Discussion

PMT is a rare entity that usually presents with a clinical picture of tumor-induced osteomalacia (TIO).^{1 - 3} To date, fewer than 500 cases have been reported in the literature.⁴ Osteomalacia is a metabolic disorder in which there is insufficient mineralization of the mature bone. The most common cause of osteomalacia is vitamin D deficiency. Other rare causes include inborn errors of metabolism and chronic kidney disease. TIO is a type of paraneoplastic syndrome that can be seen in osteoblastoma, osteosarcoma, hemangiopericytoma, and plasmacytoma.⁴

TIO was first reported by McCance in a 15-year-old teenager who presented with weakness and gait disturbance, along with hypophosphatemia.⁴ The term phosphaturic mesenchymal tumor was coined by Wiedner and Santa Cruz in 1987.⁵ PMT was included in the WHO 2013 classification of tumors for bone and soft tissue.⁶

The pathophysiology of TIO involves excessive production of FGF-23 by the tumor cells, which is a type of phosphate-regulating substance in the body.⁴ FGF-23 reduces phosphate reabsorption in the proximal renal tubules, leading to excessive renal excretion of phosphates. FGF-23 also increases bone resorption of calcium and phosphate, and decreases intestinal absorption of calcium and phosphate, decreasing bone mineralization.⁴

PMT is characteristically a benign tumor.^{5, 6} However, local recurrences and malignant behavior in the form of lung metastasis have also been reported in the literature.^{5, 7} Hence, patients need to be followed up with appropriate imaging of the chest, serum phosphates, and FGF-23 levels to detect any recurrence.^{3, 6, 8, 9}

PMT commonly affects the extremities of middle-aged patients and can originate from the bone or soft tissue. It often tends to be small and can be located anywhere in the body, mimicking many other common tumors of the bone and soft tissue.¹⁰

The diagnosis is often delayed due to vague symptomatology and low degree of suspicion of PMT.⁸ Patients usually present with recurrent fractures, bone pains, muscle pains, and generalized weakness.⁹ Biochemical findings include hypophosphatemia, hyperphosphaturia, and elevated levels of FGF-23.⁴

Imaging modalities for diagnosis may include CT, MRI, FDG PET/CT, dotatate PET/CT, and a Tc-99m sestamibi scan. Radiographic features of PMTs have been described recently in detail.¹¹ On CT scans, bone lesions are typically osteolytic, show a narrow zone of transition, and contain internal matrix.¹² On MRI, they are usually T1 isointense, T2 hyperintense, and solidly enhancing, with areas of dark T2 signal.¹²

Histologically, there are 4 types of PMTs: osteoblastoma-like variant, nonossifying fibroma-like variant, ossifying fibroma-like variant, and mixed connective tissue variant.^{1, 6} The most common type is the mixed connective tissue variant.⁴ Morphological differential diagnosis includes chondromyxoid fibroma, chondroblastoma, aneurysmal bone cyst, glomus jugulare, chordoma, vestibular schwannoma, and osteosarcoma.⁴ Histological findings of benign cartilage-forming lesion in correlation with IHC, typical clinical presentation of recurrent fractures, and biochemical profile showing hypophosphatemia with elevated levels of FGF-23 confirm the diagnosis of PMT and differentiate it from other differentials.

Treatment options include surgery for resectable lesions. Complete surgical resection with negative surgical margins of at least 10 mm is the mainstay treatment.⁴ Radiation therapy is used for surgically or medically inoperable patients, incompletely resected tumors, or positive margins after resection.⁴ Although the detailed mechanism of the effectiveness of radiation therapy for PMT is unclear, the obstruction and fibrosis of the tumor vessels could occur, thus inhibiting growth, similar to the mechanism observed in other hormone- or cytokine-producing tumors.^{13, 14} It is important to use a high-precision radiation therapy technique such as intensity-modulated radiation therapy or volumetric-modulated arc therapy for critical sites such as the skull base or the head and neck region to spare the adjacent normal anatomical structures. Data regarding radiation therapy doses for PMT are very limited. As discussed in the case report by Shah et al, 54 Gy in 30 fractions was used in the postoperative adjuvant setting.¹⁵ Another case report by Uramoto et al mentioned the use of 66 Gy in 33 fractions after marginal resection of PMT of the tongue.¹⁶ In addition to local control, radiation therapy was found effective in improving oncogenic osteomalacia.¹⁷ Radiofrequency ablation (RFA) can be used for small bony lesions.⁴ Concomitant medical management includes phosphorus and calcitriol supplementation.^{3, 6}