Dieckmann K-P, Loy V
Urologische Abteilung, Albertinen-Krankenhaus, Suentelstrasse 11a, D-22457, Hamburg, Germany.
Eur Urol. 2003 May;43(5):516-21. doi: 10.1016/s0302-2838(03)00101-5.
Testicular intraepithelial neoplasia (TIN; or carcinoma in situ of the testis) is the precursor of testicular germ-cell tumours (GCT). It is detected by conventional surgical biopsy of the testis. To date, only little information is available in regard to the accuracy of the biopsy. False-negative biopsies have been reported only sporadically.
Twenty-one patients who developed a testicular GCT despite a testicular biopsy negative for TIN were analysed clinically and histologically. The median age of the patients is 34 years. The median interval from biopsy to the clinical appearance of GCT is 39 months. Four of the 21 patients had their biopsy done within a previously reported multicentric study (n=1859 cases with negative biopsy including five cases with false-negative biopsy hitherto known). All of the biopsy specimens were re-examined immunohistologically. In 15 cases, the orchiectomy specimens were re-examined for the presence of TIN in the tumour-surrounding tissue.
In five cases, TIN was found in the biopsy specimen upon re-examination. In all of the 15 orchiectomy specimens there was evidence of TIN in the tissue adjacent to the tumour. In three biopsy specimens there were microcalcifications in the seminiferous tubules. Severe impairment of the spermatogenesis was observed histologically in only 3 of the 21 patients. The relative proportion of false-negative biopsies is 0.5% (95% confidence intervals (CI): 0.22%; 0.92%). The sensitivity of the biopsy to detect TIN is 0.914 (95% CI: 0.842; 0.959) and the overall accuracy is 0.995 (95% CI: 0.991; 0.9979). A total of 44 false-negative biopsies are reported to date.
False-negative biopsies for TIN do occur but the proportion is only 0.5%. There is no clear-cut clinical nor histological feature associated with false-negative biopsies. However, young age (i.e. <18 years) and intratubular microcalcifications should increase the clinician's and pathologist's vigilance. The majority of false-negative biopsies are caused by the non-random distribution of TIN in the testis while some few cases are caused by technical problems. Two-site biopsies would probably increase the accuracy of the biopsy in high risk cases.
睾丸上皮内瘤变（TIN；或睾丸原位癌）是睾丸生殖细胞肿瘤（GCT）的前驱病变。它通过睾丸的传统手术活检来检测。迄今为止，关于活检准确性的信息很少。仅偶尔有假阴性活检的报道。
对21例尽管睾丸活检TIN为阴性但仍发生睾丸GCT的患者进行了临床和组织学分析。患者的中位年龄为34岁。从活检到GCT临床出现的中位间隔时间为39个月。21例患者中有4例是在之前报道的一项多中心研究中进行的活检（该研究共1859例活检阴性病例，包括迄今已知的5例假阴性活检病例）。所有活检标本均进行了免疫组织学复查。15例患者的睾丸切除标本对肿瘤周围组织中是否存在TIN进行了复查。
复查时在5例活检标本中发现了TIN。在所有15例睾丸切除标本中，肿瘤邻近组织均有TIN的证据。3例活检标本的生精小管中有微钙化。21例患者中仅3例在组织学上观察到严重的生精障碍。假阴性活检的相对比例为0.5%（95%置信区间（CI）：0.22%；0.92%）。活检检测TIN的敏感性为0.914（95%CI：0.842；0.959），总体准确性为0.995（95%CI：0.991；0.9979）。迄今为止共报道了44例假阴性活检。
TIN的假阴性活检确实会发生，但比例仅为0.5%。假阴性活检没有明确的临床或组织学特征。然而，年轻（即<18岁）和小管内微钙化应提高临床医生和病理医生的警惕性。大多数假阴性活检是由TIN在睾丸中的非随机分布引起的，少数情况是由技术问题导致的。在高危病例中，两点活检可能会提高活检的准确性。
