Abstract
Phosphaturic mesenchymal tumors (PMTs) are very rare tumors which are frequently associated with Tumor Induced Osteomalacia (TIO), a paraneoplastic syndrome that manifests as renal phosphate wasting. The tumor cells produce a peptide hormone-like substance known as fibroblast growth factor 23 (FGF23), a physiologic regulator of phosphate levels. FGF23 decreases proximal tubule reabsorption of phosphates and inhibits 1-α-hydroxylase, which reduces levels of 1-α, 25-dihydroxyvitamine D3. Thus, overexpression of FGF23 by the tumor cells leads to increased excretion of phosphate in the urine, mobilization of calcium and phosphate from bones, and the reduction of osteoblastic activity, ultimately resulting in widespread osteomalacia. Patients typically present with gradual muscular weakness and diffuse bone pain from pathologic fractures. The diagnosis is often delayed due to the non-specific nature of the symptoms and lack of clinical suspicion. While serum phosphorus and FGF23 testing can assist in making a clinical diagnosis of PMT, the responsible tumor is often difficult to locate. The pathologic diagnosis is often missed due to the rarity of PMTs and histologic overlap with other mesenchymal neoplasms. While patients can experience severe disabilities without treatment, excision is typically curative and results in a dramatic reversal of symptoms. Histologically, PMT has a variable appearance and can resemble other low grade mesenchymal tumors. Even though very few cases of PMT have been reported in the world literature, it is very important to consider this diagnosis in all patients with hypophosphatemic osteomalacia. Here we present a patient who suffered for almost 5 years without a diagnosis. Ultimately, the PMT was located on a 68Ga-DOTA TATE PET/CT scan and subsequently confirmed by histologic and immunohistologic study. Interestingly, strong positivity for FGFR1 by IHC might be related to the recently described FN1-FGFR1 fusion. Upon surgical removal, the patient’s phosphate and FGF23 levels returned to normal and the patient’s symptoms resolved.
Highlights
Phosphaturic mesenchymal tumors (PMTs) are very rare tumors which are frequently associated with Tumor Induced Osteomalacia (TIO), a paraneoplastic syndrome that manifests as renal phosphate wasting
Testing for fibroblast growth factor 23 (FGF23) showed an increased serum level (240 RU/ml), which has a differential of X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), or PMT
Both pathways will converge in the activation of FGFR1 signaling, which upregulates the expression of FGF23.17 α-Klotho is an obligatory co-receptor for FGF23–FGFR1 binding, and its expression is mostly limited to renal tubules, choroid plexus, and parathyroid gland under normal physiologic condition.[18]
Summary
Phosphaturic mesenchymal tumors (PMTs) are very rare tumors which are frequently associated with Tumor Induced Osteomalacia (TIO), a paraneoplastic syndrome that manifests as renal phosphate wasting. A rheumatologic workup was negative and he was treated symptomatically with NSAIDs, glucosamine, and hydrocodone He had a pruritic rash on his lower legs. A CT scan revealed diffuse osteopenia with insufficiency fractures His serum alkaline phosphate level was elevated while serum phosphate was decreased. Testing for FGF23 showed an increased serum level (240 RU/ml), which has a differential of X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), or PMT. His lack of family history argued against XLH and ADHR. Given the high clinical suspicion for a PMT, a PET scan was performed in an attempt to locate the PMT This showed markedly PET avid right axillary adenopathy as well as a right hand mass. A 68Ga-DOTA TATE PET/CT was performed and showed prominent uptake in an enlarged right inguinal lymph node, which was subsequently excised
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