Extragonadal germ cell tumors: A clinicopathologic study with emphasis on molecular features, clinical outcomes and associated secondary malignancies

Eman Abdulfatah; Noah A Brown; Matthew S Davenport; Zachery R Reichert; Sandra Camelo-Piragua; Amer Heider; Tao Huang; Ulka N Vaishampayan; Stephanie L Skala; Jeffrey S Montgomery; Arul M Chinnaiyan; Samuel D Kaffenberger; Pushpinder Bawa; Lina Shao; Rohit Mehra

doi:10.1016/j.humpath.2024.04.015

Extragonadal germ cell tumors: A clinicopathologic study with emphasis on molecular features, clinical outcomes and associated secondary malignancies

Hum Pathol. 2024 Apr 30:148:41-50. doi: 10.1016/j.humpath.2024.04.015. Online ahead of print.

Authors

Affiliations

¹ Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
² Department of Radiology, University of Michigan Medical School, Ann Arbor, MI, USA.
³ Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA; Rogel Cancer Center, Michigan Medicine, Ann Arbor, MI, USA; Department of Internal Medicine, Divsion of Hematology/ Oncology, MI, USA.
⁴ Rogel Cancer Center, Michigan Medicine, Ann Arbor, MI, USA; Department of Internal Medicine, Divsion of Hematology/ Oncology, MI, USA.
⁵ Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Rogel Cancer Center, Michigan Medicine, Ann Arbor, MI, USA.
⁶ Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
⁷ Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA; Rogel Cancer Center, Michigan Medicine, Ann Arbor, MI, USA; Howard Hughes Medical Institute, Ann Arbor, MI, USA.
⁸ Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA.
⁹ Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, Ann Arbor, MI, USA; Rogel Cancer Center, Michigan Medicine, Ann Arbor, MI, USA. Electronic address: mrohit@med.umich.edu.

PMID: 38697270
DOI: 10.1016/j.humpath.2024.04.015

Abstract

Extragonadal germ cell tumors (EGCTs) are rare, representing <5% of all germ cell tumors (GCTs). Whilst EGCTs share morphological and immunohistochemical features with their gonadal counterparts, they tend to be more aggressive and are frequently associated with secondary somatic malignancies. The aim of our study was to evaluate the clinical, morphological and immunohistochemical features, and to analyze tumors for chromosomal abnormalities of 12p, in addition to any novel genetic alterations, in a series of EGCTs. Seventy-seven EGCTs were included. Anterior mediastinum was the most common anatomic site, followed by central nervous system, retroperitoneum, sacroccygeal area, and neck. Whole genome SNP array identified isochromosome 12p in 26% of tumors. Additional cytogenetic abnormalities included the presence of gain of chr 21 in 37% of tumors. Somatic-type malignancies were identified in 8% of patients. Disease progression (metastasis and/or recurrence) was documented in 8 patients, most of whom died from their relapse. Three patients who died of disease had somatic-type malignancies. Mediastinal seminomas had a significantly better overall survival when compared to mediastinal non-seminomatous GCTs. Our study demonstrates that EGCTs share similar histologic features, but diverse clinical outcomes compared to their gonadal counterparts. Outcomes vary according to anatomic location and histologic subtypes. Our data corroborate that somatic-type malignancies are frequently encountered in mediastinal EGCTs and that their presence portends a poorer prognosis.

Keywords: Choriocarcinoma; Embryonal carcinoma; Extragonadal; Germ cell; Isochromosome; Mediastinal; Retroperitoneal; Secondary somatic transformation; Seminoma; Single nucleotide polymorphism array; Teratoma; Yolk sac tumor; i12p.