The existence of a true mixed germ cell-sex cord stromal tumor (MGSCT) of the testis remains controversial. Based on our experience with rare testicular tumors in this spectrum, we sought to perform a detailed clinicopathologic and molecular study of MGCSCT. Eight cases of testicular MGSCT were morphologically reviewed, screened for chromosomal aberrations (using array comparative genomic hybridization (aCGH) and low pass genomic sequencing), and analyzed by next generation sequencing (The Illumina TruSight Tumor 170). Immunohistochemistry for OCT3/4, Nanog, SALL4, DMRT1, and inhibin was performed on the cohort. Clinical data and follow-up were assessed by medical record review. All patients were karyotypically normal men aged 27-74 years (median 41). All tumors had a similar biphasic morphology characterized by various proportions of the sex cord component resembling granulosa cell tumor of adult type and the germ cell component cytomorphologically akin to spermatocytic tumor. Germ cells were haphazardly scattered throughout the tumor or arranged in larger groups, without tubular formation. In 4 cases, atypical mitoses were found within the germ cells. Additionally, in 2 cases there was invasion into the spermatic cord, adjacent hilar soft tissue and into the tumor capsule, which contained both tumor components. Immunohistochemically, focal nuclear expression of DMRT1 was found in the germ cell component in 7/7 analyzable tumors, while SALL4 was positive in 6 cases and negative in one case. All tumors were negative with OCT3/4 and Nanog. The sex cord stromal component had immunoreactivity for inhibin in 7/7 analyzable cases. Four of 8 cases were cytogenetically analyzable: 4/8 by low pass genomic sequencing and 2/8 by aCGH. The results of both methods correlated well, revealing mostly multiple chromosomal losses and gains. One case revealed loss of chromosome 21; 1 case had loss of chromosomes 21 and 22 and partial gain of 22; 1 case had loss of chromosomes 22 and Y, partial loss of X, and gain of chromosomes 20, 5, 8, 9, 12, and 13; and the remaining one gain of chromosomes 20, 3, 6, 8, 2x(9), 11, 2x(12), 13, 14, 18, and 19. Three cases were analyzable by NGS; clinically significant activating mutations of either FGFR3 or HRAS were not detected in any case. Follow-up was available for 4 patients (12, 24, 84, and 288 months) and was uneventful in all 4 cases. The identification of extratesticular invasion of both the germ cell and sex cord stromal components, the DMRT1 expression, and the presence of atypical mitoses in germ cells argue for the neoplastic nature of the germ cell component. The molecular genetic study revealing multiple chromosomal losses and gains in a subset of the cases provides the first evidence that molecular abnormalities occur in testicular MGSCT. Multiple chromosomal aneuploidies, namely, recurrent losses of chromosomes 21 and 22 and gains of 8, 9, 12, 13, and 20, indicate that the germ cell component might be related to the morphologically similar spermatocytic tumor, which is characterized by extensive aneuploidies including recurrent gains of chromosomes 9 and 20 and loss of chromosome 7. In summary, our data support that rare examples of true MGSCT of the testis do exist and they represent a distinct tumor entity with admixed adult-type granulosa cell tumor and spermatocytic tumor components.

中文翻译：

---

对睾丸混合生殖细胞 - 性索间质肿瘤的新见解：检测染色体非整倍性和支持生殖细胞成分肿瘤性质的进一步形态学证据。

睾丸是否存在真正的混合生殖细胞-性索间质瘤（MGSCT）仍然存在争议。根据我们在该范围内处理罕见睾丸肿瘤的经验，我们试图对 MGCSCT 进行详细的临床病理学和分子研究。八例睾丸 MGSCT 进行形态学审查，筛查染色体畸变（使用阵列比较基因组杂交 (aCGH) 和低通基因组测序），并通过下一代测序（Illumina TruSight Tumor 170）进行分析。对队列进行了 OCT3/4、Nanog、SALL4、DMRT1 和抑制素的免疫组织化学。临床数据和随访通过病历审查进行评估。所有患者都是核型正常的男性，年龄在 27-74 岁（中位数 41）。所有肿瘤都具有相似的双相形态，其特征在于不同比例的性索成分类似于成人型颗粒细胞肿瘤，而生殖细胞成分在细胞形态学上类似于精母细胞肿瘤。生殖细胞随意散布在整个肿瘤中或排列成更大的群体，没有管状形成。在 4 例中，在生殖细胞内发现了非典型有丝分裂。此外，在 2 例中，精索、邻近的肺门软组织和肿瘤包膜均受侵，其中包含两种肿瘤成分。免疫组织化学上，在 7/7 可分析肿瘤的生殖细胞成分中发现 DMRT1 的局灶核表达，而 SALL4 6 例阳性，1 例阴性。所有肿瘤的 OCT3/4 和 Nanog 均呈阴性。在 7/7 可分析病例中，性索基质成分对抑制素具有免疫反应性。8 个病例中有 4 个可进行细胞遗传学分析：4/8 通过低通基因组测序和 2/8 通过 aCGH。两种方法的结果相关性很好，主要揭示了多条染色体丢失和增加。1 例显示 21 号染色体丢失；1例21、22号染色体丢失，22号染色体部分获得；1例22、Y染色体缺失，X部分缺失，20、5、8、9、12、13号染色体获得；其余1条获得20、3、6、8、2x(9)、11、2x(12)、13、14、18和19号染色体。NGS可分析3例；在任何情况下都未检测到 FGFR3 或 HRAS 的临床显着激活突变。对 4 名患者（12、24、84 和 288 个月）进行了随访，并且所有 4 例患者都平安无事。生殖细胞和性索间质成分的睾丸外侵袭的鉴定、DMRT1 表达以及生殖细胞中非典型有丝分裂的存在证明了生殖细胞成分的肿瘤性质。分子遗传学研究揭示了部分病例中的多条染色体丢失和增加，这为睾丸 MGSCT 中发生分子异常提供了第一个证据。多染色体非整倍体，即 21 和 22 号染色体的反复丢失和 8、9、12、13 和 20 号染色体的增加，表明生殖细胞成分可能与形态相似的精母细胞肿瘤有关，其特征在于广泛的非整倍体，包括9 号和 20 号染色体的反复获得和 7 号染色体的丢失。总而言之，