Department of Pathology, Erasmus MC-University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Int J Endocrinol. 2012;2012:671209. doi: 10.1155/2012/671209. Epub 2012 Jan 19.
Disorders of sex development (DSD) are defined as a congenital condition in which development of chromosomal, gonadal or anatomical sex is atypical. DSD patients with gonadal dysgenesis or hypovirilization, containing part of the Y chromosome (GBY), have an increased risk for malignant type II germ cell tumors (GCTs: seminomas and nonseminomas). DSD may be diagnosed in newborns (e.g., ambiguous genitalia), or later in life, even at or after puberty. Here we describe three independent male patients with a GCT; two were retrospectively recognized as DSD, based on the histological identification of both carcinoma in situ and gonadoblastoma in a single gonad as the cancer precursor. Hypospadias and cryptorchidism in their history are consistent with this conclusion. The power of recognition of these parameters is demonstrated by the third patient, in which the precursor lesion was diagnosed before progression to invasiveness. Early recognition based on these clinical parameters could have prevented development of (metastatic) cancer, to be treated by systemic therapy. All three patients showed a normal male 46,XY karyotype, without obvious genetic rearrangements by high-resolution whole-genome copy number analysis. These cases demonstrate overlap between DSD and the so-called testicular dysgenesis syndrome (TDS), of significant relevance for identification of individuals at increased risk for development of a malignant GCT.
性发育障碍（DSD）是指一种先天性疾病，其染色体、性腺或解剖性别发育异常。具有性腺发育不良或低雄激素化的 DSD 患者（包含部分 Y 染色体[GBY]），恶性 II 型生殖细胞肿瘤（GCT：精原细胞瘤和非精原细胞瘤）的风险增加。DSD 可在新生儿期（例如，生殖器模糊）诊断，也可在以后的生命中，甚至在青春期或之后诊断。在这里，我们描述了 3 名患有 GCT 的独立男性患者；其中 2 名患者基于单侧性腺中同时存在原位癌和性腺母细胞瘤的组织学鉴定，被回顾性诊断为 DSD，这是癌症前体。他们的病史中有尿道下裂和隐睾，这与这一结论一致。第三个患者的情况证明了识别这些参数的能力，其中在进展为侵袭性之前就诊断出了前体病变。基于这些临床参数的早期识别，可以预防（转移性）癌症的发展，从而进行全身治疗。这 3 名患者均表现出正常的男性 46，XY 核型，通过高分辨率全基因组拷贝数分析未显示明显的遗传重排。这些病例表明 DSD 与所谓的睾丸发育不良综合征（TDS）之间存在重叠，这对于确定具有恶性 GCT 发展风险增加的个体具有重要意义。
