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Abstract

Phosphaturic mesenchymal tumours (PMTs) are extremely rare neoplasms associated with tumor-induced osteomalacia presenting with pathologic fractures in the setting of chronic hypophosphatemic hyperphosphaturic osteomalacia, as well as gradual muscle weakness, bone pain, and difficulty walking. The most common genetic mutations in PMTs are FN1-FGFR1 and FN1-FGF1 fusion genes, which lead to overexpression of the FGFR1 oncogene and occur in about 50% of PMTs. To the best of our knowledge, only one previous case of PMT with this PDGFRA::USP35 has been previously reported. Herein, we report the second case of PMT that had PDGFRA::USP35 gene fusion in English literature.

A 35-year-old male presented with a slow growing lesion on the right index finger. An excision was performed which revealed a bland spindle cell lesion with grungy calcifications and vascularized stroma. By immunohistochemistry, the lesional ells were positive for CD56, SMA, SATB2, variably positive for ERG, focally and weakly positive for EMA, DOG1, S100, and negative for AE1/3, Desmin, SOX10, and MUC4. RNA-sequencing was positive for PDGFRA::USP35 gene fusion. Solid tumour gene panel mutation profiling was negative for any gene mutations.

In summary, we highlight a unique PDGFRA::USP35 gene, rarely described in PMT, and expand on the spectrum of molecular genetic profile of PMT. The clinical significance of this gene fusion is not known.  Future studies on larger cohorts are needed to ascertain the biological significance of these tumours with novel gene fusions.