A 25-yr-old man presenting with chest pain was admitted to Chung-Ang University Hospital (Seoul, Korea) because of an abnormal mass in the anterior mediastinal area. He had no remarkable past medical and familial history. He had been diagnosed with a malignant mediastinal GCT (immature teratoma 80%, embryonal carcinoma 10%, seminoma 5%, yolk sac tumor 5%) in January 2010. Peripheral blood examination showed the following: Hb level, 14.5 g/dL; leukocyte count, 10,770/µL (neutrophil 70%, lymphocyte 21%, no blasts); and platelet count, 257,000/µL. Serum alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH) were 11,680 ng/mL, 0.847 mIU/mL, and 187 IU/L, respectively. After surgical resection of the tumor, the patient received four cycles of adjuvant chemotherapy with bleomycin, etoposide, and cisplatin between February and April 2010. During routine follow-up in August 2010, a persistent tumor lesion was found and the patient received three cycles of adjuvant chemotherapy with pacilitaxel, ifosfamide, and cisplatin between August and October 2010. A peripheral blood examination performed in October 2010 showed pancytopenia without blasts.
After 1 week of the last chemotherapy cycle, the patient visited the emergency room with a fever. Peripheral blood examination showed the following: Hb level, 5.9 g/dL; leukocyte count, 12,920/µL with 16% neutrophils, 22% lymphocytes, 57% blasts; 5 nucleated red cells per hundred white blood cells; and platelet count, 6,000/µL (). Serum AFP and LDH levels were 234 ng/mL and 2,964 IU/L, respectively. Based on these findings, acute leukemia was suspected and a bone marrow examination was performed in November 2010. In the bone marrow aspiration, about 40.4% of all nucleated cells were blasts. The blasts were medium to large-size with round, slightly irregular nuclei and one to three nucleoli. The cytoplasm of blasts was basophilic and might show distinct bleb or pseudopod formation (). The dysplastic features of a megakaryocytic lineage (e.g. micromegakaryocytes and hypolobulation of the nucleous) were found in more than 30% of 30 megarkaryocytes (). Cytochemical staining showed that the cells had dot-like positivity for periodic acid-Schiff () and acid phosphatase, in contrast, negativity for myeloperoxidase, α-naphthyl acetate esterase and α-naphthyl butyrate esterase. The bone marrow biopsy showed about 90%-100% cellularity (). Immunophenotyping showed positivity for CD13, CD33, CD117, MPO, CD7, CD61, and HLA-DR, and was negative for CD2, CD3, CD5, CD19, CD20, cCD22, cCD79a, CD10, CD14, and TdT. Cytogenetic examination revealed a 46,XY,add(5)(q11.2),del(10)(p11.2), -17, der(18)t(17;18) (q11.2;q21), +i(12p) karyotype (). FISH analysis using AML1/ETO, BCR/ABL, MLL, PML/RARA, and CBFB gene probes (Vysis, Downers Grove, IL, USA) demonstrated no abnormalities. After conferring a diagnosis of acute megakaryoblastic leukemia, chemotherapy with idarubicin and ara-C was administered and the patient showed pancytopenia. The patient was then treated with mitoxantrone and ara-C, and bone marrow examination was performed that showed severe hypocellular marrow and reactive increase of histiocytes and plasma cells. Despite the additional chemotherapy, the disease not go into remission and the patient died of septic shock 1 month after the diagnosis of leukemia had been made. A summary of the clinical course is shown in .
Fig. 1 (A) Peripheral blood smear showing blasts (57% of nucleated cells). (B) Bone marrow smear revealed many medium-sized myeloblasts (about 40.4% of all nucleated cells). (C) Dysplasic megakaryocyte. (D) PAS positivity (granular pattern). Wright-Giemsa stain, (more ...)
Giemsa-banded karyotype showing 46,XY,add(5)(q11.2),del(10)(p11.2), -17,der(18) t(17;18)(q11.2;q21),+i(12p).
Summary of the clinical data for the patient with acute megakaryoblastic leukemia and a primary mediastinal GCT