Pembrolizumab adjuvant therapy linked to rare eosinophilic polyserositis in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is a prevalent and aggressive malignancy, often requiring adjuvant therapy to prevent recurrence after surgery. Pembrolizumab, an immune checkpoint inhibitor, is a standard adjuvant treatment for high-risk ccRCC. While effective, it can induce immune-related adverse events (irAEs), which are diverse and can mimic disease recurrence or infection. Serositis, inflammation of serous membranes, is an uncommon irAE, and its specific phenotypes, particularly those involving eosinophilia, are not well-characterized, posing diagnostic challenges in clinical practice.

This case report describes a 55-year-old man who achieved no evidence of disease following nephrectomy and metastasectomy for clear cell renal cell carcinoma. He subsequently received six cycles of adjuvant pembrolizumab. After the sixth cycle, he developed anasarca, large bilateral pleural effusions, mild ascites, peripheral eosinophilia, and a small pericardial effusion. Diagnostic workup included pleural fluid analysis, cytology, and microbiological studies. The intervention involved discontinuing pembrolizumab, administering corticosteroids, and performing thoracentesis. Clinical and laboratory improvements were monitored, with follow-up extending through March 2026 for oncologic progression.

After six cycles of pembrolizumab, the patient presented with significant fluid accumulation and peripheral eosinophilia. Pleural fluid analysis revealed an exudative effusion containing a notable 20% eosinophils. Cytology confirmed inflammatory cells but showed no evidence of malignancy, and extensive bacterial, mycobacterial, and fungal studies were negative. Adenosine deaminase levels were only mildly elevated, ruling out tuberculosis. Cardiac function and natriuretic peptides remained preserved. > Upon discontinuation of pembrolizumab and initiation of corticosteroids, the patient experienced rapid improvement in symptoms, peripheral eosinophilia, renal function, and serum albumin levels. Follow-up through March 2026 confirmed no oncologic progression, although some residual pleural and abdominal fluid persisted, potentially influenced by imaging findings suggestive of portal-hypertension physiology, which did not fully explain the eosinophilic pleural syndrome.