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.
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.
Authors: Cilla Söderhäll; Izabella Baranowska Körberg; Hanh T T Thai; Jia Cao; Yougen Chen; Xufeng Zhang; Zu Shulu; Loes F M van der Zanden; Iris A L M van Rooij; Louise Frisén; Nel Roeleveld; Ellen Markljung; Ingrid Kockum; Agneta Nordenskjöld Journal: Eur J Hum Genet Date: 2014-07-02 Impact factor: 4.246
Authors: Rebecca Nash; Kevin C Ward; Ahmedin Jemal; David E Sandberg; Vin Tangpricha; Michael Goodman Journal: Cancer Epidemiol Date: 2018-03-09 Impact factor: 2.984
Authors: Anders Juul; Kristian Almstrup; Anna-Maria Andersson; Tina K Jensen; Niels Jørgensen; Katharina M Main; Ewa Rajpert-De Meyts; Jorma Toppari; Niels E Skakkebæk Journal: Nat Rev Endocrinol Date: 2014-06-17 Impact factor: 43.330
Authors: Lauren E Hipp; Lauren H Mohnach; Sainan Wei; Inas H Thomas; Maha E Elhassan; David E Sandberg; Elisabeth H Quint; Catherine E Keegan Journal: Am J Med Genet A Date: 2015-09-26 Impact factor: 2.802