Thorup Jorgen, Clasen-Linde Erik, Cortes Dina
Department of Pediatric Surgery, Rigshospitalet, Copenhagen, Denmark.
Institute for Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Denmark.
Eur J Pediatr Surg. 2017 Aug;27(4):313-318. doi: 10.1055/s-0036-1592137. Epub 2016 Sep 8.
Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. Adult germ cell cancer immunohistochemical markers may fail to detect ITGCN in prepubertal boys with congenital cryptorchidism, because positive immunohistochemistry is commonly seen in boys younger than the age of 2 years, where most orchiopexies are performed. The aim of the study was to evaluate the diagnostic challenge to differentiate between a histological pattern of ITGCN and a histological pattern with some atypical germ cells and all positive cancer immunohistochemical markers, but no increased risk of malignancy. Histology sections from 373 testicular biopsies from 289 boys aged 1 month to 2 years operated for cryptorchidism were incubated with primary antibodies including anti-placental-like-alkaline phosphatase, antiOct-3/4, anti-C-kit, anti-D2-40, and in case of repeat biopsy with anti-stem cell factor (SCF) receptor. The prevalence of Oct-3/4 and D2-40-positive staining of germ cells in testicular biopsies were in age groups less than 6 months, 100% and 50%; 6-12 months, 60% and 17%; and 1-2 years, 12% and 4%. A 1 year, 1-month-old boy with Prader-Willi syndrome treated with growth hormone had ITGCN in both cryptorchid testes. In another three bilateral nonsyndromic cases, 8 months, 8 months and 1-year-old, a histological pattern in accordance with ITGCN was found. These three boys had a repeat biopsy from both testes performed at the age of 3 years, 4 months, 3.5 years, and 3 years, 10months, respectively. In all cases, the Oct-3/4 and D2-40 positive germ cells turned negative and the histological pattern normalized completely. The primary biopsies had SCF negative germ cells. This study is valuable in identifying the age-related change in Oct-3/4 or D2-40 immunopositive germ cells in seminiferous tubules. An ITGCN-like histological pattern in nonsyndromic cryptorchidism will vanish after the age of 3 years. Even when immunohistochemistry is applied, prepubertal ITGCN is so rarely demonstrated in cryptorchid testes, that it is not plausible that ITGCN generally originates during fetal development in cryptorchidism.
小管内生殖细胞瘤（ITGCN）是睾丸生殖细胞癌的前驱病变。成人生殖细胞癌免疫组化标志物可能无法在患有先天性隐睾症的青春期前男孩中检测到ITGCN，因为在大多数睾丸固定术施行时年龄小于2岁的男孩中，免疫组化阳性很常见。本研究的目的是评估鉴别ITGCN组织学模式与具有一些非典型生殖细胞且所有癌症免疫组化标志物均为阳性但无恶性风险增加的组织学模式的诊断挑战。对289名年龄在1个月至2岁因隐睾症接受手术的男孩的373份睾丸活检组织切片，用包括抗胎盘样碱性磷酸酶、抗Oct-3/4、抗C-kit、抗D2-40的一抗进行孵育，对于重复活检的病例则用抗干细胞因子（SCF）受体进行孵育。睾丸活检组织中生殖细胞Oct-3/4和D2-40阳性染色的患病率在年龄小于6个月的组中分别为100%和50%；6至12个月的组中分别为60%和17%；1至2岁的组中分别为12%和4%。一名患有普拉德-威利综合征并接受生长激素治疗的1岁1个月大男孩双侧隐睾中均有ITGCN。在另外3例双侧非综合征性病例中，年龄分别为8个月、8个月和1岁，发现符合ITGCN的组织学模式。这3名男孩分别在3岁4个月、3.5岁和3岁10个月时对双侧睾丸进行了重复活检。在所有病例中，Oct-3/4和D2-40阳性生殖细胞均转为阴性，组织学模式完全恢复正常。初次活检时生殖细胞SCF为阴性。本研究对于识别生精小管中Oct-3/4或D2-40免疫阳性生殖细胞的年龄相关变化具有重要价值。非综合征性隐睾中类似ITGCN的组织学模式在3岁后会消失。即使应用免疫组化，青春期前ITGCN在隐睾睾丸中也很少被证实，因此认为ITGCN通常在隐睾症的胎儿发育期间起源是不合理的。
