Oral Squamous Cell Carcinoma versus Medication-Related Osteonecrosis of the Jaw in Patients assuming Bone-Modifying Agents: A Diagnostic Challenge in a Multi-Hospital Case Series

Rodolfo Mauceri¹Martina Coppini^1*Gaetano La Mantia¹Giuseppe Seminara¹Mario Perez Sayans²Corrado Toro³Rita Vitagliano⁴Hitoshi Kawamata⁵Toshiki Hyodo⁵Giuseppe Colella⁶Vito Rodolico⁷Giuseppina Campisi⁸

• ¹Department of Medicine of Precision in the Medical, Surgical and Critical Care Areas, University of Palermo, Palermo, Italy
• ²Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Galicia, Spain
• ³Maxillofacial Surgery Unit, Clinica del Mediterraneo of Ragusa, Ragusa, Sicily, Italy
• ⁴Multidisciplinary Department of Medical-Surgical and Dental Specialties, Oral and Maxillofacial Surgery Unit, University of Campania "Luigi Vanvitelli", Naples, Italy
• ⁵Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine, Dokkyo, Japan
• ⁶Multidisciplinary Department of Medical-Surgical and Dental Specialties, Oral and Maxillofacial Surgery Unit, University of Campania 'Luigi Vanvitelli', Naples, Campania, Italy
• ⁷Department of Pathologic Anatomy and Histology, University of Palermo, Palermo, Italy
• ⁸Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Sicily, Italy

Background: Despite advances in the diagnosis of oral squamous cell carcinoma (OSCC), most cases are diagnosed in advanced stages, influencing negatively the patient's prognosis. The absence of specific signs and symptoms contributes to the diagnostic delay of OSCC, often leading to confusion with various oral conditions, including, in patients with a history of bone modifying agents (BMA) and/or anti-angiogenic (AA) molecules, the Medication-Related Osteonecrosis of the Jaw (MRONJ). This study aims to investigate the characteristics of OSCC and MRONJ, focusing on clinical and radiological features of a multicenter series. Methods: According to STROBE statements, 11 patients collected by different centers and affected by OSCC undergoing BMA or AA therapy, with clinical and radiological features resembling MRONJ were reported (6 in Italy and 5 in Japan). Due to the suspicion of a malignant neoplasia, incisional biopsies for histological examination were performed. Results: in all eleven patients under ONJ-associated therapy, discerning between OSCC and MRONJ was a real challenge due to overlapping clinical and radiological features. The present case series highlights the importance of considering the possibility of malignant disease in patients undergoing ONJassociated therapy. Conclusion: Although biopsy is commonly considered unnecessary for MRONJ diagnosis, our findings highlight the importance of selectively performing bioptic procedures in patients taking ONJassociated therapy to exclude the malignant nature of oral lesions promptly.Keywords: oral squamous cell carcinoma; squamous cell carcinoma of head and neck; oral cancer; OSCC; osteonecrosis of the jaw; medication-related osteonecrosis of the jaw; MRONJ