| Abstract|| |
Mixed gonadal dysgenesis (MGD) is a rare disorder of sexual development (DSD). A seven-year-old child with vagina and an elongated clitoris looking like a penile part of male external genitalia, presented in the Paediatric Surgery Department. Ultrasound of pelvis revealed a streak ovary on the right side and ovotestis on the left side. Uterus was not visualized. Karyotyping revealed 46, XY/45, XO genotype. Laparoscopic gonadectomy with vaginoplasty and the clitoral reduction was performed. A thorough histopathological examination of the specimen revealed structure of ovotestis-consisting of the ovary with Graafian follicles, fallopian tube, infantile testis with Leydig and Sertoli cells, epididymis, vas deference, and pampiniform plexus. Presence of Graafian follicle in the ovary, Leydig and Sertoli cells in the testis, at this age makes this case extremely interesting. The child was rehabilitated to lead her life as a girl.
Keywords: Ambiguous genitalia, histopathology of ovotestis, ovotestis
|How to cite this article:|
Agarwal PK, Ali M, Ranjan R, Pandey A. Ambiguous genitalia: A rare case report. Indian J Pathol Microbiol 2016;59:72-4
| Introduction|| |
Ambiguous genitalia is a rare condition in which child's genitalia do not appear to be clearly either male or female that is, the baby may have characteristics of both the sexes. It is not a disease instead it is a manifestation of disordered sexual development (DSD). In one out of every 4500 births, the genital appearance is abnormal and ovotesticular DSD occurs in less than 10% of all DSD.  Mixed gonadal dysgenesis (MGD), ovotesticular DSDs (45, XO/46, XY) is a type of larger group sex chromosomal DSDs previously known as true hermaphroditism  refers to the presence of gonads that contain both ovarian and testicular tissue element in the same individual. Ovotestis is the most frequent gonad present in sex chromosome DSDs (60%), followed by the ovary and then the testis.  In these patients the clinical manifestations are highly variable ranging from partial virilization and ambiguous genitalia at birth to a completely male and female phenotype. The most common feature is asymmetric development of testis, often with a dysgenetic testis on one side and a streak gonad on the other. 
Here we present a rare case of MGD, ovotesticular DSD in a 7-year-old child.
| Case report|| |
A 7-year-old child with abnormal external genitalia attended the Out-patient Department of the Pediatric Surgery Department of Vivekananda Polyclinic and Institute of Medical Sciences, Lucknow, which is a Tertiary Care Multidisciplinary Hospital. The swelling in the external genital region looking like vulva along with elongated clitoris mimicking a penile part of male external-genitalia attracted the attention of parents to seek medical advice. Initially, the child was reared as a girl.
On examination, the child had fully developed vagina and clitoromegaly [Figure 1]a]. However no skin pigmentation, labioscrotal fusion, palpable gonads were noted. The general health of the child was normal. Systemic examination of the child was within normal limits.
|Figure 1: (a) Clinical photograph showing female external genitalia with clitoromegaly (b) Postoperative photograph after vaginoplasty and reduction of the enlarged clitoris (c) Gross specimen showing female (♀) and male (♂) parts of ovotestis (d) Cut surface of gross specimen showing grayish white, yellowish areas intersected by darker areas|
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No significant personal, family or any history of drug intake such as steroids and contraceptives by the mother in the antenatal period was elicited. The child was normally delivered on full-term pregnancy.
Ultrasound studies of the pelvis of the child revealed bilateral inguinal hernia, streak ovary on the right side and ovotestis on the left side. No uterus was visualized clearly.
Karyotyping (performed at another Institute) revealed 46, XY/45, XO genotype. Preoperative routine blood and urine examinations were within normal range. The child underwent laparoscopic gonadectomy and vaginoplasty with clitoral reduction [Figure 1]b].
The excised specimen was submitted for histopathological examination in the Department of Pathology.
Specimen was fixed in 10% formal saline for paraffin sectioning. The specimen measured 7cm × 3cm. in size [Figure 1]c]. Grossly, it presented variegated nodular appearance. A tubular structure was attached to yellowish nodule. The cut surface presented flat grayish white to yellowish rounded homogeneous appearance interspersed by congested portion and a tubular portion [Figure 1]d]. Multiple sections from different parts of the specimen were submitted for paraffin sectioning for thorough microscopic examination. All the sections stained by routine H and E stain.
Microscopy revealed that the specimen was composed of ovotesticular structures. The sections from grayish white portion [Figure 1]c ♀] revealed dense ovarian stroma which was composed of a meshwork of thin collagen fibers and fusiform fibroblast like cells arranged in characteristic whorls [Figure 2]a]. Occasional primordial like structures were seen (arrow). In one section Graafian follicles like structures were also seen [Figure 2]b]. Another section showed that ovarian parenchyma was traversed by a tubular structure, the mucosa of which is thrown into longitudinal folds [Figure 2]c]. It was lined by single layer of columnar ciliated epithelium [Figure 2]c inset] and surrounded by thin muscular wall that was consistent with fallopian tube.
|Figure 2: (a) Structure of infantile ovary with primordial follicle (arrow) (H and E, ×100) (b) Graafian follicles in infantile ovary (H and E, ×400) (c) Fallopian tube traversing through ovary (H and E, ×100), (inset ×400) showing ciliated epithelium (d) Non - canalised seminiferous tubules of infantile testis (H and E, ×400) (e) One seminiferous tubule with Sertoli cells (H and E, ×100). Leydig cells in the stroma and right upper - end corner (inset) (f) Section shows tubules of variable size, lined by non - spermatogenic epithelium representing structure of epididymis. (H and E, ×100) (g) Section shows tubular structure with convoluted lumen lined by stratified epithelium and thick muscle wall of vas deference. (H and E, ×100) (h) Section showing structure of rete testis (H and E, ×400)|
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Sections from yellowish pale area [Figure 1]c ♂] showed testicular structures composed of irregularly coiled tubular structures separated by delicate fibrous and loose connective tissue [Figure 2]d]. One of the dilated tubule was occupied by large pale cells with granular cytoplasm and a nucleus, looking like Sertoli cells [Figure 2]e]. Another section of testis revealed clusters of Leydig cells having round eccentric nucleus and moderate amount of pale cytoplasm [Figure 2]e, inset] in the stroma. One of the sections revealed adipose tissue enclosing tubules, lined by non-spermatogenic epithelium, looking like structure of epididymis [Figure 2]f]. Rete testis, lined by single layer of cuboidal epithelium [Figure 2]g] was also evident. The transverse section of the tubular structure showed convoluted irregular lumen lined by psuedostratified epithelium supported by thick muscular wall representing the vas deference [Figure 2]h]. Structure of pampiniform plexus and fair amount of adipose tissue enclosing atrophied tubules were also present.
Based on clinical, radiological, detailed histopathological findings and chromosomal configuration (46, XY/45, XO), final diagnosis of MGD, ovotesticular DSD was made.
| Discussion|| |
DSD refer to congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical as proposed by 2006 Consensus statement on management of intersex disorders.  DSDs are broadly classified into male (XY), female (XX) DSDs and sex chromosomal DSDs. Sex chromosomal DSDs are further divided into 45, XO (Turner syndrome and variants), 47, XXY (Klinefelter syndrome and variants), 45, XO/46, XY (MGD/ovotesticular DSD), and 46, XX/46, XY (chimeric, ovotesticular DSD).  Congenital adrenal hyperplasia is the most common cause of DSDs in the newborn babies, incidence being 1 case/15,000 live births while MGD (ovotesticular DSDs) ranks the second.
The present case of ambiguous genitalia was brought to the hospital at the age of 7 years, until this age she was reared as a girl child. Probably, when the clitoris started getting elongated along the growth of the child and it appeared like a penile part of the male external genitalia, the parents sought the medical advice. On clinical examination and laboratory investigations including Ultrasound of the pelvis and the karyotyping, the child was diagnosed as a case of MGD/ovotetis (46, XY/45, XO).
Thorough histopathological examination of the excised specimen confirmed the diagnosis of ovotestis- consisting of elements of female genital organs e.g. ovary with Graafian follicles, fallopian tube as well as male genital organs that is, infantile seminiferous tubules of testis, epididymis, rete testis, spermatic cord, pampiniform plexus and adipose tissue. Most of the new born babies with ovotesticular DSD possess a 46, XX chromosome complement and present with ambiguous genitalia, some possess 46, XY chromosome complement or 46, XX/46, XY mosaicism. They may have either female sex organs or male sex organs or both.  The present case had female external genitalia with cloacal exostrophy and ovotestis.
We are reporting a thorough histopathological examination of ovotestis which has not been documented in literature to the best of our knowledge. Presence of Graafian follicle-like structures similar to mature follicles in the ovary and also Leydig and Sertoli cells in the infantile testis at this age makes this case extremely interesting. The Graafian follicles usually disappear at around 18 weeks of intra uterine life to reappear again at time of puberty as mature follicles do. Furthermore, fetal Leydig cells degenerate after birth and are replaced during puberty.  These findings would help in studying the etiopathogenesis and the management of DSD cases.
Gonadectomy is the choice of treatment in these cases, as has been done in the present case with vaginoplasty. The patient was reared as a girl child because of external genitalia looking like a female. After the operation the same situation was maintained after excising the enlarged clitoris and the child has the potential to become a well-adjusted functional member of the society. The privacy needs to be maintained, though the DSD is not a shameful disease. 
After 2 years of follow-up, the child was enjoying her schooling and social life with the peer girls of her age.
The authors are grateful to Mr S.K. Shukla for the technical assistance.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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Padam Kumari Agarwal
A-15, Nirala Nagar, Lucknow - 226 020, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]