Diagnostic incidence and pitfalls of rete testis hyperplasia and hyaline globules in a multi-institutional study of 348 testicular germ cell tumors

The concept of rete hyperplasia with hyaline globules simulating testicular yolk sac tumor was first reported in a mostly retrospective review over 30 years ago. Nonetheless, we continue to encounter examples where this scenario resulted in misdiagnosis. Herein, we sought to investigate the incidence of rete hyperplasia/hyaline globules in germ cell tumors and their associated subtypes and hypothesize an etiology. A consecutive series of 348 germ cell tumor orchiectomies was evaluated for the presence of rete hyperplasia and hyaline globules, with clinicopathologic features recorded. The incidence of rete hyperplasia and/or hyaline globules in our cohort was 30%, with 56% of specimens with rete hyperplasia containing concomitant hyaline globules. Hyaline globules were more often identified in specimens with nonfocal rete hyperplasia (78%) vs focal rete hyperplasia (22%). Absence of a yolk sac tumor component was seen in over half (61%) of orchiectomies with concurrent rete hyperplasia/hyaline globules (n = 105), inclusive of tumors with "pure" subtypes (ie, pure seminoma, pure teratoma, or pure embryonal carcinoma). Of these 105 specimens, rete invasion was seen in only 48%; notably, Paneth cell-like metaplasia was identified in efferent ductules/epididymis in 13%. Rete hyperplasia and hyaline globules are not uncommon findings in the setting of germ cell tumors (including occurrences in various pure/mixed germ cell tumors) and can show striking overlap with yolk sac tumor. We hypothesize that these histologic pitfalls evolve secondary to testicular obstruction by the tumor mass. Recognition of and distinguishing this morphologic mimicry is fundamental to guide appropriate clinical management.