TY - JOUR
T1 - Gonadal pathology and tumor risk in relation to clinical characteristics in patients with 45,X/46,XY mosaicism
AU - Mosaicism Collaborative Group
AU - Cools, M
AU - Pleskacova, J
AU - Stoop, H
AU - Hoebeke, P
AU - Van Laecke, E
AU - Drop, S L S
AU - Lebl, J
AU - Oosterhuis, J W
AU - Looijenga, L H J
AU - Wolffenbuttel, K P
PY - 2011/7
Y1 - 2011/7
N2 - CONTEXT: Gonadectomy is avoided whenever possible in boys with 45,X/46,XY. However, no clinical markers are currently available to guide clinicians in predicting gonadal tumor risk or hormone production.OBJECTIVE: The objective of the study was to test the hypothesis that gonadal histology and risk for development of a malignant germ cell tumor are reflected by the clinical presentation of a 45,X/46,XY individual.DESIGN: The design of the study was the correlation of clinical data [external masculinization score (EMS), pubertal outcome] with pathology data (gonadal phenotype, tumor risk).SETTING: This was a multicenter study involving two multidisciplinary disorder of sex development teams.PATIENTS: Patients included genetically proven 45,X/46,XY (and variants) cases, of whom at least one gonadal biopsy or gonadectomy specimen was available, together with clinical details.INTERVENTIONS: Patients (n = 48) were divided into three groups, based on the EMS. Gonadal histology and tumor risk were assessed on paraffin-embedded samples (n = 87) by morphology and immunohistochemistry on the basis of established criteria.MAIN OUTCOME MEASURES: Gonadal differentiation and tumor risk in the three clinical groups were measured. Clinical outcome in patients with at least one preserved gonad was also measured.RESULTS: Tumor risk in the three groups was significantly related to the gonadal differentiation pattern (P < 0.001). In boys, hormone production was sufficient and was not predicted by the EMS.CONCLUSIONS: The EMS reflects gonadal differentiation and tumor risk in patients with 45,X/46,XY. In boys, testosterone production is often sufficient, but strict follow-up is warranted because of malignancy risk, which appears inversely related to EMS. In girls, tumor risk is limited but gonads are not functional, making gonadectomy the most reasonable option.
AB - CONTEXT: Gonadectomy is avoided whenever possible in boys with 45,X/46,XY. However, no clinical markers are currently available to guide clinicians in predicting gonadal tumor risk or hormone production.OBJECTIVE: The objective of the study was to test the hypothesis that gonadal histology and risk for development of a malignant germ cell tumor are reflected by the clinical presentation of a 45,X/46,XY individual.DESIGN: The design of the study was the correlation of clinical data [external masculinization score (EMS), pubertal outcome] with pathology data (gonadal phenotype, tumor risk).SETTING: This was a multicenter study involving two multidisciplinary disorder of sex development teams.PATIENTS: Patients included genetically proven 45,X/46,XY (and variants) cases, of whom at least one gonadal biopsy or gonadectomy specimen was available, together with clinical details.INTERVENTIONS: Patients (n = 48) were divided into three groups, based on the EMS. Gonadal histology and tumor risk were assessed on paraffin-embedded samples (n = 87) by morphology and immunohistochemistry on the basis of established criteria.MAIN OUTCOME MEASURES: Gonadal differentiation and tumor risk in the three clinical groups were measured. Clinical outcome in patients with at least one preserved gonad was also measured.RESULTS: Tumor risk in the three groups was significantly related to the gonadal differentiation pattern (P < 0.001). In boys, hormone production was sufficient and was not predicted by the EMS.CONCLUSIONS: The EMS reflects gonadal differentiation and tumor risk in patients with 45,X/46,XY. In boys, testosterone production is often sufficient, but strict follow-up is warranted because of malignancy risk, which appears inversely related to EMS. In girls, tumor risk is limited but gonads are not functional, making gonadectomy the most reasonable option.
KW - Child
KW - Child, Preschool
KW - Female
KW - Genetic Predisposition to Disease
KW - Gonadal Dysgenesis, 46,XY/genetics
KW - Gonads/pathology
KW - Humans
KW - Male
KW - Mosaicism
KW - Neoplasms/genetics
KW - Phenotype
KW - Risk
KW - Sex Chromosome Aberrations
KW - Turner Syndrome/genetics
UR - http://www.scopus.com/inward/record.url?scp=79960076349&partnerID=8YFLogxK
U2 - 10.1210/jc.2011-0232
DO - 10.1210/jc.2011-0232
M3 - Article
C2 - 21508138
SN - 0021-972X
VL - 96
SP - E1171-80
JO - The Journal of clinical endocrinology and metabolism
JF - The Journal of clinical endocrinology and metabolism
IS - 7
ER -