University of Virginia Health System

Acute Erythroid Leukemia
(M6 AML, erythroleukemia, erythemic myelosis, diGuglielmo's syndrome)

(a) M6 acute leukemia- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

(b) M6b AML- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

(c) M6b AML- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

(d) M6b AML- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

(e) M6b AML- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

(f) M6 acute leukemia with PAS positivity- Bone Marrow Aspirate Smear, Wright-Giemsa stain, 1000x

(g) M6a AML- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

(h) M6a AML- Bone marrow aspirate smear, PAS stain, 1000x

(i) M6a AML- Bone marrow aspirate smear, PAS stain, 1000x

(j) M6 acute leukemia with ringed sideroblasts- Bone Marrow Aspirate Smear, Iron stain (Prussian blue stain), 1000x

Description:
This subset represents up to 5% of all cases of AMLs. The predominant cells are dysplastic proerythroblasts that are very heterogenous in size and shape, including the presence of bizarre and giant forms (a-d). Both megaloblastic and dysplastic nuclear features are prominant, including multilobated nuclei with frequent Howell-Jolly bodies (e). The lag in nuclear maturation as compared with cytoplasmic maturation is marked, similar to the picture seen in megaloblastic anemia due to either folate or B-12 deficiencies. Unlike the megaloblastic anemias, giant bands and metamyelocytes usually are not seen. Cytoplasmic vacuoles may be prominent (g) and are periodic acid-Schiff (PAS) positive (h-i). On an iron stain ring sideroblasts are frequently seen (j). An association with mediastinal germ cell tumor in young males has been observed.

A myeloblastic component is frequently present, and there is a tendency to transform to either an M1, M2, or M4 subtype with time. In many instances, the M6 subtype is a phase in the leukemic transformation of myelodysplastic syndromes. Because of these features, the diagnosis can be difficult. If there is a picture of maturation arrest in the erythroid lineage with the predominant cell being megaloblastic and dysplastic proerythroblasts (>20% of nucleated cells on a bone marrow aspirate differential), then the diagnosis should be M6 AML even though there are increased numbers of myeloblasts. In the FAB classification, because of the frequent occurrence of myelodysplasia in M6 AML, such a case would be designated as MDS with transformation to overt acute leukemia, M6 subtype. If the percentage of proerythroblasts were less than 21%, the case would be designated refractory anemia with excess blasts (RAEB). If the percentage of blasts were between 21-30%, the case would be referred to as refractory anemia with excess blasts in transformation (RAEB-t). In the WHO Classification which does not recognize the RAEB-t subset, and in order to deal with the pure erythroleukemia versus those cases with a myeloblastic component, the term M6a is used to designate those with a mix of proerythroblasts and myeloblasts (a), and M6b for those with only proerythroblasts (pure erythroid leukemia) (b-e).

Cytochemistry:

The myeloperoxidase (MPO), Sudan black B, and nonspecific esterase (NSE) stains are negative in the proerythroblasts. The myeloblastic elements may be MPO, Sudan black B or NSE positive depending on the subtype of myeloblastic leukemia present. The periodic acid-Schiff (PAS) stain frequently shows large PAS positive cytoplasmic granules in the erythroblastic elements (h-i).

Immunophenotype:

• Stem cell and hematopoietic progenitor cell markers- CD34-, HLA-DR-
• Erythroid lineage markers- The erythroid cells ae positive for glycoforin A
• Myeloid lineage markers- The myeloblasts are variably positive for CD13, CD33, and CD117.
• Monocytic lineage markers- Depending on the number of monolytic elements present, CD14, CD11b and 11a, CD4, and CD64 are variably positive.

Cytogenetics:

No signature cytogenetic abnormality has been identified in this subtype. Complex abnormalities, usually involving chromosomes 5 and 7 are most common, similar to those seen in the myelodysplastic syndromes.

Prognosis:

Very poor.

General References:

• Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. Pathology and genetics of tumors of hematopoietic and lymphoid tissues. Vol. 3 of World Health Organization classification of tumors, Lyon, France: IARC Press, 2001
• Kowal-Vern A, Abraham JR, Brunetto VL, et al: Diagnosis and characterization of acute erythroleukemia subsets by determining the percentage of myeloblasts and proerythroblasts in 69 cases. Am J Haematol 65:5, 2000
• Dameskek W, Baldini M: The diGuglielmo syndrome. Blood 13:192, 1958

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