Hematopoietic precursor cells within the yolk sac tumor component are the source of secondary hematopoietic malignancies in patients with mediastinal germ cell tumors

Attilio Orazi, Richard S. Neiman, Thomas M. Ulbright, Nyla A. Heerema, Karla John, Craig R. Nichols

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Abstract

Background. Patients withmediastinal germcell tumors (MGCT) have a high incidence of hematologic malignancies unrelated to cytotoxic chemotherapy. It has been suggested that these leukemic conditions originate from a MGCT progenitor cell capable of undergoing nongerm cell (hematopoietic) differentiation. Methods. To assess this hypotheis, histologic material from six patients with MGCTs associated with leukemia was examined using monoclonal and polyclonal antibodies capable of labeling cells of the different marrow cell lineages. Results. Morpologically identifiable hematologic cells were found within the yolk sac tumor component of the MGCT in four of these patients. In three of the four cases, the cells consisted of poorly differentiated blast cells, whereas in the fourth, clusters of erythroblasts were identified. The leukemic cellls within the MGCT and in the bone marrow had similar morphology, constnat expression of the early progenitor cell marker CD34, and variable expression of more mature myeloid, monocytic, erythroid, and megakaryocytic markers.Three cases expressed p53, a nuclear protein associated with neoplastic transformation in a wide range of malignancies, including testicular cancers, but which rarely is reported in leukemias. Karyotype of the leukemia was assessed in five cases: two showed an i(12p), a cytogenetic marker of GCT not identified in the usual cases of leukemia. Conclusions. The results support the hypothesis that these leukemic conditions originate in the MGCT through a mechanism of differentiation from a yolk sac tumor-derived progenitor cell, with subsequent homing to the marrow.

Original languageEnglish (US)
Pages (from-to)3873-3881
Number of pages9
JournalCancer
Volume71
Issue number12
DOIs
StatePublished - Jun 15 1993

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Keywords

  • hematologic differentiation
  • hematologic malignancies
  • mediatinal germ cell tumor
  • nongerm cell differentiation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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