False-negative biopsies for testicular intraepithelial neoplasia

Purpose: Testicular intraepithelial neoplasia, also called carcinoma in situ of the testis, is diagnosed by conventional surgical biopsy based on the assumption that testicular intraepithelial neoplasia is randomly distributed throughout the testis. We evaluate the frequency of and possible reasons for false-negative biopsies. Materials and Methods: Contralateral testicular biopsy was performed in 1,954 consecutive patients with testicular germ cell tumor. Of the patients 1,859 with a negative biopsy for testicular intraepithelial neoplasia were followed for a median of 6 years. Patients with a second testicular tumor despite previous negative biopsy were evaluated clinically and biopsy specimens were reexamined immunohistologically. Results: Despite negative biopsy 5 patients had a second testis tumor. Testicular intraepithelial neoplasia was detected on reexamination in 2 of the specimens, and mechanical damage to the specimen and technical problems with immunohistochemical staining accounted for the diagnostic failures. The proportion of false-negative biopsies was 0.3% (95% confidence intervals [CI] 0.087 to 0.627). The sensitivity of testicular biopsies to detect testicular intraepithelial neoplasia was 0.95 (95% CI 0.887 to 0.984) and the overall accuracy of the biopsy was 0.997 (95% CI 0.994 to 0.999). To our knowledge 14 cases have been previously reported in the literature, including 2 treated with chemotherapy before testicular biopsy. Conclusions: The overall proportion of false-negative biopsies for testicular intraepithelial neoplasia is as low as 0.3%. The main reason for diagnostic failure is probably the nonrandom distribution of testicular intraepithelial neoplasia within the testis. Previous chemotherapy and rare technical failures, in particular mechanical damage to the biopsy specimen, may also account for diagnostic failures. Surgical biopsy remains the gold standard for the diagnosis of testicular intraepithelial neoplasia.