Classification of Adult Acute Myeloid Leukemia
Morphologic and cytochemical features of acute monoblastic leukemia include the following:
- Large basophilic monoblasts with abundant cytoplasm, pseudopod formation, round nuclei, and one or more prominent nucleoli.
- Rare Auer rods.
- Typically intensely NSE positive and MPO negative.
- Hypercellular marrow with large numbers of monoblasts.
- Lysozyme positive.
Morphologic and cytochemical features of acute monocytic leukemia include the following:
- Promonocytes with an irregular nuclear configuration with a moderately basophilic cytoplasm and cytoplasmic azurophilic granules.
- Typically intensely NSE positive.
- Occasional MPO positivity.
- Lysozyme positive.
- Hemophagocytosis (erythrophagocytosis).
The extramedullary lesions of these leukemias may be predominantly monoblastic or monocytic or an admixture of the two cell types. Immunophenotyping of these leukemias may reveal expression of the myeloid antigens CD13, CD33, CD117, CD14 ( + ), CD4, CD36, CD 11b, CD11c, CD64, and CD68. The differential diagnosis of acute monoblastic leukemia includes AML without maturation, minimally differentiated AML, and acute megakaryoblastic leukemia. The differential diagnosis of acute monocytic leukemia includes AMML and microgranular APL.
An abnormal karyotype has been observed in approximately 75% of cases of acute monoblastic leukemia while approximately 30% of cases of acute monocytic leukemia are associated with an abnormal karyotype. Almost 30% of cases of acute monoblastic leukemia and 12% of cases of acute monocytic leukemia are associated with 11q23 genetic abnormalities involving the MLL gene. (Refer to the Acute myeloid leukemia with characteristic genetic abnormalities section of the Classification section of this summary.) Mutation of FLT3, a receptor tyrosine kinase gene, has been observed in about 30% of cases of acute monocytic leukemia (approximately 7% in acute monoblastic leukemia). The translocation t(8;16)(p11; p13) (strongly associated with acute monocytic leukemia, hemophagocytosis by leukemic cells, and a poor response to chemotherapy) fuses the MOZ gene (8p11) with the CBP gene (16p13). Median actuarial disease-free survival for acute monocytic leukemia has been reported to be approximately 21 months.
Acute erythroid leukemias (FAB classifications M6a and M6b)
The two subtypes of the acute erythroid leukemias, erythroleukemia and pure erythroid leukemia, are characterized by a predominant erythroid population and, in the case of erythroleukemia, the presence of a significant myeloid component. Erythroleukemia (erythroid/myeloid; M6a) is predominantly a disease of adults, comprising approximately 5% to 6% of cases of AML. Pure erythroid leukemia (M6b) is rare and occurs in all age groups. Occasional cases of chronic myeloid leukemia (CML) may evolve to one of the acute erythroid leukemias. Erythroleukemia may present de novo or evolve from an MDS, either RAEB or RCMD-RS or RCMD. (Refer to the PDQ summary on Myelodysplastic Syndromes Treatment for more information.) The clinical features of these acute leukemias include profound anemia and normoblastemia. (For information on anemia, refer to the PDQ summary on Fatigue.)
Morphologic and cytochemical features of erythroleukemia include the following:
- 50% or more erythroid precursors in the entire nucleated cell population of the bone marrow.
- 20% or more myeloblasts in the nonerythroid population in the bone marrow.
- Dysplastic erythroid precursors with megaloblastoid nuclei.
- Multinucleated erythroid cells.
- Myeloblasts of medium size, occasionally with Auer rods.
- Ringed sideroblasts.
- Positive PAS stain in the erythroid precursors.
- Hypercellular bone marrow.
- Megakaryocytic dysplasia.