Acute Erythroblastic leukemia (M6)

Definition

Erythroleukemia (or "acute Di Guglielmo syndrome") is a rare form of acute myeloid leukemia (AML) where the myeloproliferation is of erythrocyte precursors. It is defined at type "M6" under the FAB classification. M6 or erythroleukemia is rare and difficult to diagnose. More than 30-50% of the nucleated marrow cells are abnormal nucleated red blood cells.

Sample Cases

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Epidemiology

Erythroleukemia is predominantly a disease of adults. It comprises 5-6% of cases of AML. Pure erythroid leukemiais extremely rare and can occur at any age. Occasional cases of CML will transform in to AML-M6.

Possible causes

The cause is unknown.

Morphology

The leukemic red cells are frequently bizarre with extreme dysplastic features including: giant forms, multinucleation, cytoplasmic vacuolization, cytoplasmic buds, and megaloblastoid changes.  Cytoplasmic pseudopods similar to those in megakaryocytic leukemia (M7) may be present. Nuclei are round or irregular with lobulation and multinucleation.   

Example morphology of M6 blasts	Example morphology of M6 blasts	Example morphology of M6 blasts

Immunophenotyping

Using the CD45 vs SSC gating dot plot, AML-M6 blasts will be CD45 negative (green).  Lymphoblasts, megakaryoblasts and plasma cells will also fall in this region and need to be excluded.                         

CD45 vs SSC dot plot from a case of AML-M6

Below are selected dot plot examples of a AML-M6 case:          

HLA DR, CD13, CD19 and CD5 are not expressed	CD34, CD117, CD61 and CD62p are not expressed.	Bright CD38 is not present. Glycophorin A and CD71 are expressed in this case.

Other relevant tests

Cytochemistry: The blasts are MPO negative, but often positive for NSE. The malignant red cells are PAS positive, (forming PAS positive lakes or containing coarse chunks of PAS positive material).

Genetics: Chromosome Abnormalities: 8+, -5, del(5q), and -7.                     

Sub-classification

WHO recognizes two subtypes of AML-M6: erythroleukemia (erythroid/myeloid leukemia) and pure erythroid leukemia. Erythroleukemia is defined by > 50% erythroid precursors and > 20% myeloblasts.  Pure erythroid leukemia is defined by > 80% erythroid precursors.                            

Flow Diagnosis

Erythroblasts are positive for Glycophorin A (GPHA) and CD71. The erythroid component lacks MPO, CD34, CD45 and pan myeloid markers. CD117 and CD43 are often positive, when myeloblasts are present. 

References

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