Institution: VAMHCS
Additional authors:Harold Evans, MD, MBA, Qing Chen, MD, PHD
Session: Erythroleukemia and megakaryoblastic AML and mimics
HISTORY
The patient is a forty-eight year old male who presented to the University of Maryland Greenebaum Cancer Center with severe pancytopenia. A bone marrow examination was performed at outside hospital showed an aplastic marrow (<5% cellularity). A diagnosis of aplastic anemia was issued. However, review of the material showed a small fragment of marrow in the clot section that appeared to have a predominance of erythroid cells and possibly increased immature precursors, suggesting a patchy distribution of marrow cellularity and prompting a second bone marrow examination at the University of Maryland Greenebaum Cancer Center.
Upon further questioning, it was found that the patient had papillary thyroid carcinoma 10 years previously and treatment had consisted of thyroidectomy and three doses of radioactive iodine.DETAILS
The second marrow examination from right posterior iliac crest showed cellular aspirate smear, with more than 50% erythroid cells and ~15% blasts. Maturing granulocytes and megakaryocytes were extremely rare. The biopsy specimen was fixed in formalin and H&E slides from paraffin embedded block showed small but cellular (50% cellularity) bone marrow biopsy, with a predominance of erythroid precursors and increased number of blasts (10-12%).
IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Flow cytometric analysis identified a population of myeloblasts, representing 27% of the total events, expressing of CD13, CD15, CD33, CD34, CD117 and HLA-DR, with terminal deoxytransferase (TdT) expression in a subset of cells.
CYTOGENETIC FINDINGS
Cytogenetic analysis was performed on metaphase cells from the bone marrow aspirate using standard methods. Twenty metaphase cells from two cultures were analyzed at the 400 band level. Ten cells had a normal male karyotype, 46,XY, and the other ten cells had an abnormal karyotype, 46,XY,der(18)t(11;18)(q13;q21.1), with an unbalanced 11;18 translocation leading to partial gain of 11q and partial loss of 18q. Fluorescence in situ hybridization (FISH) was performed with a probe for the MLL gene at 11q23 to confirm the gain of 11q demonstrated by karyotype analysis. The probe detected three copies of MLL in 78 of 200 cells (39%).
INTERESTING FEATURES
While an increased incidence of chronic myelogenous leukemia has been documented following radioactive iodine exposure, acute leukemia in this setting has been less frequently seen. Moreover, to our knowledge, the chromosome abnormality present in our patient has not been previously reported.
PROPOSED DIAGNOSIS
A diagnosis of acute erythroid leukemia, erythroid/myeloid or FAB M6b was established. Given the history, this leukemia could be classified as t-AML.
CONSENSUS GROUP: ADDITIONAL INFORMATION/STUDIES
Patient received 7+3 induction chemotherapy and 1 cycle high-dose ara-C consolidation. Day 14 bone marrow was chemoablated and day 55 bone marrow was normocellular with no evidence of leukemia. FLT3 and NPM1 mutations were not detected.
CONSENSUS DIAGNOSIS
Erythroid predominant myeloid neoplasm (10-12% blasts):
Acute erythroid leukemia, erythroid/myeloid (WHO classification) versus refractory anemia with excess blasts-2, RAEB-2; possibly therapy related