Evaluating Sarcoid-Like Reactions in Melanoma Patients Treated With Pembrolizumab: A Systematic Review

Pembrolizumab, a programmed cell death protein‑1 (PD‑1) inhibitor, has significantly improved outcomes in melanoma but is associated with immune‑related adverse events (irAEs), including sarcoid‑like reactions (SLRs). These granulomatous reactions can closely mimic metastatic disease on imaging, creating diagnostic uncertainty and potentially leading to unnecessary treatment changes. This systematic review examined the incidence, clinical features, diagnostic strategies, management, and outcomes of SLRs in melanoma patients treated with pembrolizumab. A comprehensive search of PubMed, Scopus, and CINAHL identified 980 articles, of which 13 met eligibility criteria. Extracted data included patient demographics, SLR timing, organ involvement, radiographic patterns, histopathology, treatment approach, and clinical course. The prevalence of SLRs ranged from 1.5% to 1.8%, with a mean onset of 7.1 months after therapy initiation. Pulmonary involvement, particularly hilar and mediastinal lymphadenopathy, was most frequently reported, followed by cutaneous and osseous granulomas. SLRs often mimicked melanoma progression on FDG‑PET/CT (fluorodeoxyglucose-positron emission tomography/computed tomography), emphasizing the importance of histologic confirmation. Most cases were managed conservatively or with corticosteroids, and pembrolizumab therapy was commonly continued without compromising melanoma control. Emerging evidence suggests that SLRs may reflect heightened immune activation and could potentially serve as favorable prognostic markers. SLRs are uncommon but clinically important irAEs in pembrolizumab‑treated melanoma patients. Their ability to resemble metastatic disease underscores the need for diagnostic vigilance and routine tissue confirmation. Because SLRs are generally benign and may correlate with treatment response, standardized diagnostic and management protocols are needed to guide clinical decision‑making in this growing patient population.