Mediastinal Germ Cell Tumor and Acute Megakaryoblastic Leukemia With Co-occurring KRAS Mutation and Complex Cytogenetics

Pediatr Dev Pathol. Nov-Dec 2020;23(6):461-466. doi: 10.1177/1093526620951327. Epub 2020 Aug 20.


Young males have a unique but rare predilection to develop mediastinal nonseminomatous germ cell tumors (NSGCTs) and concomitant acute megakaryoblastic leukemia (AMKL). Common cytogenetic and molecular abnormalities such as isochromosome 12p and somatic Tumor Protein P53(TP53) and Phosphatase And Tensin Homolog (PTEN) mutations have been reported in the presumed mutual neoplastic clones of origin. We report the case of a 17-year-old male who presented with a mediastinal NSGCT with high-grade sarcomatous transformation and a diagnosis of AMKL approximately 4 months later. Next-generation sequencing revealed identical KRAS Proto-Oncogene, GTPase (KRAS) p.Ala146Thr, TP53 p.Leu257Pro, and PTEN p.Leu181Pro missense mutations at similar variant allele frequencies in both the NSGCT and AMKL samples. Cytogenetic and microarray analyses detected shared copy gains in all chromosomes except chromosomes 9, 13, and Y. Multiple additional clonal chromosomal alterations were detected in the AMKL sample when compared with the NSGCT. This case emphasizes the shared clonal origins of these malignancies and identifies KRAS and other copy number alterations as potential molecular drivers in a subset of these combined diseases.

Keywords: KRAS; acute myeloid leukemia; cytogenetics; germ cell tumor; microarray; sarcoma.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Biomarkers, Tumor / genetics*
  • Cytogenetic Analysis
  • Humans
  • Leukemia, Megakaryoblastic, Acute / complications
  • Leukemia, Megakaryoblastic, Acute / diagnosis
  • Leukemia, Megakaryoblastic, Acute / genetics
  • Leukemia, Megakaryoblastic, Acute / pathology*
  • Male
  • Mediastinal Neoplasms / complications
  • Mediastinal Neoplasms / diagnosis
  • Mediastinal Neoplasms / genetics
  • Mediastinal Neoplasms / pathology*
  • Mutation
  • Neoplasms, Germ Cell and Embryonal / complications
  • Neoplasms, Germ Cell and Embryonal / diagnosis
  • Neoplasms, Germ Cell and Embryonal / genetics
  • Neoplasms, Germ Cell and Embryonal / pathology*
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Testicular Neoplasms / complications
  • Testicular Neoplasms / diagnosis
  • Testicular Neoplasms / genetics
  • Testicular Neoplasms / pathology*


  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins p21(ras)

Supplementary concepts

  • Nonseminomatous germ cell tumor