Acute myeloblastic leukemia associated with mediastinal nonseminomatous germ cell tumors. Report on two cases.
ABSTRACT The demonstrated association with hematologic neoplasms may partially account for the poor survival of patients with mediastinal nonseminomatous germ cell tumors (MNSGCT) compared to patients with testicular and retroperitoneal counterparts. It has been shown that the median interval from the diagnosis of MNSGCT to the diagnosis of the hematologic disorders is 6 months, which contrasts sharply with the average time of 2 to 3 years for the development of therapy-related leukemias. The 2 cases herein described, 1 male and 1 female, developed acute M2 leukemia 4 and 2 years after the diagnosis of MNSGCT. In the second patient (the first female ever described), we cannot exclude a pathogenetic role of the PEB regimen (platinum, etoposide, bleomicin), even though the total dose of etoposide administered has been demonstrated to have a mild leukemogenic potential. This is not the case of the first patient, who did not receive adjuvant chemotherapy after the radical resection of primary MNGSCT and developed the hematologic disorder a few months after local recurrence. In conclusion, the time elapsed from chemotherapy administration does not discriminate the hematologic neoplasms associated to MNGSCT from those related to therapy.
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ABSTRACT: Germ cell tumor (GCT)-associated hematologic malignancies present a unique challenge to hematologists and hematopathologists. As most GCTs are of gonadal origin, only a small percentage occur at extragonadal sites in the midline. Extragonadal GCTs are believed to originate from the ectopic primordial germ cells that fail to migrate to the urogenital ridge during development. An overactive KIT pathway and overexpression of genes on chromosome 12p are strongly implicated in GCT development. Approximately 54% of extragonadal GCTs are located in the anterior mediastinum. This is disproportionally high among the midline structures, presumably due to a favorable microenvironment for GCT development in the developing thymus. The mediastinal nonseminomatous GCTs have two unique features. First, they are often refractory to current treatment modality with the worst prognosis among GCTs of all sites. Second, they have a tendency to give rise to secondary hematologic neoplasia. The outcome is grave for patients with GCT-associated hematologic malignancies. As standard chemotherapy used to treat their bone marrow-derived counterparts has been ineffective, the best treatment modality to achieve long-term survival is allogeneic hematopoietic stem cell or cord blood transplant for a very limited number of cases.Expert Review of Hematology 08/2012; 5(4):427-37. · 2.38 Impact Factor