Diagnosis and management of 46,XY mixed gonadal dysgenesis and disorder of sexual differentiation

Abstract

Objective. We present our experience in diagnosing, gender assignment, and surgical management of sexual ambiguity in 46,XY mixed gonadal dysgenesis. Material and methods. A retrospective study of five cases treated from 2003 to 2006 was performed. Clinical picture, operative findings, testosterone levels, and immunohistochemistry of gonads for the expression of FOXL2, SOX9, AMH, AMHr, C-kit, and PLAP were analyzed. Results. All patients had ambiguous genitalia, urogenital sinus, uterus, testicle on one side, and a streak gonad on the other. Four patients were reared as male and one as female. Stimulation by human chorionic gonadotropin showed good penile size and testosterone response. All patients underwent laparoscopic gonadal biopsy and/or gonadectomy. Histological studies showed the presence of sparse primordial follicles surrounded by embryonic sex cords in the streak portion of gonads. Germ cells were C-kit positive in all and PLAP positive in four patients. FOXL2 expression was detected in four streak gonads and in none of testes. AMH expression was found only in testes. SOX9 expression was found in both investigated testes and in three out of four streak gonads investigated. Conclusions. 46,XY mixed gonadal dysgenesis should be differentiated from ovotesticular and other types of 46,XY disorders of sexual differentiation by the typical gonadal histology and internal genital structure. High testosterone level after stimulation and good response to testosterone treatment in 46,XY mixed gonadal dysgenesis could orient toward male sex assignment. There are different patterns of gene expression in testicular and streak gonads with a switch to FOXL2 positivity in streak gonads. Early gonadal and genital surgery is recommended.

The disturbed gonadal differentiation: dysgenesis and ovotesticular disorder of sex formation

“…У 2 пациентов в стрековых гона-дах были обнаружены редкие примордиальные фол-ликулы. Иммуногистохимическая экспрессия ова-риального маркера (FOXL2) обнаруживалась во всех стрековых гонадах [19]. Результаты этих исследова-ний объясняют механизм развития овариальной ткани в составе дисгенетичной тестикулярной гона-ды XY у 46 пациентов.…”

Disorders of Sexual Development

“…Gonadectomy was done in all 4 patients for the known risk of malignancy. 12 They were reared as male after counseling of parents. Mullarian structure was not excised, which was found in 2 patients on laparoscopy.…”

“…On contrary, in international literature where female gender assignment is preferred in MGD however male gender assignment is recommended in cases of sever virilisation. 12,13 In such cases, gonads excision to prevent tumor developement is recommended followed by hormonal replacement therapy. If normal looking gonad is left, periodical biopsy of testis is recommended.…”

Disgenesia gonadal parcial (XY)

“…Aquellos pacientes con disgenesia gonadal que involucra al cromosoma Y, tienen mayor riesgo (25 %) de presentar malignidad. El gonadoblastoma y el disgerminoma son los tumores que más aparecen, aunque otros como el carcinoma embrionario o el tumor del seno endodérmico también han sido descritos (23)(24)(25).…”