Intracranial phosphaturic mesenchymal tumor, mixed connective tissue variant presenting without oncogenic osteomalacia

Abstract

Background: Phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT) is a rare tumor typically occurring in soft tissues and bone, causing oncogenic (tumor-induced) osteomalacia (TIO) through secretion of the phosphaturic hormone, fibroblast growth factor-23 (FGF-23). Rare tumors identical to PMTMCT occur without known TIO. Intracranial localization of PMTMCT is extremely rare, with only two cases reported in the literature. We present a very unusual case of a patient with an intracranial PMTMCT that presented with neurologic changes without osteomalacia.

Case description: A 67-year-old woman presented with progressive incontinence, apathy, and abulia after having undergone a total knee replacement 1 month earlier. Imaging disclosed a large left frontal anterior fossa mass. She underwent uncomplicated surgical resection of this tumor. Surprisingly, histopathology suggested PMTMCT. Reverse transcription polymerase chain reaction (RT-PCR) assay demonstrating FGF-23 expression in the tumor confirmed the diagnosis. Serum FGF-23 levels postoperatively were normal and she had no clinical or laboratory evidence of osteomalacia or phosphaturia.

Conclusion: This report should serve to alert clinicians to the possibility that PMTMCT can be included in the differential diagnosis of intracranial masses even in the absence of tumor-induced osteomalacia.

Keywords: Intracranial; neoplasm; neuropathology; oncogenic osteomalacia.

Figure 1

(a-c) Axial (d, e) coronal, and (f) sagittal T1 post-gadolinium MRI demonstrating a heterogeneously-enhancing, partially cystic mass in the left frontal lobe / anterior fossa. The mass extends anteriorly and inferiorly to the cribriform plate at the skull base just above the ethmoid sinus, seen clearly in a, d, and f

Figure 2

The tumor is composed of bland mesenchymal spindle cells with ovale pointed nuclei (panel a, H and E, ×200), which stains only with antibodies to vimentin (panel b, ×200). At the ultrastructural level (panel c), the cells have elongated, irregular nuclei and relatively abundant cytoplasm continuing in slender processes. Overall, their appearance is consistent with a mesenchymal neoplasm, but they lack features to suggest a precise lineage of differentiation. The FGF-23 gene analysis by rtPCR[1] demonstrated positive amplification within tumor cells (panel d)