A case of neuroendocrine oncogenic osteomalacia associated with a PHEX and fibroblast growth factor-23 expressing sinusidal malignant schwannoma.
Oncogenic osteomalacia is a rare paraneoplastic syndrome that is characterized biochemically by hypophosphatemia and low plasma 1,25-dihydroxyvitamin D3, and clinically by osteomalacia, pseudofractures, bone pain, fatigue, and muscle weakness. We present a patient with a malignant schwannoma as the underlying cause of this disorder. A permanent cell line (HMS-97) derived from this tumor showed evidence of neuroendocrine differentiation by immunohistochemistry and of neurosecretory activity by electron microscopy. The cell line did express PHEX (phosphate-regulating gene with homologies to endopeptidases located on the X-chromosome) and FGF-23 (fibroblast growth factor-23) transcripts on northern hybridization; however, none of the known mutations from the related mendelian disorders of X-linked hypophosphatemic rickets or autosomal-dominant hypophosphatemic rickets could be detected. Tumor cell (HMS-97)-derived conditioned medium did not inhibit phosphate transport in a standard opossum kidney cell assay and in animal experiments. The medium also showed no PTH1- or PTH2-receptor-stimulating bioactivity. HMS-97 cells might be useful for further studies that aim to determine the genetic mechanism that leads to the observed PHEX and FGF-23 expression, both of which might have a direct role in the pathogenesis of oncogenic osteomalacia. In addition, these cells might be a useful tool for the investigation of neuroendocrine Schwann cell function and autoimmune peripheral nerve disease.
John
M R
MR
Department of Internal Medicine I, Endocrinology and Metabolism, University of Heidelberg, Heidelberg, Germany. mjohn@helix.mgh.harvard.edu
Wickert
H
H
Zaar
K
K
Jonsson
K B
KB
Grauer
A
A
Ruppersberger
P
P
Schmidt-Gayk
H
H
Murer
H
H
Ziegler
R
R
Blind
E
E
D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009442:Neurilemmoma / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D010018:Osteomalacia / Q000000981:diagnostic imaging / Q000209:etiology*; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D011877:Radionuclide Imaging; D014407:Tumor Cells, Cultured
C000717427:FGF23 protein, human; D011506:Proteins; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human