Phosphaturic mesenchymal tumors (PMT) are rare neoplasms characterized by secretion of FGF23, resulting in renal phosphate wasting and osteomalacia. This tumor-induced osteomalacia (TIO) is cured by complete resection; thus, diagnosis is important, particularly on biopsy. Although PMT have a classic histologic appearance of bland spindled cells with conspicuous vascular network and characteristic smudgy basophilic matrix, there is a broad histologic spectrum and variant histologic patterns can make recognition difficult. Recent studies have demonstrated FN1-FGFR1 and FN1-FGF1 gene fusions in PMT; however, approximately 50% of cases are negative for these fusions. We sought to characterize 6 cases of PMT in-depth, compare fusion detection methods, and determine whether alternative fusions could be uncovered by targeted RNA sequencing. Of the 6 cases of PMT in our institutional archive, 3 were not given diagnoses of PMT at the time of initial pathologic examination. We characterized the immunoprofile (SMA, D2-40, CD56, S100 protein, desmin, SATB2, and ERG) and gene fusion status (FN1 and FGFR1 rearrangements by fluorescent in situ hybridization (FISH) and two targeted RNA sequencing approaches) in these cases. Tumors were consistently positive for SATB2 and negative for desmin, with 5/6 cases expressing ERG and CD56. One specimen was acid-decalcified and failed FISH and RNA sequencing. We found FN1 gene rearrangements by FISH in 2/5 cases, and a FN1-FGFR1 fusion by targeted RNA sequencing. No alternative gene fusions were identified by RNA sequencing. Our findings suggest that IHC and molecular analysis can aid in the diagnosis of PMT, guiding excision of the tumor and resolution of osteomalacia.

磷酸间充质肿瘤（PMT）是罕见的肿瘤，其特征在于FGF23的分泌，导致肾磷酸盐消耗和骨软化症。这种肿瘤诱导的骨软化症（TIO）可以通过完全切除来治愈；因此，诊断非常重要，尤其是在活检方面。尽管PMT具有温和的梭形细胞的经典组织学外观，具有明显的血管网络和特征性的嗜污嗜碱性基质，但是组织学谱范围广，并且不同的组织学模式会使识别变得困难。最近的研究表明FN1-FGFR1和FN1-FGF1PMT中的基因融合；但是，大约有50％的病例对这些融合阴性。我们试图深入表征6例PMT，比较融合检测方法，并确定靶向RNA测序是否可以发现其他融合。在我们机构档案中的6例PMT病例中，有3例在初始病理检查时未诊断为PMT。我们表征了免疫特征（SMA，D2-40，CD56，S100蛋白，结蛋白，SATB2和ERG）和基因融合状态（FN1和FGFR1）在这些情况下，可通过荧光原位杂交（FISH）和两种靶向RNA测序方法进行重排。肿瘤对SATB2始终呈阳性，对结蛋白呈阴性，其中5/6例表达ERG和CD56。1个标本被酸脱钙，FISH和RNA测序失败。我们在2/5个病例中发现FN1基因通过FISH重排，并通过靶向RNA测序发现FN1 -FGFR1融合。RNA测序未鉴定出其他基因融合体。我们的研究结果表明，IHC和分子分析可以帮助诊断PMT，指导肿瘤切除和消除骨软化症。