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Testicular development in the complete androgen insensitivity syndrome.
J Pathol. 2006 Mar; 208(4):518-27.JP

Abstract

The complete androgen insensitivity syndrome (CAIS), caused by mutations in the androgen receptor (AR) gene, is associated with abnormal testicular development and an increased risk of germ cell malignancy. Previous histological studies in CAIS have selected patients purely on the basis of clinical diagnosis and were mostly based on small numbers, many of whom were post-pubertal. Here, we present 44 cases of CAIS, each with molecular pathological confirmation of an AR mutation. The median age at gonadectomy was 5.5 years (5.5; IQR 1-13). We have been able, therefore, to investigate testicular development in infancy, childhood and puberty, and estimate the incidence of premalignant change in this series. In addition, we have investigated whether the presence of epididymides and/or vasa deferentia in CAIS, previously shown to be associated with residual activity of mutant ARs, is related to a particular testicular phenotype. Epididymides/vasa deferentia were present in 36% of cases and these patients showed varying degrees of seminiferous tubule maturation at puberty above those without epididymides/vasa deferentia (p = 0.003). There were no other histological differences between these patient groups. In both groups, features of testicular degeneration and dysgenesis were present and germ cell development was delayed, with prolonged expression of the gonocyte markers, placental-like alkaline phosphatase and activator protein-2gamma. Germ cell numbers rapidly declined after the first year of life (R(2) = 0.42). Only two cases of carcinoma in situ were identified in our study and both patients were postpubertal (17 and 53 years). From these results and the literature, we conclude that the risk of premalignant change in germ cells is low before and during puberty. Patients can be advised, therefore, that gonadectomy can be delayed to allow for a natural puberty, with low risk of malignant transformation. Our study only included one patient over 18 years, so we cannot comment on the risk of malignant transformation in later life.

Authors+Show Affiliations

Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. sehannema@cantab.netNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16400621

Citation

Hannema, S E., et al. "Testicular Development in the Complete Androgen Insensitivity Syndrome." The Journal of Pathology, vol. 208, no. 4, 2006, pp. 518-27.
Hannema SE, Scott IS, Rajpert-De Meyts E, et al. Testicular development in the complete androgen insensitivity syndrome. J Pathol. 2006;208(4):518-27.
Hannema, S. E., Scott, I. S., Rajpert-De Meyts, E., Skakkebaek, N. E., Coleman, N., & Hughes, I. A. (2006). Testicular development in the complete androgen insensitivity syndrome. The Journal of Pathology, 208(4), 518-27.
Hannema SE, et al. Testicular Development in the Complete Androgen Insensitivity Syndrome. J Pathol. 2006;208(4):518-27. PubMed PMID: 16400621.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Testicular development in the complete androgen insensitivity syndrome. AU - Hannema,S E, AU - Scott,I S, AU - Rajpert-De Meyts,E, AU - Skakkebaek,N E, AU - Coleman,N, AU - Hughes,I A, PY - 2006/1/10/pubmed PY - 2006/6/29/medline PY - 2006/1/10/entrez SP - 518 EP - 27 JF - The Journal of pathology JO - J Pathol VL - 208 IS - 4 N2 - The complete androgen insensitivity syndrome (CAIS), caused by mutations in the androgen receptor (AR) gene, is associated with abnormal testicular development and an increased risk of germ cell malignancy. Previous histological studies in CAIS have selected patients purely on the basis of clinical diagnosis and were mostly based on small numbers, many of whom were post-pubertal. Here, we present 44 cases of CAIS, each with molecular pathological confirmation of an AR mutation. The median age at gonadectomy was 5.5 years (5.5; IQR 1-13). We have been able, therefore, to investigate testicular development in infancy, childhood and puberty, and estimate the incidence of premalignant change in this series. In addition, we have investigated whether the presence of epididymides and/or vasa deferentia in CAIS, previously shown to be associated with residual activity of mutant ARs, is related to a particular testicular phenotype. Epididymides/vasa deferentia were present in 36% of cases and these patients showed varying degrees of seminiferous tubule maturation at puberty above those without epididymides/vasa deferentia (p = 0.003). There were no other histological differences between these patient groups. In both groups, features of testicular degeneration and dysgenesis were present and germ cell development was delayed, with prolonged expression of the gonocyte markers, placental-like alkaline phosphatase and activator protein-2gamma. Germ cell numbers rapidly declined after the first year of life (R(2) = 0.42). Only two cases of carcinoma in situ were identified in our study and both patients were postpubertal (17 and 53 years). From these results and the literature, we conclude that the risk of premalignant change in germ cells is low before and during puberty. Patients can be advised, therefore, that gonadectomy can be delayed to allow for a natural puberty, with low risk of malignant transformation. Our study only included one patient over 18 years, so we cannot comment on the risk of malignant transformation in later life. SN - 0022-3417 UR - https://www.unboundmedicine.com/medline/citation/16400621/Testicular_development_in_the_complete_androgen_insensitivity_syndrome_ L2 - https://doi.org/10.1002/path.1890 DB - PRIME DP - Unbound Medicine ER -