Bilateral Germ Cell Tumors and Androgen Insensitivity Syndrome

Abstract Purpose: Although it was common in the 1970s-1990s to assign female gender of rearing to 46,XY infants with limited virilisation of varying etiologies, including those with partial androgen insensitivity syndrome (PAIS), long-term data on outcomes for these individuals are sparse. Therefore, our goal was to use the power of an international registry to evaluate clinical features, surgical management and pubertal data in patients with a molecularly confirmed diagnosis of PAIS who were born before 2008 and were raised as girls. Methods: The current study interrogated the I-DSD Registry for available data on management and pubertal outcomes in individuals with genetically confirmed PAIS who were raised as girls. Results: Among the 11 individuals who fulfilled the key criteria for inclusion the external masculinization score at presentation (EMS) ranged from 2 to 6 (median 5); 7 girls underwent gonadectomy before the age of 9 years, whereas 4 underwent gonadectomy in the teenage years (≥ age 13). Clitoral enlargement at puberty was reported for 3 girls (27%) who presented initially at the time of puberty with intact gonads. In the 9 individuals (82%) for whom gonadal pathology data were provided, there was no evidence of germ cell tumor at median age of 8.1 years. All girls received estrogen replacement and 8/11 had attained Tanner stage 4-5 breast development at last assessment. Conclusion: In general, although it appears that female assignment in PAIS is becoming uncommon, our data provide no evidence to support the practice of prophylactic prepubertal gonadectomy with respect to the risk of a germ cell tumour.

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Incidence of intratubular germ cell neoplasia in androgen insensitivity syndrome

Acta Endocrinologica ◽

10.1530/acta.0.1230416 ◽

1990 ◽

Vol 123 (4) ◽

pp. 416-422 ◽

Cited By ~ 36

Author(s):

Alessandra Cassio ◽

Emanuele Cacciari ◽

Antonia D'Errico ◽

Antonio Balsamo ◽

Franco W. Grigioni ◽

...

Keyword(s):

Germ Cell ◽

Periodic Acid ◽

Immunohistochemical Analysis ◽

Androgen Insensitivity Syndrome ◽

Prophylactic Measure ◽

Androgen Insensitivity ◽

Morphological Aspects ◽

Gonadal Histology ◽

Intratubular Germ Cell Neoplasia ◽

Conventional Microscopy

Abstract. Gonadal histology was investigated by means of conventional microscopy in 6 patients with complete androgen insensitivity syndrome, in 11 with incomplete androgen insensitivity syndrome, and in 3 with 5α-reductase syndrome. Twelve subjects were prepubertal and 8 pubertal. In all patients gonadal tissue was removed as a prophylactic measure and no patients gave rise to any clinical suspicion of a tumour. Eight patients with incomplete androgen insensitivity syndrome, 5 of whom (62.5%) were prepubertal, showed intratubular germ cell neoplasia and in 6 of them it was bilateral. Histochemical and immunohistochemical analysis showed considerable agreement between atypical morphological aspects and positive response to Schiff's periodic acid and to staining with the anti-placenta alkaline phosphatase antibody. Our patients were characterized by one of the highest reported incidences of intratubular germ cell neoplasia, particularly at prepubertal age. These findings would seem to indicate that a rethink is needed concerning the general opinion that patients with androgen intensivity syndrome have practically no risk of developing malignancy, and that orchidectomy is not advisable before puberty is completed.

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Management of Gonads in Adults with Androgen Insensitivity: An International Survey

Hormone Research in Paediatrics ◽

10.1159/000493645 ◽

2018 ◽

Vol 90 (4) ◽

pp. 236-246 ◽

Cited By ~ 8

Author(s):

Lloyd J.W. Tack ◽

Ellen Maris ◽

Leendert H.J. Looijenga ◽

Sabine E. Hannema ◽

Laura Audi ◽

...

Keyword(s):

Germ Cell ◽

Health Care Professionals ◽

Cell Cancer ◽

Early Adulthood ◽

Androgen Insensitivity Syndrome ◽

Adult Women ◽

Androgen Insensitivity ◽

Increased Risk ◽

Partial Androgen Insensitivity Syndrome ◽

Evidence Based Guidelines

Background: Complete and partial androgen insensitivity syndrome (CAIS, PAIS) are associated with an increased risk of gonadal germ cell cancer (GGCC). Recent guidelines recommend gonadectomy in women with CAIS in late adolescence. Nevertheless, many adult women prefer to retain their gonads. Aims: This study aims to explore attitudes towards gonadectomy in AIS in centres around the world, estimate the proportion of adults with retained gonads and/or who developed GGCC, and explore reasons for declining gonadectomy. Methods: A survey was performed among health care professionals who use the International DSD Registry (I-DSD). Results: Data were provided from 22 centres in 16 countries on 166 women (CAIS) and 26 men (PAIS). In CAIS, gonadectomy was recommended in early adulthood in 67% of centres; 19/166 (11.4%) women refused gonadectomy. Among 142 women who had gonadectomy, evidence of germ cell neoplasm in situ (GCNIS), the precursor of GGCC, was reported in 2 (1.4%) out of 8 from whom pathology results were formally provided. Nine out of 26 men with PAIS (34.6%) had retained gonads; 11% of centres recommended routine gonadectomy in PAIS. Conclusion: Although development of GGCC seems rare, gonadectomy after puberty is broadly recommended in CAIS; in PAIS this is more variable. Overall, our data reflect the need for evidence-based guidelines regarding prophylactic gonadectomy in AIS.

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