Submitting Author: Sun, Tsieh, MD
Institution: University of Texas MD Anderson Cancer Center
Session: Erythroleukemia and megakaryoblastic AML and mimics

A 71-year-old man was admitted for fever and chills with altered mental status. He was diagnosed with seminoma, underwent chemotherapy and had a complete remission in 2006. On 3/21/12, he was found to have anemia and thrombocytopenia. A bone marrow biopsy showed trilineage dysplasia with 9% blasts and was diagnosed as myelodysplastic syndrome (refractory anemia with excess blasts-1), therapy-related. Cytogenetic study demonstrated a complex karyotype but a study panel of 9 genes showed no abnormalities. A subsequent bone marrow biopsy on 6/26/12 revealed persistent myelodysplastic syndrome with 19% blasts. A complex karyotype was again detected. The current admission was on 8/13/12 and the peripheral blood showed anemia (hemoglobin 10.2 g/dL), thrombocytopenia (platelets 2,000/uL) and 4% blasts. A bone marrow biopsy revealed 78% pronormoblasts, 9% normoblasts and 4% myeloblasts. The patient’s condition deteriorated rapidly and he expired 3 days after the biopsy.

Histologic sections of formalin-fixed, paraffin-embedded bone marrow tissue show 90% cellularity with sheets of erythroid cells of various stages, but most cells are immature normoblasts with round nuclei, fine chromatin pattern and 1-2 prominent nucleoli. Myeloid cells are markedly decreased and only rare megakaryocytes are present. The aspirate smears and touch imprint demonstrate 78% pronormoblasts, 9% normoblasts and 4% myeloblasts. The pronormoblasts are pleomorphic with variable size and shape. The nuclei are round with a delicate chromatin pattern and a few nucleoli. Rare binucleated and multinucleated cells are present. The cytoplasm of pronormoblasts is basophilic with many vacuoles and some cells have irregular cell border. Only 1% metamyelocytes, 3% granulocytes and 2% monocytes are present.

Immunohistochemical studies show that the immature cells are positive for Ecadherin, CD117 and glycophorin A, but glycophorin A stains mainly mature erythroid cells. There are approximately 2% CD34 positive cells demonstrated. MPO stains mature myeloid cells. Placenta leukocyte alkaline phosphatase (PLAP) stain is negative for the presence of metastatic seminoma.

Cytochemical studies reveal that the PAS stain is positive in erythroid cells with a globular pattern. The MPO stain is negative for the blasts.

Flow cytometry demonstrates no increase in blasts, as identified by CD34 staining or CD45 vs SC analysis.

42~47,Y,add(x)(q13),add(1)(p13),add(1)(q20),-3,ins(3;7)(p25;?),add(4)(q55),5,add(7)(p15),-6,-9,-10,del(13)(q12q22),-14,add(15)(p11.2)x2,-16,-17,-18,-19,add(19)(q13.3),+1~2r,+2~11mar[cp14]

PCR analysis shows no mutation in JAK2, FLT3, KRAS, NRAS, NPM1, CEBPA, IDH1, IDH2 and KIT.

FISH analysis reveals no del(5q).

This is an interesting case to demonstrate the sequential development from a seminoma to therapy-related myelodysplatic syndrome (MDS) and finally the rapid transformation from MDS to pure erythroid leukemia (PEL) in 5 months. PEL is a rare entity comprising <1% of all cases of acute myeloid leukemia (AML). It usually carries a poor prognosis and is often associated with unfavorable karyotypes. Therefore, it is interesting to see that none of the 9 genes studied in this case show abnormalities. Class 1 mutations, including FLT3, KIT, RAS and JAK2, are usually associated with poor prognosis in AML cases. However, in a recent study in MD Anderson Cancer Center, AML cases with erythroid predominance, including acute erythroid/myeloid leukemia, are associated with lower frequency of mutation involving NPM1, NRAS and FLT3, as compared with AML without erythroid predominance. Nevertheless, no study has been done on the frequency of gene mutation in PEL cases. It may be of value to explore whether there is discordance between karyotypic abnormalities and gene mutation in PEL cases and the mechanism of this discordance through a large-scale study.

Pure erythroid leukemia arising from myelodysplastic syndrome, therapy-related vs acute myeloid leukemia, myelodysplasia-related changes

The patient had history of seminoma. The t-MDS was associated with a very complex karyotype, bone marrow of t-MDS showed 9% blasts which then increased to 19% blasts. The t-MDS was not erythroid predominant. The patient was treated with clofarabine plus decitabine. However, 5 months later, disease progressed to pure erythroid leukemia with only 2% CD34+ cells. The patient died 3 days later.

Progression of therapy-related myelodysplastic syndrome to acute erythroid leukemia (pure erythroid leukemia)

Case 47