Pseudoprogression of pleural effusion in lung cancer treated with immunotherapy: a case report

Pseudoprogression (PsP) is an atypical response phenomenon increasingly recognized in patients treated with immune checkpoint inhibitors (ICIs), characterized by transient radiologic worsening before subsequent tumor regression. This response pattern complicates the interpretation of treatment efficacy and poses a challenge in distinguishing true disease progression from a treatment-related immune effect. While PsP is most commonly observed as an initial increase in tumor size or the appearance of new lesions, its presentation as pleural effusion is exceedingly rare and may be misdiagnosed as disease progression or immune-related adverse events (irAEs). Prompt recognition of this phenomenon is essential to avoid premature discontinuation of potentially effective therapy.

Here, we report a rare case of PsP manifesting as pleural effusion in a 56-year-old woman with lung adenocarcinoma and pleural dissemination who was treated with first-line pembrolizumab. Three weeks after treatment initiation, the patient developed new pleural effusion without accompanying symptoms. Pleural fluid analysis revealed adenocarcinoma cells with a predominance of lymphocytes. Despite the cytological findings, the patient's clinical stability and subsequent imaging demonstrated spontaneous resolution of the effusion and regression of disease with continued ICI therapy. The pleural effusion did not recur, and the patient remained on pembrolizumab for over 1 year until eventual progression.

This case highlights that PsP can manifest as new-onset pleural effusion, even in the presence of malignant cells in pleural fluid. Clinicians should be aware of this rare presentation, especially when the patient remains clinically stable. Differentiating PsP from irAEs and true progression remains challenging and emphasizes the need for improved biomarkers to guide decision-making. Continuation of ICIs may be appropriate in selected patients with manageable pleural effusion and controlled tumor burden, as inappropriate discontinuation could forfeit potential therapeutic benefit.