Tumor biology and incidence
Tumor-induced osteomalacia (also known as oncogenic osteomalacia) is a very rare acquired neoplasm of mesenchymal origin that causes a paraneoplastic syndrome of renal phosphorus loss through the secretion of "phosphatonins". The best characterized of these molecules is fibroblast growth factor 23, (FGF-23). FGF-23 leads to decreased expression of a sodium-phosphate cotransporter in proximal tubule of nephron resulting in hyperphosphaturia and hypophosphatemia. This is very similar to the pathophysiology of X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemic rickets. FGF-23 also decreases activity of renal 1-alpha-hydroxylase, resulting in low 1,24 (OH) Vit D and normal 25 (OH) Vit D. Hypophosphatemia affects many physiologic pathways.
Primarily described in adults, however it can affect adolescents and children.
Patients typically present with unexplained muscle aches, weakness, and skeletal demineralization. In severe disease there may be a history of insufficiency fractures. If growth plates are still open, rickets can occur.
Plain films will essentially reveal skeletal demineralization and possible insufficiency fractures secondary to the paraneoplastic effects of the tumor. The above images are of a patient with severe disease who has sustained multiple insufficiency fractures.
Tumor effect on bone
The hypophosphatemia and low 1,24 (OH) Vit D cause diffuse skeletal demineralization and possibly insufficiency fractures.
Soft tissue mass
- Elevated Fibroblast growth factor 23 (FGF-23)
- Normal or low serum calcium
- Normal intact PTH
- Normal 25 (OH) Vit D
- Low 1,25 (OH)2 Vit D (Secondary to effects of FDF-23)
- Hyperphosphaturia (Secondary to effects of FDF-23)
- Hypophosphatemia (Secondary to effects of FDF-23)
Localizing the causative tumor is often challenging. Indium 111-pentetreotide scintigraphy is the imaging modality of choice for tumor localization. Many mesenchymal tumors associated with TIO express somatostatin receptors (SSTRs) (pentetreotide is a somatostatin analog). However, some TIO-associated tumors do not express SSTRs.
F-18 FDG PET-CT may also be useful. However, this marker is not ideal for detecting neoplasms with low metabolic rates such as those found in tumor-induced osteomalacia.
- Abnormal vitamin D metabolism
- Inhibitors of mineralization
- aluminum, fluoride, bisphosphonates
- Impaired renal phosphorus reabsorption
- X-linked hypophosphatemic rickets (typically presents in childhood)
- Autosomal dominant hypophosphatemia (typically presents in childhood)
- (Tumor-induced osteomalacia)
- Dietary deficiency
- Vitamin D Deficiency Osteomalacia
- Calcium deficiency
- Phosphorus deficiency
- Abnormal Vitamin D metabolism
- Enzyme deficiencies
- Renal Osteodystrophy
Progressive skeletal demineralization, weakness, and pain. Severe disease may result in numerous insufficiency fractures and render the patient wheelchair-bound.
Tumor-induced osteomalacia can be caused by a variety of tumors, however they are usually benign bone or soft tissue tumors. Benign or low-grade malignant vascular or fibrous tissue tumors are the most common causes. Polyostotic fibrous dysplasia, neurofibromatosis, and metastatic prostate carcinoma may also cause tumor-induced osteomalacia (McCarthy & Frassica, 1998).
A) H&E 40x
B) H&E 100x
C) H&E 200x
D) H&E 400x
Diagnosis and treatment
Diagnosis is made based on laboratories and finding a causative tumor. Finding the responsible tumor can be a challenge.
Surgical excision of the entire lesion is curative. The serum phosphorus level returns to normal within days, bone density is typically restored within one year. Inability to localize tumor often delays definitive treatment. If the tumor is undetectable, medical therapy with calcitrol and phosphate is effective in some cases. There has been one case report of successful medical therapy with octreotide while a patient was awaiting surgery . It is hypothesized that somatostatin receptors regulate secretory activity, as in many other endocrine tumors
. However, there are also reports of octreotide therapy being ineffective. At least one group does not recommend the widespread use of somatostatin analogues for the treatment of this disease
. There has been one case report of a femoral head lesion successfully treated with radiofrequency ablation.
Case 1: 61 y/o male...
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