Ovotesticular Disorder of Sexual Development: Background, Pathophysiology, Epidemiology

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Ovotesticular Disorder of Sexual Development

Sections Ovotesticular Disorder of Sexual Development
Overview
Presentation
- History
- Physical
- Causes
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Workup
Treatment
Follow-up
References

Overview

Background

Ovotestis refers to the histology of a gonad that contains both ovarian follicles and testicular tubular elements. Such gonads are found exclusively in people with ovotesticular disorder of sexual development (OT-DSD), formerly known as true hermaphroditism. Those diagnosed with this rare condition represent a small fraction of patients within the diagnostic category of the disorders of sexual development (DSD), formerly known as intersex. Within the spectrum of DSD, there are varying degrees of discordant genitalia to sex chromosomes. A diagnosis of OT-DSD is based solely on the presence of ovarian and testicular tissue in the gonad and not on the characteristics of the internal and external genitalia, even if ambiguous.

Pathophysiology

People with ovotesticular disorder of sexual development are individuals who have both ovarian and testicular tissue. This diagnostic nomenclature is applied regardless of the peripheral karyotype. The gonads may be ovotestis, or they may be a combination of an ovary on one side and a testis or ovotestis on the other. Ovotestes are usually compartmentalized, with connective tissue separating the ovarian components from the testicular components. However, on rare occasions, an intermixture of these elements may occur. Additionally, testicular and ovarian tissue may develop on the same side of the pelvis as a separate ovary and testis.

Ovotestes are the most frequent gonad present (60%), followed by the ovary and then the testis (9%). The ovotestis tends to be anatomically located in an ovarian position, in the labioscrotal fold, in the inguinal canal, or at the internal inguinal ring. Ovaries, when found, can occupy the normal abdominal position, although they may occasionally be found at the internal inguinal ring. Interestingly, ovaries occur more commonly on the left side than the right. The reason for this predilection is unknown. Testes are usually found in the scrotum, although they can be found at any level along the path of embryonic descent from abdomen to scrotum, frequently presenting as inguinal hernias.

Ovaries and ovarian portions of ovotestes appear normal and demonstrate follicular growth with estradiol production. Approximately 50% of ovotestes show evidence of ovulation. The presence of estradiol in developing ovarian follicles usually inhibits spermatogonia development in adjacent or contralateral seminiferous tubules. Degeneration and hyalinization of the seminiferous tubules with poor germ cell development is frequently observed. In all documented biopsied cases, there is a significant decline in germ cell development and an increase in tubular sclerosis by puberty. Leydig cell hyperplasia may also occur with aging. Spermatogenesis in testis and ovotestis is rare.

Internal duct development usually corresponds to the adjacent gonad. Many patients with ovotesticular disorder of sexual development have a uterus. Müllerian duct structures typically develop on the gonad side(s) not containing testicular tissue. Wolffian duct structures tend to be observed on the gonad side(s) containing functioning testicular tissue.

People with OT-DSD are born with ambiguous genitalia. Most affected individuals are reared as males due to the size of the phallus. Most have varying degrees of labioscrotal fusion and/or hypospadias. However, because of functioning normal ovarian tissue, most people experience breast development at puberty, and approximately two-thirds of those with a 46,XX peripheral karyotype menstruate.^[1]

Frequency

International

Ovotesticular disorder of sexual development is a rare condition. Most cases have a sporadic distribution, although there are a few documented cases of familial recurrence. Genital ambiguity occurs in 1 in 4,500 births, and ovotesticular disorder of sexual development occurs in fewer than 10% of all disorders of sexual development. More than 400 cases have been reported worldwide.^[2]

Mortality/Morbidity

Aside from the physical and emotional consequences associated with genital ambiguity, patients with true hermaphroditism usually do not possess other developmental malformations. These individuals usually possess average intelligence and in general have a normal life expectancy.

Neoplasia
- Gonadal tumors with malignant potential occur in 2.6% of all cases of ovotesticular disorder of sexual development. The testis or testicular component of an ovotestis is likely to be dysgenetic; dysgerminomas, seminomas, gonadoblastomas, and yolk sac carcinomas have all been reported.
- Those with the 46,XY karyotype are at the greatest risk of developing a gonadal malignancy. Benign tumors, including mucinous cystadenomas, benign teratomas, and Brenner tumors, have also been reported.
- If a testis is located in the scrotum, maintaining rigorous follow-up with sonography and/or pelvic MRI is prudent, and a biopsy after puberty is indicated to detect early premalignant or malignant transformation.
- One case report of a 47-year-old 46,XX/46,XY woman with a malignant phyllodes tumor in the right breast and an invasive lobular carcinoma in the left breast suggests a modified breast cancer risk similar to that observed in Klinefelter syndrome.^[3]
- Another case reported an invasive squamous cell carcinoma of the vagina, serving as a reminder that malignant changes can occur in residual müllerian tissue.^[4]
Obstructed genital tract: Cryptomenorrhea, hematometra, and lower abdominal pain associated with endometriosis may occur in individuals with cervical atresia or other forms of müllerian duct anomalies.
Hernias and cryptorchism: Because of malposition of the gonads, gonadal torsion, and associated duct structures, a variety of organs have been encountered within the inguinal canal, and inguinal hernias are a common occurrence. Complications associated with undescended or partial testicular descent also may be encountered.

Race

Geographic variation has been noted, with the highest incidence occurring in the black population of southern Africa.

Age

Despite the fact that most people with true hermaphroditism present with genital ambiguity, less than 20% are diagnosed before age 5 years. Seventy-five percent are diagnosed by age 20 years.

Clinical Presentation

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This histologic section of an ovotestis demonstrates both seminiferous tubules and ovarian follicles.

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Sections Ovotesticular Disorder of Sexual Development
Overview
Presentation
- History
- Physical
- Causes
- Show All
Workup
Treatment
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Ovotesticular Disorder of Sexual Development

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