SUN-212 Differences of Sex Development Patients: Characterization of Histological Findings and Immunohistochemistry Markers in 46,Xx Gonads During Early Childhood.

Abstract

Differences of sex development (DSDs) comprise a group of congenital conditions, affecting human sex determination and/or differentiation. Patients with DSD are classified in: sex chromosome DSD, 46,XY DSD and 46,XX DSD. Gonadal germ cell tumors(GCC) are more prevalent in individuals with DSD. The aim was to characterize the precursor lesions of GCC in 46,XX DSD testicular (T) / ovotesticular (OT) gonads in prepubertal patients. We studied 25 gonads of 14 46,XX DSD patients. The age of the first biopsy was 14 (1.16-50) months (median and range). Molecular studies confirmed the absence of SRY by PCR and/or MLPA in blood DNA of all and in DNA from available gonads of 8 patients. Samples were classified as T, ovarian (O) or OT parenchyma, undifferentiated gonadal tissue (UGT) and gonadoblastoma (GB). Immunohistochemical (IHC) studies was used to identify Sertoli cells (SOX9), ovarian follicular cells (FOXL2), somatic cells (Inhibin B), germ cells (CD117), pluripotent germ cells (OCT3/4), and steroidogenic cells (HSD3B2 and CYP17A1). Twenty one gonads (12 patients) were OT, while 4 gonads (2 patients)were T. No histological alterations were found in the O. In T parenchyma signs of dysgenesis in all cases were found. In 6/21 gonads with OT (29%) a pattern of streak with clusters of germ cells was found (UGT). Structures like GB were found in 7/21 gonads with OT. The two OT of one patient showed UGT and GB and in both positive Inhibin B expression was observed. SOX9 staining allowed diagnosing as seminiferous cords in some hard-to-identify structures. FOXL2 was positive in all GB, and SOX9 expression was found in 3/7 GB. FOXL2 and SOX9 was positive in 3/6 UGT. OCT3/4 was positive in 2/7 GB and in 3/6 UGT and the presence of germ cells was also confirmed by CD117 positive staining. In all samples positive expression of HSD3B2 and CYP17A1 revealed the presence of steroidogenic cells. Regarding the patients with OT, in 3/12 the first biopsy showed only T tissue and a second biopsy revealed ovarian or OT tissue. In contrast to previously reported (1) high expression of SOX9 in GB was detected suggesting the presence of T somatic cells. A careful histological analysis including IHC markers is crucial to achieve a rigorous characterization of 46XX DSD gonads. These results reinforce the concept of the requirement of a close clinical follow up of DSD patients. 1)Hersmus R et al. J Pathol 2008; 215:31-38