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GYNECOLOGIC and INTERSEXUAL CONSIDERATIONS

medicines



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GYNECOLOGIC and INTERSEXUAL CONSIDERATIONS

A. Labial Adhesions in Infants

Minor labial adhesions is a common pediatric gynecologic problem occasionally confused with imperforate hymen. Most cases are in children 2-6 y/o and involve labial adhesions secondary to diaper rash. The process causing fusion is a natural one: two normally covered surfaces with squamous epithelium in contact with each other is traumatized eventually forming a fibrous tissue union (agglutinate) between them when healing occurs. A small opening near the clitoris is always present through which urine escapes. This seldom causes symptoms except recurrent UTI if it covers the urethral meatus. Treatment consists of applying estrogenic creams (0.1%) for two weeks. Manual separation can be painful and adhesion recurs. Unless the urethral meatus is covered, there is no reason to be further aggressive in management. Prolonged use of estrogenic cream can cause precocious isosexual development.

B. Ovarian Cysts & Torsion

Ovarian cysts in fetus and infants are usually follicular in nature and less than 2 cm in size. They are commonly diagnosed between the 28th and 39th wk. of gestation by sonography. Hypotheses on etiology are: (1) Excessive fetal gonadotropic activity, (2) enzymatic abnormalities of the theca interna, and (3) abnormal stimulation by the mother HCG. Obstetric management consists on observation and vaginal delivery. After birth, diagnostic assessment and management will depend on the size and sonographic characteristics of the cyst. Simple anechoic cysts and those less than 5 cm in size can be observed for spontaneous resolution. Cyst with fluid debris, clot, septated or solid (complex nature), and larger than 5 cm should undergo surgical excision due to the higher incidence of torsion, perforation and hemorrhage associated to them.  Percutaneous aspiration of large simple cysts with follow-up sonography is a well‑accepted therapy, preserving surgery for recurrent or complicated cases. Surgical therapy is either cystectomy or oophorectomy that can result in loss of normal ovarian tissue.

Ovarian torsion is a true surgical emergency mostly affecting woman during their first three decades of life. Ovarian torsion results from partial or complete twisting of the ovarian pedicle on its axis causing vascular compromise, congestion and hemorrhagic infarction. Clinically, most children present with an abrupt onset of low abdominal pain, low-grade fever, nausea and vomiting sometimes mimicking symptoms of acute appendicitis. Mean age is 12 years. Symptoms may be recurrent. Pain is localized toward the affected ovary. Most ovarian torsion are associated with a concomitant ovarian cystic or solid  mass. Neonates with ovarian torsion are usually diagnosed during prenatal ultrasound studies when a cystic mass is identified. Ultrasound is the imaging study of choice. An enlarged solid ovarian mass with peripheral cysts noted at US suggests the diagnosis of torsion and should be followed by diagnostic laparoscopy or exploration. A prepubertal child will have a complex mass. CT Scan demonstrates a heterogenous, retrovesical mass. Color Doppler US sometimes confirms the absence of ovarian blood flow. Management is established at exploration. Removal of a mass carrying a twisted ovary is standard therapy. Untwisting of  torsed adnexa and observation in case of absence of a mass (normal ovaries) are accepted modes of treatment. Most common encountered morbidity is postoperative fever. Contralateral oophoropexy in cases of torsion of a normal adnexum is advice.

C. Breast Disorders

Most breast disorders in children of either sex are benign. Congenital lesions are: absent or multiple breast. Transplacental hormonal influence in neonates may cause hyperplasia of breast tissue with predisposition to infection (Mastitis neonatorum). Premature hyperplasia (thelarche) in females is the most common breast lesion in children. It occurs before the age of eight as a disk‑shaped concentric asymptomatic subareolar mass. Remains static until changes occur in the opposite breast 6‑12 mo later. It can regress spontaneously or stay until puberty arrives. Biopsy may mutilate future breast development. On the contrary, discrete breast masses in males cause concern and excision is warranted. Gynecomastia is breast enlargement cause by hormonal imbalance, usually in obese pre‑adolescent boys. If spontaneous regression does not occur, it can be managed by simple mastectomy. Virginal hypertrophy is rapid breast enlargement after puberty due to estrogen sensitivity. If symptomatic, management is reduction mammoplasty.

Breast enlargement is commonly seen in newborns babies, a condition associated with clear or milky nipple discharge. Maternal hormones are considered the culprit. On rare occasions the mother of an infant will bring to you the attention that the child is having intermittent episodes of bleeding through the nipple. In infants it is a benign, self‑limited condition that should be managed conservatively (it could take six months to go away). The main reason of bloody nipple discharge is mammary ductal ectasia, which extends down to the collecting tubules. Mammary duct ectasia was first reported in 1983, characterized by dilatation of the subareolar duct system, and by inflammatory reaction and fibrosis. The infant's own endocrine system is responsible for breast enlargement and mammary duct ectasia, though infection has also been postulated as etiologic factor. Surgical procedures should be avoided, because injury to the breast bud may cause permanent damage. Stimulation or massages to the breast should also be avoided. When associated with hypertrophied mammary glands, prepubertal gynecomastia should be sought.


D. Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) involves a functional defect in any of the five enzymatic steps required for cortisol synthesis, most commonly 21‑ (involved in 90‑95% of cases) and 11‑hydroxylase level. This primary genetic defect transmitted as autosomal recessive impairs the ability of the adrenal cortex to synthesize cortisol causing increase feedback secretion of ACTH and adreno‑cortical hyperplasia of the gland. Increase output of steroids proximal to the block (androgenic precursors) causes virilization in affected males and females. Its more severe form is associated with aldosterone deficiency and life‑threatening salt wasting. Female pseudohermaphrodite due to virilizing CAH is the most frequent form of intersexuality found. The phenotypic picture varies from mild clitoral enlargement alone to complete masculinization of the urethral meatus at the tip of the penis. Prenatal diagnosis (southern blotting of DNA) is based on finding the disease gene on the short arm of chromosome 6. Likewise management in the mother (dexamethasone) is started empirically until the affected status is known by chorionic villus sampling. After birth management consists of cut‑back or flap vaginoplasty with clitoral recession at 3‑6 months of age. Children with high vaginal entry proximal to the urethra external sphincter can undergo early one‑stage reconstruction at 8‑12 months of age. Long term surgical results of female children show adequate sexual identification, reproduction, intellectual functioning and acceptable genitalia.

E. Testicular Feminization Syndrome

Testicular feminization syndrome (TFS) is a genetic form of male pseudohermaphroditism (patient who is genetically 46 XY but has deficient masculinization of external genitalia) caused by complete or partial resistance of end organs to the peripheral effects of androgens. This androgenic insensitivity is caused by a mutation of the gene for androgenic receptor inherited as an X‑linked recessive trait. In the complete form the external genitalia appear to be female with a rudimentary vagina, absent uterus and ovaries. The infant may present with inguinal hernias that at surgery may contain testes. Axillary/pubic hair is sparse and primary amenorrhea is present. The incomplete form may represent undervirilized infertile men. Evaluation should include: karyotype, hormonal assays, pelvic ultrasound, urethrovaginogram, gonadal biopsy and labial skin bx for androgen receptor assay. These patients will never menstruate or bear children. Malignant degeneration (germ cell tumors) of the gonads is increased (22‑33%). Early gonadectomy is advised to: decrease the possible development of malignancy, avoid the latter psychological trauma to the older child, and eliminate risk of losing the pt during follow‑up. Vaginal reconstruction is planned when the patient wishes to be sexually active.

F. Mixed Gonadal Dysgenesis

Mixed gonadal dysgenesis (MGD) is an intersexual genetic abnormality caused by a defect in the sex chromosomes (gonosomes) associated with dysgenetic gonads and retained Müllerian structures. The most common gonosomal aberration in MGD is 45 X0/46 XY mosaic karyotype. The external genitalia could be normal looking female and these children will present later in life with primary amenorrhea. Otherwise, it could be ambiguous: clitoromegaly and urogenital sinus to a sizable phallus with hypospadia. A uterus and one or both fallopian tubes may also be present. MGD is characterized by a streak gonad and a contralateral testis (that is typically cryptorchid) or bilateral streak testes. The testis might show prepubertal tubules lined by a few spermatogonia and immature Sertoli cells. Female gender assignment is usually preferred, but male assignment is an alternative in instances of extreme virilization. Dysgenetic gonads with the presence of a Y chromosome or a translocated fragment have a significant risk of developing malignant gonadoblastoma (though seminoma and dysgerminoma can occur). Routine early bilateral gonadectomy is advice in MGD. The child to be raised as a female will need clitoral recession and vaginoplasty in early infancy. If it is to be raised as male, then various types of hypospadias repair can be done, gonads can be replaced with prostheses, the prepenile scrotum reconstructed and Müllerian structures removed.

G. Müllerian Duct Syndrome

Müllerian Duct Syndrome (MDS) refers to a genetic disorder of male pseudohermaphroditism (46 XY karyotype) characterized by normal masculinization of the external genitalia and the presence of uterus and fallopian tubes. Most cases are discovered during surgery for undescended testis, inguinal hernia or transverse testicular ectopia. MDS is caused by a deficient activity (most cases) or receptor insensitivity of antimüllerian hormone (also known as Müllerian inhibitor factor). This hormone is produced by testicular Sertoli cells and is responsible of producing fetal regression of Müllerian structures (uterus & fallopian tubes) in genetic males. Most cases are transmitted as autosomal recessive restricted to males (sex‑linked). Anatomic variants include fallopian tube or uterus within the inguinal canal, testis and tubes in a hernia sac or bilateral cryptorchidism with the testes embedded in the broad ligaments. The vas deferens is intimately adhered to the uterus lateral wall. Initial procedure consists of hernia repair, replacement of structure within pelvis and karyotype. After diagnosis follow‑up management has been controversial. A few suggest partial removal of the uterus (leaving vas deferens intact on a thin pedicle of myometrium) and fallopian tubes with testicular fixation. Most content that surgical excision of persistent MDS structure may result in ischemic or traumatic damage to the vasa deferentia and testes and optimal management is orchiopexy leaving the uterus and fallopian tubes in situ. The testes in MDS are at risk of malignant degeneration.

H. Bleeding Nipple

Breast enlargement is commonly seen in newborns babies, a condition associated with clear or milky nipple discharge. Maternal hormones are considered the culprit. On rare occasions the mother of an infant will bring to you the attention that the child is having intermittent episodes of bleeding through the nipple. In infants it is a benign, self-limited condition that should be managed conservatively (it could take six months to go away). The main reason of bloody nipple discharge is mammary ductal ectasia, which extends down to the collecting tubules. Mammary duct ectasia was first reported in 1983, characterized by dilatation of the subareolar duct system, and by inflammatory reaction and fibrosis. The infant's own endocrine system is responsible for breast enlargement and mammary duct ectasia, though infection has also been postulated as etiologic factor. Surgical procedures should be avoided, because injury to the breast bud may cause permanent damage. Stimulation or massages to the breast should also be avoided. When associated with hypertrophied mammary glands, prepubertal gynecomastia should be sought.

I. Breast Fibroadenoma, Cysts & Papillomas

Fibroadenoma is a common benign tumor found in the breast of adolescent girls. It is also considered the most common discrete solid mass found within the adolescent breast tissue. Most girls harboring a fibroadenoma have between thirteen and 16 years of age, the tumor is slow growing, tends to develop in the upper outer quadrant and is more common in African-American race. Though females may develop breast masses early in life, the risk of malignancy is extremely low. The tumor is usually solitary, with an average diameter of two to 4 cm, characterized by rich cellular stroma and prominent glandular epithelium. At physical exam the mass feels like a well-circumscribed movable nodule. Fibroadenomas may be related to an exaggerated local response to the estrogenic effects of puberty. Mammography, due to the inherent radiation risk and dense fibrous tissue, is not recommended for routine screening or routine imaging of breast masses in adolescents. Alternatively, sonography of the breast is diagnostic on most cases. The tumor looks well-circumscribe, hyperechoic and homogenous on ultrasound. Ten percent of cases harbor a giant juvenile fibroadenoma, a large lesion that distorts the normal breast architecture eroding through the skin and areolar complex. Management of fibroadenoma could be observation or cryoablation. Growing, symptomatic or anxiety-producing masses should be managed with excision through a periareolar incision to preserve cosmesis.

Juvenile or giant fibroadenoma of the breast is a benign lesion that can obtain a large formidable proportional size during breast development in female adolescent patients. Most cases in children  are seen between the ages of 10 and 15 years. The tumor is solitary in most affected children with a diameter of 4-6 centimeters. Multiple and bilateral involvement has been reported in a few cases. Differential diagnosis includes cystosarcoma phyllodes, benign virginal hypertrophy (juvenile gigantomastia) or rhabdomyosarcoma. FNA or Tru-cut needle biopsy can establish a precise histological diagnosis. Growth is so fast that it can cause non-tender cellulitis of the skin by way of stretching. Microscopically the tumor is characterized by a rich cellular stroma and a prominent glandular epithelium. Juvenile adenofibromas regardless of size should be excised so as to preserve as much breast tissue as possible. Management options include local excision with reconstruction, reduction mammoplasty, or simple mastectomy with reconstruction.

Breast cysts are very common in the adolescent female, while not so common in males. Rapid cyst growth causes pain and a palpable mass in the breast that brings the child to seek medical help. Other times breast cysts get infested and are managed as a breast abscess with antibiotics and drainage. In males solitary, large male breast cysts are extremely rare. They occur mainly in children up to the age of seven years and should be removed under surgery. Whenever a breast mass develops the next step in diagnosis is an ultrasound-mammography studies. This will corroborate the cystic or solid nature of the cyst along with its size. Radiation exposure in children using mammography is not necessary or warrant. Management of breast cysts in females consists of observation or aspiration of the cyst with cytological exam. The overwhelming majorities of breast cyst in children are benign and will go spontaneously with time. Follow-up breast ultrasound of the child for persistent of the mass or bloodstained aspirate should be done.

Breast juvenile papilloma in children is a rare benign lesion featuring atypical papillary duct hyperplasia and numerous cysts. They manifest clinically as a localized, multinodular mass that is usually interpreted as a juvenile fibroadenoma. Most cases occur in females, though some cases in males have been reported. Mean age of diagnosis occurs during the late adolescent years. Left breast is affected slightly more often than the right. Patterns of menarche, marital history, parity, and use of birth control pills are not exceptional for women in this age group. No instance is found of maternal use of estrogens during pregnancy. Family history of breast carcinoma is seen in one-thirds of all cases of papillomatosis. Juvenile secretory carcinoma can be associated with papillomatosis. Breast ultrasonography will show an ill-defined, inhomogeneous mass with numerous small, hypoechoic areas, but cannot differentiate a fibroadenoma from papilloma. Excisional biopsy through a periareolar incision will establish the diagnosis. Should a secretory carcinoma be found wide local excision is warranted. Due to the precancerous nature of papillomatosis, long-term yearly follow-up is recommended.


J. Supernumerary Nipple

Supernumerary (or accessory) nipple, also known as polythelia, is a congenital developmental abnormality that occurs most commonly over the anterior aspect of the trunk in the pathway of the embryonic milk line extending from the axilla to pubic region. Supernumerary nipple shows all the histologic components observed in the normal nipple including epidermal thickening, pilosebaceous structures, smooth muscles and mammary glands. Incidence of supernumerary nipple is 25 per 1000 live births with a higher prevalence for the left side and male gender. The accessory nipple is a cosmetic defect with the potential to give rise to a neoplasm since any disease process that involves anatomically normal breasts may affect aberrantly located breasts or nipples as well. Due to its atypical appearance and ectopic location, diagnosis of the anomaly may require a high index of suspicion along with histologic verification. Once thought to have an association with renal defects, the presence of supernumerary nipple in asymptomatic children is not an indication to do additional diagnostic studies of the urinary tract. Supernumerary nipple and ectopic breast are different entities. Supernumerary nipples can be identified at birth, whereas ectopic breast tissue becomes noticeable only after hormonal stimulation, usually during puberty, pregnancy or lactation. Management of supernumerary nipple consists of excision for diagnosis, treatment of symptoms, or cosmesis.

K. Vaginal Conditions

Transverse vaginal septum is a congenital condition of females that can block the passage of vaginal secretions causing primary amenorrhea, hematocolpos and cyclic pelvic pain. Different to imperforate hymen, in a transverse vaginal septum you find a rim of nonbulging hymenal tissue on the vestibular floor with an intravaginal bulging membrane. The septum can be found in the upper, middle or lower vagina varying in thickness. Most common location of the septum is the upper vagina. Histologically, the diagnosis of transverse vaginal septum is made due to the presence of müllerian duct (mesodermal origin) tissue in the septum. Transverse vaginal septum is a defect of vertical fusion during embryogenesis of the vagina. The estimated incidence is one per 30,000 to 84,000 women. It is sometimes associated with genitourinary tract, gastrointestinal tract, musculoskeletal, and cardiac malformations. Physical exam and pelvic ultrasound are diagnostic. Surgical resection is the treatment of choice. The mucosa on either side of the blockage should be mobilized for approximation with interrupted sutures, while the underlying fibrous septum should be excised. Postoperative dilation may be necessary to prevent restenosis and dyspareunia. Patients with a complete transverse septum in the middle or upper vagina are less likely to conceive than patients with a septum in the lower vagina. Prompt diagnosis and surgical correction to drain accumulated blood may preserve fertility possibly through the prevention of endometriosis.

A septate vagina is another congenital condition that occurs from failure of longitudinal fusion of the lower müllerian ducts leaving a variable amount of an asymptomatic longitudinal vaginal septum in the child. Two vaginal canals are created by the septum completely or partially. As time passes the septate vagina goes unnoticed until the adolescent child start to use tampons or engage in sexual activity. The affected patient might complain of menstrual leakage with the use of tampons since menstruation will continue to egress from the other vaginal canal not occluded by the tampon. This is the case with complete duplication of the müllerian system. Reassurance and vaginal hygiene is all that is required in these cases. Physical exams including endoscopy along with pelvic ultrasound are diagnostic. The identification of a duplicated cervix and a vaginal septum is consistent with several uterine malformations, which leads to frequent misdiagnosis and errors in management. On the other hand when the defect is an isolated partial vaginal septum the patient will complain of dyspareunia during sexual intercourse. Management in these cases consists of excision of the thick septa (septectomy) maintaining good hemostasis.

Vaginal bleeding in the pre-menstrual female infant is cause for concern both medically and socially. Differential diagnosis of vaginal bleeding in this age group includes estrogen stimulation, vulvovaginitis, tumors of the lower genital tract, ovarian tumors, foreign bodies, or trauma. Transplacental estrogen stimulation can cause self-limited vaginal bleeding in newborns during the first two weeks of life. Vulvovaginitis is the most common gynecological infection in children caused by ascending enteric organisms due to poor hygiene and is managed with systemic antibiotics. Condyloma can cause painless vaginal bleeding. Tumors of the genital tract associated with vaginal bleeding include hemangiomas of the vulva, arteriovenous malformation of the uterus, rhabdomyosarcoma botryoid (the most common malignant tumor of the low genital tract in young females), endodermal sinus tumors of the vagina and endometrial carcinomas.  Functional ovarian or adrenal tumors that produce estrogen can be associated with sexual precocity and vaginal bleeding.  Foreign bodies in the vagina of a small girl produce local inflammation resulting in a foul smelling discharge which can be serosanguineous. The debris (foreign body) is often wads of toilet paper.  Redundant urethral mucosa may prolapse through the urethral meatus and present as a friable polypoid lesion. Finally genital injury is a major cause of vaginal bleeding including those associated with child sexual abuse.



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