Hiding in plain sight: Gene panel and genetic markers reveal 26-year undiagnosed tumor-induced osteomalacia of the rib concurrently misdiagnosed as X-linked hypophosphatemia

Bone Reports

Andrew L. Folpe, MD¹  Erin A. Gillaspie, MD, MPH²  Kathryn M. Dahir, MD³  Joseph A. DeCorte, BS⁴  Juan M. Colazo, BSc⁴ 

[1] Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st St SW, Rochester, MN 55902, United States of America;Department of Thoracic Surgery, Vanderbilt University Medical Center, Room 609 Oxford House, 1313 21st Avenue South, Nashville, TN 37232, United States of America;Program for Metabolic Bone Disorders at Vanderbilt, Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, 8210 Medical Center East, 1215 21st Avenue South, Nashville, TN 37232-8148, United States of America;Vanderbilt Medical Scientist Training Program, Vanderbilt University Medical Center, 2nd Floor Eskind Biomedical Library and Learning Center, Vanderbilt University School of Medicine, 2209 Garland Avenue, Nashville, TN 37240, United States of America;

关键词: Tumor-induced osteomalacia;    TIO;    Fibroblast growth factor 23;    FGF23;    Paraneoplastic;    Phosphaturic mesenchymal tumor;   

DOI  :  

来源: DOAJ

【 摘 要 】

Tumor-induced osteomalacia (TIO), caused by phosphaturic mesenchymal tumors (PMTs), is a rare paraneoplastic syndrome characterized by frequent bone fractures, bone pain, muscle weakness, and affected gait. These tumors typically secrete high levels of Fibroblastic Growth Factor 23 (FGF23), a hormone which acts on the kidney to cause hypophosphatemia, ultimately impairing bone mineralization. In this case report, we present a 41-year-old female with FGF23-mediated hypophosphatemia with a 26-year delay in TIO diagnosis and a concurrent misdiagnosis of X-linked hypophosphatemic rickets (XLH). Given an absence of family history of hypophosphatemia, a 13-gene hypophosphatemia panel including XLH (PHEX gene) was performed and came back negative prompting a diagnostic search for a PMT causing TIO. A 68Ga-DOTATATE PET/CT scan revealed the presence of a 9th right rib lesion, for which she underwent rib resection. The patient's laboratory values (notably serum phosphorus, calcium, and vitamin D) normalized, with FGF23 decreasing immediately after surgery, and symptoms resolving over the next three months. Chromogenic in situ hybridization (CISH) and RNA-sequencing of the tumor were positive for FGF23 (CISH) and the transcriptional marker FN1-FGFR1, a novel fusion gene between fibronectin (FN1) and Fibroblast Growth Factor Receptor 1 (FGFR1), previously determined to be present in the majority of TIO-associated tumors. This case demonstrates the notion that rare and diagnostically challenging disorders like TIO can be undiagnosed and/or misdiagnosed for many years, even by experienced clinicians and routine lab testing. It also underscores the power of novel tools available to clinicians such as gene panels, CISH, and RNA sequencing, and their ability to characterize TIO and its related tumors in the context of several phenotypically similar diseases.

【 授权许可】

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