HIGH FREQUENCY OFCARCINOMA-IN-SITU AND GONADOBLASTOMA IN CHILDREN AND ADOLESCENTS WITH ANDROGEN INSENSITIVITY (AI) AND GONADAL DYSGENESJS (GD)

Abstract

Individuals with AI and GD with a karyolype including a Y chromosome have a substantial increased risk of developing germ cell tumours as adults. We have previously reported a high frequency of carcinoma-in-situ (CIS) in children and adolescents with these disorders of sexual differentiation, and we herein update our experience with a total of 33 patients between 1 month and 20 years of age at the time of gonadectomy or biopsy. 21 patients with either complete or incomplete AI, and 12 patients with GD and 46,XY karyotype or 45,X/46,XY mosaicism were studied. The latter individuals had either female phenotype, ambiguous or male external genitalia. The gonadeclomy and biopsy specimens were removed for prophylactic reasons, and neither ultrasound nor peroperative examination of the gonads raised suspicion of a germ cell tumour. The tissue was fixed in Stieve's or Cleland's fluid and analysed by conventional microscopy. The diagnosis of CIS and gonadoblastoma was made on morphological criteria. 5 (24%) of 21 patients with AI had CIS, and the preinvasive neoplasia was detected in patients with both complete and incomplete AI. 4 of 6 individuals with GD and a female phenotype had gonadoblastoma or CIS including a 9 year old girl with 46,XY GD, who additionally had areas with invasive neoplasia. 2 of 3 patients with 45,X/46,XY GD and ambiguous genitalia had CIS, and CIS was found in 3 of 6 males with GD. Thus, a total of 60% of the patients with GD had either CIS or gonadoblastoma. Since both CIS and gonadoblastoma can be considered to be preinvasive lesions, we recommend gonadectomy when the diagnosis of AI and GD is made, provided a female gender has been decided. In patients with GD and male phenotype, we suggest a biopsy at the time of diagnosis. If CIS is detected, either gonadeclomy or close surveillance is advisable. If orchidectomy is not performed, a biopsy after puberty is recommended.