Frequent expression of fibroblast growth factor-23 (FGF23) mRNA in aneurysmal bone cysts and chondromyxoid fibromas

Abstract

Osteomalacia has multiple aetiologies including the least common, tumour-induced osteomalacia (TIO). Recently, most cases of TIO have been confirmed to be due to phosphaturic mesenchymal tumour of mixed connective tissue type (PMTMCT). Most cases of TIO are the result of production of the fibroblast growth factor-23 (FGF-23) by the tumour. The authors recently showed reverse transcriptase PCR (RT-PCR) for FGF-23 to be valuable in the diagnosis of PMTMCT. However, the authors also noted FGF-23 expression in some cases of aneurysmal bone cyst (ABC) and chondromyxoid fibroma (CMF). For the present study, the authors studied FGF-23 expression by RT-PCR in 19 cases of ABC and eight cases of CMF, all with typical clinical and radiographic features and without evidence of TIO. Seven of 16 (44%) ABC and two of seven (29%) CMF were positive for FGF-23. These results confirm that ABC and CMF not uncommonly express FGF-23. These results strongly suggest caution and careful integration with all other clinical and radiographic data in the use of FGF-23 RT-PCR for the diagnosis of PMTMCT.

A Novel Chromogenic In Situ Hybridization Assay for FGF23 mRNA in Phosphaturic Mesenchymal Tumors

“…9,29 A very well-developed capillary network is typically present, with some cases also showing larger vessels arranged in a "staghorn" pattern or in a pattern resembling cavernous hemangioma. 22,23 Given the distinctive morphologic features of PMT, and the increasingly widespread availability of serum FGF23 testing, one might legitimately question the additive value of FGF23 mRNA CISH testing. The calcified matrix of PMT seems to recruit osteoclasts and bland "fibrohistiocytic" spindled cells, sometimes producing an appearance reminiscent of giant cell tumor of bone or solid forms of aneurysmal bone cyst.…”

“…17 It also decreases expression of the sodium/ phosphate cotransporters NPT2a and NPT2c and alters the activity of renal hydroxylases involved in vitamin D metabolism. 23 In addition, conventional PCR-based techniques do not permit tissue visualization of FGF23 mRNA. Although immunohistochemistry offers the potential advantages of widespread availability and tissue visualization, commercially available FGF23 antibodies lack sufficient specificity to reliably diagnose PMT.…”

Rarely metastasizing soft tissue tumours

“…It should be cautioned, however, that FGF23 expression has been demonstrated in other tumour types that are not associated with oncogenic osteomalacia. 18 Although cases have been subjected to cytogenetic analysis, no consistently characteristic genetic changes have been identified in this tumour. 19 Figure 1 illustrates a typical case of PMTMCT.…”

“…Of considerable use in diagnosis, particularly on small needle biopsies where the characteristic matrix may not be represented, is the immunohistochemical detection of FGF23. It should be cautioned, however, that FGF23 expression has been demonstrated in other tumour types that are not associated with oncogenic osteomalacia …”

From epistaxis to bone pain—report of two cases illustrating the clinicopathological spectrum of phosphaturic mesenchymal tumour with fibroblast growth factor receptor 1 immunohistochemical and cytogenetic analyses

“…A few studies have also described strong and diffuse expression of somatostatin receptor 2A (SSTR2A), detected by immunohistochemistry, in PMT; however, neither FGF-23 nor SSTR2A is specific for PMT, as they are expressed in other mesenchymal tumours. [16][17][18] More recently, a novel FN1-FGFR1 genetic fusion was described in nine of 15 (60%) PMTs. 7 FGFR1 is a member of the FGF receptor (FGFR) family of receptor tyrosine kinases that has been implicated in the tumorigenesis of a wide range of solid tumours and haemopoietic malignancies.…”