title: The risk of neoplasm associated with dysgenetic testes in prepubertal and pubertal/adult patients.
abstract: BACKGROUND
  In patients with Y-chromosome in the karyotype, partial gonadal dysgenesis and disorders of male reproductive sex organs development are usually resected in childhood because of the high risk of germ cell tumours (GCT). In patients with Y-chromosome, complete gonadal dysgenesis and female genitalia gonadectomy is performed markedly later. However, due to the relatively low number of adult patients with preserved dysgenetic gonads, the true risk of neoplasm is unknown. The aim of the study was to evaluate the prevalence of neoplasia in dysgenetic gonads of children and adults with Y-chromosome in a retrospective study.
  
  
  METHODS
  A review of medical documentation of 94 patients with disorders of sex development (DSD), Y-chromosome and gonadal dysgenesis (GD), aged 1.2-32 years (47 prepubertal, 1.2-10 years; 47 pubertal/adult, 13-32 years), was conducted. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone were determined. Bilateral gonadectomy was performed in 73.4% of patients, and unilateral gonadectomy with biopsy of the contralateral gonad in 26.4%. All gonadal tissues were subjected to immunohistochemical evaluation with antibodies against PLAP and OCT3/4 (markers of malignant germ cells, but also foetal multipotent germ cells), while gonads of prepubertal patients were examined by c-KIT, as well.
  
  
  RESULTS
  Streak gonads were identified on both sides (complete GD) in 30.8%, a streak gonad on one side and an underdeveloped testis on the other (asymmetric GD) in 38.3%, and underdeveloped testicular structure on both sides (partial GD) in 30.8% of cases. Germ cell neoplasia was found in 53.2% of patients (51.1% in children, 55.3% in pubertal/adults). Invasive GCT were identified in 11.7% of cases, of which 90.9% were in pubertal/adult patients. Other neoplastic lesions included gonadoblastoma (16% prevalence) and testicular carcinoma in situ (25.5%). In younger patients FSH serum levels were increased in 81% of cases (mean 2.82 ± 2.18 IU/L), while LH in 58% (mean 1.82 ± 1.69 IU/L). Hypergonadotropic hypogonadism was diagnosed in most of the pubertal/ /adult patients (mean FSH 54.2 ± 23.3 IU/L, mean LH 21.7 ± 12.1 IU/L, mean testosterone 5.5 ± 4.5 nmol/L).
  
  
  CONCLUSIONS
  Dysgenetic gonads in patients with Y chromosome have a high risk of germ cell neoplasia (ca. 50%). If they are preserved until puberty/early adulthood, they may develop overt, invasive GCT. The gonads also have poor hormonal activity (hypergonadotropic hypogonadism) in most of the pubertal/adult patients. Each of these cases must be considered individually and a decision to remove the gonad or not should be based on the comprehensive analysis of the phenotype by a multidisciplinary team of specialists in consultation with the patient and the parents. If dysgenetic gonads are not resected in childhood, these patients need careful ongoing follow-up examination, including biopsy and histopathological evaluation.
authors: Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Lodz, Poland. jolanta.slowikowska-hilczer@umed.lodz.pl.
authors: Jolanta
authors: J
authors: Slowikowska-Hilczer
authors: Maria
authors: M
authors: Szarras-Czapnik
authors: Jan K
authors: JK
authors: Wolski
authors: Elzbieta
authors: E
authors: Oszukowska
authors: Maciej
authors: M
authors: Hilczer
authors: Lucjusz
authors: L
authors: Jakubowski
authors: Renata
authors: R
authors: Walczak-Jedrzejowska
authors: Katarzyna
authors: K
authors: Marchlewska
authors: Eliza
authors: E
authors: Filipiak
authors: Bogdan
authors: B
authors: Kaluzewski
authors: Malgorzata
authors: M
authors: Baka-Ostrowska
authors: Jerzy
authors: J
authors: Niedzielski
authors: Krzysztof
authors: K
authors: Kula
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D006059:Gonadal Dysgenesis / Q000150:complications* / Q000473:pathology*; D006062:Gonadotropins / Q000097:blood; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D013736:Testicular Neoplasms / Q000150:complications* / Q000453:epidemiology; D013737:Testis / Q000473:pathology*; D013739:Testosterone / Q000097:blood
chemical_list: D006062:Gonadotropins; D013739:Testosterone
keywords: germ cell tumours; gonadal dysgenesis; gonadoblastoma; hypergonadotropic hypogonadism; testicular carcinoma in situ; testis