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Burkitt's Leukemia After Treatment of Primary Mediastinal Nonseminomatous Germ Cell Tumor

Department of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

Rajive Kumar, Anita Chopra, Dipti Kalita

Department of Laboratory Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

Pratibha Amare Kadam

Cancer Cytogenetics Laboratory, Tata Memorial Hospital, Mumbai, India

A 37-year-old man presented to us in February 2007 with reports of rising total leukocyte count (32 x 10⁹/L to 92 x 10⁹/L in 3 days). This had been detected in the course of a routine check after chemotherapy and surgery done for primary mediastinal germ cell tumor (GCT) 3 months earlier, in another hospital. His hemoglobin was 12 g/dL and platelet count was 25 x10⁹/L. There was no lymphadenopathy or hepatosplenomegaly. Previous to this the patient had been investigated in February 2006 for a 3-month history of breathlessness, cough, and expectoration. Chest x-ray and contrast-enhanced computed tomogram of the chest had revealed a large mediastinal mass with necrosis (Fig 1, arrows) and small pleural effusion (Fig 1). Computed tomography scan of abdomen and pelvis, and examination and ultrasound of testes were normal. Serum -fetoprotein was 14,571 IU/mL and β-human chorionic gonadotropin was 157.6 mIU/mL. Tru-cut biopsy from mediastinal mass showed variegated areas characteristic of mixed GCT: undifferentiated cells in solid sheets with necrosis, and areas showing ectodermal (squamous epithelium), endodermal (mucosal glands), and mesodermal (cartilage and smooth muscle) differentiation as well as an immature component consisting of primitive neuroepithelium (Figs 2A to 2D). A diagnosis of nonseminomatous GCT (embryonal carcinoma and immature teratoma) was made. The patient was treated with etoposide 100 mg/m² days 1 through 5 and cisplatin 20 mg/m² days 1 through 5 every 3 weeks from April 2006. Bleomycin was omitted due to apprehension about pulmonary toxicity. Five cycles of etoposide and cisplatin had been given until July 2006; at this point serum markers had become normal. Contrast-enhanced computed tomogram chest revealed almost 70% to 80% reduction in the size of the tumor, with a residual mass measuring 9 cm that was invading pericardium and myocardium with effacement of coronary vessels. Fluorodeoxyglucose positron emission tomography showed mildly increased uptake along the margins of the mass. Given that the mass was considered inoperable, the patient was given two courses of chemotherapy with etoposide 100 mg/m² days 1 through 5, ifosfamide 2 g/m² days 1 through 5 with mesna, and cisplatin 20 mg/m² days 1 through 5. Surgical resection R0 type was then carried out in November 2006. Histopathologic examination showed residual immature teratoma. Postoperative computed tomography scan of the chest showed no residual disease and both markers continued to be normal. Our investigations in February 2007 showed 12% blasts in the peripheral-blood smear and 75% blasts in the bone marrow. The blasts had deeply basophilic cytoplasm with oil red-O–positive vacuoles (Fig 3, arrows); they were negative for myeloperoxidase and nonspecific esterase. Mitotic figures were present. The overall morphologic features were those of Burkitt leukemia. Flow cytometry showed blasts to be positive for CD19, CD22, CD 79a, HLA-DR, and CD45, and negative for all T-cell and myeloid markers. Fluorescent in situ hybridization technique was applied on interphase and metaphase cells using LSI MYC and LSI immunoglobulin heavy chain (IgH) dual-color, break-apart probes and CEP 8 probe (Vysis Abbott, Wiesbaden-Delkenheim, Germany). The IgH probe revealed normal copies of red/green signals. The signal pattern of MYC revealed two red/green signals (normal MYC copies; Fig 4, long arrows) and red signal at band 8q24 (Fig 4, short arrow) in 25% of interphase cells (large blast-like cells). Metaphase cells (15 of 15) with red/green signals and a red signal at 8q24 on copies of chromosome 8 indicated three copies of chromosome 8 with break in C-MYC followed by deletion of distal segment of MYC (green signal) on a derivative 8 (Fig 4). The trisomy 8 was confirmed by fluorescent in situ hybridization with CEP 8. A final diagnosis of Burkitt's leukemia was made and the patient was started on cyclophosphamide, vincristine, doxorubicin, plus methotrexate; and ifosfamide, etoposide, and cytarabine.¹ Although he went into remission after cycle 1A, his tolerance to additional chemotherapy was poor; he developed grade 3 neurotoxicity, significant and prolonged liver and marrow toxicity, and disseminated intravascular coagulation. His drug schedule thus had to be modified significantly and curtailed, given that this protocol also contained etoposide and ifosfamide that he had received as part of his treatment for GCT. The patient had a frank relapse in August 2007 and died soon after.

View larger version (83K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 1.

View larger version (132K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2.

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AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

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