Submitting Author: Moore, Erika, MD
Institution: Hospital of the University of Pennsylvania
Additional authors:Chitra Kohli, MD, Adam Bagg, MD
Session: Erythroleukemia and megakaryoblastic AML and mimics

Clinical History: A bone marrow biopsy and clot section were received in consultation with a preliminary diagnosis of refractory anemia with excess blasts (RAEB-2) versus acute myeloid leukemia (AML). The only provided clinical history was of a 72-year-old man with pancytopenia. A CBC showed a white blood cell count of 2.7 x 109/L, hemoglobin of 8.5 g/dL, and platelets of 78 x 109/L. Subsequently, a bone marrow aspirate was sent.

Clinical Follow-Up: Additional laboratory values were requested. The MCV was 104 fL (somewhat lower than might be anticipated for megaloblastic anemia), Vitamin B12 was 53 (Normal Range: 211-946 pg/ml), and folate was within normal limits. The patient subsequently received Vitamin B12 therapy and the pancytopenia later resolved.

Bone marrow trephine and clot sections: H&E stained sections show a markedly hypercellular marrow (95% cellularity) with a marked expansion of immature mononuclear cells (~80%) that are large, with round to somewhat irregular nuclei, dispersed chromatin, occasionally prominent nucleoli and variable amounts of cytoplasm. Mitotic figures and apoptotic bodies are frequent. Easily recognizable normal erythroid elements are not well represented. Myeloid elements are decreased through all phases of maturation. Megakaryocytes are markedly decreased. Stainable iron is present. Ringed sideroblasts are not seen.

Bone marrow aspirate smear: The Wright-Giemsa stained smear reveals hypercellular spicules. The myeloid to erythroid ratio is reversed at ~1:8. The majority of the cells consist of large erythroid precursors. The erythroid elements show marked megaloblastic features through all phases of maturation, with nuclear cytoplasmic dissociation, karyorhexis and karyolysis. Myeloid elements are somewhat decreased through all phases of maturation, with mild megaloblastic features (occasional giant myelocytes and bizarrely nucleated metamyelocytes are present).

Immunohistochemistry: Immunohistochemical stains (that were probably not necessary) performed on the aspirate clot show that the vast majority of the immature mononuclear cells express CD43, CD235a and E-Cadherin; a minor subset (~5%) expresses CD117. They are negative for CD34, CD45 and MPO.

Flow cytometry: By report, no abnormalities are evident in myeloid or lymphoid cells, and there is not an expansion of blasts. CD235a and CD71 confirm the presence of an erythroid population; a proportion of this population (~9% of total events) reportedly shows partial expression of CD117 and appears to be large.

Normal karyotype

Not performed

This is a classic case of megaloblastic anemia which was initially mistaken for a high grade myelodysplastic syndrome/acute myeloid leukemia on histology. The morphology on the aspirate clearly shows profound megaloblastosis. The case highlights the potential dangers of making diagnoses on a bone marrow biopsy/clot section only, in the absence of an aspirate smear. It highlights the absolute requirement that histology be reviewed in parallel with cytology, lest cases (such as this one) be potentially misdiagnosed as a lethal hematologic neoplasm (requiring aggressive chemotherapy) rather than an easily remediable vitamin deficiency.

Megaloblastic anemia (mimicking acute leukemia on histology alone)

Megaloblastic anemia

Case 407