Classification of Adult Acute Myeloid Leukemia
AML with multilineage dysplasia is characterized by 20% or more blasts in the blood or bone marrow and dysplasia in two or more myeloid cell lines, generally including megakaryocytes. To make the diagnosis, dysplasia must be present in 50% or more of the cells of at least two lineages and must be present in a pretreatment bone marrow specimen.[4,44] AML with multilineage dysplasia may occur de novo or following MDS or a myelodysplastic and myeloproliferative disorder (MDS and MPD). (Refer to the PDQ summaries on Myelodysplastic Syndromes Treatment and Myelodysplastic/ Myeloproliferative Neoplasms for more information.) The diagnostic terminology "AML with multilineage dysplasia evolving from a myelodysplastic syndrome" should be used when an MDS precedes AML.
This category of AML occurs primarily in older patients.[4,45] Patients with this type of AML frequently present with severe pancytopenia.
Common morphologic features include the following:
- Multilineage dysplasia in the blood or bone marrow.
- Dysplasia in 50% or more of the cells of two or more cell lines.
- Dysgranulopoiesis (neutrophils with hypogranular cytoplasm, hyposegmented nuclei or bizarrely segmented nuclei).
- Dyserythropoiesis (megaloblastic nuclei, karyorrhexis, or multinucleation of erythroid precursors and ringed sideroblasts).
- Dysmegakaryopoiesis (micromegakaryocytes and normal size or large megakaryocytes with monolobed or multiple separated nuclei).
The differential diagnosis of AML with multilineage dysplasia includes acute erythroid-myeloid leukemia and acute myeloblastic leukemia with maturation (FAB classifications M6a and M2). Some cases may overlap two morphologic types.
As evidenced in several Southwest Oncology Group studies, such as SWOG-8600 and NCT00023777, the numerous chromosome abnormalities observed in AML with multilineage dysplasia were similar to those found in MDS and frequently involved gain or loss of major segments of certain chromosomes, predominately chromosomes 5 and/or 7.[45,46,47,48] The probability of achieving a complete remission has been reported to be affected adversely by a diagnosis of AML with multilineage dysplasia.[45,46,47]
Acute Myeloid Leukemias and Myelodysplastic Syndromes, Therapy Related
This category includes AML and MDS that arise secondary to cytotoxic chemotherapy and/or radiation therapy. The therapy-related (or secondary) MDS are included because of their close clinicopathologic relationships to therapy-related AML. Although these therapy-related disorders are distinguished by the specific mutagenic agents involved, a recent study suggests this distinction may be difficult to make because of the frequent overlapping use of multiple potentially mutagenic agents in treating cancer.