PHOSPHATURIC MESENCHYMAL HEEL TUMOR PRESENTING WITH TUMOR-INDUCED OSTEOMALACIA

To help clinicians identify and treat patients with tumor-induced osteomalacia (TIO) resulting from a phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT).

Describe the history, presentation, laboratory findings, diagnostic studies, treatment, and literature review.

A 58-year-old female with no significant past medical history presents with ongoing multiple bone pain for years. She had a bone scan showing multiple focal areas of increased uptake involving bilateral ribs, distal right tibia, and left femoral neck, representing previously healed fractures. Her bilateral lower-extremity magnetic resonance imaging showed stress fractures of the anteromedial cortex, right tibia, and the left femoral neck. Phosphorus was noted to be 1.9 mg/dL (normal range, 2.0 to 4.0 mg/dL), and alkaline phosphatase was 179 U/L (normal range, 25 to 110 U/L). Tubular maximum re-absorption of phosphate to glomerular filtration rate ratio was 0.438, which was low. An outside physician initiated patient on teriparatide, which showed bone mineral density improvement after 1 year, and then the teriparatide was stopped. Later, she developed a nontraumatic pubic ramus fracture; teriparatide was resumed. While on teriparatide, she developed several new rib fractures. Due to declining phosphorus levels, further investigation led to an elevated fibroblast growth factor 23 (FGF-23) level of 243 RU/mL (normal, <50 RU/mL). TIO was strongly suspected, and a nuclear medicine positron emission tomography/computed tomography trunk with ⁶⁸Ga-1,4,7,10-tetraazacyclododecane 1,4,7,10-tetraacetic acid tyrosine-3-octreotate (i.e., ⁶⁸Ga-DOTATATE) showed a right heel soft-tissue nodule. Fine-needle aspiration biopsy was performed, confirming PMTMCT, positive for FGF-23 mRNA. After surgery, her symptoms resolved and her phosphorus normalized.

TIO is a rare paraneoplastic syndrome characterized by bone pain, muscle weakness, and fractures associated with persistent hypophosphatemia. Clinicians now have new imaging tools to help identify and treat patients with PMTMCT.