Challenges in Evaluation and Management in Tumor-Induced Osteomalacia: A Retrospective Institutional and Literature-Based Scoping Review in Korean Patients

Abstract

Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by hypophosphatemia and osteomalacia, resulting from excessive production of fibroblast growth factor 23 by mesenchymal tumors. Although various imaging techniques are used to localize the tumor, the rarity of the disease poses significant challenges in tumor detection. Methods: After retrospectively analyzing 25 TIO patients who visited the Severance bone and mineral clinic between 2004 and 2024, we added all reported TIO cases in Korea by searching PubMed, Embase, and Web of Science. Using the PRISMA method, an additional 14 reports comprising 22 patients were included. Results: Among the 47 patients, 25 (53.2%) were male, with a median age of 52 years. Tumors were most commonly located in the lower extremities (57.5%), with a median size of 1.9 cm. Surgical resection, including radiofrequency ablation, was performed in 45 patients; reoperation was required in 26.7% (12/45) due to residual tumors. After gallium scans were covered by insurance, 83.3% (25/30) of patients underwent galliumbased imaging for tumor localization with 77.3% of tumors successfully localized in initial scan. Of the five patients with negative initial scans, four (80%) showed positive findings on a second scan conducted 1 to 2 years later. Conclusions: Although gallium scans are the most commonly employed imaging modality for detecting tumors responsible for TIO, localization remains challenging due to the small tumor size, potential for widespread anatomical distribution, and prolonged diagnostic delay. Repeating gallium imaging can yield positive results in previously negative cases, and additional imaging modalities may be necessary to facilitate accurate localization.