title: A novel morphological approach to gonads in disorders of sex development.
abstract: Disorders of sex development are defined as congenital conditions with discordance between the phenotype, the genotype, the karyotype, and the hormonal profile. The disorders of sex development consensus classification established in 2005 are mainly based on chromosomal and biological data. However, histological anomalies are not considered. The aims of this study were to define the specific pathological features of gonads in various groups of disorders of sex development in order to clarify the nosology of histological findings and to evaluate the tumor risk in case of a conservative approach. One hundred and seventy-five samples from 86 patients with disorders of sex development were analyzed following a strict histological reading protocol. The term 'gonadal dysgenesis' for the histological analysis was found confusing and therefore excluded. The concept of 'dysplasia' was subsequently introduced in order to describe the architectural disorganization of the gonad (various degrees of irregular seminiferous tubules, thin albuginea, fibrous interstitium). Five histological types were identified: normal gonad, hypoplastic testis, dysplastic testis, streak gonad, and ovotestis. The analysis showed an association between undifferentiated gonadal tissue, a potential precursor of gonadoblastoma, and dysplasia. Dysplasia and undifferentiated gonadal tissue were only encountered in cases of genetic or chromosomal abnormality ('dysgenesis' groups in the disorders of sex development consensus classification). 'Dysgenetic testes', related to an embryonic malformation of the gonad, have variable histological presentations, from normal to streak. Conversely, gonads associated with hormonal deficiencies always display a normal architecture. A loss of expression of AMH and α-inhibin was identified in dysplastic areas. Foci of abnormal expression of the CD117 and OCT4 immature germ cells markers in dysplasia and undifferentiated gonadal tissue were associated with an increased risk of neoplasia. This morphological analysis aims at clarifying the histological classification and gives an indication of tumor risk of gonads in disorders of sex development.
authors.affiliation: Service d'Anatomie Pathologique, Centre de Biologie et de Pathologie Est, Bron, France.|Université Lyon 1, Lyon, France.
authors.forename: Laureline
authors.initials: L
authors.lastname: Lepais
authors.affiliation: Université Lyon 1, Lyon, France.|Service d'Endocrinologie Moléculaire et Maladies Rares, Centre de Biologie et de Pathologie Est, Bron, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Morel
authors.affiliation: Université Lyon 1, Lyon, France.|Service de Chirurgie Urologique Pédiatrique, Hôpital Femme Mère Enfant, Bron, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mouriquand
authors.affiliation: Service de Chirurgie Urologique Pédiatrique, Hôpital Femme Mère Enfant, Bron, France.
authors.forename: Daniela
authors.initials: D
authors.lastname: Gorduza
authors.affiliation: Université Lyon 1, Lyon, France.|Service d'Endocrinologie Moléculaire et Maladies Rares, Centre de Biologie et de Pathologie Est, Bron, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Plotton
authors.affiliation: Service d'Anatomie Pathologique, Centre de Biologie et de Pathologie Est, Bron, France.|Université Lyon 1, Lyon, France.
authors.forename: Sophie
authors.identifier: 0000-0001-8604-1089
authors.initials: S
authors.lastname: Collardeau-Frachon
authors.affiliation: Service d'Anatomie Pathologique, Centre de Biologie et de Pathologie Est, Bron, France.|Université Lyon 1, Lyon, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Dijoud
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D012734:Disorders of Sex Development / Q000145:classification* / Q000473:pathology*; D005260:Female; D006066:Gonads / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male