Ovotesticular Disorder of Sex Development Presenting as a Scrotal Emergency Free

A male child (13 years old) was admitted to our hospital late at night with the complaint of left scrotal pain that had persisted for the past 15 hours. No accompanying symptoms were recorded, such as fever or vomiting. He had no previous history of any specific disease.

The patient had a BMI of 17.9 and exhibited gynecomastia (Tanner stage II; Figs 1A and 1B). The genital inspection revealed that the patient’s pubic hair had a female distribution (Fig 1C). The examination of the scrotal skin revealed erythema on the left side, in which the testis was in its proper location, with no upward lifting or retraction. Palpation of the left testis revealed palpable swelling (33 × 25 × 45 mm) with accompanying tenderness. No thickening of the left spermatic cord was observed. The right scrotal skin was normal, and the measured size of the testis was 26 × 11 × 19 mm. A hard-textured, palpable tubercle, ∼0.8 × 1.0 cm in size, was detected on the surface of the upper pole of the right testicle with a clear boundary.

The emergency scrotal B-ultrasonography revealed an enlarged left testicle with an uneven texture and a slightly stronger internal heterogeneous echo. No blood flow signal was detected in the left testicle, whereas blood flow in the right testicle was normal. The patient was admitted to the hospital with a presumptive diagnosis of acute left testicular torsion. Surgical exploration of the left testicle revealed a ruptured tunica with hematoma and hydrocele (Fig 2A). The surface color of the testis revealed a pale appearance, albeit there was no torsion in the proximal spermatic cord (Fig 2B). Because the cause of the clinical symptoms was unknown at that time, the tunica was repaired but the gonad was left in place. Surgical exploration of the right gonad was performed because of the finding of an attached small nodular mass, and this was excised (Figs 3A and 3B).

Ovotesticular malformation was diagnosed after the histopathological examination of the nodular mass revealed ovarian tissues with ovarian stroma and follicles, surrounded by a few immature spermatogenic tubules with testicular stroma (Supplemental Fig 5).

Five days after the surgical exploration, further endocrinological, genetic, and radiographic assessments were performed. The evaluation results are presented in Table 1. The patient was advised to undergo psychological counseling because of the finding of a 46,XX karyotype.

Four months after the initial evaluation and treatment, the patient returned to our hospital seeking removal of the ovarian tissues. A multidisciplinary team was assembled to evaluate the patient’s sexual psychology, gonads and external genitalia, and the requirements of the patient’s family before determining the best course of action. On the basis of the evaluation, the team decided to preserve the testes and remove the ovarian tissues. To confirm the presence of ovarian tissues, a human menopausal gonadotropin (HMG) stimulation test was performed. This test resulted in an increase in estradiol levels from a baseline of 85.50 pg/mL to 174.50 pg/mL after HMG, which confirmed the presence of ovarian tissues.

Cystoscopy and laparoscopy revealed the presence of a widely opened vagina located at the distal verumontanum, which was ∼3 cm in length, and a dysplastic cervix (Supplemental Fig 6). However, no obvious uterus was detected (Supplemental Fig 7). Through the previously employed scrotal-incision approach, the left gonad was confirmed to have both ovarian and testicular elements through intraoperative freezing pathology. During the removal of the gonadal tissues, we first identified the testicular or ovarian components based on the appearance and morphology of the gonad and then determined the marginal tissue with frozen pathologic sections. The ovarian tissues and fallopian tubes were removed from both sides, and the testicular tissues, epididymis, and vas deferens were retained.

Two months after the surgery, human chorionic gonadotropin and HMG tests were conducted to evaluate the testicular functions and the presence of residual ovarian tissue, respectively (Table 2). Meanwhile, the results of the ultrasonography revealed an increase in the size of the left testicle (from 11 × 5 × 8 mm to 14 × 7 × 12 mm) and a decrease in the size of the right testicle (from 21 × 8 × 14 mm to 12 × 10 × 12 mm). Twenty-two months after the first surgical procedure, the patient reported feeling well and had not experienced recurrent scrotal pain. Sex hormone levels were monitored during the follow-up period (Fig 4).

Ovotesticular disease of sex development is a rare disorder with varying karyotypes, accounting for nearly 3% to 10% of all DSD cases.⁴  The most common karyotype is 46,XX which accounts for 60% to 90% of all cases.^3,5  The presence of SRY has been considered to be necessary for determining maleness. Therefore, this gene may be present in 46,XX patients with OT-DSD due to the aberrant translocation to the X chromosome, or less frequently, to an autosome.³  However, in 90% of 46,XX OT-DSD cases, the SRY gene is absent, and it is not clear how the male phenotype manifests in these cases.²  Despite extensive research, the underlying mechanism of OT-DSD remains largely unknown, and further studies are necessary to understand this condition fully.^3,6 

From a clinical perspective, the 46,XX phenotype in OT-DSD primarily depends on the dominance of testicular or ovarian tissues. This manifests as a typical male or female appearance, with varying degrees of manifestation of the other sexual phenotype, resulting in the development of signs, such as genital ambiguity, cryptorchidism, hypospadias, and gynecomastia in “males,” or menstruation and periodic hematuria in “females.”⁴ 

In the present case, the only symptom was scrotal pain, which initially suggested testicular torsion. Although B-ultrasound imaging was performed, the abnormality remained undetected. Previous studies have revealed that B-ultrasonography can detect the ovotestis.^7–9  However, the age, clinical symptoms, physical examination, and B-ultrasound results support the diagnosis of testicular torsion from a clinical standpoint. For the present case, the initial diagnosis of testicular torsion was not confirmed after surgical examination of the left testicle, which led to the unexpected diagnosis of OT (pathologic findings of the second surgery). The discovery of a nodular mass on the surface of the right testicle was key to establishing the definitive diagnosis after the first surgery.

This case raises the possibility that similar cases of scrotal emergencies in male children may occur in the setting of OT-DSD should be considered, especially in patients who present with a hematoma detected by ultrasonography or surgical exploration and who have no history of scrotal trauma. Previous reports have revealed that ovulating ovarian tissues in OT can rupture the ovarian follicle/corpus luteum and induce bleeding, leading to scrotal swelling or pain.^10,11  The gonads on the affected side are typically removed during the first surgical exploration for the unexplained bleeding. One reported case underwent another surgery for pain in the contralateral scrotum a month after the first surgery.¹⁰  In the present case, the gonad was not removed because the intraoperative diagnosis was unknown during the first surgery. This finding highlights the need for careful evaluation and consideration of other possible diagnoses in cases in which the initial clinical diagnosis is not confirmed.

In the postoperative follow-up, the patient presented with a notable increase in testosterone levels due to the removal of the ovaries, which had a suppressive effect on testosterone production due to the elaboration of estrogen.¹  Ovotesticular conditions often result in a predominance of ovarian tissues. Because testicular tissues are often dysgenetic (eg, demonstrate hyalinization of the seminiferous tubules and poor germ cell development), the age at the time of diagnosis, the anatomy of the external and internal genitalia, and patient/family preferences¹²  play crucial roles in determining the advisability of gender reassignment.¹³  These factors were considered in determining that the patient would continue to identify as male. On the basis of the pathology, we judged that this patient would not exhibit spermatogenesis, although we conducted no sperm tests. In addition, the risk for gonadal tumors was lower than other DSDs because of the XX karyotype and the lack of SRY.¹⁴  Nonetheless, we plan to monitor this patient’s testicular functions and morphologic changes over the longer term.

The present report was limited by the absence of chromosome and SRY analysis in the excised gonad specimens. In addition, pathogenic mutations may have been overlooked because whole genome sequencing was not conducted for the specimens. Moreover, the upper vagina was not removed because this does not lead to clinical symptoms in most cases.¹⁵ 

The present case highlights the importance of considering the diagnosis of OT-DSD in adolescent males who present with scrotal emergencies. The phenotype of the OT-DSD can vary and depends on the function of the testis and ovary during sexual differentiation and development. Thus, it remains challenging to arrive at an accurate diagnosis. We recommend that OT-DSD be considered in cases of apparent scrotal emergency in which surgical findings are not consistent with the clinical diagnosis. Long-term postoperative follow-ups and supervision are necessary to assess the reproductive capacity, endocrine functions, and potential for gonadal malignancy in patients with OT-DSD.

The authors gratefully acknowledge the contributions of the doctors and nurses in our hospital.

DSD

disorder of sex development

HMG

human menopausal gonadotropin

OT

ovotesticular/ovotesticle

SRY

sex-determining region on the Y chromosome