[Atypical genital development and tumor risk]. / Atypie du développement génital et risque tumoral : synthèse de la réunion scientifique du 25 mai 2018 organisée par le « Centre de référence des maladies rares du développement génital du fœtus à l'adulte ¼.

Atypical genital development (AGD), also called disorders of sex development are a set of miscellaneous pathologies who have in common a morphological and/or functional abnormality of the internal and/or external genital organs. The Chicago classification identifies 3 major groups based on karyotype, hormone balance and genetic studies. Some AGD predispose to the occurrence of tumors, mainly malignant germ cell tumors. The tumor risk depends on many factors: the type of AGD, the position of the gonad, the age of the patient, the phenotype, the function of the gonad and the presence of germ cells in the gonad. AGD with the highest tumor risk are those with gonadal dysgenesis, implying an incomplete differentiation of the bipotential gonad (dysplasia). Monitoring of patients with AGD and indication of prophylactic gonadectomies should be individualized according to tumor risk.

Perspectives in Pediatric Pathology, Chapter 5. Gonadal Dysgenesis.

One of the most challenging areas in pediatric testicular pathology is the appropriate understanding and pathological diagnosis of disorders of sexual development (DSD), and in particular, the issue of gonadal dysgenesis. Here we present the main concepts necessary for their understanding and appropriate classification, with extensive genetic correlations.

Complete gonadal dysgenesis in clinical practice: the 46,XY karyotype accounts for more than one third of cases.

OBJECTIVE: To determine the frequency of XY karyotypes among females with complete gonadal dysgenesis (CGD) and to investigate the frequency of both gonadal tumors and SRY mutations. DESIGN: Retrospective study based on data from all patients with CGD seen in our service from 1989 to 2010. SETTING: Clinic for disorders of sex development, University Hospital, State University of Campinas. PATIENT(S): Thirty-two patients with hypergonadotropic hypogonadism, streak gonads, internal and external female genitalia, and normal karyotype (46,XX or 46,XY); 31 were index cases and 29 did not have a previously determined karyotype. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): The percentage of XY karyotypes among patients with CGD was 34.5% (10/29). Mean age at diagnosis among XY and XX patients was 17.4 years and 19.9 years, respectively. Gonadal tumors were found in 4 of 9 XY girls, and 7 of 10 had SRY gene mutations. CONCLUSION(S): The previously unreported finding of an elevated frequency of 46,XY karyotype among patients with CGD and the high risk of gonadal neoplasia in such cases indicate that this diagnosis must be kept in mind by clinicians and strengthen the importance of karyotype analysis in females with primary hypogonadism. In addition, the frequency of SRY mutations in XY CGD might be higher than previously considered.

[Gonadal dysgenesis and agenesis: anatomical expression]. / Dysgénésies et agénésies gonadiques expression anatomique.

The term of gonadal dysgenesis designates generically any anatomical alteration due to abnormal embryological development of a gonad. The spectrum of these gonadal abnormalities is large and includes the following entities: The gonadal agenesis is characterized by a rudimentary streak gonad. It is composed of a dense, hyalinized fibrous tissue in which the germ cells or the germ structures are entirely missing. Usually the gonadal dysgenesis is a bilateral and symmetrical lesion. The gonadal dysgenesis is characterized by the presence of residual germ structures (follicles or tubules). These structures can be more or less easily identified within a dense fibrous tissue. The gonadal dysgenesis alterations are often unilateral and always asymmetrical. Usually the ipsilateral gonad is a testis. The ovotestis is characterized by the coexistence within the same gonad of differentiated germ structures. Most commonly, the gonadal dysgenesis are associated with sexual chromosome abnormalities and an increased risk of neoplastic change (gonadoblastoma). This risk can reach 30% in the asymmetrical gonadal dysgenesis.

Brief historical note: the concept of "gonadal dysgenesis".

The history of gonadal by dysgenesis cautions against overinterpretation of data: The streak gonads are neither the result of dysgenesis nor of embryonic origin but represent late fetal/neonatal degeneration; the X-chromatin-negative character of the buccal smear and the frequency of color vision defects did not indicate male sex in the Ullrich-Turner syndrome but rather an XO constitution; severity of dysgenesis did not correlate with risk of gonadal neoplasia but with genotype; the gonadal lesion in the Ullrich-Turner syndrome was not due to a pituitary defect but a primary ovarian lesion; patients with the Noonan syndrome do not have the Turner phenotype. The concept of gonadal dysgenesis, introduced to Kermauner in 1912, has outlived its usefulness. Improved methods of phenotype analysis, family studies, and endocrine and cytogenetic methods have showen it to be causally and pathogenetically heterogeneous and have contributed to a better identification and delineation of the several different genetic entities which it formerly comprised.