一小部分睾丸性索间质肿瘤,指定为支持间质细胞肿瘤(SSCT),包含Sertoli的混合物,纺锤体和/或Leydig细胞。这些肿瘤的临床病理特征尚未得到任何详细研究,它们的分子特征是未知的。我们,因此,评估了14个SSCT的形态和基因组特征,包括1例特征与卵巢睾丸支持-睾丸间质细胞瘤(SLCT)相似的肿瘤,伴有肾小管。患者的中位年龄为24岁(范围10-55岁),中位肿瘤大小为2.3cm(范围0.7-4.7cm)。所有肿瘤均显示Sertoli样性索细胞排列在不同发育的管状结构中,通常还形成巢和绳索。这些与肿瘤梭形细胞基质或不可察觉的混合,在SLCT中,空泡成嗜酸性Leydig细胞。基因组分析表明,SLCT(患者1)中存在热点功能丧失DICER1突变,而患者2和3的肿瘤中存在热点功能获得CTNNB1突变,后者均认为可能发生亚克隆事件。突变是患者1和2的肿瘤中唯一的相关发现,而患者3的肿瘤同时具有染色体臂水平和染色体水平的拷贝数增加。其余11种肿瘤中的9种(包括9种可解释的和2种不可解释的拷贝数变异结果)具有多个复发性染色体臂水平和染色体水平拷贝数增加,提示倍性发生改变,而没有并发致病性突变。本研究的结果表明,CTNNB1突变(可能是亚克隆的)仅在SSCT中很少出现;相反,它们中的大多数具有类似于睾丸性索间质肿瘤的基因组改变,这些肿瘤具有纯的或主要的梭形细胞成分。一个值得注意的例外是睾丸支持-睾丸间质细胞肿瘤,其形态学特征与卵巢对应物相同,带有DICER1突变。
A small subset of testicular sex cord-stromal tumors, designated as Sertoli-stromal cell tumors (SSCTs), comprises a mixture of Sertoli, spindle, and/or Leydig cells. The clinicopathologic features of these tumors have not been studied in any detail, and their molecular features are unknown. We, therefore, assessed the morphologic and genomic features of 14 SSCTs, including 1 tumor with features similar to the ovarian Sertoli-Leydig cell tumor (SLCT) with retiform tubules. The median age of the patients was 24 years (range, 10-55 years), and the median tumor size was 2.3 cm (range, 0.7-4.7 cm). All tumors showed Sertoli-like sex cord cells arranged in variably developed tubular structures, typically also forming nests and cords. These imperceptibly blended with a neoplastic spindle cell stroma or, in the SLCT, vacuolated to eosinophilic Leydig cells. Genomic analysis demonstrated the presence of a hotspot loss-of-function DICER1 mutation in the SLCT (patient 1) and hotspot gain-of-function CTNNB1 mutations in the tumors of patients 2 and 3, with both CTNNB1 variants being interpreted as possible subclonal events. The mutations were the only relevant findings in the tumors of patients 1 and 2, whereas the tumor of patient 3 harbored concurrent chromosomal arm-level and chromosome-level copy number gains. Among the remaining 11 tumors, all of those that had interpretable copy number data (9 tumors) harbored multiple recurrent chromosomal arm-level and chromosome-level copy number gains suggestive of a shift in ploidy without concurrent pathogenic mutations. The results of the present study suggest that CTNNB1 mutations (likely subclonal) are only rarely present in SSCTs; instead, most of them harbor genomic alterations similar to those seen in testicular sex cord-stromal tumors with pure or predominant spindle cell components. A notable exception was a testicular SLCT with morphologic features identical to the ovarian counterpart, which harbored a DICER1 mutation.