Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Genes Chromosomes Cancer. 2020 Mar;59(3):203-208. doi: 10.1002/gcc.22814. Epub 2019 Oct 21.
We report a primary renal synovial sarcoma with a novel gene fusion and unusual morphology. The patient was a 35-year-old female who was found to have a 5 cm hypocellular, myxoid spindle cell renal neoplasm that subtly permeated amongst native renal tubules. The tumor cells showed elongated hyperchromatic nuclei with ill-defined pale cytoplasm, lacking significant mitotic activity or necrosis. Based on its deceptively bland morphology, the differential diagnosis included mainly benign entities, such as metanephric stromal tumor, mixed epithelial stromal tumor (MEST), and myxoid peripheral nerve sheath tumors. A definitive diagnosis of synovial sarcoma was made only subsequently to RNA-sequencing, which revealed a novel SS18-NEDD4 gene fusion. These results were further confirmed by fluorescence in situ hybridization using custom design break-apart probes for both genes. This case illustrates the utility of targeted RNA-sequencing in the classification of challenging tumors with deceptive morphology and identification of novel gene fusion variants. Apart from the canonical SS18-SSX fusion, this is only the second alternative gene fusion variant described in synovial sarcoma to date, in addition to two cases harboring the SS18L1-SSX1 fusion.
我们报告了一例具有新颖基因融合和不寻常形态的原发性肾脏滑膜肉瘤。患者为 35 岁女性，发现有 5 厘米大小的低细胞性、黏液样梭形细胞肾肿瘤，微妙地渗透在固有肾小管之间。肿瘤细胞显示出拉长的深染核，细胞质界限不清，呈淡染，缺乏明显的有丝分裂活性或坏死。基于其看似温和的形态，鉴别诊断主要包括良性实体，如后肾间质肿瘤、混合上皮间质肿瘤（MEST）和黏液样外周神经鞘肿瘤。只有在 RNA 测序后，才能明确诊断为滑膜肉瘤，RNA 测序显示了一种新颖的 SS18-NEDD4 基因融合。这些结果进一步通过使用针对这两个基因的定制设计的断裂探针的荧光原位杂交得到证实。该病例说明了靶向 RNA 测序在具有欺骗性形态的具有挑战性的肿瘤分类中的实用性，并鉴定了新型基因融合变体。除了典型的 SS18-SSX 融合外，这是迄今为止滑膜肉瘤中描述的第二个替代基因融合变体，此外还有两个携带 SS18L1-SSX1 融合的病例。
