Background: Recent data describe that the gonads of patients with partial gonadal dysgenesis (PGD) and mutation in the NR5A1 gene can present with a different histological pattern.
Objective and hypotheses: To evaluate histological aspects of PGD caused by NR5A1 mutations.
Method: Five patients with PGD, a history of gonadal biopsy or gonadectomy and confirmed mutation on NR5A1 gene were selected from a Brazilian Center for DSD. The histological aspects were evaluated with H&E standard staining. All patients presented with ambiguous genitalia and a hormonal analysis suggesting gonadal dysgenesis. Patient 1 (p.D293N) was gonadectomised at age 20 years old. Patient 2 (p.Lys38*) had gonadal biopsy at age 4 years. Patient 3 (p.L80Wfs*8) had left and right gonads biopsied with 2.5 and 4 years respectively. Patient 4 (c.1138+1G>T) had gonadectomy at age 1.5 years. Patient 5 (p.Lys396Argfs*34) had gonadal biopsy at age 8 years.
Results: P1: Leydig cell (LC) hyperplasia with vacuolated cytoplasm (foamy aspect); Sertoli-cell-only-syndrome (SCOS) and wide tubules (bilaterally). P2: small primitive tubules within ovarian-type stroma; few germ cells and no definite LC (left gonad). P3: right gonad showing SCOS within small fibrosis areas. Left gonad: prepubertal testis. P4: SCOS, fibrosis and presence of enlarged LC with vacuolated cytoplasm (bilaterally). P5: atrophic tubules within a fibrotic stroma; few germ cells, some of them showing atypical nucleus (bilaterally).
Conclusion: We found an unusual LC pattern in 2/5 patients hyperplasia with vacuolated cytoplasm in the 20-year-old patient and the presence of LC (enlarged and vacuolated) in the 1.5-year-old patient, not expected in this age. We also found atypical germ cells that can be an early sign of tumour development in one patient. In conclusion, histological pattern can be useful to differentiate PGD caused by NR5A1 mutations from others. Although it is believed that those patients have a lower tumour risk, more studies are necessary to assess such risk.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology