Autopsy and Case Reports
http://autopsyandcasereports.org/article/doi/10.4322/acr.2017.031
Autopsy and Case Reports
Article / Clinical Case Report

Phosphaturic mesenchymal tumor (PMT): exceptionally rare disease, yet crucial not to miss

Amir Ghorbani-Aghbolaghi; Morgan Angus Darrow; Tao Wang

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Abstract

Phosphaturic mesenchymal tumors (PMTs) are very rare tumors which are frequently associated with Tumor Induced Osteomalacia (TIO), a paraneoplastic syndrome that manifests as renal phosphate wasting. The tumor cells produce a peptide hormone-like substance known as fibroblast growth factor 23 (FGF23), a physiologic regulator of phosphate levels. FGF23 decreases proximal tubule reabsorption of phosphates and inhibits 1-α-hydroxylase, which reduces levels of 1-α, 25-dihydroxyvitamine D3. Thus, overexpression of FGF23 by the tumor cells leads to increased excretion of phosphate in the urine, mobilization of calcium and phosphate from bones, and the reduction of osteoblastic activity, ultimately resulting in widespread osteomalacia. Patients typically present with gradual muscular weakness and diffuse bone pain from pathologic fractures. The diagnosis is often delayed due to the non-specific nature of the symptoms and lack of clinical suspicion. While serum phosphorus and FGF23 testing can assist in making a clinical diagnosis of PMT, the responsible tumor is often difficult to locate. The pathologic diagnosis is often missed due to the rarity of PMTs and histologic overlap with other mesenchymal neoplasms. While patients can experience severe disabilities without treatment, excision is typically curative and results in a dramatic reversal of symptoms. Histologically, PMT has a variable appearance and can resemble other low grade mesenchymal tumors. Even though very few cases of PMT have been reported in the world literature, it is very important to consider this diagnosis in all patients with hypophosphatemic osteomalacia. Here we present a patient who suffered for almost 5 years without a diagnosis. Ultimately, the PMT was located on a 68Ga-DOTA TATE PET/CT scan and subsequently confirmed by histologic and immunohistologic study. Interestingly, strong positivity for FGFR1 by IHC might be related to the recently described FN1-FGFR1 fusion. Upon surgical removal, the patient’s phosphate and FGF23 levels returned to normal and the patient’s symptoms resolved.

Keywords

Neoplasm, Connective Tissue, Oncogenic Osteomalacia, Fibroblast Growth factors, Hypophosphatemia, Bone Diseases, Metabolic

References

Shimada T, Mizutani S, Muto T, et al. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA. 2001;98(11):6500-5.

Sundaram M, McCarthy EF. Oncogenic osteomalacia. Skeletal Radiol. 2000;29(3):117-24.10794548 10.1007/s002560050581.

Gaasbeek A, Meinders AE. Hypophosphatemia: an update on its etiology and treatment. Am J Med. 2005;118(10):1094-101.16194637 10.1016/j.amjmed.2005.02.014.

Fukumoto S, Yamashita T. Fibroblast growth factor-23 is the phosphaturic factor in tumor-induced osteomalacia and may be phosphatonin. Curr Opin Nephrol Hypertens. 2002;11(4):385-9.12105387 10.1097/00041552-200207000-00003.

Cho SI, Do NY, Yu SW, Choi JY. Nasal hemangiopericytoma causing oncogenic osteomalacia. Clin Exp Otorhinolaryngol. 2012;5(3):173-6.22977716 10.3342/ceo.2012.5.3.173.

Folpe AL. Phosphaturic mesenchymal tumour. In: Fletcher CDM, Bridge JA, Hogendoorn PCW et al. editors. World Health Organization classification of tumours of soft tissue and bone. Lyon: IARC Press; 2013. chap. 2.

Folpe AL, Fanburg-Smith JC, Billings SD, et al. Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. Am J Surg Pathol. 2004;28(1):1-30.14707860 10.1097/00000478-200401000-00001.

Honda R, Kawabata Y, Ito S, Kikuchi F. Phosphaturic mesenchymal tumor, mixed connective tissue type, non-phosphaturic variant: report of a case and review of 32 cases from the Japanese published work. J Dermatol. 2014;41(9):845-9.25182295 10.1111/1346-8138.12602.

White KE, Evans WE, et al. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000;26(3):345-8.11062477 10.1038/81664.

Tajima S, Fukayama M. Fibroblast growth factor receptor 1 (FGFR1) expression in phosphaturic mesenchymal tumors. Int J Clin Exp Pathol. 2015;8(8):9422-7.26464698

Lee JC, Jeng YM, Su SY, et al. Identification of a novel FN1–FGFR1 genetic fusion as a frequent event in phosphaturic mesenchymal tumour. J Pathol. 2015;235(4):539-45.25319834 10.1002/path.4465.

Pankov R, Yamada KM. Fibronectin at a glance. J Cell Sci. 2002;115(Pt 20):3861-3.12244123 10.1242/jcs.00059.

Puls F, Hofvander J, Magnusson L, et al. FN1-EGF gene fusions are recurrent in calcifying aponeurotic fibroma. J Pathol. 2016;238(4):502-7.26691015 10.1002/path.4683.

Han S, Khuri FR, Roman J. Fibronectin stimulates non-small cell lung carcinoma cell growth through activation of Akt/mammalian target of rapamycin/S6 kinase and inactivation of LKB1/AMP-activated protein kinase signal pathways. Cancer Res. 2006;66(1):315-23.16397245 10.1158/0008-5472.CAN-05-2367.

Ornitz DM, Xu J, Colvin JS, et al. Receptor specificity of the fibroblast growth factor family. J Biol Chem. 1996;271(25):15292-7.8663044 10.1074/jbc.271.25.15292.

Beenken A, Mohammadi M. The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov. 2009;8(3):235-53.19247306 10.1038/nrd2792.

Lee JC, Changou CA, Yang RS et al. Characterization of FN1-FGFR1 and novel FN1-FGF1 fusion genes in a large series of phosphaturic mesenchymal tumors. Modern Pathology 2016;29:1335-1346.

Nabeshima Y. Klotho: a fundamental regulator of aging. Ageing Res Rev. 2002;1(4):627-38.12362891 10.1016/S1568-1637(02)00027-2.

Quarles LD. Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism. Nat Rev Endocrinol. 2012;8(5):276-86.22249518 10.1038/nrendo.2011.218.

Jüppner H. Phosphate and FGF-23. Kidney Int Suppl. 2011;79(121):S24-7.21346724 10.1038/ki.2011.27.

Perwad F, Zhang MY, Tenenhouse HS, Portale AA. Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro. Am J Physiol Renal Physiol. 2007;293(5):F1577-83.17699549 10.1152/ajprenal.00463.2006.

Wu AL, Feng B, Chen MZ, et al. Antibody-mediated activation of FGFR1 induces FGF23 production and hypophosphatemia. PLoS One. 2013;8(2):e57322.23451204 10.1371/journal.pone.0057322.

 

 

 

 

 

 

 

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