False-negative biopsies for the diagnosis of testicular intraepithelial neoplasia (TIN)--an update.

Abstract

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.