Gonadoblastoma in Turner syndrome and Y‐chromosome‐derived material

Abstract

The identification of Y-chromosome material is important in females with Ullrich-Turner syndrome (UTS) due to the risk of developing gonadoblastoma or other gonadal tumors. There is controversy regarding the frequency of the Y-chromosome-derived material and the occurrence 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 gonadoblastoma, and the incidence of possible neoplastic degeneration. An unselected series of 171 patients with UTS (1-34 years old), diagnosed cytogenetically, was studied for Y-chromosome markers (SRY and Y-centromeric DYZ3 repeats). The follow-up was of 2-22 years; 101 of these patients were followed during pubertal age. Y-chromosome 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 conventional cytogenetic analysis, one was included in the 45,X group and one in the X + 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 screening to detect the presence of Y-chromosome material; PCR is a rapid and inexpensive technique. 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.

Laboratory guideline for Turner syndrome

“…25 Although the frequency of gonadoblastoma in Turner syndrome with occult Y chromosome mosaicism without evidence of virilization is not fully appreciated, additional studies are recommended in these cases to help prevent a potential life-threatening cancer. 32 FISH with X and Y centromere probes should be performed on a minimum of 200 interphase cells. An appropriate database should be created and normal cutoff values should be established for a Y chromosome signal using normal female controls.…”

TRANSITION IN ENDOCRINOLOGY: Treatment of Turner's syndrome during transition

“…Patients with TS, in particular those with 45,X or a marker chromosome at conventional cytogenetic analysis, may benefit from molecular screening analysis to detect the presence of Y-chromosome material (98,99). An unselected series of 171 patients with TS diagnosed cytogenetically was studied for Y-chromosome markers (SRY and Y-centromeric DYZ3 repeats).…”

“…Of the 14 patients, 12 were gonadectomised and in four (33%) gonadoblastoma was detected under 16 years of age. According to the authors, the epidemiological studies in the past underestimated the risk of gonadal neoplasms in this group of patients (98). A different study confirmed the association of Y fragments with gonadoblastoma at an early age; however, the presence of Y material was not combined with virilisation (99).…”

Genomic-based nursing care for women with Turner Syndrome: genomic-based nursing care

“…However, recent epidemiological studies have questioned the postulated high incidence of gonadoblastoma in these cases (7) .…”

“…This risk has previously been estimated to be almost 30%, and it is directly proportional to age, being significantly higher after puberty due to a lower degree of virilization of the external genitalia and to the intraabdominal localization of the gonad (7) . Gonadectomy is generally recommended; however, this consensus is questioned by some recent studies.…”