1. Paraneoplastic Secretion of Multiple Phosphatonins From a Deep Fibrous Histiocytoma Causing Oncogenic Osteomalacia.
- Author
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Leow MKS, Dogra S, Ge X, Chuah KL, Liew H, Loke KSH, and McFarlane C
- Subjects
- Adult, Fibroblast Growth Factor-23, Fibroblast Growth Factors genetics, Foot Diseases diagnosis, Foot Diseases etiology, Foot Diseases genetics, Foot Diseases metabolism, Gene Expression Regulation, Neoplastic, Histiocytoma, Benign Fibrous complications, Histiocytoma, Benign Fibrous diagnosis, Histiocytoma, Benign Fibrous genetics, Humans, Malaysia, Male, Osteomalacia diagnosis, Osteomalacia genetics, Osteomalacia metabolism, Paraneoplastic Syndromes diagnosis, Paraneoplastic Syndromes genetics, Paraneoplastic Syndromes metabolism, Singapore, Soft Tissue Neoplasms diagnosis, Soft Tissue Neoplasms genetics, Soft Tissue Neoplasms metabolism, Fibroblast Growth Factors metabolism, Histiocytoma, Benign Fibrous metabolism, Osteomalacia etiology, Paraneoplastic Syndromes etiology, Soft Tissue Neoplasms etiology
- Abstract
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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)
- Published
- 2021
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