Abstract
The authors describe a case of oncogenic osteomalacia due to a mesenchymal phosphaturic tumour in the maxillary sinus. This is a paraneoplastic syndrome in which a tumour produces a peptide hormone-like substance (phosphatonin) that causes a urinary loss of phosphates resulting in a debilitating systemic condition. In this case, the patient experienced muscle stiffness, reduction of muscle tone, loss of weight and pathological fractures. Clinical and radiological examination revealed a tumour in the right maxillary sinus; all other results were negative. The diagnosis following pathology examination was mesenchymal phosphaturic tumour with a haemangiopericytoma-like vascular pattern. Different histological types of mesenchymal tumours can be associated with paraneoplastic syndrome, but their localization in the paranasal sinuses is rare. The correct diagnosis allows the appropriate therapeutic approach, which can lead to an almost immediate resolution of the clinical situation after surgical removal of the neoplasm as in the present case. Oncogenic osteomalacia is rare, particularly in the maxillofacial region, and only a few cases have been reported.
Oncogenic osteomalacia is a paraneoplastic syndrome in which a tumour, often of mesenchymal origin and frequently benign, results in renal phosphate wasting with hypophosphataemia . It is thought that the tumour cells produce a peptide hormone-like substance, originally called phosphatonin , then identified as fibroblast growth factor 23 (FGF 23) . FGF 23 is a physiological regulator of phosphate balance. It decreases the resorption of phosphates by the proximal tubule and inhibits the 1α hydroxylase enzyme, which results in reduced levels of 1α,25-dihydroxyvitamine D 3 . FGF 23 overexpression leads to increased phosphate urine clearance, the mobilization of Ca and P from bone and the reduction of osteoblastic activity . The result is a gradual onset of muscular weakness and bone pain with pathological fractures. This theory is supported by the clinical resolution of the disease after surgical removal of the neoplasm.
The rare literature reports show different histological types of mesenchymal tumours associated with paraneoplastic syndrome . These are frequently tumours derived from vascular tissue (haemangiopericytomas) or bone (osteoblastoma-like tumours, non-ossifying fibroma-like tumours, ossifying fibroma-like tumours). These neoplasms are often located in the legs, maxillofacial region (frequently the nasal cavity and mandible) and brain .
Oncogenic osteomalacia is frequently associated with prostatic carcinoma and pulmonary microcytoma. As shown here, this pathological condition may lead to a severe debilitating clinical condition. Early diagnosis can be difficult, because the neoplasm rarely produces signs indicating its localization.
The authors describe a case of oncogenic osteomalacia due to a mesenchymal phosphaturic tumour in the maxillary sinus.
Case report
A 37-year-old woman started experiencing severe pain in the left ankle that was initially diagnosed by a general practitioner as tendon inflammation and treated with rest, a topical application of anti-inflammatory drugs and iontophoresis. Despite this therapy, her clinical condition worsened and the pain became generalized, with associated muscle stiffness, a progressive reduction of muscle tone, and loss of weight (1 kg/month) over 6 months.
The patient was admitted to the Department of Rheumatology, and total body scintiscanning showed diffuse areas of hyperfunction throughout the skeleton. She underwent a biopsy of the sixth right rib, which showed particularly intense activity at scintiscan examination. Histological examination revealed severe demineralization but was not diagnostic.
Treatment with corticosteroids and methotrexate was started, but there was no improvement in the clinical condition. The patient developed pathological fractures of eight ribs, microfractures of the upper and lower limbs and vertebral collapse involving a loss of about 5 cm in height. As a result, the patient was placed on bed rest.
Two years later, laboratory findings revealed severe hypophosphataemia, hypocalcaemia, and hyperphosphaturia. After excluding a diagnosis of hyperparathyroidism, therapy with P (2 g/day), Ca (2 g/day), and vitamin D was started. Laboratory tests suggested a paraneoplastic syndrome. Further testing was planned. A second total body scintiscan and an iliac bone biopsy were performed but none was diagnostic. The patient’s clinical and biochemical condition improved and 2 months after beginning pharmacological therapy the patient felt better.
To identify the cause of this syndrome, ultrasonography, chest axial computerized tomography (CT), and brain and maxillofacial magnetic resonance imaging (MRI) were performed. The latter examination showed a mass localized in the right maxillary sinus ( Fig. 1 ), but all the other results were negative. A scintiscan using 111 indium-labelled pentreotide showed areas of hyperactivity localized in the skeleton and right maxillary sinus.
The patient was subsequently referred to the authors’ maxillofacial department for evaluation of the lesion in the right maxillary sinus. Under local anaesthesia, a biopsy was performed with a mucosal incision at the upper vestibular fornix, raising a flap in a subperiosteal plane of the anterior right maxillary wall, which did not appear to be affected by the neoplasm. A bone window was created with a round burr, which revealed a soft brown-red lesion that was biopsied. The biopsy caused significant bleeding from the lesion, so the antrum was compressed with iodoform gauze. The bleeding suggested a vascular origin for the neoplasm. Histology showed a mesenchymal phosphaturic tumour with a haemangiopericytoma-like vascular pattern.
The patient underwent surgical removal of the neoplasm under general anaesthesia, using the previous surgical access. With a large round burr, the bone window in the anterior right maxillary wall was widened, allowing the removal of the lesion with accurate curettage of the sinus ( Figs. 2 and 3 ).
The epidemiological data on paraneoplastic syndrome suggests that the tumours are not very aggressive . The postoperative course was uneventful, and the patient was discharged 3 days later. The substitutive pharmacological therapy was stopped, and after 3 weeks, the serum Ca and P levels were both within the normal range.
After 7 years of follow-up, the patient is healthy and her activities are normal. The most recent CT shows no signs of disease recurrence ( Fig. 4 ).
Histopathological examination of the tumour ( Fig. 5 ) revealed heterogeneous connective tissue comprising small primitive spindle oval and fusiform mesenchymal cells ( Fig. 6 ) with myofibroblastic features, ill-defined eosinophilic cytoplasm and vesicular nuclei without cytological atypia. The cells were arranged in sheets and interlacing fascicles with mixoid and microcystic networks. Well developed vascular areas with haemangiopericytoma-like patterns, haemorrhagias, haemosiderin deposits, cluster of multinucleated osteolastic-like giant cells and foci of osseous metaplasia were also present ( Figs. 7 and 8 ).
