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.