By ProPath Staff

 

A 63-year-old man presented with a three-week history of increasing shortness of breath and dyspnea upon exertion. One week prior to admission the patient’s CBC results demonstrated mild pancytopenia with WBC count of 4,700 cells/cmm, hemoglobin of 9.2 gm/dl, and platelets of 71,000 per cmm. The peripheral smear also revealed the presence of circulating blasts. The past medical history included heart transplantation approximately eight years prior to admission.

Physical examination revealed hepatosplenomegaly. A bone marrow aspiration was performed and revealed a predominance of immature atypical cells. These atypical cells were large, had abundant basophilic cytoplasm with cytoplasmic projections, convoluted nuclear contours with immature nuclear chromatin and occasional nucleoli.

Peripheral blood smear with abnormal red blood cell morphology (teardrop cells, schistocytes, and elliptocytes) and a single large erythroblast.

 

These results were diagnostic of acute leukemia without morphologic features specific to a particular cell lineage. The diagnosis was supported by flow cytometry results which demonstrated a distinct population of large cells with the following phenotype: CD71 positive, glycophorin A positive, CD33 positive, CD13 partially positive, and CD34 negative. These findings were consistent with an erythroid lineage for the atypical cells. A cytogenetic study was also performed on the bone marrow and revealed numerous complex structural and numerical abnormalities including a 5q-.

In the FAB classification scheme, this neoplasm is classified as an M6 acute erythrocytic leukemia. The new WHO classification scheme subdivides erythroid leukemia into two variants, M6A, the more common myeloid erythroid variant, and M6B, the less common, pure erythroid leukemia. M6A is defined by greater than 50% erythroid precursor cells in the bone marrow aspirate plus greater than 20% of the remaining nucleated cells must be myeloblasts. M6B is defined by erythroid precursors greater than 80% of the marrow cells without an increase in myeloblasts.

 

Bone marrow smear demonstrating a small but distinct population of abnormal erythroblasts.

The flow cytometry features of an acute erythocytic leukemia can be useful in its distinction from other subtypes of leukemia. In the M6A variant, there is a population of myeloblasts that typically express variable myeloid markers such as CD13, CD33, CD117 and CD45. In addition, a population of erythroid precursors may be identified that express glycophorin A, CD71 (transferrin receptor), CD36, dim to negative CD45 and CD38. Of these antigens, the only erythroid-specific marker is glycophorin A. The M6B variant contains the erythroid precursor population without the expanded population of myeloblasts. Our patient had a typical immunophenotype for an M6B erythroid leukemia, including bright expression of CD36, partial expression of glycophorin A, expression of CD71, moderate expression of CD45, and no expression of CD34 (which is commonly expressed by myeloblasts).

Cytogenetic abnormalities in cases of M6 leukemia are not specific but are present in about 50% of cases. These can include complex abnormalities (i.e. multiple abnormal chromosomes), often with alterations and deletions involving chromosomes 5 and 7. Our patient had complex cytogenetic abnormalities, including a 5q-.

In general, the outcome of patients with either type of acute erythroleukemia is poor with most patients experiencing an aggressive course.

This case highlights the complexities which can be experienced in the subclassification of acute leukemia by morphology alone, and also provides a good example of the utility of flow cytometry and cytogenetics in confirming morphologic impressions and/or providing information which allows the morphologist to render a diagnosis.

 

References:

1. A Kowal-Vern, F.M., J Cotelingam, M Shrit, J Rector and H Schumacher (2000). “Diagnosis and Characterization of Acute Erythroleukemia Subsets by Determining the Percentages of Myeloblasts and Proerythroblasts in 69 Cases.” American Journal of Hematology 65:5-13.

2. F Mazella, C. A., A Kowal-Vern and H Schumacher (200). “The Acute Erythroleukemias.” Clinics in Laboratory Medicine 20(1):119-131.

3. Knowles, D., Ed. (2001). Neoplastic Hematopathology. Philadelphia, Lippincott, Williams, and Wilkins.