Exploring the role of FGF7 in tumor-induced Osteomalacia. Clinic–pathologic analysis in a patient with a Sino-Nasal Phosphaturic Mesenchymal Tumor

Tumor-induced osteomalacia (TIO) is an ultrarare paraneoplastic syndrome due to the overproduction of Fibroblast Growth Factor 23 (FGF23). Although other phosphate-regulating substances (i.e., “phosphatonins”) have been demonstrated to be expressed in tumors associated with TIO, very limited information is available about their circulating levels and clinical significance. Here, we report a patient with a long-standing history of low serum phosphate values due to a sino-nasal phosphaturic mesenchymal tumor (PMT), in which the co-expression of FGF23 and FGF7 was detected in the neoplastic tissue and their serum levels determined before and after surgical tumor excision. The serum level of FGF23 was increased (312.0 pg/mL) before surgery and promptly normalized 24 h after tumor excision. In contrast, the value of FGF7 was high (202.6 pg/mL) before surgery, fell at 24 h after surgery (108.6 pg/mL), increased again after one week (252.0 pg/mL), and finally normalized (33.4 pg/mL) one year later, when also serum phosphate was in the normal range. This is the first sino-nasal PMT in which expression of FGF7 was observed and the first case of TIO in which the serum levels of FGF7 were monitored during the course of the disease (i.e., before and after tumor excision). Even though “phosphatonins” in addition to FGF23 are thought to contribute to the phosphate wasting leading to TIO, the observed increase in FGF7 levels one week after surgery (+ 31.66% compared to the preoperative value), when phosphate levels tended to normalize, may suggest a mild, if ever, phosphaturic effect of FGF7. Further studies are needed to define the mechanisms underlying the different post-surgical time-dependent decrease in the serum levels of FGF23 and FGF7 and the role of FGF7 in patients with TIO and more in general in phosphate homeostasis.