Gonadoblastoma in Patients with Ullrich-Turner Syndrome

Abstract

Ullrich-Turner syndrome (UTS) is a common chromosomal abnormality caused by partial or complete X chromosome monosomy. One half of the patients have a 45,X karyotype, whereas the remaining patients display other X chromosome anomalies. In 6% to 11% of UTS, a normal or partly deleted Y chromosome has been found. A 10% to 30% risk of developing gonadoblastoma was found in the latter patients. The aim of this study was to evaluate the prevalence of Y chromosome-derived material, the occurrence of gonadoblastoma, and the incidence of possible neoplasms in patients with UTS. Of 217 patients studied with UTS and chromosome analysis of peripheral-blood lymphocytes, Y chromosome material was found in 20 patients. Fluorescence in situ hybridization (FISH) testing was performed to characterize the structurally abnormal Y chromosome in 13 cases. Molecular analysis of the SRY gene could only be performed in 20 patients with 45,X karyotype. Two patients had the SRY genomes. Of the 20 patients with Y chromosome-derived material, 17 underwent gonadectomy. The incidence of gonadoblastoma development in our series was 35.5%. Furthermore, 1 patient also showed a pure dysgerminoma, and another showed a mixed dysgerminoma and embryonal carcinoma. We emphasize the importance of complete processing of the gonadectomy specimen, including step sections, molecular studies, and FISH, in addition to the classic cytogenetic searching for Y chromosome sequences, in patients who present with a nonmosaic 45,X karyotype. Finally, we propose to routinely collect a sample for storage in the tumor bank for future studies.

Prevalência de sequências do Y e de gonadoblastoma em síndrome de Turner

“…Another study published recently reported 35.3% incidence of gonadoblastoma 28. Twenty patients with TS had Y-chromosome sequences from a total of 217 and 17 of them underwent gonadectomy 28. An even higher frequency was reported by Alvarez-Nava et al29 who investigated 52 patients and detected four with Y-chromosome sequences (7.7%), all underwent gonadectomy and two had gonadoblastoma (50%).…”

“…In the two patients with gonadoblastoma alone, age at surgery was 1.5 and 11.7 years 6. Another study published recently reported 35.3% incidence of gonadoblastoma 28. Twenty patients with TS had Y-chromosome sequences from a total of 217 and 17 of them underwent gonadectomy 28.…”

“…Nas duas pacientes com gonadoblastoma apenas, a idade na cirurgia em anos foi 1,5 e 11,7 6. Outro estudo publicado recentemente relatou incidência de 35,3% de gonadoblastoma 28. Vinte pacientes com ST exibiram sequências do cromossomo Y de um total de 217 e 17 delas foram submetidas à gonadectomia 28.…”

A Rare Case of Embryonal Carcinoma in a Patient with Turner Syndrome without Y Chromosomal Material but Mutations in <b><i>KIT</i></b>, <b><i>AKT1</i></b>, and <b><i>ZNF358</i></b> Demonstrated Using Exome Sequencing

“…The other case involved a 14-year-old TS patient with findings of bilateral gonadoblastoma and a mixed dysgerminoma and embryonal carcinoma [Zelaya et al, 2015]. The patient had a Y chromosome mosaicism, and interphase FISH analysis showed Y chromosomal material in the gonadal tissue; thus, the development of the tumor could be explained by the presence of Y chromosomal material.…”

“…Embryonal carcinoma is, however, a very rare event in TS without Y chromosomal material and has to our knowledge only been described once in a patient with putative 45,X [Soh et al, 1992], while a mixed dysgerminoma and embryonal carcinoma was described in another patient [Zelaya et al, 2015].…”