A case of neuroendocrine oncogenic osteomalacia associated with a PHEX andfibroblast growth factor-23 expressing sinusidal malignant schwannoma

Oncogenic osteomalacia is a rare paraneoplastic syndrome that is characteri zed biochemically by hypophosphatemia and low plasma 1,25-dihydroxyvitamin D-3, and clinically by osteomalacia, pseudofractures, bone pain, fatigue, a nd 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 immuno histochemistry and of neurosecretory activity by electron microscopy. The c ell line did express PHEX (phosphate-regulating gene with homologies to end opeptidases located on the X-chromosome) and FGF-23 (fibroblast growth fact or-23) transcripts on northern hybridization; however, none of the known mu tations from the related mendelian disorders of X-linked hypophosphatemic r ickets or autosomal-dominant hypophosphatemic rickets could be detected. Tu mor cell (HMS-97)derived conditioned medium did not inhibit phosphate trans port 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 gene tic mechanism that leads to the observed PHEX and FGF-23 expression, both o f which might have a direct role in the pathogenesis of oncogenic osteomala cia. In addition, these cells might be a useful tool for the investigation of neuroendocrine Schwarm cell function and autoimmune peripheral nerve dis ease. (Bone 29:393-402; 2001) (C) 2001 by Elsevier Science Inc. All rights reserved.