mixed gonadal dysgenesis
Miced gonadal dysgenesis is a type of asymmetrical gonadal dysgenesis (one side is more developed than the other):
(a) testis plus contralateral streak gonad
(b) testis and contralateral gonadal agenesis
(c) hypoplastic gonads with tubules in one gonad
(d) streak gonad with contralateral tumor
The gonads can consist of a macroscopic testis and a streak gonad; or variants, including bilateral testes and bilateral streak gonads or tumors. Functionally, the gonads were incompetent.
Testes:
1) failed to completely inhibit mullerian development
2) failed to support full differentiation of mesonephric duct structures
3) failed to adequately masculinize development of the external genitalia
4) often failed to mediate their own descent, resulting in asymmetry of the internal and external genitalia.
Testes with seminiferous tubules usually develop to a moderately advanced state, macroscopically resembling testes, the hilar zone remains architecturally disorganized; the cortex invariably lacks more than a rudimentary tunica albuginea or exhibited partial ovarian differentiation, sometimes even with a rare primordial follicle. Over time, the seminiferous tubules are atrophied and hyalinized.
Streak gonads:
composed of a stroma resembling that of normal ovarian cortex
Synopsis
bilateral testes
- streak testis: streak tissue identified at periphery of differentiated testis
bilateral streak gonads
- streak gonad: ovarian-type stroma without differentiated gonadal structures
mullerian structures present since no/minimal anti-Mullerian hormone produced
usually bilateral fallopian tubes; occasionally vas deferens
external genitalia
- female: clitoromegaly
- male: hypospadias or normal male
phenotypic females may develop virilization at puberty, often complete; no breast development except with tumors
chromatin negative Barr bodies
karyotypes: 45 X0/46 XY, 46 XY, 45 X0/47 XXY
elevated FSH
deficient immunoglobulin levels
aberrant bony development of inner ear structures
cardiovascular anomalies
renal anomalies
short stature
90-degree penile torsion
undescended testis
Microscopical synopsis
prepubertal patients: 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-cordlike structures with or without germ cell components within the ovarian-type stroma, mimicking gonadoblastoma, granulosa cell tumor or Sertoli cell tumors
classic form : unilateral streak gonad and unilateral dysgenetic fibrotic testis, retained müllerian ducts and incomplete genital masculanization (testosterone deficiency)
Tumor predisposition
high risk for gonadoblastoma (30%) if Y chromosome material is present
Early removal of gonads will prevent the development of gonadoblastoma and dysgerminoma.
Differential diagnosis
true hermaphroditism (ovary has numerous primordial follicles containing primary oocytes, nature of internal or external genitalia is not relevant)
Cytogenetics
most often : 46,X0-46,XY mosaic karyotype
46,XY karyotype in 40% of patients
See also
gonadal dysgenesis
References
Robboy SJ, Miller T, Donahoe PK, Jahre C, Welch WR, Haseltine FP, Miller WA, Atkins L, Crawford JD. Dysgenesis of testicular and streak gonads in the syndrome of mixed gonadal dysgenesis: perspective derived from a clinicopathologic analysis of twenty-one cases. Hum Pathol. 1982 Aug;13(8):700-16. PMID: 7106733