Search

Testicular spermatocytic seminoma (SS) is a rare tumor type predominantly found in elderly men. It is thought to originate from spermatogonia and shows cytological and genetic heterogeneity. In this study, we performed for the first time a comprehensive analysis of epigenetic modifications in a series of 36 SS samples. We assessed by immunohistochemistry tumor DNA methylation levels, the expression of methyltransferases DNMT3A, DNMT3B and DNMT3L as well as levels of histone modifications H3K9me2, H3K27me3, H3K4me1, H3K4me2/3, H3K9ac, and H2A.Z. We did not identify any epigenetic marks that matched the pattern of the supposed cell-of-origin, the spermatogonia, and found no correlation between specific marks and the size of the SS cells. The emerging epigenetic picture of SS is a heterogeneous "salt-and-pepper"-like pattern, with neighboring cells displaying very variable levels of epigenetic marks. We conclude that SS cells display apparent epigenetic heterogeneity and instability, with loss of the organized manner typical for normal germ cell maturation in the adult testis, likely due to the lack of regulatory signals from the absent somatic cell niche.

Spermatocytic seminoma is a clinical pathologic distinct entity that has a good prognosis and rarely is associated with other neoplastic elements. Two cases of testicular spermatocytic seminoma with a sarcomatous element are reported. Both patients were older than 40 years and presented with 1-year and 2-year histories of progressive testicular enlargement and recent onset of testicular pain. Histologically, the spermatocytic seminoma in both cases consisted of three distinct cell types as has been previously described. Ultrastructurally, one case showed crystalloid structures similar to the Lubarsch's crystalloids described in spermatogonia of human testis. The sarcomatous component in one case was a rhabdomyosarcoma confirmed by light and by electron microscopic study whereas the second case was a primitive mesenchymal spindle cell sarcoma. Only the sarcomatous element metastasized; metastatic sites included lung and paraaortic lymph nodes in the first patient and lung and liver in the second. Despite aggressive treatment with combined surgery and multiagent chemotherapy, the first patient died within 1 year of diagnosis and the second at 14 months.