Non-seminomatous mediastinal germ cell tumor and acute megakaryoblastic leukemia

Abstract

The association between mediastinal germ cell tumors (MGCT) and acute megakaryoblastic (M7) leukemia has been known for many years. We hereby present this review to better characterize the coexistence of these entities as well as the salient features, the treatment options, and the overall prognosis. A search of PUBMED, Medline, and EMBASE databases via OVID engine for primary articles and case reports under keywords "germ cell tumors" and "acute myeloid leukemia" revealed a total of 26 cases in English that reported MGCT and M7 leukemia. The median age at diagnosis of MGCT was 24 (13-36) years. All cases were stage III. All cases of MGCT were of non-seminomatous origin and one case was unclassified. MGCT occurred prior to the diagnosis of leukemia in 46% of cases and concomitantly in 31% of cases. M7 leukemia was never reported prior to the appearance of MGCT. Complex cytogenetics and hyperdiploidy were the most commonly reported cytogenetic abnormalities. In the 23 cases where the treatment regimen was available, platinum-based chemotherapy directed towards management of the germ cell tumors was used initially in 21 cases and leukemia-directed treatment was used initially in 2 cases only. The median time from diagnosis of MGCT to development of M7 leukemia was 5 (2.25-39) months. Median time to death from the initial diagnosis of MGCT was 6 (0.5-60) months. Patients with a history of MGCT are at higher risk of developing M7 leukemia. They need long-term follow-up with a particular attention to the development of hematological malignancies. The overall prognosis remains poor.

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

“…13 , 14 Almost all acute leukemias are diagnosed concomitantly with the NSGCT or within a median time interval of 5 months; the onset of acute leukemia antecedent to the diagnosis of NSGCT has not been reported. 15 In this case, the use of cytogenomic and molecular profiling confirmed the biologic association between the mediastinal NSGCT and AMKL despite a metachronous presentation.…”

“…There are scattered case reports and small case series documenting the association between mediastinal GCTs and hematologic malignancies in young males with clear association between mediastinal NSGCT and AMKL. 15 This case highlights several interesting findings that merit further discussion. Saito et al described a combined NSGCT with angiosarcomatous transformation and myeloid sarcoma.…”

“…We observed a complex cytogenetic profile with numerous copy gains without isochromosome 12p which has been reported in rare instances. 15 Microarray analysis of the NSGCT revealed additional copy gains compared with conventional karyotyping. This discrepancy may in part be due to the analysis of composite tumor DNA rather than analysis of cultured cells.…”

Acute myeloid leukemia following a primary mediastinal germ cell tumor

“…Here, a low dose of cytarabine was given, but the patient did not respond to the antileukemic treatment. Allogenic stem cell transplantation may be curative for a subset of patients 1,10 ; however, this requires further study.…”

“…Hematologic disorders have been found to be associated with mediastinal germ cell tumors, including acute megakaryocytic leukemia (M7), acute monocytic leukemia (M5), malignant tissue cell disease, and acute myelomonocytic leukemia (M4). Multicenter data showed that the incidence of leukemia in patient s with germ cell tumors was 5.9% 1 ; the most common type was M7 2,3 . Hartmann et al 2 found that the risk of developing a germ cell tumor‐related leukemia was highest during the 1st year after the diagnosis of a PMGCT, and the risk decreased from 4.8% in the first 12 months to 1.5% and 0.6% during the 2nd and 3rd years, respectively.…”