Phosphaturic mesenchymal tumors: what an endocrinologist should know



Tumor-induced osteomalacia (TIO), also known as “oncogenic osteomalacia”, is a rare cause of osteomalacia. TIO often has an insidious onset characterized clinically by progressive muscle weakness and bone pain with fractures. The hallmark biochemical finding is a persistent low serum phosphorus concentration due to renal phosphate wasting. The vast majority of cases of TIO result from production of the phosphaturic hormone fibroblast growth factor 23 (FGF23) by a histologically distinctive mesenchymal tumor, termed “phosphaturic mesenchymal tumor” (PMT). Circulating FGF23 induces internalization of renal sodium/phosphate co-transporters resulting in reduced proximal tubular phosphate reabsorption. FGF23 also inhibits production of 1α,25-dihydroxyvitamin D which is inappropriately low or normal in the context of hypophosphatemia. Diagnosis is often delayed owing to the rarity of the condition and an underappreciation for the role of phosphorus as a cause for the constellation of symptoms. Primary treatment for TIO is identification of the offending tumor and surgical removal. However, these tumors are notoriously difficult to find, precluding the opportunity for a curative surgery in many. In such cases, phosphate and calcitriol therapy is used to improve symptoms and heal the osteomalacia. Recently, molecular genetic studies have shown recurrent genetic events in PMT, including the novel fusions FN1FGFR1 and less commonly FN1FGF1. These fusion events are hypothesized to result in autocrine/paracrine signaling loops within the tumor, spurring tumorigenesis. This review will cover the clinical features, imaging characteristics, pathologic features, molecular genetic aspects, and therapy of PMT, with a brief discussion of other neoplasms that may cause TIO.


Tumor-induced osteomalacia Phosphaturic mesenchymal tumor Hyperphosphaturia Hypophosphatemia Rickets 



This study received no grant from any funding agency in the public, commercial or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

Drs. Boland, Tebben, and Folpe declare that they have no conflicts of interest or relevant financial relationships.

Ethical approval

This manuscript is a review of the literature and does not contain original research either on animal or on human subjects.

Informed consent

For this type of study, formal consent is not required.


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Copyright information

© Italian Society of Endocrinology (SIE) 2018

Authors and Affiliations

  1. 1.Division of Anatomic Pathology, Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA
  2. 2.Division of Pediatric EndocrinologyMayo ClinicRochesterUSA

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