Phosphaturic Mesenchymal Tumor

Not clinically relevant

Nearly half of all PMTs contain either FN1-FGFR1 or, rarely, FN1-FGF1 fusion. FGFR1 expression is common in PMTs regardless of the fusion status. These findings suggest that activated receptor tyrosine kinase FGFR1 signaling pathways could drive PMT tumorigenesis and upregulation of FGF23. Excess production of FGF23, a phosphaturic hormone that acts to inhibit renal proximal tubule phosphate reuptake, is responsible for TIO in most instances. However, low-level expression of FGF23 can also occasionally be identified in non-PMT tumors, including occasional cases of fibrous dysplasia, aneurysmal bone cyst, and chondromyxoid fibroma of bone. Rare cases of PMT with known TIO are FGF23-negative, presumably reflecting production of other phosphaturic hormones.

Most PMTs present as nonspecific soft tissue or bone masses, often with a component of fat. Some may be highly calcified.

PMTs are usually composed of bland, spindle to stellate cells, which produce an unusual hyalinized to smudgy-appearing matrix. A very well-developed capillary network is typically present, with some cases also showing larger vessels arranged in a staghorn pericytoma-like pattern, or in a pattern resembling cavernous hemangioma. The matrix of PMT typically calcifies in an unusual grungy or flocculent fashion, sometimes forming flower-like slate-grey crystals, and in some instances, it may contain foci closely resembling primitive cartilage or osteoid. Osteoclasts, fibrohistiocytic spindled cells, mature adipose tissue, microcystic change, and a peripheral shell of woven bone may be present. Mitotic activity and necrosis are usually absent. In the jaws, PMTs with admixed epithelial (odontogenic) elements have been described. It is unclear whether these epithelial elements are neoplastic or entrapped/induced by the adjacent PMT.

Malignant PMT most often develops in lesions that have recurred locally, often more than once, and then show obvious features of malignancy including high nuclear grade, marked pleomorphism, high cellularity, necrosis, and elevated mitotic activity, resembling undifferentiated pleomorphic sarcoma or fibrosarcoma.
By immunohistochemistry, most PMTs express CD56, ERG, FGFR1, SATB2, and/or SSTR2A. Expression of FGF23 protein has been documented in some cases of PMT, although commercially available antibodies to FGF23 have questionable specificity and are not widely available.

Isolated case reports have noted bland spindle cells with finely granular chromatin, indistinct nucleoli, and scant delicate cytoplasm; scattered osteoclasts associated with stromal matrix can also be found.

The overwhelming majority of PMTs are histologically and clinically benign, with complete excision resulting in dramatic improvement of phosphate wasting and osteomalacia. Malignant tumors may metastasize and cause death.

Detection of FN1-FGFR1 or FN1-FGF1 fusion is confirmatory but not required for routine diagnosis of PMT.

Essential: a usually bland spindle cell tumor with matrix deposition, grungy calcification, and/or a rich vascular network; clinical evidence of hypophosphatemia and/or osteomalacia, corrected by complete tumor excision.

Desirable: FGF23 overproduction in the serum or in the neoplastic tissue (in selected cases).