肾肿瘤的分类继续以新颖的方式发展,新兴,和临时实体不断被描述。与体细胞NF2突变相关的双相玻璃样肾细胞癌(BHPRCC)是一种新的肾脏实体,由于其数据非常有限,因此被认为是RCC的临时类别。为新提议的实体提供进一步支持,我们确定了另外三例BHPRCC,临床病理,免疫组织化学,和各种分子分析。有2名男性和1名女性,65岁、56岁和69岁,分别。肿瘤没有包囊,并且都具有特征性的双相外观,即较小的细胞聚集在较大的腺泡内的基底膜材料周围,形成假结球或肾小球样。在2例病例中,透明质化的硬化基质和砂膜体是丰富的,在1例中是局灶性的。还注意到外观不明显的局灶性区域;一个在粘液样基质中还具有细长的管状图案,让人联想到粘液性管状和梭形细胞癌;一个由上皮样透明细胞的固体肺泡结构组成,与透明细胞RCC有一些相似之处。肿瘤没有独特的免疫组织化学(IHC)特征,虽然都标有波形蛋白和CK7。靶向DNA测序发现一例NF2基因携带致病性体细胞移码突变,Sanger测序进一步证实了这一点。另外两个病例缺乏NF2突变,而是通过甲基化特异性聚合酶链反应证明NF2启动子甲基化。随后的IHC评估显示在所有3例病例中NF2表达缺失,在蛋白质水平上评估NF2状态。根据基于RNA测序的聚类分析,这3例病例形成了一个不同的组,具有与其他已确定的肾脏肿瘤类型不同的共同特异性转录谱。此外,磷酸肌醇3-激酶(PI3K)/AKT途径显着富集,在所有富集途径的顶部。临床上,1例患者在确诊后2年发生骨转移并死于疾病.另外两名患者没有复发或转移的证据,在4年和5年的随访。这些发现不仅验证了先前描述的临床病理特征,而且扩展了潜在的遗传改变和可用的临床结果数据。
The classification of renal neoplasms continues to evolve with novel, emerging, and provisional entities being described constantly.
Biphasic hyalinizing psammomatous renal cell carcinoma (BHP RCC) associated with somatic NF2 mutations is one such new renal entity and is considered as a provisional category of RCC due to its very limited data. To provide further support for the newly proposed entity, we identified three additional cases of BHP RCC, with clinicopathological, immunohistochemical, and various molecular analyses. There were 2 males and 1 female, aged 65, 56, and 69 years, respectively. The neoplasms were unencapsulated, and all had a characteristic
biphasic appearance of smaller cells clustering around basement membrane material within larger acini, forming pseudorosettes or a glomeruloid pattern. Hyalinized sclerotic stroma and psammoma bodies were abundant in two cases and focally present in one case. Focal areas of a less distinctive appearance were also noted; one additionally had an elongated tubular pattern in the myxoid stroma that is reminiscent of mucinous tubular and spindle cell carcinoma; one consisted solid alveolar architectures of epithelioid clear cells, bearing some resemblance to clear cell RCC. The neoplasms did not have a distinctive immunohistochemistry (IHC) profile, though all labeled for vimentin and CK7. Targeted DNA sequencing revealed that one case harbored a pathogenic somatic frameshift mutation in the NF2 gene, which was further confirmed by Sanger sequencing. The other two cases lacked NF2 mutations and instead demonstrated NF2 promoter methylation by methylation-specific polymerase chain reaction. Subsequent IHC assessment showed loss of expression of NF2 in all 3 cases, which evaluated NF2 status at the protein level. According to RNA sequencing-based clustering analysis, the 3 cases formed a distinct group with a shared specific transcriptional profile different from that of other established renal tumor types. In addition, phosphate inositide 3-kinase (PI3K)/AKT pathway was enriched significantly and on the top of all enriched pathways. Clinically, one patient developed bone metastases and died of disease two years after diagnosis. The other two patients had no evidence of recurrence or metastases, at 4- and 5-year follow-up. These findings not only validate previously described clinicopathological features but also expand the potentially genetic alterations and available clinical outcome data.