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Ovary - nontumor

Gonadal dysgenesis

Mixed gonadal dysgenesis


Reviewer: Carolina Sforza, M.D., Pocono Medical Center (see Reviewers page)
Revised: 8 June 2012, last major update August 2010
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

Description
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● Mixed gonadal dysgenesis refers to an individual who usually has a differentiated gonad on one side and a streak gonad or streak testis on the other side
● Either (a) testis plus contralateral streak gonad, (b) testis and contralateral gonadal agenesis, (c) hypoplastic gonads with tubules in one gonad or (d) streak gonad with contralateral tumor
● A type of asymmetrical gonadal dysgenesis due to chromosomal abnormality
● Often mosaicism: 45X / 46XY, 45X / 46XX or 45X / 47XXY; may also have 46XX but missing part of one X chromosome

Terminology
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● In 2005, the Chicago Consensus of Intersex Disorders proposed the term "mixed gonadal dysgenesis" to substitute for disorders of sex development, defined by congenital conditions in which the development of chromosomal, gonadal or anatomical sex is altered
● There is much confusion about the nomenclature for patients with gonadal dysgenesis
● Asymmetrical gonadal dysgenesis is the term used if one gonad displays more complete development and can be identified as a testis or ovary (usually is a testis), and the other gonad is a streak
Streak testis: streak tissue identified at periphery of differentiated testis
Streak gonad: ovarian-type stroma without differentiated gonadal structures

Etiology
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● A reproductive system developmental disorder characterized by progressive loss of primordial cells on the developing glands of an embryo
● This loss leads to extremely hypoplastic and dysfuctioning gonads, which are mainly composed of fibrous tissue, hence the name streak glands
● During embryogenesis, the reproductive system is intrinsically conditioned to give rise to a female, unless altered by hormone production
● As a result, if a gonad cannot express hormones, as occurrs with gonadal dysgenesis, the affected person will still develop both internal and external genitalia
● In gonadal dysgenesis, the accompanying hormonal failure prevents the development of secondary sex characteristics in either sex, resulting in the appearance of a sexually infantile female and infertility

Clinical
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● Phenotype may be ambiguous, male, female, Turner-like syndrome or intersex
● Mullerian structures present since no / minimal anti-Mullerian hormone is produced
● Usually bilateral fallopian tubes are present, occasionally vas deferens
● Females may exhibit clitoromegaly; no breast development except with tumors
● Phenotypic males may have short stature, 90 degree penile torsion, undescended testis, chordae without hypospadias, hypospadias or no obvious abnormalities
● Patients with 45X mosaicism are often considered to have a variant of Turnerís syndrome
● Phenotypic females may develop virilization at puberty, often complete
● High risk for gonadoblastoma (30%) if Y chromosome material is present, which may obliterate testicular elements and cause incorrect diagnosis
● Higher risk for other medical problems, including deficient immunoglobulin levels, aberrant bony development of inner ear structures, cardiovascular and renal anomalies (horseshoe kidney)

Laboratory
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● Elevated FSH
● Chomatin negative Barr bodies
● Low immunoglobulins levels

Prognostic factors
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● High risk for gonadoblastoma (30%) if Y chromosome material is present, which may obliterate testicular elements and cause incorrect diagnosis

Case reports
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● Short stature in phenotypic male with 45X0 / 46XY mosaicism (Nat Clin Pract Endocrinol Metab 2008;4:524)
● Mistaken diagnosis of testicular dysgenesis (Arq Bras Endocrinol Metabol 2010;54:331)

Treatment
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● Excise gonads early to prevent tumors
● Hormone replacement therapy

Micro description (Histopathology)
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● Prepubertal patients show normal immature testis
● At/after puberty, tubules exhibit mild hypospermatogenesis to total sclerosis
● Streak gonad has ovarian stroma without primordial ovarian follicles
● Streak ovary is streak gonad with primordial follicles and primitive sex cord-like structures with or without germ cell components within the ovarian-type stroma, mimicking gonadoblastoma, granulosa cell tumor or Sertoli cell tumors

Micro images
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Mixed gonadal dysgenesis: in above image, streak tissue and rete (top) are separated by tunica albuginea from testis (bottom)

Moelcular/cytogenetics description
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● FISH may be helpful (Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2008;25:570)
● Usually no mutations of SRY (Eur J Obstet Gynecol Reprod Biol 2004;115:55), but see J Med Genet 1993;30:655

Differential diagnosis
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True hermaphroditism (ovary has numerous primordial follicles containing primary oocytes, nature of internal or external genitalia is not relevant, Mod Pathol 2002;15:1013)

Additional references
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Ann Saudi Med 1994;14:267

End of Ovary - nontumor > Gonadal dysgenesis > Mixed gonadal dysgenesis


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