Immune-related Osteitis mimicking Femoral Head Osteonecrosis during Dual Checkpoint Blockade: A case report

Enrica Teresa Tanda^1,2Agostina Lagodin D'Amato²Giovanni Rossi¹Maria Maddalena Latocca¹Andrea Boutros^2,3,4*Andrea Zanirato^5,6Matteo Formica^5,6Silvia Bozzano⁷Bruno Spina⁸Francesco Spagnolo^1,5

• ¹U.O.C. Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy
• ²Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genoa, Genova, Italy
• ³Melanoma Institute Australia, The University of Sydney, Sydney, Australia
• ⁴U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
• ⁵Department of Integrated Surgical and Diagnostic Sciences (DISC), University of Genoa, Genova, Italy
• ⁶Clinica Ortopedica, IRCCS Ospedale Policlinico San Martino, Genova, Italy
• ⁷Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genova, Italy
• ⁸U.O.C. Anatomia Patologica Ospedaliera, IRCCS Ospedale Policlinico San Martino, Genova, Italy

Immune checkpoint inhibitors (ICIs) have dramatically reshaped the therapeutic landscape of oncology, offering long-term survival benefits across multiple tumor types. However, ICIs are associated with a broad range of immune-related adverse events (irAEs), most of which are now well characterized and manageable. A subset of irAEs, however, remains rare, unpredictable, and poorly understood, both in terms of clinical presentation and pathogenesis. Here, we describe the case of a patient with advanced melanoma treated with combined anti-CTLA-4 and anti-PD-1 therapy who developed severe left hip pain during treatment. Imaging findings were initially suggestive of osteonecrosis of the femoral head. However, histopathological analysis of the resected femoral head revealed a dense lymphoplasmacytic infiltrate with fibrosis and vascular congestion, without evidence of bone necrosis, consistent with an immune-mediated osteitis. To our knowledge, this represents the first documented case of direct immune-related inflammation selectively affecting bone tissue during ICI therapy. Recognition of such atypical skeletal irAEs may be critical for improving diagnosis and management strategies in the expanding field of immuno-oncology.