Disorders of Sexual Differentiation: A Clinicopathological and Histological Study

Introduction: The term ‘Disorders of Sexual Differentiation’ (DSD) is defined as a congenital discrepancy between external genitalia, gonadal and chromosomal sex. The Chicago consensus based on the primary genetic defect is used for current nomenclature and classification. A child with DSD, if identified and treated early, may grow to become a well-adjusted, functional member of the society. Patients with DSD carry a low but definite risk of developing germ cell tumours which necessitates a histological analysis in all cases.

Aim: To describe the clinicopathological features of individuals with DSD and to classify the available cases according to the Chicago consensus which is based on karyotype and histopathology.

Materials and Methods: This retrospective descriptive study was done at a tertiary referral centre in South India, for a period of four months from May 2016 to August 2016. Case charts and histopathology slides of cases received in the Department of Pathology from January 2011 to May 2016 were included and reviewed. Cases where the histopathology slides/blocks were not retrievable/difficult to assess due to technical issues were excluded. Case charts and slides were reviewed retrospectively with a view to classify as per karyotypic or histological classification. The slides were reviewed by two Pathologists to help in the classification wherever possible. Statistical measures like mean and percentages were used to describe the results.

Results: A total of 22 cases of DSD were studied for which karyotype was available in 13 cases. Common clinical presentations were primary amenorrhoea, cryptorchidism and ambiguous genitalia. Age at presentation varied from nine months to 30 years. The initial diagnosis based on karyotype, clinical findings, hormonal assays and imaging were concordant with the final diagnosis in 11 cases. In two cases, histopathology was essential in arriving at a definitive diagnosis. Of the 13 cases with karyotype reports available, five were sex chromosome DSD, five were 46XY DSD and three were 46XX DSD. Gonadoblastoma was seen in three cases.

Conclusion: Histopathological examination together with karyotype plays a crucial role in proper categorisation of disorders of sexual differentiation. A multidisciplinary team approach for early diagnosis and management of DSD is essential for the psychosexual development of these individuals.