Aplastic Anemia Versus Hypoplastic Myelodysplastic Syndrome: A Diagnostic Dilemma

Aplastic anemia (AA) may be idiopathic or associated with a variety of causes, including immune diseases. Although rare, AA has been associated with large granular lymphocyte (LGL) leukemia. The diagnosis of AA is established by peripheral blood pancytopenia with markedly hypocellular marrow. Myelodysplastic syndrome (MDS) is also characterized by cytopenia and most cases exhibit a hypercellular marrow, but in 10% to 15% of MDS, the marrow is hypocellular, posing a diagnostic challenge in distinguishing MDS from AA. We report a case of a 62-year-old female with a history of chemotherapy and radiation treatment for breast cancer who presented with bleeding, severe thrombocytopenia, mild anemia, and a normal white blood cell count. She was managed for idiopathic thrombocytopenic purpura; however, the thrombocytopenia worsened with new onset of neutropenia. The peripheral blood smear revealed LGLs with clonal T-cell receptor gene rearrangement consistent with LGL leukemia. Subsequently, the patient developed rapid onset of severe leukopenia and anemia. A diagnosis of aplastic anemia was made based on marrow cellularity of less than 10%. Cytogenetic studies revealed an abnormal karyotype with trisomy 8. This raised the differential diagnosis of hypocellular MDS since trisomy 8 is associated with the latter. An acute onset of peripheral blood pancytopenia with markedly hypocellular marrow without significant dysplastic features favored a diagnosis of AA. While cytogenetic abnormalities are not usually found in AA, transient MDS-like clonal cytogenetic abnormalities have been reported in AA, and the sole presence of trisomy 8 does not definitively distinguish AA from hypoplastic MDS. Therefore, differentiating aplastic anemia from hypocellular MDS may be difficult without clinical follow-up and repeat bone marrow biopsy to demonstrate the transient nature of the clonal abnormality. This case illustrates the challenges of establishing a diagnosis of aplastic anemia in the setting of hypocellular marrow with clonal cytogenetic abnormality.