Pembrolizumab-associated hemophagocytic lymphohistiocytosis in recurrent metastatic squamous cell carcinoma of the ovary arising in a teratoma

• Describes a rare case of pembrolizumab-associated hemophagocytic lymphohistiocytosis in ovarian squamous cell carcinoma arising from a mature teratoma. • Illustrates the diagnostic challenges of HLH in the setting of immune checkpoint inhibition, including overlap with infection, treatment-related toxicity, and malignancy progression. • Demonstrates successful management of immune-related HLH with corticosteroid therapy alone and highlights the importance of early multidisciplinary collaboration. The expanding use of immune checkpoint inhibitors (ICIs) in gynecologic oncology has been accompanied by an increasing incidence of immune related adverse events (irAEs), requiring rapid recognition and management to prevent significant morbidity and mortality ( Conroy and Naidoo, 2022 , Liu et al., 2023 , Kanji et al., 2022 ). Hematologic immune related adverse events remain particularly challenging due to their rarity, nonspecific presentation, and diagnostic complexity ( Kroll et al., 2022 ). Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome that is life-threatening if not promptly identified and treated ( Henter, 2025 ). We report a case of pembrolizumab associated HLH in a patient with recurrent metastatic squamous cell carcinoma of the ovary arising in a teratoma. The patient presented with persistent fevers, cytopenias, and laboratory abnormalities concerning for immune mediated toxicity following pembrolizumab therapy. Diagnostic evaluation highlighted the challenges of distinguishing HLH from other causes of systemic inflammation and infection in the oncology setting. Both HLH 2024 criteria and the HScore were utilized to support the diagnosis ( Naymagon et al., 2025 ). The patient was successfully treated with steroid monotherapy with clinical and laboratory improvement. HLH remains a rare but potentially fatal immune related adverse event associated with immune checkpoint inhibitors. We review previously reported cases of HLH in gynecologic malignancies, including two cases in cervical cancer, two in ovarian cancer, and one in endometrial cancer ( Wei et al., 2024 , Rollet et al., 2024 , Nosratian-Baskovic et al., 2016 , Li et al., 2022 ). Increased awareness, early diagnostic consideration, and prompt treatment are essential to improve outcomes in patients receiving immune checkpoint inhibitors.