Diagnostic Findings and Treatment in a 51-Year-Old Woman With Oncogenic Osteomalacia

Abstract

A 51-year-old woman presented with recurrent insufficiency fractures of the right midfoot, the left femoral condyle, and the ribs. Furthermore, she complained of unspecific muscle and joint tenderness as well as lower back pain that had evolved over the past few years. Initial laboratory testingrevealedhypophosphatemiaand elevated alkaline phosphatase levels; vitamin D and PTH were within normal limits. Subsequent analyses showed elevated levels for fibroblast growth factor 23 (FGF-23) and urinary phosphorus loss at the upper normal limit. Differential diagnoses included congenital forms of hypophosphatemicricketsandrenalphosphatewasting,aswellas (especially in a previously asymptomatic patient) oncogenic osteomalacia due to a phosphaturic mesenchymal tumor. Although bone scintigraphy performed to localize an osseous tumor was negative, whole-body positron emission tomography (PET)/computed tomography (CT) using the radiolabeled somatostatin analog [Ga]DOTATATE revealed a suspicious lesion measuring approximately 20 mm in diameter within the right gluteal region (Figure 1, A–C). Magnetic resonance imaging (MRI) for further surgical planning confirmed the PET finding (Figure 1D) and illustrated markedly increased tumor blood supply (Figure 1E). The patient underwent surgery. Macroscopy showed a sharply demarcated gray tumor without necrosis. Upon histologicalexamination, thetumorwasofmediumcelldensitywith a rich capillary supply and a characteristic deposition of a homogenous eosinophilic substance between the evenly spaced tumor cells (Figure 1, F and G). No signs of atypia, mitosis, or necrosiscouldbeobserved, thus leadingtothefinaldiagnosisof aphosphaturicmesenchymal tumorofmixedconnective tissue type (PMTMCT) (1). Postoperatively, musculoskeletal pain and tenderness relieved and biochemical parameters of disease burden (FGF-23, serum phosphorous) recovered subsequently (Figure 2). Oncogenic osteomalacia (synonym, tumor-induced osteomalacia, or TIO) is a rare cause of hypophosphatemic rickets. Main symptoms include musculoskeletal tenderness, recurrent bone marrow edema, or insufficiency fractures associated with severe hypophosphatemia, hyperphosphaturia, elevated levels of FGF-23, and typically alkaline phosphatase (2, 3). In most cases, hyperphosphaturia is caused by a benign mesenchymal tumor with unregulated secretion of phosphaturic factors/phosphatonins such as FGF-23 and secreted frizzled-related protein 4 (1, 2, 4). However, some reports indicate that this syndrome (as a paraneoplastic condition) is underdiagnosed in malignant tumors, eg, prostate, colon, and small-cell lung cancer (3). Surgical removalof the tumor is thecausative treatment that will stop phosphaturia and normalize bone metabolism (2, 4). Because these tumors may be very small and indolent and occur at unusual anatomic sites, they are generally difficult to localize. Typical manifestations include the long bones (55% of cases) and the soft tissues (45%, including the skin)—with most lesions localized in the lower limbs (ie, femur and tibia) (5). Conventional x-ray, MRI, and CT scans are usually not sufficient for tumor identification and localization. Because these tumors typically express somatostatin receptors, functional imaging with radiolabeled somatosta-