eMedicine Specialties > Hematology > Stem Cells and Disorders

Erythroleukemia: Differential Diagnoses & Workup

Author: Beata Holkova, MD, Oncology Fellow, NIH/NCI, National Cancer Institute
Coauthor(s): Kenichi Takeshita, MD, Adjunct Associate Professor, Department of Medicine, Division of Hematology, New York University School of Medicine; Medical Director, Clinical Research and Development, Celgene; Asher A Chanan-Khan, MD, Assistant Professor, Department of Medicine, Division of Lymphoma and Bone Marrow Transplantation, Roswell Park Cancer Institute, State University of New York at Buffalo
Contributor Information and Disclosures

Updated: Nov 4, 2009

Differential Diagnoses

Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Pernicious Anemia

Other Problems to Be Considered

Erythropoietin therapy (may induce increased erythroblasts in bone marrow and, in some situations, may complicate the interpretation of bone marrow morphology)

Workup

Laboratory Studies

• Complete blood cell count
  • Most patients present with pancytopenia.
  • The WBC count can range from 1000-100,000/mm³.
  • Anemia may be mild.
• Peripheral blood smear: Findings may vary and include blasts (may not be present in as many as 50% of cases), macrocytosis, nucleated erythrocytes, schistocytes, and thrombocytopenia.
• Obtain a chemistry profile, liver function tests, and serum electrolytes to assess organ dysfunction resulting from leukemic infiltration. Elevated lactate dehydrogenase (LDH) and uric acid levels may be present.
• Blood and urine cultures should be obtained in patients with fever or signs of infection.
• Rheumatoid factor, antinuclear antibody, Coombs test, and immunoglobulins should be evaluated. Autoantibodies and hypergammaglobulinemia have been reported in patients with erythroleukemia who have joint or bone pain.
• Vitamin B-12 and folate levels should be measured because severe pernicious anemia sometimes mimics acute erythroleukemia.
• For details of the bone marrow examination, see Procedures.
• Flow cytometry
  • As a result of the multilineage nature of erythroleukemia, the leukemic cells often express both erythroid and myeloid markers. They are often positive for myeloid markers, such as CD117, CD13, CD33, and MOP, while the expression of HLA-DR and CD34 is often decreased or absent. The megakaryocytes antigens CD41 and CD61 can be positive in some cases.
  • Erythroid markers such as glycophorin A and transferrin receptor (CD71 and CD45) may be increased, but they are negative in many patients with erythroleukemia. Therefore, while the expression of glycophorin A and/or transferrin receptor may be helpful, the absence of erythroid antigens does not exclude erythroleukemia.
• Cytogenetics
  • The assessment of chromosomal abnormalities in patients with erythroleukemia is critical in the diagnosis and prognosis of disease. Multiple chromosomal abnormalities have been described, but none of them is specific for M6 AML.
  • Results from many studies demonstrate that certain chromosomal abnormalities are associated with different prognoses in all AMLs, including acute erythroleukemia, as follows:
    • Prognosis is favorable with t(8;21), inv16/t(16;16), and +14.
    • Prognosis is unfavorable with -5/5q, -7/7q-, inv3, 11q, 17p, del20q, +13, t(9;22), or more than 2 cytogenetic abnormalities.
    • Prognosis is intermediate with normal karyotype and all other cytogenetic abnormalities.

Imaging Studies

• Echocardiogram or multiple-gated acquisition (MUGA) scan is used to evaluate cardiac function prior to chemotherapy (chemotherapy regimens contain cardiotoxic drugs).
• Normal findings on chest radiograph help exclude potentially complicating factors such as pulmonary infection, cardiomegaly, pulmonary vascular congestion, or pleural effusion.
• Noncontrast CT scan of the head can be used to rule out CNS bleed.
• Perform a CT scan or MRI if neurologic signs are present (fifth and seventh cranial nerves are most commonly involved). The affected cranial nerve may show thickening of the nerve sheath. This can occur even in the absence of CNS involvement.

Other Tests

• P-glycoprotein (product of MDR1 gene)
  • This test should be considered in patients who do not respond to induction chemotherapy.
  • P-glycoprotein (Pgp) can be measured by (1) immunohistochemistry (low sensitivity) or (2) flow cytometry with MRK16 or U1C1 antibodies (specific).

Procedures

• Bone marrow aspiration and biopsy are critical in making the diagnosis of acute erythroleukemia.
  • Bone marrow smears from aspirate and touch preparations from biopsy should be stained with Wright-Giemsa and other histochemical stains.
  • The FAB classification used since 1985 is based on cell morphology to identify the lineage of the blasts, the degree of differentiation, the number of blasts (quantification), and cytochemistry. This classification does not include cytogenetics. Erythroleukemia is required to have both erythroblastic and myeloblastic components. The assessment of a bone marrow specimen is based on a 500-cell count.
  • FAB criteria require (1) a 50% or more erythroid component in all nucleated cells and (2) at least one of the following: 30% or more nonerythroid blasts, excluding erythroblasts, or less than 30% blasts in all nucleated cells. Nonerythroid blast cells are blast I (ie, myeloblast with no cytoplasmic granules, distinct nucleoli) or blast II (ie, granules, centrally placed nucleus) and monoblast.
  • The World Health Organization (WHO) proposed a new subclassification that recognizes 2 subtypes of acute erythroid leukemia⁴ :
    • Erythroleukemia is 50% or more erythroid precursors in the nucleated cells population and 20% or more nonerythroid elements (ie, myeloblasts I, myeloblasts II, monoblasts).
    • In pure erythroid leukemia, the erythroid component seems to be singularly involved. The erythroid component is 80% or more of bone marrow. The myeloblast count is usually less than 30%, and distinguishing the myeloblasts from primitive erythroblasts is difficult. For this reason, Auer rods are never observed in this subtype.
• Severe pernicious anemia manifesting with pancytopenia can occasionally mimic erythroleukemia on bone marrow morphology. In such instances, waiting for the results of a complete workup, including cytogenetics and flow cytometry, before initiating treatment is recommended. B-12 and folate levels should similarly be reviewed prior to treatment.
• Periodic acid-Schiff (PAS) stain findings are usually positive in erythroblasts and abnormal erythroid precursors and negative in normal erythroid precursors of all stages of maturation.
• Lumbar puncture
  • Lumbar puncture (LP) is performed if CNS or meningeal signs are present. LP usually reveals an elevated opening pressure, increased protein, and a low glucose level in the cerebrospinal fluid. If circulating blasts are present at the time of LP, intrathecal chemotherapy should be administered.
  • LP is also suggested for patients who are asymptomatic but have circulating leukemic cell counts of higher than 50,000/mm³ or an elevated LDH level.

Histologic Findings

See FAB classification, flow cytometry, and cytogenetics, under Procedures.

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