Testicular
germ cell tumors (TGCTs) and
sex cord-stromal tumors (SCSTs) are the most common
testicular neoplasms. The morphologic spectrum of such
tumors is wide, with several histologic subtypes within each group.
Testicular tumors often represent a diagnostic challenge, requiring proper identification of their biologic potential for accurate risk stratification and selection of
therapy. In the era of
precision medicine, molecular
biomarkers are increasingly assuming a critical role in the management of patients with
cancer. Given the overall rarity of certain types of
testicular neoplasms, progress in
biomarker research has been relatively slow. However, in recent years, we have witnessed a multitude of important contributions, including both tissue-based and liquid biopsy
biomarkers, stemming from important discoveries of
tumor pathobiology, accurate histopathological analysis, multi-institutional studies, and genome-wide molecular analyses of specific
tumor subtypes. In this review, we provide an overview of the progress in molecular
biomarkers of TGCTs and SCSTs, focusing on those with greatest potential for clinical application. In TGCTs, developmental biology has been the key to understanding these
tumors and identifying clinically useful
biomarkers (from classical serum
tumor markers to pluripotency factors and circulating
microRNAs of the 371-373 cluster). For SCSTs, studies have focused on tissue
biomarkers only, and genome-wide investigations have recently contributed to a better understanding of rare phenotypes and the aggressive biological behavior of some
tumors within this nosologic category. Several new
biomarkers are moving toward clinical implementation in this field. Therefore, the practicing pathologist should be aware of their strengths and limitations in order to utilize them properly and maximize their clinical benefits.