Myeloperoxidase deficiency

Acute erythroid leukemias are acute myeloid leukemias that are characterized by a predominant erythroid proliferation. According to the recent World Health Organization classification,1 acute erythroid leukemias are divided into erythroleukemia and pure erythroid leukemia, based on the presence or absence of a significant myeloid component. Pure erythroid leukemia represents a neoplastic proliferation of immature cells committed exclusively to the erythroid lineage with no evidence of a significant myeloblastic component. Pure erythroid leukemia is extremely rare and is frequently associated with complex cytogenetic abnormalities. This article describes a rare case of pure erythroid leukemia in a 51-year-old man with no evidence of cytogenetic abnormality.

The patient presented to his physician in late June 2002 with fatigue. Laboratory studies showed pancytopenia with a white blood cell count of 3500/µL, hemoglobin level of 7.0 g/dL, and platelet count of 1.04 × 10^sup 5^/µL. No circulating blasts were identified. Subsequently, bone marrow aspirate smear showed numerous erythroblasts with intermediate-sized to large, round nuclei; fine chromatin; and 1 or more prominent, inclusion-like nucleoli (Figure, A). The cytoplasm was deeply basophilic and contained poorly demarcated vacuoles, which showed characteristic intense, globular periodic acid-Schiff positivity (Figure, A [inset]). The blasts were negative for myeloperoxidase and Sudan black B by cytochemistry. Immunophenotypic analysis by flow cytometry demonstrated the blast population was positive for CD34 with a subset expression of glycophorin A and CD41, but was totally negative for myeloid antigens CD13 or CD33. Bone marrow core biopsy showed a sheet of blasts with fine chromatin and prominent nucleoli, as well as occasional multinucleate giant cells (Figure, B). Immunohistochemistry demonstrated that the blasts were weakly positive for CD34 and CD117 and were focally positive for hemoglobulin A. The blasts were completely negative for myeloperoxidase (Figure, B [inset]). The diagnosis of acute myeloid leukemia consistent with pure erythroid leukemia was made. The patient received several cycles of chemotherapy and achieved partial remission before undergoing allogeneic bone marrow transplantation, but failed with early relapse. No cytogenetic abnormalities, including FLT3 length mutation, were demonstrated on initial or relapsed bone marrow specimens.

Erythroleukemia (acute myeloid leukemia, FrenchAmerican-British category M6 [AML-FAB M6]) is predominantly a disease of adults and comprises approximately 5% to 6% of cases of acute myeloid leukemia.1 Pure erythroid leukemia was originally termed erythremic myelosis and lately has been termed AML-FABM6b, and is extremely rare (3% of acute erythroid leukemia cases).2 It can occur at any age, including childhood.

Morphologically, pure erythroid leukemia is usually characterized by the presence of medium-sized to large erythroblasts with deeply basophilic, often agranular cytoplasm with poorly demarcated vacuoles, round nuclei, fine chromatin, and 1 or more nucleoli. Immunophenotypic features of pure erythroid leukemia are dependent on the differential stage of the erythroblasts.1,3 The expression of glycophorin A and hemoglobin A, and the absence of myeloperoxidase and other myeloid markers (CD13, CD33), can be detected in the most differentiated forms. The blasts are often negative or weakly positive for CD34 and HLA-DR. The more immature forms are usually negative for glycophorin A, or it is only weakly expressed in a minority of blasts. Antigens associated with megakaryocytes (CD41 and CD61) are typically negative but may be partially expressed in some cases.1 Cytogenetically, no specific chromosome abnormality has been described in this type of acute myeloid leukemia. However, complex karyotypes with multiple structural abnormalities are common, with chromosomes 5 and 7 being affected most frequently.1,4

One of the most important differential diagnoses of pure erythroid leukemia is reactive erythroid hyperplasia, such as vitamin B^sub 12^ or folate deficiency, which can display profound left-shifted erythroid hyperplasia. Other entities in the differential diagnosis may include other types of acute myeloid leukemia, as well as acute lymphoblastic leukemia and lymphoma. Cytochemical and immunophenotypic analyses can be helpful in distinguishing these entities from pure erythroid leukemia. Pure erythroid leukemia is usually associated with a more aggressive clinical course and higher relapse rate, despite extensive chemotherapy or bone marrow transplantation.

References

1. Bruning RD, Bennett J, Matutes E, et al. Acute myeloid leukemia not otherwise categorised. In: Jaffe ES, Harris NL, Stein H, eds. Pathology and Genetics: Tumors oi Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001: 91-105. WHO Classification of Tumors.

2. Domingo-Claros A, Larriba I, Rozman M, et al. Acute erythroid neoplastic proliferations: a biological study based on 62 patients. Haematologica. 2002;87: 148-153.

3. Garand R, Duchayne E, Blanchard D, et al. Minimally differentiated erythroleukemia (AML M6 'Variant'1: a rare subset of AML distinct from AML M6. Croupe Francais d'Hematologie Cellulaire. Br I Haematol. 1995;90:868-875.

4. Olopade OI, Thangavelu M, Larson RA, et al. Clinical, morphologic, and cytogenetic characteristics of 26 patients with acute erythroblastic leukemia. Blood. 1992:80:2873-2882.

Qin Huang, MD, PhD

Accepted for publication September 11, 2003.

From the Division of Pathology, City of Hope National Medical Center, Duarte, Calif.

Reprints: Qin Huang, MD, PhD, Division of Pathology, City of Hope National Medical Center, Duarte, CA 91010 (e-mail: qhuang@coh.org).

Copyright College of American Pathologists Feb 2004
Provided by ProQuest Information and Learning Company. All rights Reserved