Abdominal Mass in a Phenotypic Female with 46,XY Differences in Sex Development.

We present a case of a large intra-abdominal mass found to be localized pure seminoma within a retained gonad of a 53-year-old phenotypic female with 46,XY differences in sex development (DSD) and androgen insensitivity syndrome (AIS). Our management included extirpation of the mass with contralateral gonadectomy. Historically, patients with AIS would undergo gonadectomy to mitigate the lifetime risk of testicular germ cell tumor development; however, growing evidence suggests safety in retention and surveillance of these gonads into adulthood. This case highlights the importance of lifetime surveillance of patients with 46,XY DSD who elect to retain their gonads.

Alam R ，Gabrielson AT ，Rabinowitz MJ ，Kates M ，Di Carlo HN ... -  《-》

Frequency of gonadal tumours in complete androgen insensitivity syndrome (CAIS): A retrospective case-series analysis.

Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive disorder of sex development (DSD) where affected individuals are phenotypically female, but have an XY karyotype and testes. The risk of gonadal tumour development in CAIS may increase with age; incidence rates have been reported to be 0.8-22% in patients who have retained their gonads into adulthood. Consequently, gonadectomy has been recommended either during childhood or after puberty is complete, although there is no consensus on the optimal timing for this procedure. To establish the frequency of histological abnormalities in CAIS in relation to the age at gonadectomy. Data were collected from the Cambridge DSD database on patients with CAIS (n = 225; age range 3-88 years) who had undergone gonadectomy, and their age of gonadectomy, gonadal histology and immunohistochemistry. Evaluable data were obtained from 133 patients. Median age at gonadectomy was 14.0 years (range: 18 days-68 years). Pubertal status was: prepuberty, n = 62; postpuberty, n = 68. Thirteen cases were aged >20 years at gonadectomy. The pattern of histology is summarised in the Summary table. In this large case series of CAIS patients who had undergone gonadectomy, while the combined malignant and premalignant gonadal histology prevalence was 6.0%, the findings confirm the low occurrence of gonadal malignancy in CAIS, with a frequency of 1.5%. The two cases of malignancy were postpubertal. Germ cell neoplasia in situ (GCNIS) was observed in six cases, of which one occurred prepuberty and five postpuberty. The study highlighted difficulties in diagnosis of GCNIS and the need for histological analysis in expert centres. The results support the current recommendation that gonads in CAIS can be retained until early adulthood. The small number of individuals with gonadectomy after age 20 years do not allow firm conclusion regarding later adulthood. Therefore, it is recommended that the option of gonadectomy be discussed in adulthood. Some form of regular surveillance of the gonads is then recommended, although none of the available options are ideal.

Chaudhry S ，Tadokoro-Cuccaro R ，Hannema SE ，Acerini CL ，Hughes IA ... -  《-》

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

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. 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. A survey was performed among health care professionals who use the International DSD Registry (I-DSD). 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. 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.

Tack LJW ，Maris E ，Looijenga LHJ ，Hannema SE ，Audi L ，Köhler B ，Holterhus PM ，Riedl S ，Wisniewski A ，Flück CE ，Davies JH ，T'Sjoen G ，Lucas-Herald AK ，Evliyaoglu O ，Krone N ，Iotova V ，Marginean O ，Balsamo A ，Verkauskas G ，Weintrob N ，Ellaithi M ，Nordenström A ，Verrijn Stuart A ，Kluivers KB ，Wolffenbuttel KP ，Ahmed SF ，Cools M ... -  《-》

A Management Protocol for Gonad Preservation in Patients with Androgen Insensitivity Syndrome.

Historically, individuals with androgen insensitivity syndrome (AIS) were managed with removal of gonadal tissue at various ages to avert the risk of gonadal malignancy. Recently, clinical practice changed, with gonadectomy being postponed until late adolescence. Adolescents and adults with complete AIS have questioned this approach. Additionally, testicular germ cell tumors are increasingly believed to be quite rare with rates as low as 0% in molecularly confirmed individuals with AIS. Gonadectomy deprives patients of the benefits of their endogenous hormones and potential fertility. Furthermore, human rights organizations advocate for deferring irreversible surgery in conditions known as differences of sex development, which includes AIS, to allow patient autonomy in decision-making. Recent literature supports an approach that uses risk stratification to manage gonads in AIS. Herein we review what is known about malignancy risk in the different subtypes of AIS and propose a management protocol for gonad retention.

Weidler EM ，Linnaus ME ，Baratz AB ，Goncalves LF ，Bailey S ，Hernandez SJ ，Gomez-Lobo V ，van Leeuwen K ... -  《-》

Patients with disorders of sex development (DSD) at risk of gonadal tumour development: management based on laparoscopic biopsy and molecular diagnosis.

Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? In some individuals with disorders of sex development (DSD), gonadal tumour risk is increased. The individual risk is estimated based on the molecular diagnosis and the age and approaches 30% in the high-risk group. In the past, early gonadectomy has been advised for all individuals with 46XY DSD. Gonadectomy clearly represents an overtreatment for many individuals with 46XY DSD. Thus, further clinical indicators of individual tumour risk are urgently needed. The present study provides a comprehensive description of gonadal morphology, as seen during laparoscopy. For the first time, laparoscopic features, molecular diagnosis and histopathological findings are presented in a comprehensive context. The present study adds a detailed morphological description of the variability found in different subgroups of 46XY DSD. As three of four detected tumours were microscopic, early diagnosis by inspection appears unfeasible. Biopsy, gonadopexy and precise localisation of the gonad will potentially allow for gonadal preservation in well-defined clinical situations. • To investigate the role of laparoscopy for the early detection of gonadal tumours, with emphasis on gonadal preservation, in patients with 46XY disorders of sex development (DSD). In patients with DSD, gonadectomy is frequently recommended and depending on the age and the molecular diagnosis, an increased gonadal tumour risk exists and undesired hormone effects may arise. However, gonadectomy is irreversible and impacts considerably on body image. It represents an overtreatment for some patients and should be considered after a comprehensive diagnostic evaluation. Laparoscopy is an important technique, because it is able to retrieve small gonads and allows guided biopsies. • We performed laparoscopic assessment of the gonads in 40 patients with various 46XY DSD. • In all, 77 gonads were evaluated, images were analysed and compared with histological findings. • Laparoscopic procedures included gonadectomy, biopsy, laparoscopic orchidolysis or the Fowler-Stephens procedure as well as the removal or splitting of uterine remnants. • In all, 19 patients underwent gonadectomy and tumours were discovered in four. • Three patients had only microscopic evidence of tumour, in one the tumour was diagnosed intraoperatively. • In 21 patients, biopsies were taken and the gonads preserved. • Laparoscopic biopsy and gonadopexy was performed in six patients with complete androgen insensitivity syndrome (CAIS). • Laparoscopy and biopsy detected three microscopic tumours, one tumour was macroscopically evident. • In CAIS, gonadopexy improved the visibility of the gonads on postoperative ultrasonography. This procedure facilitated the examination of the gonad at follow-up. • In complete gonadal dysgenesis, a highly variable morphology of the gonads was found. Laparoscopy improved exposure of gonads and Müllerian structures, and facilitated biopsies and organ-preserving procedures.

Wünsch L ，Holterhus PM ，Wessel L ，Hiort O ... -  《-》