Neoplasm resembling normal developing gonad (hence the name) composed of germ cell type and sex cord cells similar to immature granulosa cells.
Very rare neoplasia.
1st–2nd decade of life.
Descended or undescended testis.
It frequently occurs in patients with DSD (Disorders of Sex Development) such as Turner Syndrome, Swyer Syndrome, and Complete Androgen Insensitivity Syndrome. All these disorders have in common a mutation in one or multiple genes implicated in normal development of gonads, such as WT1, SOX9, SF1, DHH, ARX, and TSPY. These mutations lead to altered maturation of both sex cord cells component and germ cells component: the former resemble granulosa cells instead of normal Sertoli cells while the latter are prone to neoplastic transformation toward GCNIS-like cells (Ulbright and Young 2014).
Surgical excision of the tumor and orchiectomy is required. Timing of surgery (before or after puberty) depends on the underlying DSD.
There is a significant risk of progression towards Germ Cell Tumors (seminoma/dysgerminoma in 80% of cases and non-seminomas in the remaining cases) but the prognosis is excellent if tumor is removed before the progression.
It presents as a firm grey/yellowish mass; it frequently displays many calcifications so that the cut surface appears granular and gritty. In some cases, it is located near an invasive germ cell tumor which appears as a solid tan yellow lobulated lesion (Scully 1970).
Multiple round nests on low power examination; within the nests, deposits of eosinophilic material frequently calcified can be found. Sometimes the calcification process is so prominent that the cellular component of the lesion tends to regress leaving only large coalescent calcifications (so called “burn-out” gonadoblastoma”). The nests are interspersed in a spindle cells gonadal stroma containing Leydig-like cells lacking Reinke crystals. At high power examination, the germ cells component displays variable appearance: some cells appear as spermatogonium-like cells, with scant cytoplasm, finely granular chromatin, and inconspicuous nucleoli, while others resemble GCNIS cells, which have more abundant pale/clear cytoplasm, polygonal angulated nuclei, and prominent multiple nucleoli (Fig. 1).
Frequently, the residual non-involved parenchyma contains undifferentiated gonadal tissue that consists of germ cells and sex cord cells organized in loose clusters or cords and embedded in gonadal stroma. This undifferentiated tissue is considered to be the precursor lesion of gonadoblastoma (Kersemaekers et al. 2006).
The germ cell component is OCT3/4, PLAP, VASA, KIT, NANOG, and CD117 positive whereas sex cord cells express WT-1, alpha-inhibin, calretinina, and sometimes Kit-ligand (Kao et al. 2014). Furthermore, the latter component expresses FOXL2, like granulosa cells, and SOX9, like Sertoli cells.
Gonadoblastoma shares some genetic characteristics with GCNIS and germinomas: overexpression of 12p chromosome and sometimes tetraploidization.
Gonadoblastoma may be mistaken for Sertoli cell nodules that have been colonized by GCNIS (Ye and Ulbright 2012). However in Sertoli cell nodules, GCNIS cells are only focally distributed within the nodules, the surrounding stroma is not of nonspecific gonadal type and finally the accompanying Sertoli cells are strongly positive for SOX9 and negative for FOXL2. Furthermore, this lesion does not occur in patients with DSD.