Gonadal tumor development in 46,XX disorders of gonadal development

COSTANZO M; TOUZON, MARIA SOL; MARINO R; GUERCIO G; RAMIREZ P; MATTONE, MARÍA C.; PEREZ GARRIDO N,; BAILEZM,; VAIANI E; CIACCIO M; GALLUZZO M; BELGOROSKY A; BERENSZTEIN E

EUROPEAN JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2022 vol. 187 p. 451 - 462

0804-4643

Background: Differences/disorders of sex development (DSD) are congenital conditions in which the development ofchromosomal, gonadal, or anatomical sex is atypical.Objective: The aim of this study is to report the histological characteristics and immunoexpression patterns of gonadalparenchyma in patients with 46,XX testicular and ovotesticular DSD, with a focus on the detection of germ cellmalignancies.Design: Inclusion criteria were SRY-negative 46,XX testicular and ovotesticular DSD with available samples fromgonadal biopsy or gonadectomy for the review of histological findings. Gonadal histology was assessed onhematoxylin and eosin-stained sections and immunohistochemical analysis. Histopathological criteria from the lastWorld Health Organization classification of urogenital tumors were used to identify undifferentiated gonadal tissue,gonadoblastoma, and dysgerminoma.Results: Median age at first histological evaluation of gonadal samples was 1.46 years (range: 0.16–16 years).Totally 15 patients were classified as ovotesticular and only 1 as testicular DSD. Most individuals had bilateral ovotestes(12/15). No histological alterations were found in the ovarian parenchyma, while signs of dysgenesis were seen in allcases of testicular parenchyma. In 4/15 ovotesticular DSD, a prepubertal biopsy failed to identify ovarian parenchyma.We detected early prepubertal preinvasive and invasive malignancies in this cohort (five patients had undifferentiatedgonadal tissue, five gonadoblastoma, and one dysgerminoma).Conclusion: 46,XX disorders of gonadal development are historically considered at a low risk for germ cell cancer, andthe need for assessment of gonadal histology has been questioned. The finding of early germ cell malignancies in ourcohort brings awareness and needs further research.