Journal of Clinical Oncology, Vol 20, Issue 17
(September), 2002: 3739-3742
© 2002 American Society for Clinical Oncology
Unusual Hematologic Malignancies
Case 2. Mediastinal Germ Cell Tumor, Malignant Histiocytosis, and Acute Leukemia
Ulka Vaishampayan,
Maria E. Dan
Wayne State University, Barbara Ann Karmanos Cancer Institute, Detroit, MI
A 30-year-old man with mediastinal germ cell nonseminoma was treated with four cycles of bleomycin, etoposide, and cisplatin (BEP). Normalization of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) levels occurred, but imaging of the thorax showed a residual mass in the mediastinum. The mass was excised, and pathologic examination revealed a residual nonseminomatous tumor mainly composed of teratoma and yolk sac elements. The patient received two additional cycles of BEP. Seven months later, the patient presented with bilateral hip pain and daily high fevers. His serum AFP and HCG levels were normal. His peripheral-blood count demonstrated an absolute neutrophil count of 600/mm3, hemoglobin level of 9.5 g/dL, and platelet count of 136,000/mm3. Numerous splenic nodules were visible on the computed tomography scan of the abdomen (Fig 1) in an enlarged spleen. Splenic biopsy specimens showed extramedullary hematopoiesis. Plain radiographs of the hips were nondiagnostic, but a bone scan revealed increased uptake in the region of the right femur. Magnetic resonance imaging of the pelvis revealed a hyperintense marrow signal in the right midfemur neck extending into the inferior femoral head and intertrochanteric region (Fig 2). A femur biopsy revealed multifocal infiltration by bizarre giant cells with hyperchromatic lobulated nuclei suggestive of malignant histiocytosis or acute megakaryocytic leukemia/M7 by the French-American-British classification (FAB) (Fig 3). Immunoperoxidase staining demonstrated CD41and CD61 (megakaryocytic markers) negativity but CD68 (histiocyte marker) positivity in the giant cells, thereby confirming a diagnosis of malignant histiocytosis. Cytokeratin, B- and T-cell markers, and CD30 negativity eliminated diagnoses of metastatic epithelial tumor and lymphoma. Cytogenetic analysis showed trisomy 1 and monosomy 13. At this time, multiple lytic lesions were visible on plain films, and the patient received palliative radiation therapy followed by systemic chemotherapy. A year later he demonstrated clonal evolution to FAB M1 acute myelogenous leukemia. Figure 4 shows the morphology of blasts in peripheral blood with absence of cytoplasmic granules but with fine nuclear chromatin and prominent nucleolus. Cytogenetic analysis revealed an additional 5q deletion. The patient died of progressive disease refractory to an aggressive induction regimen.
The association of mediastinal germ cell tumor (MGCT) and malignant histiocytosis is an uncommon but well-recognized entity.1 This syndrome has been reported only in nonseminomatous MGCT. The etiology seems to be unrelated to therapy, and the findings of isochromosome 12p in leukemic blasts suggest an origin in a common progenitor cell.1 There are few reports of other cases of MGCT and malignant histiocytosis (MEDLINE search from 1966 to present).2-6 All of these cases were seen in young males and demonstrated a clinically fulminant course. Pathology of associated MGCT was that of teratoma with yolk sac elements similar to the case described above. One of these cases occurred in a patient with Klinefelter’s syndrome, and another occurred in a renal allograft recipient receiving immunosuppressive corticosteroid therapy. The remaining patients presented simultaneously with both disorders. The cytogenetics have not been well characterized. Our case demonstrated trisomy 1 and monosomy 13, the significance of which remains unknown. Prospective karyotyping of future cases may provide insight into the pathogenesis and management of this syndrome.
NOTES
Copyright © 2002 American Society of Clinical Oncology
REFERENCES
1. 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]
2. Ashby MA, Williams CJ, Buchanan RB, et al: Mediastinal germ cell tumor associated with malignant histiocytosis and high rubella titres. Hematol Oncol 4: 183-194, 1986[Medline]
3. Beasley SW, Tiedemann K, Howat A, et al: Precocious puberty associated with malignant thoracic teratoma and malignant histiocytosis in a child with Klinefelter’s syndrome. Med Pediatr Oncol 15: 277-280, 1987[Medline]
4. Hernandez NL, Bombi JA, Caralps A, et al: Histiocytic medullary reticulosis (Robb-Smith’s disease) in renal transplant patient. Lancet 1: 261-262, 1977[Medline]
5. Landanyi M, Roy I: Mediastinal germ cell tumors and histiocytosis. Hum Pathol 19: 586-590, 1988[Medline]
6. Dement SH, Eggleston JC, Spivak JL: Association between mediastinal germ cell tumors and hematologic malignancies. Am J Surg Pathol 9: 23-30, 1985[CrossRef][Medline]
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