Pathogenesis and Active Prevention of Testicular Germ Cell Neoplasia

Journal für Reproduktionsmedizin und Endokrinologie - Journal of Reproductive Medicine and Endocrinology 2007; 4 (6): 313-321

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Keywords: Andrologie,  Gonaden,  Hoden,  Karzinom,  Keimzelltumor,  Onkologie,  Reproduktionsmedizin,  andrology,  Carcinoma in situ,  germ cell tumor,  gonads,  oncology,  reproductive endocrinology,  Testis

Most testicular neoplasms originate from fetal germ cells (germ cell tumors [GCT]). Intratubular germ cell neoplasia (ITGCN) or testicular carcinoma in situ (CIS) are terms used for the state when these cells are present in the seminiferous epithelium. The highest risk of neoplastic lesions occurs in testes with disturbed organogenesis (in our study, 65 %). Genetic, hormonal, and environmental factors are suspected to lead to disturbed testicular organogenesis (dysgenesis), which creates the milieu favorable for GCT development. An external environment can cause a block or delay in fetal germ and somatic cell differentiation. CIS cells in dysgenetic testes of children reveal a predominantly aneuploid DNA pattern (62.2–97.6 % of germ cells) and they do not express an RBM protein (present in normal germ cells), this indicates that CIS cells are neoplastic from fetal life on. Most of the neoplastic germ cells die, however, some survive and proliferate, leading to a clonal expansion and giving rise to gonadoblastoma, CIS, and GCT. Neoplastic germ cells located inside underdeveloped testicular tubules have an intratesticular environment favorable for their survival – this was confirmed by the finding that the highest incidence of neoplastic lesions occurred in patients with partial (90.9 %) and mixed gonadal dysgenesis (76.9 %). It was hypothesized that the transformation of CIS into overt GCT may be promoted by gonadotropin action. We found that in gonadal dysgenesis, serum concentrations of FSH and LH reveal highly significant, positive correlations with the number of CIS cells, even in childhood. At present, surgical biopsy of the testis is the only reliable method to detect CIS and hence to actively prevent the development of overt GCT. Accordingly, early bilateral gonadectomy is recommended in all types of disturbance of testicular organogenesis because of the high risk of various neoplastic lesions in dysgenetic testes (86 % of adult patients with retained dysgenetic gonads developed GCT, CIS, gonadoblastoma or combinations). In other risk groups, the most frequently recommended method of CIS treatment is radiotherapy, with the exception of unilateral CIS, for which orchiectomy is the treatment of choice.