Paraneoplastic secretion of multiple phosphatonins from a deep fibrous histiocytoma causing oncogenic osteomalacia

Leow, Melvin Khee Shing, Dogra, Shaillay, Ge, Xiaojia, Chuah, Khoon Leong, Liew, Huiling, Loke, Kelvin Siu Hoong, and McFarlane, Craig (2021) Paraneoplastic secretion of multiple phosphatonins from a deep fibrous histiocytoma causing oncogenic osteomalacia. The Journal of Clinical Endocrinology & Metabolism, 106 (5). e2299-e2308.

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Context: Literature suggests that oncogenic osteomalacia is usually caused by a benign mesenchymal tumor secreting fibroblast growth factor subtype-23 (FGF-23), but the involvement of other phosphatonins has only been scarcely reported. We have previously published a seemingly typical case of oncogenic osteomalacia. Following curative neoplasm resection, we now report unique molecular characteristics and biology of this tumor.

Case Description: A 25-year-old man had been diagnosed with severe oncogenic osteomalacia that gradually crippled him over 6 years. 68Ga-DOTA-TATE positron emission tomography/computed tomography scan localized the culprit tumor to his left sole, which on resection revealed a deep fibrous histiocytoma displaying a proliferation of spindle cells with storiform pattern associated with multinucleated giant cells resembling osteoclasts. Circulating FGF-23, which was elevated more than 2-fold, declined to undetectable levels 24 h after surgery. Microarray analysis revealed increased tumor gene expression of the phosphatonins FGF-23, matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein subtype 4, with elevated levels of all 3 proteins confirmed through immunoblot analysis. Differential expression of genes involved in bone formation and bone mineralization were further identified. The patient made an astonishing recovery from being wheelchair bound to fully self-ambulant 2 months postoperatively.

Conclusion: This report describes oncogenic osteomalacia due to a deep fibrous histiocytoma, which coincidentally has been found to induce profound muscle weakness via the overexpression of 3 phosphatonins, which resolved fully upon radical resection of the tumor. Additionally, genes involved in bone formation and bone remodeling contribute to the molecular signature of oncogenic osteomalacia.

Item ID: 65946
Item Type: Article (Research - C1)
ISSN: 1945-7197
Keywords: phosphatonin; oncogenic osteomalacia; hypophosphatemia; FGF-23; deep fibrous histiocytoma
Copyright Information: © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (, which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact
Funders: Agency for Science Technology and Research (A*STAR)
Research Data:
Date Deposited: 21 Jun 2021 02:24
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320208 Endocrinology @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3211 Oncology and carcinogenesis > 321199 Oncology and carcinogenesis not elsewhere classified @ 30%
31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310204 Genomics and transcriptomics @ 20%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 50%
28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 30%
20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 20%
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