with recurrent gastrointestinal stromal tumor. Pleural fluid analysis was consistent with an exudative effusion. Extensive evaluation including microbiological, cytological, imaging, autoimmune and cardiac failed to identify a specific cause for effusion, prompting to consider imatinib as the most likely etiology. Additionally, she experienced recurrent effusion upon re-challenge with a reduced dose of imatinib, reinforcing the suspicion of drug-induced effusion. This case underscores the importance of maintaining a high index of suspicion for drug-related, including imatinib-induced pleural effusion, especially once the conventional causes are excluded. Proposed mechanisms include endothelial dysfunction due to PDGFR inhibition, increased vascular permeability, impaired lymphatic drainage, immune dysregulation, and renal-mediated fluid retention. Therapeutic options beyond thoracentesis and diuretics include interrupting or reducing the TKI dose and concomitant steroids.