ABSTRACT
Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome associated with tumors that secrete phosphaturic hormones, most notably fibroblast growth factor 23 (FGF23). The majority of tumors associated with this syndrome show stereotypical histological features and are now known as phosphaturic mesenchymal tumors (PMTs). We postulated that immunohistochemistry for somatostatin receptor 2A (SSTR2A) could be used to definitively identify PMTs or other tumors that cause TIO. Immunohistochemistry for FGF23 and SSTR2A was performed on 15 tumors from 14 patients with a definite diagnosis of TIO. All showed positive staining for both markers. While FGF23 staining was quite focal in some tumors, SSTR2A showed diffuse strong expression. In 40 control tumors not known to be associated with the clinical or biochemical features of TIO, FGF23 expression was found in 2 cases (one aneurysmal bone cyst and one osteosarcoma). SSTR2A expression was found in 9 control tumors (4 synovial sarcomas, 2 hemangiomas, 2 aneurysmal bone cysts and one osteosarcoma). Only one tumor (an aneurysmal bone cyst) showed positive staining for both FGF23 and SSTR2A. SSTR2A also commonly stained neoplastic and non-neoplastic endothelial cells. We conclude that neither FGF23 nor SSTR2A expression are specific for the diagnosis of PMT. However both stains are highly sensitive. Because of its diffuse strong expression and widespread availability, immunohistochemistry for SSTR2A is useful to confirm the diagnosis of PMT in an appropriate setting particularly if material is limited. Negative staining can serve as an excellent rule out test for this diagnosis.
Subject(s)
Hypophosphatemia, Familial/diagnosis , Mesenchymoma/diagnosis , Neoplasms, Connective Tissue/diagnosis , Osteomalacia/diagnosis , Paraneoplastic Syndromes/diagnosis , Receptors, Somatostatin/metabolism , Adult , Drugs, Chinese Herbal , Eleutherococcus , Female , Fibroblast Growth Factor-23 , Humans , Hypophosphatemia, Familial/metabolism , Hypophosphatemia, Familial/pathology , Male , Mesenchymoma/metabolism , Mesenchymoma/pathology , Middle Aged , Neoplasms, Connective Tissue/metabolism , Neoplasms, Connective Tissue/pathology , Osteomalacia/metabolism , Osteomalacia/pathology , Paraneoplastic Syndromes/metabolism , Paraneoplastic Syndromes/pathologySubject(s)
Hyperparathyroidism, Primary/diagnosis , Mesenchymoma/complications , Osteomalacia/etiology , Phosphorus/blood , Soft Tissue Neoplasms/complications , Aged , Calcium/blood , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/metabolism , Humans , Male , Mesenchymoma/metabolism , Parathyroid Hormone/blood , Parathyroid Neoplasms/diagnosis , Soft Tissue Neoplasms/metabolismABSTRACT
Phosphaturic mesenchymal tumor is an extremely rare disease and is frequently associated with oncogenic osteomalacia showing paraneoplastic syndrome, which is characterized by phosphaturia, hypophosphatemia, normocalcemia, and decreased levels of 1,25-dihydroxyvitamin D3 associated with a tumor. A 2-year-old boy, who had a soft tissue tumor on his right thigh and previously diagnosed as myositis ossificans at 9-months-old, was presented with rachitic rosary and mildly enlarged tumor. Biochemical investigations showed hypophosphatemia, hyperphosphaturia, and an increased alkaline phosphatase level of 440 U/l (25-100 U/l), suggesting rickets, which was resistant to vitamin D dietary supplementation. We were certain of intractable rickets because of oncogenic hypophosphatemia and thus decided to excise the soft tissue mass. We observed laboratory improvement of rickets after 2 weeks. On the basis of surgical and histopathological examinations, the tumor was finally diagnosed as the phosphaturic mesenchymal tumor.