Germ Cell Tumors in 46, XY Gonadal Dysgenesis

Abstract

Introduction: To present the clinical data, investigative profile, management, and follow-up of patients with 46, XY gonadal dysgenesis with germ cell tumors from the endocrine unit of a tertiary care university hospital.

Materials and methods: This retrospective study included 3 cases of 46, XY gonadal dysgenesis with germ cell tumors evaluated and managed at the Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, over a period of 13 years from (September 2008 to December 2021).

Results: Over a period of 13 years, we diagnosed and managed 7 patients with 46, XY gonadal dysgenesis. This included 4 patients with pure gonadal dysgenesis (PGD; Swyer syndrome), 2 patients with mixed gonadal dysgenesis (MGD), and one patient with partial gonadal dysgenesis. Out of these 7 patients, three patients developed germ cell tumors, one patient with MGD, and two patients with pure PGD (Swyer syndrome). In all three patients, germ cell tumor was the first presentation of DSD. The patient with MGD presented with primary amenorrhea and virilization, while the two patients with PGD presented as phenotypic females with primary amenorrhea and pelvic mass. All three patients developed seminomatous cancers. Patient with MGD developed seminoma and the two patients with PGD (Swyer syndrome) developed dysgerminoma. The patients were managed with bilateral gonadectomy with removal of the tumor. In addition, the 2 patients with PGD (Swyer syndrome) received combined chemotherapy. On a follow up ranging from 1 to 10 years, all three patients are disease free.

Conclusions: we conclude that germ cell tumors may be the first presentation of 46, XY gonadal dysgenesis. In all phenotypic females with primary amenorrhea and dysgerminoma, karyotype is a must to uncover the diagnosis of PGD. In addition virilization may be clue to the presence of germ cell tumor in a patient with 46, XY gonadal dysgenesis.

Keywords: 46; XY gonadal dysgenesis; disorders of sex development; dysgerminoma; germ cell tumors; seminoma.

Figure 1

(a) Upper part showing seminoma sharply demarcated from the lower part showing atrophic seminiferous tubules; (b) Section showing Sheets of seminoma cells separated by fibrovascular septa infiltrated by lymphocytes (hematoxylin and eosin, ×10; b, hematoxylin and eosin, ×40).

Figure 2

Monomorphic population of tumor cells arranged in diffuse sheets as well as in vague nests pattern separated by delicate fibrous septa infiltrated by lymphocytes. The individual tumor cells are round to polygonal having coarse nuclear chromatin, occasionally prominent nucleoli and clear cytoplasm (a, hematoxylin and eosin, ×20; b, hematoxylin and eosin, ×40).