Final Diagnosis -- Acute erythroid leukemia

DIAGNOSIS

Acute erythroid leukemia (erythroid/myeloid subtype)

DISCUSSION

Acute erythroid leukemia (AEL) can be further classified into the erythroleukemia (erythroid/myeloid) and pure erythroid leukemia subtypes. The bone marrow in the erythroid/myeloid subtype has ?50% erythroid precursors and ?20% myeloblasts (calculated as a percentage of non-erythroid cells). Pure erythroid leukemia is less common and is composed of >80% neoplastic erythroid precursors in the bone marrow (1). In this case, 62% of the cells in the bone marrow were erythroid precursors and 9.8% of the cells in the bone marrow were blasts. As a fraction of non-erythroid cells in the bone marrow, the percentage of blasts was greater than 20%, and thus, this case was classified as acute erythroid leukemia (erythroid/myeloid subtype).

AEL accounts for less than 5% of cases of acute myeloid leukemia (AML) (2). One study of 20 patients found the median age at diagnosis to be 53 years old with a male-to-female ratio of 4:1 (3). The AEL in this patient was unusual in that it occurred in a young female. The majority of cases arise de novo; however, there have been cases reported to arise from myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and toxin exposure (2). There have also been rare familial cases described (4). AEL often presents with vague symptoms due to anemia such as fatigue (1). Patients can also present with symptoms due to leukopenia and thrombocytopenia (2).

Peripheral blood findings in AEL are generally non-specific and include anisopoikilocytosis, as in this case (Figure 1), basophilic stippling, schistocytes, and anisochromia. In some cases, normoblasts can be found. The erythroid precursors in the marrow are dysplastic and include cells with abnormal nuclear shapes, nuclear budding, multinucleation, cytoplasmic vacuoles, and megaloblastoid forms (Figures 2 and 3). In addition, dysplastic changes can also be seen in the megakaryocytic and myeloid cell lines. An iron stain may reveal the presence of ring sideroblasts. Also, erythroid precursors may show coarse granular cytoplasmic positivity with the Periodic-acid-Schiff (PAS) stain (Figure 4). The bone marrow is generally hypercellular (2).

The erythroblasts in AEL are usually positive for CD71. The myeloblast component variably expresses CD34 and is usually positive for myeloid markers including CD13 and CD33, myeloperoxidase (MPO), and CD117 (2).

It is common for AEL to demonstrate a complex karyotype, as in this case. Frequent cytogenetic abnormalities in AEL include hypodiploidy, monosomies of chromosomes 5, 7, and 16, deletions of chromosomes 5 and 7, and triploidy of chromosome 8 (5, 6). FLT3 and RAS mutations are rare in AEL (7).

It is important to exclude other entities which can resemble AES. MDS with erythroid predominance can appear cytologically similar in the marrow as a predominance of dysplastic erythroid precursors can be seen; however, in MDS with erythroid predominance, blasts account for less than 20% of the non-erythroid cells. AML with myelodyspasia-related changes can also be an important entity in the differential diagnosis, but can be distinguished by the presence of dysplasia in 50% or more of cells in two or more cell lineages and the blast count is always greater than 20% of all bone marrow cells. Additionally, therapy related AML can present with erythroid predominance and a clinical picture which resembles AEL (2). Congenital dyserythropoiesis is a non-neoplastic process that can present in a similar fashion (8). Other possible mimickers include the marrow findings associated with megaloblastic anemia and growth factor therapy, such as with erythropoietin.

AEL is usually considered to have a poor prognosis (1). However, more recent studies have found that AEL by itself does not have a worse prognosis than AML (9).

Treatment for AEL is similar to treatment for AML, not otherwise specified (2), with cytarabine being particularly effective. The patient in this case underwent induction with idarubicin and cytarabine and achieved remission.

REFERENCES

1. Arber D, Brunning R, Orazi A, et al. Acute myeloid leukemia, not otherwise specifiec. In: Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H, Thiele J, Vardiman J (Eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press: Lyon, France, 2008, pp 134-136.
2. Zuo Z, Polski J, Kasyan A, Medeiros L. Acute erythroid leukemia. Archives of Pathology and Laboratory Medicine 2010;134(9):1261-1270.
3. Kasyan A, Medeiros L, Zuo Z, et al. Acute erythroid leukemia as defined in the World Health Organization classification is a rare and pathogenetically heterogeneous disease. Modern Pathology 2010;23:1113-1126
4. Novik Y, Marino P, Makower D, Wiernik P. Familial erythroleukemia: a distinct clinical and genetic type of familial leukemias. Leukemia and Lymphoma 1998;30(3-4):395-401.
5. Lessard M, Struski S, Leymarie V, et al. Cytogenetic study of 75 erythroleukemias. Cancer Genetics and Cytogenetics 2005;163(2):113-122.
6. Olopade OI, Thangavelu M, Larson RA, et al. Clinical, morphologic, and cytogenetic characteristics of 26 patients with acute erythroblastic leukemia. Blood 1992;80(11):2873-2882.
7. Hasserjian R, Zuo Z, Garcia C, et al. Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification. Blood 2010 Mar 11;115(10):1985-92.
8. Tso A, Kumaran T, Bain B. Case 41: a misdiagnosis of erythroleukemia. Leukemia and Lymphoma 2009;50(6):1030-1032.
9. Santos F P, Faderl S, Garcia-Manero G, et al. Adult acute erythroleukemia: an analysis of 91 patients treated at a single institution. Leukemia 2009;23(12):2275-2280.

Contributed by Stephen Hastings, MD