Intratubular Germ Cell Neoplasia in a Man with Ambiguous Genitalia, 45,X/46,XY Mosaic Karyotype, and Y Chromosome Microdeletions

Abstract

We report the case of a 17-yr-old male with ambiguous genitalia, 45,X/46,XY mosaic karyotype, and Y chromosome microdeletions. The patient underwent a testicular biopsy at the age of 6 with normal findings. A second biopsy at the age of 17 established the diagnosis of intratubular germ cell neoplasia (ITGCN), which was treated with bilateral orchidectomy. This case report deals with three important issues regarding ITGCN: First, although a prepubertal biopsy can be performed in order to provide evidence for future fertility, it is very unreliable for making a diagnosis of ITGCN. Second, because ITGCN tends to be a generalized procedure that affects both testes in a uniform pattern, a small number of biopsies, even a single one, could be adequate for diagnostic purposes in the majority of cases. Third, although the population that requires screening for ITGCN remains controversial, the early postpubertal period could be the optimum time for a testicular biopsy.

Y-chromosome microdeletions are not associated with SHOX haploinsufficiency

“…Twenty years of interest in Y-chromosome microdeletions has produced a collection of numerous articles, but only a minority of these studies aimed to define whether Yq deletions might lead to other pathological conditions, beside spermatogenic failure. Microdeletions were reported in association with 45,X/46,XY mosaic karyotype and ambiguous genitalia (Papadimas et al, 2001;Patsalis et al, 2002Patsalis et al, , 2005Papanikolaou et al, 2003;Tian et al, 2012); consistently, our data provide further evidence that Yq microdeletions do associate with mosaicism (as four samples presented 45,X cell lines), supporting the hypothesis that Y chromosomes bearing AZF deletions are more instable and thus predispose to the formation of Y-chromosome nullisomic cell lines.…”

Genetic Factors of Non-Obstructive Azoospermia: Consequences on Patients’ and Offspring Health

“…Some studies reported an association between Yq microdeletions and an overall Y-chromosomal instability, which might result in the formation of 45,X0 bearing spermatozoa [51,52]. This finding is in accordance with the relatively high incidence of AZF deletion in patients bearing a mosaic 46,XY/45,X0 karyotype with sexual ambiguity and/or Turner stigmata [53][54][55][56]. The PGD has been performed by two groups with conflicting data about the risk of monosomy X in embryos [57,58].…”