Case ReportOsteomalacia-Inducing Tumors of the Brain: A Case Report, Review and a Hypothesis
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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Cited by (15)
A rare brain tumor encountered: Phosphaturic mesenchymal tumor. Case report and review of the literature
2019, Interdisciplinary Neurosurgery: Advanced Techniques and Case ManagementCitation Excerpt :Presenting with abnormalities similar to previous reports, (hypophosphatemia and normal calcium levels) this patient underwent a gross total resection with phosphate levels returning to normal and being able to ambulate on her own with a cast on her ankle. The authors mention the possibility of suspected meningiomas seen on imaging which are treated with conservative management eventually turning out to be PMTs, therefore leading do misdiagnosis and a lower prevalence of these tumors [8]. Similarly to our patient, these above-mentioned papers advocate gross total resection which has led to recovery of the metabolic bone disease, complete resolution of symptoms with no recurrence seen on long term follow up periods.
Clinical utility of bone markers in various diseases
2018, BoneCitation Excerpt :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].
Tumour-induced osteomalacia: An emergent paraneoplastic syndrome
2016, Endocrinologia y NutricionTumor-induced osteomalacia – Current imaging modalities and a systematic approach for tumor localization
2019, Clinical ImagingCitation Excerpt :This is especially important in sinonasal tumors, as contrast MRI can delineate tumors accurately and identify extension to critical structures such as the cavernous sinus and orbit. Interestingly, a few cases of intra-cranial osteomalacia inducing-tumors have also been reported, particularly in the anterior cranial fossa where contrast-enhanced MRI has proven to be extremely useful [80,81]. Osteomalacia-inducing tumors in the anterior cranial fossa may be mistaken for meningiomas in MRI, since they tend to be extra-axial, well circumscribed and demonstrate contrast enhancement.
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.