Granulomatous Panniculitis in a Patient Treated With Cemiplimab: Case Report and Literature Review

ABSTRACT Immune checkpoint inhibitors (ICIs) have become a cornerstone in the treatment of advanced malignancies by enhancing antitumor immunity, but they may also trigger a broad spectrum of immune‐related adverse events (irAEs) involving multiple organs. Cutaneous irAEs are among the most frequent, yet their clinical spectrum is wide and sometimes challenging to recognize. Granulomatous panniculitis represents an uncommon manifestation and remains poorly characterized in the literature. We describe the case of a 77‐year‐old man with stage IVb lung adenocarcinoma receiving cemiplimab, a PD‐1 inhibitor, who developed progressive bilateral leg pain and symmetrical swelling after 20 cycles of immunotherapy. On physical examination, erythematous and edematous plaques were observed over the pretibial areas, without palpable nodules or systemic symptoms. Deep skin biopsy demonstrated a mixed septolobular panniculitis with non‐necrotizing granulomas, and microbiological studies excluded infectious causes. Oral corticosteroid therapy with a tapering regimen led to rapid clinical improvement, and cemiplimab treatment could be safely continued without recurrence of cutaneous lesions or additional irAEs. This case highlights the diagnostic challenge of panniculitis in patients undergoing ICI therapy, since clinical findings may overlap with more common entities such as cellulitis, erythema nodosum, or lipodermatosclerosis. Histopathological confirmation through deep biopsy is essential for accurate diagnosis. The pathogenesis may involve aberrant immune activation and macrophage polarization induced by checkpoint blockade. Recognition of this rare adverse event is crucial, as prompt initiation of corticosteroids is usually effective and unnecessary discontinuation of immunotherapy can be avoided. Awareness of granulomatous panniculitis as a potential ICI‐related cutaneous toxicity will contribute to better clinical management and to maintaining oncologic benefit in affected patients.