Department of Anatomic Pathology, Graduate School of Medical Sciences, Fukuoka-ken, Japan.
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka-ken, Japan.
Histopathology. 2018 Feb;72(3):460-471. doi: 10.1111/his.13377. Epub 2017 Nov 16.
Phosphaturic mesenchymal tumour, mixed connective tissue variant (PMT-MCT), is a tumour of uncertain differentiation, characterised by 'smudgy/grungy' calcification and vitamin D-resistant phosphaturic osteomalacia. Fibroblast growth factor (FGF)23 is recognised as a reliable marker of PMT-MCT, but quantitative evaluation has never been performed. We reviewed cases of tumour-associated osteomalacia or histologically definitive PMT-MCT without osteomalacia using histological, immunohistochemical and genetic methods and evaluated the diagnostic significance of these findings.
A total of 19 tumours from 14 cases diagnosed previously as PMT-MCT were retrieved, on which immunohistochemical staining, reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in-situ hybridisation (FISH) analysis were performed. Histologically, fibrous capsule, calcification and giant cell reaction tended to be observed in soft-tissue PMT-MCT, while PMT-MCT of bone and multiple PMT-MCT showed an infiltrative growth pattern. The immunohistochemical results were as follows: the tumour cells were positive for FGF23 (nine of 12, 75%), FGFR1 (11 of 11, 100%), CD56 (12 of 14, 85.7%) and E26 oncogene homologue (ERG) (5 of 13, 38.4%). The sole malignant tumour was positive for p53. FGF23 mRNA was detected in seven of 14 formalin-fixed paraffin-embedded (FFPE) specimens and all five frozen specimens by RT-PCR. The level of FGF23 mRNA, which was determined by real-time PCR, varied among the phosphaturic cases. Two of 17 tumours were positive for FGFR1 gene rearrangement.
It was considered that PMT-MCT is a histopathological entity with or without phosphaturia, with varying levels of FGF23 mRNA, and with or without fibronectin 1 (FN1)-FGFR1 fusion gene. The authors propose that the histology of PMT-MCT differs depending on its location, such as bone or soft tissue, which could complicate the differential diagnosis.
磷酸尿基质肿瘤，混合结缔组织型（PMT-MCT）是一种分化不确定的肿瘤，其特征为“污浊/肮脏”样钙化和维生素 D 抵抗性佝偻病。成纤维细胞生长因子（FGF）23 被认为是 PMT-MCT 的可靠标志物，但从未进行过定量评估。我们通过组织学、免疫组织化学和遗传学方法回顾了肿瘤相关性佝偻病或组织学明确的 PMT-MCT 而无佝偻病的病例，并评估了这些发现的诊断意义。
共检索到 14 例先前诊断为 PMT-MCT 的 19 例肿瘤，对其进行免疫组织化学染色、逆转录聚合酶链反应（RT-PCR）和荧光原位杂交（FISH）分析。组织学上，软组织 PMT-MCT 中倾向于观察到纤维囊、钙化和巨细胞反应，而骨 PMT-MCT 和多个 PMT-MCT 则表现为浸润性生长模式。免疫组织化学结果如下：肿瘤细胞对 FGF23（12 例中的 9 例，75%）、FGFR1（11 例中的 11 例，100%）、CD56（14 例中的 12 例，85.7%）和 E26 癌基因同系物（ERG）（13 例中的 5 例，38.4%）呈阳性。唯一的恶性肿瘤对 p53 呈阳性。RT-PCR 检测 14 例福尔马林固定石蜡包埋（FFPE）标本中的 7 例和 5 例冷冻标本中的 FGF23 mRNA。通过实时 PCR 确定的 FGF23 mRNA 水平在磷酸尿病例中有所不同。17 例肿瘤中有 2 例 FGFR1 基因重排阳性。
PMT-MCT 被认为是一种具有或不具有磷酸尿的组织病理学实体，其 FGF23 mRNA 水平不同，且存在或不存在纤连蛋白 1（FN1）-FGFR1 融合基因。作者提出，PMT-MCT 的组织学因位置而异，如骨或软组织，这可能使鉴别诊断复杂化。
