Tumor-induced osteomalacia caused by a mandibular phosphaturic mesenchymal tumor misdiagnosed as giant cell reparative granuloma: case report.

Abstract

Tumor-induced osteomalacia (TIO) is a rare syndrome caused by FGF23-secreting phosphaturic mesenchymal tumors (PMTs). Clinicians frequently misdiagnose mandibular PMTs due to their histological mimicry of giant cell lesions. We report a 16-year-old female with mandibular PMT-induced TIO who endured a 5-year diagnostic delay across eight hospitals. Two factors confounded her diagnosis: histological mimicry of giant cell reparative granuloma and an incidental SMARCAL1 variant misdirecting clinical attention toward a genetic disorder. Ultimately, integrated histopathologic evaluation and focal FGF23 immunohistochemistry supported the diagnosis of PMT, with serum P1NP reaching 435.00 ng/mL and β-CTX exceeding 6.00 ng/mL at peak disease severity, while ¹⁸F-AlF-NOTA-TATE PET/CT localized the lesion. Tumor resection with fibula free flap reconstruction achieved early postoperative improvement in serum phosphate levels and symptoms, although long-term clinical, biochemical, and radiographic follow-up remains necessary to assess durable remission and monitor for recurrence. This case illustrates multiple diagnostic pitfalls in TIO with mandibular PMT, emphasizing that a high index of suspicion and integration of biochemical, histological, and imaging findings are essential to avoid delayed diagnosis.