Elsevier

World Neurosurgery

Volume 84, Issue 1, July 2015, Pages 189.e1-189.e5
World Neurosurgery

Case Report
Osteomalacia-Inducing Tumors of the Brain: A Case Report, Review and a Hypothesis

https://doi.org/10.1016/j.wneu.2015.02.030Get rights and content

Background

Osteomalacia-inducing tumors (OIT) are mesenchymal tumors that characteristically secrete fibroblast growth factor 23, resulting in a paraneoplastic syndrome of hypophosphatemic osteomalacia. These tumors are known to occur in soft tissues and bones in various sites. It is very unusual for OITs to occur intracranially, with only 10 reported intracranial cases since their discovery in 1959. The most common intracrainal OITs are phosphaturic mesenchymal tumors and hemangiopericytomas. We report a case of hypophosphatemic osteomalacia caused by a tumor in the right anterior cranial fossa. We also hypothesize, based on our review of the literature, that this entity is underdiagnosed.

Case Description

A 49-year-old woman had a history of a nonhealing ankle fracture that required repeated surgery over 3 years. She subsequently was found to have severe hypophosphatemia and evidence of osteomalacia together with multiple occult fractures. A diagnosis of tumor-induced osteomalacia was suspected. An elevated serum fibroblast growth factor 23 level confirmed the diagnosis. An octreotide scan that was performed to locate the responsible tumor revealed an area of avid uptake in the right frontal lobe. Magnetic resonance imaging showed a large right anterior fossa extra-axial mass. The patient was referred for surgical intervention and was cured clinically after surgical removal of the tumor. Pathologic examination revealed a phosphaturic mesenchymal OIT. Her phosphate levels returned to normal 3 weeks after surgery.

Conclusions

The diagnosis of OIT should be considered in a case of severe hypophosphatemia and metabolic bone disease that is not explained by any other metabolic or hereditary disease. These tumors can occur intracranially and may be confused with a meningioma or a hemangiopericytoma. Taking OIT into consideration in such cases could lead to a shorter time to diagnosis and management, which in our case took 4 years.

Introduction

Osteomalacia-inducing tumors (OITs) are mesenchymal tumors that characteristically secrete fibroblast growth factor 23 (FGF23) 3, 4, 8, 16. Elevated levels of FGF23 cause inhibition of renal reabsorption of phosphorus and downregulation of 25-hydroxyvitamin D-1α-hydroxylase, resulting in a paraneoplastic syndrome of hypophosphatemic osteomalacia with progressive weakness, muscle and bone pain, and recurrent fractures 4, 8. Although there are several mesenchymal tumors that can be classified as OITs, >70% of these tumors belong to a single pathologic entity named phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT) (4). The other common pathology is hemangiopericytoma (HCT). Although OITs are known to occur in soft tissue and bone in various sites (4), it is very unusual for them to occur intracranially. There have been only 10 reported intracranial cases 1, 2, 3, 6, 8, 12, 13, 15, 16 since the discovery of OITs by Prader et al. in 1959 (11).

We report a case of hypophosphatemic osteomalacia caused by a tumor in the right anterior cranial fossa. Our literature review led us to hypothesize that this entity is probably underdiagnosed. In addition to the fact that in almost every case report of intracranial OIT there was a radiologic resemblance to a meningioma preoperatively, 2 studies reported cases of OIT that was not associated with osteomalacia 2, 17, denoting that this pathologic entity may not be associated with clinical symptoms or signs in some rare instances. There also have been pathologic reports of areas resembling OITs inside en plaque meningiomas (9). This means that in many cases of meningiomas, especially cases that are followed conservatively, there is a small chance that OITs are missed.

Section snippets

History and Examination

A 49-year-old woman with developmental delay presented with a nonhealing ankle fracture with multiple complications requiring 5 surgeries over a period of 3 years. During an admission for removal of hardware from her ankle secondary to osteomyelitis, a subtle presentation of hip discomfort led to a computed tomography scan that revealed bilateral femoral stress fractures. Metabolic bone disease was suspected, and an endocrinologist was consulted. Blood tests revealed severe hypophosphatemia

Discussion

The first case of an intracranial OIT was reported in 1996 by David et al. (3). Several intracranial mesenchymal tumors can cause osteomalacia including HCTs 8, 13 and PMTMCT, with the latter accounting for >70% of the cases (4). The present case is the 11th reported case of an intracranial OIT in the English literature since the discovery of this pathologic entity by Prader et al. in 1959 (11). A review of some previous cases is provided in a more recent article by Mathis et al. (8). Our case

Conclusions

We hypothesize that OIT is an underdiagnosed entity, and perhaps some are being missed in patients given a diagnosis of meningioma. In the future, with reports of more cases and investigations searching for new biomarkers, it is hoped that we can gain more insight about this entity. Future studies should focus on new imaging, pathologic, and diagnostic methods to diagnose these tumors accurately and differentiate them from similar entities.

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    Increased concentrations of ALP and OC are found in TIO patients [56–58]. The measurement of FGF23 is useful for diagnosis of TIO, revealing inappropriate high concentrations of FGF23 [52, 55, 57, 59, 60]. Nuclear imaging techniques and sometimes venous FGF23 sampling [52, 57, 59] are used to detect the exact location of the tumor which can be challenging due to fluctuating concentrations of plasma FGF23 [59].

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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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