Differentials
Acute lymphoblastic leukemia (ALL)
SIGNS / SYMPTOMS
Clinically indistinguishable from AML.
INVESTIGATIONS
Bone marrow biopsy and aspirate, peripheral blood smear, and immunophenotyping can establish the diagnosis.
Blast cells in ALL are positive for terminal deoxynucleotidyl transferase (TdT) and lack staining for myeloperoxidase; also demonstrate presence of lymphoid markers.
Biphenotypic leukemia
SIGNS / SYMPTOMS
Clinically indistinguishable from AML.
INVESTIGATIONS
Expression of antigens representing both myeloid and lymphoid leukemia in the leukemic clone suggests biphenotypic leukemia.
The presence of the Philadelphia chromosome (BCR::ABL1 fusion gene) supports a diagnosis of biphenotypic leukemia, but does not exclude Philadelphia chromosome-positive AML.
Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes (MLNE)
SIGNS / SYMPTOMS
Blast phase MLNE may be clinically indistinguishable from AML.
Myelodysplastic syndrome (MDS)
SIGNS / SYMPTOMS
History of longstanding anemia and transfusion dependence.
INVESTIGATIONS
The distinction between high-risk MDS and AML is based on the numbers of blasts present. However, the estimation of blast counts can be difficult and is subjective. The blood film shows dysplasia in >10% of cells of any lineage, and the bone marrow may show ≤19% blasts.
Micromegakaryocytes and acquired Pelger-Huet (spectacle eye nucleus) neutrophils are specific for MDS. Associated chromosomal deletions or unbalanced chromosomal abnormalities, particularly of chromosomes 8, 7, and 5, are common. Complex cytogenetic changes may occur.
The presence of dysplasia may suggest that AML has evolved from MDS.
Chronic myeloid leukemia (CML) blast crisis
SIGNS / SYMPTOMS
There may be a history of preceding CML.
INVESTIGATIONS
Blood film may be indistinguishable from AML but may have an excess of basophils and eosinophils.
The presence of the Philadelphia chromosome (BCR::ABL1 fusion gene) supports a diagnosis of CML, but does not exclude Philadelphia chromosome-positive AML.
Typically no other karyotypic abnormalities are present.
Myelofibrosis
SIGNS / SYMPTOMS
Symptoms (constitutional, bleeding, infections) are less acute.
Moderate to massive splenomegaly is more common.
INVESTIGATIONS
Blood film shows teardrop red blood cells and a leukoerythroblastic film.
Bone marrow biopsy shows reticulin fibrosis.
Aplastic anemia
SIGNS / SYMPTOMS
May have history of medications that cause aplastic anemia, such as chloramphenicol and nonsteroidal anti-inflammatory drugs.
INVESTIGATIONS
A negative Coombs test suggests aplastic anemia.
Bone marrow biopsy and aspirate are hypocellular.
Low percentage of blast cells in peripheral blood (<10%). Precursors are morphologically normal.
Patients may have concurrent paroxysmal nocturnal hemoglobinuria clone and evidence of intravascular hemolysis (reticulocytosis, elevated serum lactate dehydrogenase, indirect bilirubin, decreased haptoglobin).
Drug-induced bone marrow failure
SIGNS / SYMPTOMS
History of using drugs that may cause pancytopenia (e.g., chloramphenicol, methotrexate, and chemotherapeutic agents).
Cessation of the implicated agent, or administration of an antidote (e.g., folic acid for methotrexate), reverses the pancytopenia.
INVESTIGATIONS
Bone marrow biopsy and aspirate will be hypocellular, and no excess of blasts are present.
Peripheral blood smear may be helpful.
Megaloblastic erythropoiesis is seen with methotrexate.
Bone marrow should be reassessed after drug cessation.
Leukemoid reaction
SIGNS / SYMPTOMS
Recent history of hematopoietic growth factor treatment may be present.
Appropriate treatment (i.e., stopping the growth factor) results in normalization of the blood count.
INVESTIGATIONS
Bone marrow biopsy and aspirate, and peripheral blood smear are helpful in differentiating diagnosis.
Bone marrow shows no excess of blasts, but does show mature hematopoietic cells. Increased macrophage activity and toxic granulation of myeloid cell series may be present, suggesting infections; Dohle bodies may also be seen in infections.
Vitamin B12 deficiency
SIGNS / SYMPTOMS
May have a family history consistent with pernicious anemia.
Paresthesia is an early symptom.
Glossitis and neurologic signs, such as cognitive impairment or subacute combined degeneration (ataxia, decreased vibration sense, muscle weakness, and hyporeflexia), occur with severe deficiency.
INVESTIGATIONS
Macrocytic anemia will be present unless there is an associated iron deficiency.
Peripheral blood smear shows megaloblastic changes.
Serum vitamin B12 levels are low.
Use of this content is subject to our disclaimer