PS5-06-09: Immunotherapy induced Kikuchi Fujimoto (Histiocytic Necrotizing Lymphadenitis): A Rare Immune Related Adverse Event

Abstract Introduction Immunotherapy (IO) agents can cause a range of rare immune-related adverse events (irAEs) due to immune system activation. Kikuchi-Fujimoto disease (KFD), a benign inflammatory condition characterized by self-limiting lymphadenopathy, fever, and occasional night sweats, is extremely uncommon and often associated with autoimmune diseases. Its atypical presentation can mimic infection or malignancy, making diagnosis challenging in oncology patients. We report a case of pembrolizumab-induced KFD in a patient with early-stage triple-negative breast cancer (TNBC). Case report: A 28-year-old woman with early-stage TNBC undergoing treatment with chemoimmunotherapy presented to the hospital with fever, left ear pain, left neck tenderness, and swelling. Magnetic resonance imaging (MRI) brain revealed edema of the left external auditory canal, mastoid and middle ear effusion, and soft tissue thickening, raising concern for necrotizing infection. Laboratory studies showed elevated erythrocyte sedimentation rate and aminotransferases. She was empirically started on broad spectrum antibiotics. Computed tomography (CT) neck showed rapidly progressing left neck/face inflammatory edema and possible early subperiosteal abscess. Given disease progression despite antibiotics, additional coverage was initiated for possible herpes zoster, atypical organisms, and fungal infection. Despite broadening infectious disease coverage, the patient continued to develop high grade fevers. With an unrevealing infectious workup, non-infectious etiologies including macrophage activation syndrome/HLH, autoimmune conditions, and KFD were considered. A left supraclavicular lymph node biopsy revealed benign reactive changes with expanded paracortical T lymphocytes, histiocytes, and polytypic plasma cells. Due to suspected inflammatory etiology, she was started on 250 mg methylprednisolone daily, resulting in prompt resolution of symptoms. The clinical presentation, disease course, and pathological findings were most consistent with a Kikuchi-Fujimoto reaction, a rare inflammatory condition likely triggered by pembrolizumab. She was able to safely resume pembrolizumab following a slow steroid taper without recurrence of symptoms. Discussion: Although IO has transformed the treatment landscape across many cancer types, it has also introduced a range of rare irAEs. IO-induced Kikuchi-Fujimoto is a very rare phenomenon, with only one previously reported case involving sintilimab. To our knowledge, there have been no reported cases of pembrolizumab-induced Kikuchi-Fujimoto like reactions. Given its nonspecific presentation and overlap with infectious and malignant etiologies, KFD can pose a diagnostic challenge. Clinicians should consider this rare entity in the irAE differential diagnosis when patients on pembrolizumab present with unexplained fever and lymphadenopathy. Notably, patients with IO-induced KFD often respond well to steroids and, may, in selected cases, be safely re-challenged with IO under close surveillance allowing oncologic treatment optimization. Conclusion KFD is a rare inflammatory condition that may occur as an irAE in patients with breast cancer receiving IO. A high index of suspicion is essential for early recognition and timely treatment. Citation Format: B. To, V. Prasath, L. Adorni, G. Bader, M. Cherian, A. Davenport, K. C. Johnson, N. Lopetegui-Lia, D. Quiroga, S. Sardesai, D. Stover, R. Wesolowski, N. Williams, M. E. Gatti-Mays, A. Meara, A. M. Roy. Immunotherapy induced Kikuchi Fujimoto (Histiocytic Necrotizing Lymphadenitis): A Rare Immune Related Adverse Event [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-09.