Early Bilateral Gonadoblastoma Associated With 45,X/46,XY Mosaicism: The Spectrum of Undifferentiated Gonadal Tissue and Gonadoblastoma in the First Months of Life

Abstract

45,X/46,XY mosaicism is one of a heterogenous group of congenital conditions known as differences (disorders) of sex development (DSD) that results in abnormal development of internal and external genitalia. Patients with DSD, particularly those with segments of the Y chromosome, are at increased risk for germ cell tumors including gonadoblastoma. Gonadoblastoma is a neoplasm comprised of a mixture of germ cells and elements resembling immature granulosa or Sertoli cells with or without Leydig cells or lutein-type cells in an ovarian type stroma. Gonadoblastoma has an increased prevalence of 15% to 40% in patients with 45,X/46,XY mosaicism and has been previously reported in patients as young as 5 months of age with that karyotype. Herein, we describe a 3-month-old child with 45,X/46,XY karyotype who was referred for the evaluation of asymmetric labia majora. Additional evaluation revealed left streak gonad and right dysplastic/dysgenetic testis. Both gonads contained foci of cells typical for gonadoblastoma as well as undifferentiated gonadal tissue, underscoring the potential for very early infantile gonadoblastoma and the spectrum of developmental anomalies associated with this karyotype.

Next-generation sequencing analysis of embryos from mosaic patients undergoing in vitro fertilization and preimplantation genetic testing

“…It is interesting that, compared with that of sex chromosomal mosaicism, we found an increased ratio (16.07%, 9 of 56) of unbalanced embryos involving parental abnormal karyotypes in autosomal structural abnormality mosaicism. Of the 56 embryos, 5 (8.93%) exhibited a 16q21-q24.3 copy number abnormality that was associated with the parental karyotype mos.46,XY,ctg(16)(q22) [8]/ 46,XY[64], and 4 (7.14%) exhibited 46,XX,dup(8p23.1-8p11.21) and 46,XY,del(8p22-8p11.21), which were related to the parental karyotype mos.47,XY,del(8)(p23p10),þ r(8)(p23p10)[55]/46,XY,del(8)(p23p10) [5]. In addition, 8 (14.29%) exhibited de novo autosomal abnormalities.…”

“…Traditionally, chromosomal mosaicism is detected with karyotyping, and the mosaic ratio of different body tissues may be different. Although chromosomal mosaicism does not have s clinical impact in most cases, there are still some studies showing that the altered clinical phenotypes can be caused by mosaicism (5). However, it is very difficult to predict the clinical outcome of mosaic patients simply based on mosaic rate and the genotype-phenotype correlation (6).…”

Gender-Discordant Monochorionic-Diamniotic Twins Both With 45,X/46,X, Idic(Y) Mosaicism and a Novel Deletion Within the TBC1D5 Gene

“…6 Gonadoblastomas and other gonadal neoplasms have a prevalence of up to 40% in 45,X/46,XY patients. 7 The presence of the gonadoblastoma (GBY) locus near the Yq centromere in 45,X/46,XY females predisposes to development of such neoplasms. 6,8,9 In particular, the Testis-specific Y-encoded protein 1 (TSPY) gene within the GBY region is thought to promote germ cell tumors in individuals with gonadal dysgenesis.…”

“…12 In males, germ cell tumors are more often associated with intra-abdominal gonads. 7 It has been suggested that 45, X/46,XY males with nearly normal external genitalia may be assessed periodically by ultrasound or physical palpation of the gonads. 6 However, dysgenetic gonads in any individual with Y chromosome increases the risk of gonadoblastoma.…”

Testicular Tumors: A Contemporary Update on Morphologic, Immunohistochemical and Molecular Features

“…109,124 Karyotypic analysis shows almost always the presence of Y chromosome, usually as 45, X/46, XY mosaicism or 46, XY. 126,127 The testis-specific protein in the GBY region of the Y chromosome, which contains gene encoding for testis-specific Y-encoded protein, has been linked to the development of gonadoblastoma and dysgerminoma/seminoma. 127,128 The sex-determining gene Y (SRY) on Y chromosome also plays some role in the development of gonadoblastoma.…”