2 Patients and Methods
We followed the STROBE reporting guidelines. Between 1998 and 2022, 67 patients with TIO were identified in our hospital’s database. Among them, nine patients with PMT in the head and neck regions who underwent surgical excision were involved in this research. In comparison, 32 patients with PMT in the extremities and trunk who had surgical excision were analyzed. Regarding the remaining 26 patients, tumors were not detected by imaging studies in 18, the histology and clinical courses were consistent with malignant tumors in 3, and only examinations were conducted at our hospital in 5. These 41 patients’ clinical records and imaging studies were reviewed retrospectively.
Most patients suspected of having TIO were referred to the corresponding department (oral and maxillofacial, orthopaedic, otolaryngology, neurosurgery, etc.) from the endocrinology department. Multiple examinations were carried out to identify the primary tumor, including FGF23 venous sampling, 18-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT),99mTc bone scintigraphy, somatostatin receptor scintigraphy, or magnetic resonance imaging (MRI).9The diagnosis and localization were made following a review of the histopathology and radiology results with a multidisciplinary discussion. Serum phosphate, alkaline phosphatase (ALP), and bone-specific alkaline phosphate levels were measured regularly for postoperative monitoring. All the patients were asked to visit the endocrinology department for follow-up at 2–3 months postoperatively and every 3–6 months thereafter. Endocrinologists continued medical treatments for patients whose serum phosphate levels did not return to normal after surgery. Biochemical remission was defined as normalized serum phosphate and serum ALP levels without any medication. Pathology findings were consistent with PMT, showing the proliferation of bland spindle to stellate cells that were immunohistochemically positive for FGF23.
FGF23 values were measured by an FGF-23 ELISA Kit, which exclusively detects biologically active intact FGF23. FGF23 levels ≥30 pg/ml under hypophosphatemic condition clearly differentiate FGF23-related hypophosphatemia from hypophosphatemia due to other causes.10,11 Immunohistochemistry for FGF23 was conducted with monoclonal FGF23 antibody.
All patients underwent surgical excision of the tumor with the aim of achieving R0 or R1 margin.12 Extended curettage was used in patients with bone tumors at the extremity or trunk who were expected to have functional impairment after surgery: the tumor was removed with a curette, and the margin was expanded with high-speed burring.13
Case reports for cases 414 and 515in Table 1 are available elsewhere. The detailed results of these multimodal tests for cases 2, 8, and 9 were reported in our group’s previous article (cases 2, 8, and 9 in the current study are equivalent to cases 4, 1, and 27 in ref. 9).
Chi-square tests were used to compare the categorical variables between the groups. Two-tailed probability (P) value of <0.05 was considered to be statistically significant. To conduct statistical analyses, R version 4.2.1 was used.
All procedures were carried out in accordance with the Declaration of Helsinki’s ethical standards and were approved by our institutional ethical board [Ref. P2017016 and 2879]. All the patients provided written informed consent.