Primary mediastinal seminomas: a comprehensive immunohistochemical study with a focus on novel markers

Hum Pathol. 2015 Mar;46(3):376-83. doi: 10.1016/j.humpath.2014.11.009. Epub 2014 Nov 26.

Abstract

Primary mediastinal seminomas are unusual tumors that can present in a pure form or as part of a mixed germ cell tumor. Contrary to testicular seminomas, little is known about the expression of novel immunohistochemical markers in mediastinal seminomas. This study investigates the immunohistochemical features of these tumors with a focus on novel markers. Thirty-two cases of primary mediastinal seminomas were reviewed; and representative whole-tissue sections were selected for immunohistochemical studies using antibodies directed against high molecular weight cytokeratin 5/6 (CK5/6), low molecular weight cytokeratin (CAM5.2), octamer-binding transcription factor 3/4 (OCT3/4), spalt-like transcription factor 4 (SALL4), GATA binding protein 3 (GATA-3), sry-related HMG box 2 (SOX2), SOX17, human T cell leukemia/lymphoma 1 (TCL1), glypican 3, melanoma associated antigen C2 (MAGEC2), and paired box gene 8 (Pax8). The percentage of positive tumor cells as well as the intensity of staining was evaluated and scored. Thirty-one cases (97%) expressed SOX17, whereas 29 cases (91%) were positive for OCT3/4 and SALL4, respectively. Twenty-eight cases (88%) expressed MAGEC2 and CAM5.2, respectively. Two cases (6%) were positive for Pax8, and a single case (3%) was positive for TCL1. None of the cases stained with CK5/6, GATA-3, SOX2, or glypican 3. Similar to testicular seminomas, mediastinal seminomas show consistent expression of OCT3/4, SALL4, SOX17, and MAGEC2 and are negative for SOX2, glypican 3, GATA-3, and CK5/6. Pax8 positivity is only inconsistently identified in mediastinal seminomas. Contrary to their testicular counterparts, mediastinal tumors show diffuse expression of low-molecular-weight cytokeratin in up to 90% of cases and are commonly negative for TCL1. Although there is some immunohistochemical overlap between testicular and mediastinal seminomas, considerable differences also exist and should be acknowledged when dealing with these tumors.

Keywords: Germ cell tumor; Immunohistochemistry; Mediastinum; Seminoma; Thymus.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Antigens, Neoplasm / analysis
  • Biomarkers, Tumor / analysis*
  • GATA3 Transcription Factor / analysis
  • Glypicans / analysis
  • Humans
  • Immunohistochemistry
  • Keratin-5 / analysis
  • Keratin-6 / analysis
  • Male
  • Mediastinal Neoplasms / chemistry*
  • Mediastinal Neoplasms / pathology
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Octamer Transcription Factor-3 / analysis
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors / analysis
  • Proto-Oncogene Proteins / analysis
  • SOXB1 Transcription Factors / analysis
  • SOXF Transcription Factors / analysis
  • Seminoma / chemistry*
  • Seminoma / pathology
  • Testicular Neoplasms / chemistry*
  • Testicular Neoplasms / pathology
  • Transcription Factors / analysis*
  • Young Adult

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • GPC3 protein, human
  • Glypicans
  • Keratin-5
  • Keratin-6
  • MAGEC2 protein, human
  • Neoplasm Proteins
  • Octamer Transcription Factor-3
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • POU5F1 protein, human
  • Paired Box Transcription Factors
  • Proto-Oncogene Proteins
  • SALL4 protein, human
  • SOX17 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • SOXF Transcription Factors
  • TCL1A protein, human
  • Transcription Factors