DSS Sarah E. Martin, M.D. Eyas M. Hattab, M.D. Indiana University School of Medicine 86 th Annual Meeting of the AANP June 10-13, 2010

Clinical History 61 yo woman with a history of multiple fractures and hypophosphatemia for 6 yrs Presented with bilateral weakness and shooting pains in her legs after a fall MRI: multi-lobulated, vividly enhancing, heterogeneous T12 mass with extension into epidural space and paraspinal musculature

Diagnosis?

Phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT)

PMTMCT Definition – –Largely benign, morphologically distinct mesenchymal neoplasm almost invariably associated with oncogenic osteomalacia Incidence – –Extremely rare, ~ 150 cases described in the literature Historical perspective – –1987: Weidner and Santa Cruz coined term – –2004: Folpe et al. fully characterized PMTMCT

PMTMCT Location – –Soft tissues and bones of the extremities – –Only rarely in axial skeleton (index case) Etiology – –FGF-23 overexpression: inhibits trans-epithelial phosphate transport in renal tubules, resulting in renal phosphate wasting and subsequent osteomalacia Clinical features: – –25-77 years; female predominance – –Bone pain, multiple fractures – –Hypophosphatemia, hyperphosphaturia, and osteomalacia; fail vitamin D therapy – –Chronic, protracted history before tumor is discovered

PMTMCT: pathology Gross: – –Superficial and deep soft tissues – –Well-circumscribed Microscopic – –Low cellularity, bland spindled cells – –Myxochondroid/osteoid-like matrix – –Dystrophic calcification, incomplete rim of ossification – –HPC-like vessels, microcysts, hemorrhage – –Osteoclast-like giant cells Immunohistochemistry – –FGF-23

PMTMCT: pathology Differential diagnosis: – –Hemangiopericytoma – –Giant cell tumor – –Osteoblastoma – –Osteosarcoma – –Mesenchymal chondrosarcoma – –Hemangioma Keys to diagnosis: – –Awareness of entity – –Clinical history of osteomalacia (not universal) – –Morphologic heterogeneity

PMTMCT: management Treatment – –Surgical resection is curative of both tumor and osteomalacia Prognosis – –Generally excellent after complete resection – –Rare malignant forms have been reported   Increased mitoses, high nuclear grade and high cellularity   Local recurrence; lung and skeletal metastases reported

The end.