Postchemotherapy phenotypes of GCNIS-derived testicular germ cell tumors, focusing on yolk sac tumor variants, trophoblastic tumors, and somatic-type malignancies

Semin Diagn Pathol. 2026 Jan;43(1):150974. doi: 10.1016/j.semdp.2025.150974. Epub 2025 Nov 11.

Abstract

Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimens from patients with testicular germ cell tumors (TGCTs) often reveal a complex mix of residual tumor components and treatment-related changes. This review focuses on the morphologic spectrum of yolk sac tumor (YST) variants, trophoblastic tumors, and somatic-type malignancies in PC-RPLNDs, which continue to pose significant diagnostic and clinical challenges. Accurate identification of these entities is critical, as they carry distinct prognostic implications and influence management decisions. A multidisciplinary approach-integrating histopathology, immunohistochemistry, clinical history, and imaging-is essential for navigating these complex specimens. Emerging insights into chemotherapy resistance and tumor evolution are refining our understanding of TGCT biology and informing future diagnostic and therapeutic strategies. Herein, we highlight the increased frequency in postchemotherapy resections of glandular, hepatoid, parietal, and sarcomatoid differentiation in YSTs, as well as cystic, epithelioid, and placental site trophoblastic tumors, sarcomas, adenocarcinomas, and embryonic-type neuroectodermal tumors.

Keywords: Chemotherapy; Somatic-type malignancy; Teratoma; Testicular cancer; Testicular germ cell tumors; Yolk sac tumor.

Publication types

  • Review

MeSH terms

  • Endodermal Sinus Tumor* / pathology
  • Humans
  • Male
  • Neoplasms, Germ Cell and Embryonal* / drug therapy
  • Neoplasms, Germ Cell and Embryonal* / pathology
  • Phenotype
  • Testicular Neoplasms* / drug therapy
  • Testicular Neoplasms* / pathology
  • Trophoblastic Neoplasms* / pathology

Supplementary concepts

  • Testicular Germ Cell Tumor