Leydig-cell tumour in children: variable clinical presentation, diagnostic features, follow-up and genetic analysis of four cases.
BACKGROUND
Testicular tumours are relatively uncommon in infants and children, accounting for only 1-2% of all paediatric solid tumours. Of these approximately 1.5% are Leydig-cell tumours. Further, activating mutations of the luteinizing hormone receptor gene (LHR), as well as of the G protein genes, such as Gsalpha (gsp) and Gialpha (gip2) subunits, and cyclin-dependent kinase gene 4(CDK4) have been associated with the development of several endocrine neoplasms.


OBJECTIVE
In this report, the clinical variability of Leydig-cell tumours in four children is described. The LHR-, gsp-, gip2- and CDK4 genes were investigated to establish the possible molecular pathogenesis of the variable phenotype of the Leydig-cell tumours.


RESULTS
No activating mutations in these genes were found in the four Leydig-cell tumours studied. Therefore, the absence of activating mutations in LHR, as well as in both the 'hot spot' regions for activating mutations within the G-alpha subunits and in the regulatory 'hot spot' on the CDK4 genes in these tumours indicates molecular heterogeneity among Leydig-cell tumours.


CONCLUSIONS
Four children with a variable phenotype caused by Leydig-cell tumours are described. A molecular analysis of all the 'activating' genes and mutational regions known so far was performed, but no abnormalities were found. The lessons learnt from these clinically variable cases are: perform ultrasound early and most importantly, consider discrepancies between testicular swelling, tumour size and androgen production.
Petkovic
Vibor
V
Paediatric Endocrinology, University Children's Hospital, Inselspital, Bern, Switzerland.
Salemi
Souzan
S
Vassella
Erik
E
Karamitopoulou-Diamantis
Evanthia
E
Meinhardt
Udo J
UJ
Flück
Christa E
CE
Mullis
Primus E
PE
D000728:Androgens / Q000097:blood; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007984:Leydig Cell Tumor / Q000235:genetics / Q000473:pathology; D008297:Male; D013736:Testicular Neoplasms / Q000235:genetics / Q000473:pathology; D013737:Testis / Q000000981:diagnostic imaging / Q000473:pathology; D014463:Ultrasonography
D000728:Androgens