Submitting Author: Jaso, Jesse Manuel, MD
Institution: University of Texas MD Anderson Cancer Center
Additional authors:Sa A. Wang, M.D.
Session: Erythroleukemia and megakaryoblastic AML and mimics

The patient is a 45-year-old male with a past medical history of Myelodysplastic Syndrome with isolated del(5q) who was treated with lenalidomide. He achieved complete morphologic and cytogenetic response, which was maintained for approximately 6 years. He then began to develop worsening cytopenias and weight loss. A bone marrow sample was obtained as part of the patient’s routine follow-up.

Bone marrow aspirate from the right posterior iliac crest was obtained using standard techniques. A bone marrow biopsy was not obtained. The clot section was fixed in formalin and stained with hematoxylin and eosin. The aspirate smears were air-dried and stained with Wright-Giemsa.

The peripheral blood showed pancytopenia with left shifted granulocytes and circulating nRBC’s:

WBC: 1.3, HGB: 7.7, MCV: 75, Platelet: 33, Neutrophils: 46.0, Lymphs: 36.0, Monos: 8.0, Eos: 6.0, Basos: 3.0, Metas: 1.0 NRBC: 2.0

The bone marrow aspirate was predominantly composed of left-shifted, dysplastic erythroid cells containing vacuolated cytoplasm, nuclear membrane irregularities, and occasional megaloblastoid, binucleated forms. The granulocyte lineage was severely decreased, showed left-shifted maturation and marked dysplasia (hypolobation and hypogranularity). The megakaryocytes were decreased and were composed of dysplastic, monolobated forms.

Cytochemical stain for myeloperoxidase (MPO) was negative in the blasts. A periodic acid-Schiff (PAS) stain showed marked granular and globular staining in the cytoplasm of the dysplastic erythroids.

Blasts 20 % H (0-5)

Progranulocytes 0 % L (2-8)

Myelocytes 1 % L (5-20)

Metamyelocytes 1 % L (13-32)

Granulocytes 11 % (7-30)

Eosinophils 3 % (0-4)

Basophils 1 % (0-1)

Lymphocytes 12 % (3-17)

Plasma cells 2 % (0-2)

Monocytes 0 % (0-5)

Reticulum Cells 0 % (0-2)

Pronormoblasts 0 % L (1-8)

Normoblasts 50 % H (7-32)

M:E Ratio 0.3 L (3-4)

The bone marrow clot section showed 50-60% cellularity with decreased, small, hypolobated megakaryocytes and sheets of immature cells.

Immunohistochemical stains on the bone marrow clot showed that the immature cells were positive for Glycophorin A, E-Cadherin, and CD117. The immature cells were negative for CD34 and CD61.

Flow cytometry was not performed on the specimen.

Conventional cytogenetics showed an extremely complex karyotype:

Hyperdiploid clones

47,XY,del(5)(q13q33),-13,der(15;?)(q10;?),del(18)(q12),add(19)(p13.3),

del(22)(q12),+2mar[7]

2 metaphases photographed/karyotyped

47,XY,del(5)(q13q33),-13,der(15;?)(q10;?),del(18)(q12),add(19)(p13.3),

del(22)(q12),+r,+mar[6]

2 metaphases photographed/karyotyped

48,XY,del(5)(q13q33),-13,der(15;?)(q10;?),del(18)(q12),add(19)(p13.3),

del(22)(q12),+r,+2mar[5]

2 metaphases photographed/karyotyped

Hyperdiploid metaphases

48,XY,dup(3)(q13.3q29),del(5)(q13q33),-13,der(15;?)(q10;?),del(18)(q12),

add(19)(p13.3),del(22)(q12),+2mar[cp2]

2 metaphases photographed/karyotyped

Fluorescence In Situ Hybridization (FISH) was positive for a clone with del(5q) and negative for monosomy 7 or del(7q).

Molecular analysis was not performed on this specimen.

After the bone marrow, the patient was treated with induction chemotherapy, achieved complete remission, and eventually received a stem cell transplant. However, the patient was later re-admitted with multi-organ failure and expired approximately 6 months after diagnosis.

This case meets the morphologic criteria for Pure Erythroid Leukemia. However, based on the most recent WHO 2008 classification, this case would be assigned to the category “Acute Myeloid Leukemia with Myelodysplasia-related changes” (AML-MRC).

A recent study reported several similar cases that met the morphologic criteria for Pure Erythroid Leukemia. Several of these cases arose from pre-existing myelodysplastic syndromes and had complex karyotypes. Similarly, these cases would be classified as AML-MRC based on WHO 2008 criteria. However, the authors showed that these cases had worse overall survival compared to cases of AML-MRC that did not meet the morphologic criteria of Pure Erythroid Leukemia (1). Other authors have described cases meeting the morphologic criteria for Pure Erythroid Leukemia arising from MDS and MPN as well as therapy-related cases.

Given the sudden and dismal clinical course, this case highlights the prognostic impact of morphology in AML-MRC and argues for the continued designation of such cases as Pure Erythroid Leukemia rather than simply AML-MRC.

(1) Liu W, Hasserjian RP, Hu Y, Zhang L, Miranda RN, Medeiros LJ, Wang SA. Pure erythroid leukemia: a reassessment of the entity using the 2008 World Health Organization classification. Mod Pathol. 2011 Mar;24(3):375-83.

PURE ERYTHROID LEUKEMIA ARISING FROM PRE-EXISTING MYELODYSPLASTIC SYNDROME WITH DEL(5Q),

Patient received induction chemotherapy and achieved complete remission, followed by stem cell transplant. Disease recurred in 2 months, and patient died. Total 5 months of survival after diagnosis.

Myelodysplastic syndrome with isolated del(5q), with progression to acute leukemia (pure erythroid leukemia)

Case 404