Current models of tumorigenesis postulate that testicular germ cell cancer uniformly develops through a preinvasive lesion termed testicular intraepithelial neoplasia (TIN). An open testicular biopsy ...is a simple and highly sensitive method to diagnose TIN, and this procedure constitutes the basis for curative treatment of TIN. Patients with testis cancer carry a significantly increased risk of developing contralateral testicular tumors. Therefore, a contralateral biopsy has been recommended in these patients. A negative biopsy was assumed to exclude the risk of a subsequent germ cell cancer in the testis due to the high sensitivity of the method. Reports on false-negative biopsies gave rise to the idea that TIN is not uniformly distributed throughout the testis. Consequently, double biopsies are thought to increase the diagnostic sensitivity.
A 24-year-old patient with nonseminomatous testis cancer is reported. The patient had TIN-negative double biopsies in the contralateral testis. He received three cycles of standard PEB (cisplatin, etoposide, bleomycin) chemotherapy for visceral metastasis. 1 year after treatment the patient developed a nonseminomatous contralateral testis cancer which was treated by partial orchiectomy and subsequent local radiotherapy with 20 Gy.
The case presented here highlights some clinically important aspects: a) even double biopsies of the testis may fail to detect TIN. b) Systemic cisplatin-based chemotherapy may fail to prevent contralateral testicular germ cell cancer. c) A metachronous contralateral testis cancer may-in contrast to common clinical perception-develop even soon after the diagnosis of the first testis tumor. Furthermore, the case could foster the hypothesis that testicular germ cell tumors may in some cases develop without a preceding stage of TIN.
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.
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.
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.
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.
The present study was carried out on the basis of the question of "whether it is possible to use mathematical methods meaningfully for the evaluation of the environmental effects of chemicals." The ...analysis of the evaluation process showed that this may be considered as a relation between the set of test data and a target set, that of the danger classes. The very general structure of a relation considerably restricts the use of algorithms; in particular it can be shown that algorithms which would map the data directly onto the danger classes like a functional coordination are, in general, excluded. This is partly due to the highly nonhomogeneous parameter set which must be determined for evaluation purposes, and partly to the high degree of randomness or human participation in the selection of the parameters. Moreover, there was no indication whether or to what extent the parameters are interdependent, i.e., whether there are interdisciplinary regularities which could be expressed algebraically and interpreted scientifically. Questions of this kind remain components of interdisciplinary research, and they cannot be explained from a mathematical--i.e., theoretical--point of view. Considerably more empirical material needs to be available for use as the foundation for a reasonable theory.
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