The diagnostic impact of testicular biopsies for intratubular germ cell neoplasia in cryptorchid boys and the subsequent risk of testicular cancer in men with prepubertal surgery for syndromic or non-syndromic cryptorchidism.
BACKGROUND
Cryptorchidism is a risk factor for testicular cancer in adult life. It remains unclear how prepubertal surgery for cryptorchidism impacts later development of adult testicular cancer. The aim of study was to investigate tools to identify the cryptorchid boys who later develop testicular cancer.


METHODS
The study cohort consisted of 1403 men operated prepubertally/pubertally for undescended testis between 1971 and 2003. At surgery testicular biopsies were taken from the cryptorchid testes. The boys were followed for occurrence of testicular cancer. The testicular cancer risk was compared to the risk in the Danish Population. Testicular biopsies from the boys who developed testicular cancer during follow-up underwent histological examination with specific diagnostic immunohistochemical markers for germ cell neoplasia.


RESULTS
The cohort was followed for 33,627 person years at risk. We identified 16 cases with testicular cancer in adulthood. The standardized incidence ratio was 2.66 (95% CI: 1.52-4.32). At time of primary surgery in prepubertal/pubertal age Intratubular Germ Cell Neoplasia (ITGCN) was diagnosed in 5 cases and the boys were unilaterally orchiectomized. At follow-up new immunohistochemical staining indicated ITGCN in two of the 16 cancer cases at reevaluation of the original biopsies from time of prepubertal/pubertal surgery. One had syndromic cryptorchid and developed seminoma, and another showed nonsyndromic cryptorchidism and developed embryonic teratocarcinoma. Totally, ITGCN was diagnosed in 0.5% (7/1403) of prepubertal cryptorchid boys, whereof 57% (4/7) in syndromic-cryptorchidism.


CONCLUSIONS
ITGCN is predominantly observed prepubertally in boys with syndromic-cryptorchidism. In nonsyndromic cryptorchidism testicular cancer develops postpubertally, generally not based on dormant germ cells of ITGCN caused by an early fetal maldevelopment.


METHODS
LEVEL I.
The Department of Paediatric Surgery, Copenhagen University Hospital Rigshospitalet, DK-2100, Copenhagen.
Lene
L
Osterballe
The Department of Pathology, Copenhagen University Hospital Rigshospitalet, DK-2100, Copenhagen.
Erik
E
Clasen-Linde
Section of Endocrinology, Department of Paediatrics, Copenhagen University Hospital, Hvidovre, Copenhagen; Faculty of Health and Medical Sciences, University of Copenhagen.
Dina
D
Cortes
Department of Documentation & Quality, Danish Cancer Society, Copenhagen, Denmark.
Gerda
G
Engholm
Department of Documentation & Quality, Danish Cancer Society, Copenhagen, Denmark.
Rasmus
R
Hertzum-Larsen
The Department of Paediatric Surgery, Copenhagen University Hospital Rigshospitalet, DK-2100, Copenhagen.
Susanne
S
Reinhardt
The Department of Paediatric Surgery, Copenhagen University Hospital Rigshospitalet, DK-2100, Copenhagen; Faculty of Health and Medical Sciences, University of Copenhagen. Electronic address: j-thorup@rh.dk.
Jorgen
J
Thorup
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D003456:Cryptorchidism / Q000150:complications / Q000473:pathology* / Q000601:surgery; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D056126:Orchiopexy; D015995:Prevalence; D012307:Risk Factors; D013577:Syndrome; D013736:Testicular Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D013737:Testis / Q000473:pathology*; D055815:Young Adult
Cryptorchidism; Immunohistochemistry; Testicular cancer