Florid Cemento-Osseous Dysplasia with Superimposed Infection Mimicking MRONJ and Plasma Cell Neoplasia: A Clinicoradiopathologic Image-Based Challenge.

Florid cemento-osseous dysplasia (FCOD) is a benign fibro-osseous condition typically presenting as multifocal, sclerotic masses throughout the jaws. While often asymptomatic, the hypovascular nature of the dysplastic bone predisposes it to secondary infection, which can mimic more aggressive pathologies. We present a complex diagnostic challenge involving a 76-year-old female with a history of intravenous ibandronic acid therapy for 18 months. The patient presented with a purulent mandibular fistula and exposed bone, leading to an initial clinical suspicion of Stage 2 Medication-Related Osteonecrosis of the Jaw (MRONJ). Radiographic evaluation, however, revealed generalized "cotton-wool" opacities across all four quadrants, characteristic of FCOD, with multifocal mixed radiolucent-radiopaque changes and a localized demarcated sequestrum in the symptomatic area. Accordingly, the diagnostic reasoning progressed from an initial clinical suspicion of MRONJ, to radiologic consideration of infected FCOD, and finally to exclusion of plasma cell neoplasia by immunohistochemical evaluation. The diagnostic dilemma intensified during histopathological analysis, which revealed an unusually dense, sheet-like infiltration of plasma cells within the fibro-osseous stroma. This striking plasmacytosis initially raised suspicion for a plasma cell neoplasm, such as plasmacytoma or multiple myeloma. To differentiate reactive inflammation from malignancy, immunohistochemical staining for kappa and lambda light chains was performed, demonstrating a polyclonal pattern that confirmed a reactive process. The final diagnosis was determined as FCOD with superimposed secondary osteomyelitis. Following conservative surgical debridement and targeted antibiotic therapy, the patient showed clinical resolution and remained stable at a 6-month follow-up. Recognizing these overlaps is essential for preventing over-treatment and ensuring appropriate management in elderly patients with complex medical backgrounds.