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Journal of Clinical Oncology, Vol 26, No 28 (October 1), 2008: pp. 4686-4688 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.17.5372
Primary Mediastinal Germ Cell Tumor Evolving Into an Extramedullary Acute Megakaryoblastic Leukemia Causing Cord CompressionWilliam Beaumont Hospital, Royal Oak, MI
Indiana University School of Medicine, Indianapolis, IN
William Beaumont Hospital, Royal Oak, MI
Indiana University School of Medicine, Indianapolis, IN
William Beaumont Hospital, Royal Oak, MI
Indiana University School of Medicine, Indianapolis, IN
In November 2006, a 28-year-old male presented with a 3-week history of pleuritic chest pain. Computed tomography (CT) scan demonstrated a 10.4- x 11.2-cm right-sided anterior mediastinal mass (Fig 1). Positron emission tomography/CT revealed [18F]fluorodeoxyglucose (FDG) maximum standard uptake value (SUVmax, 16.8) in the mediastinum. A CT-guided biopsy revealed a poorly differentiated malignancy with elements of yolk sac components. A few clusters of mature–appearing nucleated RBCs as well as occasional aggregates of poorly differentiated, immature appearing myeloid precursors were seen (Fig 2). Serum beta human chorionic gonadotropin was 82 µ/mL (
An association between PMGCT and hematologic malignancies was first recognized in 1985.1,2 All of the patients who developed hematologic malignancies had a nonseminomatous PMGCT.3 Acute megakaryocytic leukemia is the commonest hematologic malignancy associated with PMGCT.3 So far, less than 20 cases of PMGCT with evolution into acute megakaryocytic leukemia have been reported in the literature.2-10 Most of the reported cases of PMGCT associated with acute megakaryoblastic leukemia (including our patient) have had a yolk sac tumor component. The causal relationship between nonseminomatous PMGCT and leukemia is still elusive. It is quite possible that the nonseminomatous PMGCT, after spreading to the marrow cavity, becomes capable of transforming into leukemia in that microenvironment. Alternatively, it has been suggested that the mesenchyme-like component of yolk sac tumors acts as a pluripotential source for the transformation of primordial germ cells into malignancies typical of nongerminal tissue. A partial confirmation of this hypothesis lies in the presence of hematologic precursors within the PMGCT stroma and vessels within the yolk sac tumor component of these tumors.11 It can be further speculated that expression of hematopoietic growth and differentiation factors in some PMGCT could drive the differentiation of primordial germ cells into hematopoietic progeny. The differentiation factors involved may be responsible for the preferred commitment of the transformed precursors to megakaryocytic and monocytic lineage. Additionally, in a few cases of PMGCT-associated leukemia in which the immunophenotype of the leukemic cells was compared with that of the intratumoral hematopoietic precursors, a comparable result was observed. This suggests a spread of hematopoietic tumor cells from the PMGCT to blood, bone marrow, and/or extramedullary sites.12 The median time for the development of hematologic neoplasia associated with PMGCT is 6 months (range, 0 to 47 months).3 The clinical course of the hematologic neoplasia is very aggressive with a median survival of 5 months (range, 0 to 16 months) after diagnosis.3 Hematologic malignancies occurring in patients with PMGCT are thought to be primary, and not therapy related.11-14 In some cases, immunohistochemical and cytogenetic evidence (especially presence of i12p chromosome) had previously suggested the clonal relationship between the PMGCT and the hematologic malignancy.11-14 As in other previously reported cases, the short interval between the PMGCT and the occurrence of the hematopoietic malignancy argues against a therapy-related origin of the acute megakaryocytic leukemia. There have been two reported cases of PMGCT complicated by acute megakaryotic leukemia, one presenting with an extradural mass and the other with organomegaly.8 However, our patient is the first, to our knowledge, to be ever reported in English literature of a PMGCT evolving into an extramedullary acute megakaryocytic leukemia manifesting as a mass causing cord compression. Furthermore, the aggressive course of the acute megakaryoblastic leukemia involving the CNS with sparing of the bone marrow is striking. AUTHORS DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES 1. DeMent SH, Eggleston JC, Spivak JL: Association between mediastinal germ cell tumors and hematologic malignancies: Report of two cases and review of the literature. Am J Surg Pathol 9:23-30, 1985[Medline] 2. Nichols CR, Hoffman R, Einhorn LH, et al: Hematologic malignancies associated with primary mediastinal germ cell tumors. Ann Intern Med 102:603-609, 1985 3. Hartmann JT, Nichols CR, Droz JP, et al: Hematologic disorders associated with primary mediastinal nonseminomatous germ cell tumors. J Natl Cancer Inst 92:54-61, 2000 4. Case records of the Massachusetts General Hospital: Weekly clinicopathological exercises—Case 40-1997. A 23-year-old man with a mediastinal embryonal carcinoma and hematologic abnormalities. N Engl J Med 337:1904-1912, 1997 5. Domingo A, Romagosa V, Callis M, et al: Mediastinal germ cell tumor and acute megakaryoblastic leukemia. Ann Intern Med 111:539, 1989 6. Mihál V, Dusek J, Jarosova M, et al: Mediastinal teratoma and acute megakaryoblastic leukemia. Neoplasma 36:739-747, 1989[Medline] 7. Nichols CR, Hoffman R, Glant MD, et al: Malignant disorders of megakaryocytes associated with primary mediastinal germ cell tumors. Prog Clin Biol Res 215:347-353, 1986[Medline] 8. Nichols CR, Roth BJ, Heerema N, et al: Hematologic neoplasia associated with primary mediastinal germ cell tumors. N Engl J Med 322:1425-1429, 1990[Abstract] 9. Vazquez DD, Sancho GMI, Curbera GA, et al: Non-seminomatous germ-cell tumour associated with acute megakaryoblastic leukaemia. Clin and Transl Oncol 9:329-331, 2007[CrossRef] 10. Wang SE, Fligiel S, Naeim F: Acute megakaryocytic leukemia following chemotherapy for a malignant teratoma. Arch Pathol Lab Med 108:202-205, 1984[Medline] 11. Orazi A, Neiman RS, Ulbright TM, et al: Hematopoietic precursor cells within the yolk sac tumor component are the source of secondary hematopoietic malignancies in patients with mediastinal germ cell tumors. Cancer 71:3873-3881, 1993[CrossRef][Medline] 12. Wick MR, Perlman EJ, Orazi A, et al: Pathology and genetics of tumours of the lung, pleura, thymus and heart, in Travis WD, Brambilla E, Muller-Hermelink HK, et al (eds): World Health Organization Classification of Tumors. Lyon, IARC, 2004, pp 198 13. Ladanyi M, Samaniego F, Reuter VE, et al: Cytogenetic and immunohistochemical evidence for the germ cell origin of a subset of acute leukemias associated with mediastinal germ cell tumors. J Natl Cancer Inst 82:221-227, 1990 14. Neiman RS, Orazi A: Mediastinal nonseminomatous germ cell tumours: Their association with non–germ cell malignancies. Pathol Res Pract 195:589-594, 1999[Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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