Sarcoidosis‐Like Granulomatous Reaction During Adjuvant Pembrolizumab for High‐Risk Resected Melanoma

Introduction Immunotherapy with immune checkpoint inhibitors has transformed the management of advanced melanoma and resected high‐risk disease. However, their use is associated with immune‐related adverse events, including sarcoidosis‐like granulomatous reactions—an uncommon toxicity that may be mimic disease progression or infection. Clinical Case We report the case of a 70‐year‐old woman with Stage IIC cutaneous melanoma (pT4bN0M0), harboring an NRAS Q61L mutation, treated with adjuvant pembrolizumab. After three cycles, she developed subcutaneous nodules, lower‐limb edema, and ocular symptoms. Histological evaluation confirmed a sarcoidosis‐like granulomatous reaction. Pembrolizumab was discontinued and systemic corticosteroid therapy was initiated, resulting in partial clinical improvement. Discussion Sarcoidosis‐like reactions (SLRs) are rare but clinically relevant adverse events associated with PD‐1 inhibitors. Their differential diagnosis is challenging and requires exclusion of tumor progression and infectious processes. These reactions should be considered in patients receiving immunotherapy who develop atypical systemic manifestations. This phenomenon may have prognostic implications and warrants multidisciplinary management approach. Conclusion This case highlights the importance of recognizing immune‐mediated SLRs during immunotherapy, particularly in melanoma, and underscores the need for a high index of suspicion and further evidence to guide optimal management strategies.