Increased risk of gonadal malignancy and prophylactic gonadectomy: a study of 102 phenotypic female patients with Y chromosome or Y-derived sequences.
OBJECTIVE
What is the optimal protocol of management for phenotypic female patients with Y chromosome or Y-derived sequences, in particular for adult patients?


CONCLUSIONS
Immediate gonadectomy, long-term hormone therapy and psychological care are suggested to be the optimal management for older phenotypic female patients with Y chromosome or Y-derived sequences.


BACKGROUND
Phenotypic female patients with Y chromosome or Y-derived sequences are at increasing risk of developing gonadal tumors with age. Early diagnosis and safe guidelines of management for these patients are needed.


METHODS
One hundred and two phenotypic women with Y chromosome or Y-derived sequences were included in a straightforward, retrospective-observational study conducted over a period of 26 years from January 1985 to November 2010.


METHODS
Patients aged 16-34 years presenting to our Academic Department of Gynecology with symptoms of disorders of sex development were subjected to history taking, hormonal evaluation, conventional cytogenetic analysis, PCR, histopathology and immunohistochemistry. Features of the gonads were examined and the outcome of prophylactic gonadectomy evaluated.


RESULTS
Among the patients recruited in our study, 48 patients (47.1%) were diagnosed with complete/partial androgen insensitivity syndrome (CAIS/PAIS) (46XY), 33 cases (32.4%) with gonadal dysgenesis (46XY) and the remaining subjects (20.1%) with mixed gonadal dysgenesis (with sex chromosome structural abnormalities). The total incidence of malignancy was 17.6%. Seventeen patients (16.7%) had gonadoblastoma, while one patient (1.0%) with gonadal dysgenesis had dysgerminoma. Gonadoblastoma were observed in 2/21 patients with sex chromosome structural abnormalities (9.5%), 3/33 patients with gonadal dysgenesis (9.1%), 9/30 patients with CAIS (30.0%) and 3/18 patients with PAIS (16.7%).


CONCLUSIONS
Selection bias in this cohort study may affect data interpretation due to the low incidence of disorders of sex development in the general population.


CONCLUSIONS
The risk for malignant transformation may occur in early life and highly increase with age in patients with Y chromosome or Y-derived sequences. Optimal timing of gonadectomy should be decided by multiple factors including the subgroup of disorder, age and degree of patient's maturity. In addition, gonadal biopsy is suggested when the disease is diagnosed and any evidence of premalignancy warranties gonadectomy.


BACKGROUND
This work was supported by the National Key Scientific Research Project (2013CB967404), Natural Science Funds of Zhejiang Province (Y13H04005), Zhejiang Qianjiang talent plan (2013R10027), the Fundamental Research Funds for the Central Universities and Key Projects in the National Science & Technology Pillar Program during the Eleventh Five-Year Plan Period (2012BAI32B04). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER None.
Ai-Xia
AX
Liu
Hai-Yan
HY
Shi
Zhe-Jun
ZJ
Cai
Aiping
A
Liu
Dan
D
Zhang
He-Feng
HF
Huang
Hang-Mei
HM
Jin
D000293:Adolescent; D000328:Adult; D013734:Androgen-Insensitivity Syndrome / Q000175:diagnosis / Q000235:genetics; D002869:Chromosome Aberrations; D041322:Chromosomes, Human, Y / Q000648:ultrastructure*; D003582:Cytogenetics; D005260:Female; D005835:Genitalia / Q000473:pathology; D006058:Gonadal Disorders / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D006059:Gonadal Dysgenesis / Q000175:diagnosis / Q000235:genetics; D018238:Gonadoblastoma / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010641:Phenotype; D012189:Retrospective Studies; D012306:Risk; D012737:Sex Factors; D055815:Young Adult