American Journal of Medical Genetics 135A:150–154 (2005) Gonadoblastoma in Turner Syndrome and Y-Chromosome-Derived Material Laura Mazzanti, 1 * Alessandro Cicognani, 1 Lilia Baldazzi, 2 Rosalba Bergamaschi, 1 Emanuela Scarano, 1 Simona Strocchi, 1 Annalisa Nicoletti, 2 Francesca Mencarelli, 1 Mariacarla Pittalis, 3 Antonino Forabosco, 4 and Emanuele Cacciari 1 1 Department of Pediatrics, Pediatric Clinic, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy 2 Department of Pediatrics, Molecular Genetics Laboratory, S.Orsola-Malpighi Hospital, Bologna, Italy 3 Department of Gynecology and Obstetrics, Cytogenetic Service, S.Orsola-Malpighi Hospital, Bologna, Italy 4 Department of Mother and Child, University of Modena and Reggio Emilia, Modena, Italy The identification of Y-chromosome material is important in females with Ullrich–Turner syn- drome (UTS) due to the risk of developing gona- doblastoma or other gonadal tumors. There is controversy regarding the frequency of the Y-chromosome-derived material and the occur- rence of gonadoblastoma in these patients. The aim of our study was to evaluate a large number of patients with UTS, followed before and during the pubertal age for the prevalence of Y-chromosome derived material, the occurrence of gonadoblas- toma, and the incidence of possible neoplastic degeneration. An unselected series of 171 patients with UTS (1–34 years old), diagnosed cytogeneti- cally, was studied for Y-chromosome markers (SRY and Y-centromeric DYZ3 repeats). The fol- low-up was of 2–22 years; 101 of these patients were followed during pubertal age. Y-chromo- some material was found in 14 patients (8%): 12 of these were gonadectomized (2.8–25.9 years). A gonadoblastoma was detected in four patients under 16 years of age: in two, Y-material was detected only at molecular analysis (at conven- tional cytogenetic analysis, one was included in the 45,X group and one in the X þ mar group) and one had also an immature teratoma and an endodermal sinus carcinoma. The prevalence of gonadoblastoma in our series of gonadectomized UTS patients with Y-positive material was of 33.3% (4/12). Our data suggest that the age of appearance and the possibility of malignant degeneration of gonadoblastoma can occur early in life. These patients, in particular those with 45,X or a marker chromosome may benefit from molecular screen- ing to detect the presence of Y-chromosome material; PCR is a rapid and inexpensive techni- que. At the moment, laparoscopy and preventive gonadectomy performed as soon as possible remain the procedures of choice for patients with UTS, when Y-chromosome has been identified, as we are still unable to predict a future malignant evolution of gonadoblastoma. ß 2005 Wiley-Liss, Inc. KEY WORDS: Ullrich–Turner syndrome; gona- dal dysgenesis; gonadoblastoma; gonadectomy; PCR INTRODUCTION The Ullrich – Turner syndrome (UTS) is a relatively common chromosomal abnormality, occurring in about 1/2,500 live female births. About 40%–60% of UTS patients have a 45,X karyotype and the others have X-structural abnormalities or various kinds of mosaicism [Hook and Watburton, 1983]. In addition, a cell line with a normal or abnormal Y-chromosome is identified in 5%–6% of females with UTS [Magenis et al., 1980; Verp and Simpson, 1987; Medlej et al., 1992]. Improved cytogenetic and molecular techniques have shown hidden Y-mosaicism or Y-derived material in patients with UTS and 45,X karyotype [Binder et al., 1995; Lopez et al., 1998; Ferna ´ ndez-Garcı ´a et al., 2000; Gravholt et al., 2000; Nishi et al., 2002; Alvarez-Nava et al., 2003] ranging from 0% [Larsen et al., 1995] to 61% [Coto et al., 1995]. This wide range probably depends on the different Y-specific sequences studied, the sensitivity of the techniques [Kokova et al., 1993; Binder et al., 1995; Nishi et al., 2002] and on the selection bias [Binder et al., 1995; Patsalis et al., 1997; Osipova et al., 1998; Mendes et al., 1999]. Gonadoblastomas were found in females with gonadal dysgenesis and Y-chromosome-derived material in their genome, whereas these tumors are rare in normal males or females [Zhao et al., 2000], and are not found in patients with 46,XY testicular feminization syndrome, in patients with 47,XXY karyotype, or 46,XX males [Sultana et al., 1995]. The incidence of gonadoblastoma is more than 30% in patients with XY gonadal dysgenesis [Manuel et al., 1976; Verp and Simpson, 1987] and 15%–20% in X/XY patients [Simpson and Photopulos, 1976; Gantt et al., 1980; Verp and Simpson, 1987]. This tumor has also been found in patients with mutations of the WT1 and SOX9 genes, 9p deletions and sex reversal [Livadas et al., 2003]. Gonadoblastoma is considered to be an in situ germ cell neoplasm, composed of aggregates of neoplastic germ cells, intermixed with sex cord cells resembling immature Sertoli and granulosa cells [Scully, 1970], and it is associated with an increased risk of developing dysgerminoma or other malignant germ cell tumors [Scully, 1970; Jørgensen et al., 1997]. Gonadectomy is generally recommended in females with gonadal dysgenesis and Y-chromosome-derived material to preclude this evolution [Scully, 1970; Verp and Simpson, 1987; Gravholt et al., 2000; Saenger et al., 2001; Elsheikh et al., 2002]. However, there is a controversy regarding the frequency of the Y-chromosome-derived material in UTS and the *Correspondence to: Laura Mazzanti, Department of Pedia- trics, Pediatric Clinic, S.Orsola-Malpighi Hospital, Via Massar- enti 11, 40138 Bologna, Italy. E-mail: laura.mazzanti@unibo.it Received 22 October 2004; Accepted 22 November 2004 DOI 10.1002/ajmg.a.30569 ß 2005 Wiley-Liss, Inc.