Mediastinal Germ Cell Tumor and Acute Megakaryoblastic Leukemia– a Systematic Review of Cases Reported in the Literature
Authors: John Sonia , Muqeet Adnan Mohammed Abdul , Khalil Mohammad O. , Selby George , Asch Adam S. , Cherry Mohamad , Khawandanah Mohamad 
Published: October 2019

Abstract
Background and Aim:
The association of mediastinal germ cell tumors and acute megakaryoblastic leukemia has been known for many years. Characterization of this association is not well reported systematically in the literature. We hereby present this systematic review to describe the salient features of this association, treatment options and overall prognosis. Material and Methods: A systematic review of PUBMED, Medline and EMBASE databases via OVID engine was conducted to search for primary articles and case reports under keywords “germ cell tumors” and “acute myeloid leukemia”. Search was extensive from 1946 to 2014; all the cases that were written in English language in pediatric and adult patients were included. The search yielded 679 results and was individually examined by two authors. All the studies that described acute lymphoblastic leukemia or other malignancies aside from AML were excluded. A total of 25 studies reported mediastinal germ cell tumors (MGCT) and acute megakaryoblastic leukemia (M7). We also included in this analysis, one additional case with mediastinal germ cell tumor with subsequent development of acute megakaryoblastic leukemia that was recently diagnosed and treated at our institution.
Results: After our extensive review of the literature a total of 25 previous patients with MGCT + M7 were found from 1946-2014. With the inclusion of our case we report a total of 26 cases from 1946-2014.Twenty of the included patients were males and in 6 cases there was no mention of the gender. Median age at diagnosis of MGCT was 23 years (range - 15 to 36 y). In 92 % of cases the germ cell tumor was of non-seminomatous origin with 27% cases reporting teratoma and 40.7 % of cases reporting embryonal carcinoma. All the reported cases were stage III and had elevated tumor markers with significant elevation in serum AFP compared to beta-HCG.
MGCT occurred prior to appearance of leukemia in 46% of cases and concomitantly in 30% of cases. The rest of the cases did not describe the sequence of disease occurrence. M7 leukemia was never reported prior to the appearance of GCT. All the patients were treated with platinum based chemotherapy which was primarily directed towards management of the germ cell tumors. The time from diagnosis of MGCT to development of M7 leukemia ranged from 9 weeks to 39 months with the median time being 4 months.
Median time to death from the initial diagnosis of NSGCT was 6 months (range - 3 to 39 months). Only one reported case with MGCT+M7 combination was successfully treated with an allogenic stem cell transplant for the M7 leukemia with surgical resection of the mediastinal mass. Among the cases that reported cytogenetic abnormalities, trisomy 8 and complex cytogenetics were reported in 18.6 % cases each and hyperdiploidy was reported in 22 % cases. Surprisingly, Klinefelters syndrome (47, XXY) that is historically associated in 20 % of cases of mediastinal germ cell tumors was only reported in one case in this review. The i(12p) abnormality was reported only in 14.8 % of cases.
Conclusion: Patients with history of mediastinal germ cell tumors are at higher risk of developing acute leukemia especially the megakaryoblastic subtype. This warrants long term follow up of such patients with regular monitoring of blood counts and a high degree of suspicion for hematological malignancies. In selected cases, allogeneic stem cell transplant may be considered in those who achieve leukemia remission after optimal surgical resection. In spite of the advances in chemotherapeutic options, the overall outcome in patients with mediastinal germ cell tumors who have acute megakaryoblastic leukemia remains poor.

Disclosures
No relevant conflicts of interest to declare.