3.1 Patient demographics, imaging, and biochemical work-up
The patient details were included in Table 1. There were six male and three female patients. The median age at diagnosis was 53 years (interquartile range [IQR], 41–63 years), the median follow-up after initial resection was 64 months (IQR, 20–98 months), and the median maximum tumor size was 20 mm (IQR, 11–36 mm).
The patient’s symptoms on presentation to a doctor were bone or joint pain in multiple locations. The time elapsed between the initial patient’s complaints and the diagnosis of TIO ranged from 5 to 126 months with a median delay of 72 months. Only 22% of patients were correctly diagnosed within 2 years, while 56% were correctly diagnosed between 5 and 10 years after the onset of symptoms. X-rays revealed pseudofractures in all of the patients (Fig. 1a–e). Whole-body99mTc bone scintigraphy demonstrated increased uptake in multiple bones, including ribs, vertebrae, and femur, in four available cases. The endocrine work-up revealed the following laboratory findings: low serum phosphate (median 1.3 [IQR, 1.2–1.7] mg/dL, normal range, 2.7–4.6 mg/dL), high serum ALP (median 281 [IQR, 251–355] U/L, normal range, 38–113 U/L), normal to low serum corrected calcium (median 8.7 [IQR, 8.5–9.0] mg/dL, normal range, 8.8–10.1 mg/dL), and normal to high intact parathyroid hormone (median 64 [IQR, 43–123] pg/mL, normal range, 15–65 pg/mL). The serum FGF23 was elevated (median 241 [IQR, 194–3750] pg/mL). The clinical signs, imaging studies, low serum phosphate levels, and elevated serum FGF23 levels all pointed TIO.
To determine the localization of the primary tumor, systemic venous sampling of FGF23 was performed in five patients. FGF23 levels were highest in the internal jugular vein in two patients, the external jugular vein, subclavian vein, and superior vena cava in one patient each (Table 1). In all patients, MRI revealed a tumor in the head and neck region. Somatostatin receptor scintigraphy was performed, which enabled tumor visualization in all four available patients. FDG-PET/CT revealed mild uptake (SUV max median 5.7, IQR 5.1–6.2) in the suspected tumor.