Classification of Pediatric Myeloid Malignancies
WHO classification of AML
- AML with recurrent genetic abnormalities:
- AML with t(8;21)(q22;q22), RUNX1-RUNX1T1(CBFA/ETO).
- AML with inv(16)(p13;q22) or t(16;16)(p13;q22), CBFB-MYH11.
- Acute promyelocytic leukemia with t(15;17)(q22;q11-12), PML-RARA.
- AML with t(9;11)(p22;q23), MLLT3-MLL.
- AML with t(6;9)(p23;q34); DEK-NUP214.
- AML with inv(3)(q21;q26.2) or t(3;3)(q21;q26.2), RPN1-EVI1.
- AML (megakaryoblastic) with t(1;22)(p13;q13), RBM15-MKL1.
- AML with mutated NPM1.
- AML with mutated CEBPA.
- AML with myelodysplasia-related features.
- Therapy-related myeloid neoplasms.
- AML, not otherwise specified:
- AML with minimal differentiation.
- AML without maturation.
- AML with maturation.
- Acute myelomonocytic leukemia.
- Acute monoblastic and monocytic leukemia.
- Acute erythroid leukemia.
- Acute megakaryoblastic leukemia.
- Acute basophilic leukemia.
- Acute panmyelosis with myelofibrosis.
- Myeloid sarcoma.
- Myeloid proliferations related to Down syndrome:
- Transient abnormal myelopoiesis.
- Myeloid leukemia associated with Down syndrome.
- Blastic plasmacytoid dendritic cell neoplasm.
The treatment for children with AML differs significantly from that for ALL. As a consequence, it is crucial to distinguish AML from ALL. Special histochemical stains performed on bone marrow specimens of children with acute leukemia can be helpful to confirm their diagnosis. The stains most commonly used include myeloperoxidase, periodic acid-Schiff (PAS), Sudan Black B, and esterase. In most cases the staining pattern with these histochemical stains will distinguish AML from AMML and ALL (see below). This approach is being replaced by immunophenotyping using flow cytometry.
Table 1. Histochemical Staining Patterns
a These reactions are inhibited by fluoride.
|�||M0||AML, APL (M1-M3) ||AMML (M4)||AMoL (M5)||AEL (M6)||AMKL (M7)||ALL|
|Nonspecific esterases ||�||�||�||�||�||�||�|
|�||Alpha-naphthol acetate||-||-||+ a||+ a||-||� a||-|
|Sudan Black B||-||+||+||-||-||-||-|
The use of monoclonal antibodies to determine cell-surface antigens of AML cells is helpful to reinforce the histologic diagnosis. Various lineage-specific monoclonal antibodies that detect antigens on AML cells should be used at the time of initial diagnostic workup, along with a battery of lineage-specific T-lymphocyte and B-lymphocyte markers to help distinguish AML from ALL and bilineal (as defined above) or biphenotypic leukemias. The expression of various CD proteins that are relatively lineage-specific for AML include CD33, CD13, CD14, CDw41 (or platelet antiglycoprotein IIb/IIIa), CD15, CD11B, CD36, and antiglycophorin A. Lineage-associated B-lymphocytic antigens CD10, CD19, CD20, CD22, and CD24 may be present in 10% to 20% of AMLs, but monoclonal surface immunoglobulin and cytoplasmic immunoglobulin heavy chains are usually absent; similarly, CD2, CD3, CD5, and CD7 lineage-associated T-lymphocytic antigens are present in 20% to 40% of AMLs.[13,14,15] The aberrant expression of lymphoid-associated antigens by AML cells is relatively common but generally has no prognostic significance.[13,14]
Immunophenotyping can also be helpful in distinguishing some FAB subtypes of AML. Testing for the presence of HLA-DR can be helpful in identifying APL. Overall, HLA-DR is expressed on 75% to 80% of AMLs but rarely expressed on APL. In addition, APL cases with PML/RARA were noted to express CD34/CD15 and demonstrate a heterogenous pattern of CD13 expression. Testing for the presence of glycoprotein Ib, glycoprotein IIb/IIIa, or Factor VIII antigen expression is helpful in making the diagnosis of M7 (megakaryocytic leukemia). Glycophorin expression is helpful in making the diagnosis of M6 (erythroid leukemia).