Pure erythroid leukemia: The value of E‐cadherin in making the diagnosis
Authors: Imogen Caldwell, Anna Ruskova, Gordon Royle, James Liang, Barbara J. Bain
Journal: American Journal of Hematology (2019)

A 69-year-old man presented with a 3-week history of progressive fatigue, two episodes of melena, fevers, and blurred vision. Examination revealed bilateral retinal hemorrhages but no lymphadenopathy or organomegaly. His blood count showed severe bicytopenia: hemoglobin 43 g/L, platelets 11 × 109/L, neutrophils 4.4 × 109/L, monocytes 0.1 × 109/L, and lymphocytes 6.4 × 109/L. Rare circulating blast cells were seen. Bone marrow could not be aspirated but a trephine biopsy was performed. Imprints from the biopsy specimen were markedly hypercellular and showed replacement of normal hematopoietic cells by a relatively monomorphic population of large immature blastoid cells (Left image). The cells had a high nucleocytoplasmic ratio and round nuclei with immature chromatin and large nucleoli. The cytoplasm was deeply basophilic and showed occasional blebs. Both cytoplasmic and nuclear vacuoles were seen. The blastoid cells tended to occur in clusters. They were negative for Sudan black B. Flow cytometric immunophenotyping was performed but no clearly abnormal population of cells could be identified. The trephine biopsy sections showed a diffuse sheet-like infiltrate of large immature cells with round nuclei, fine chromatin, and prominent nucleoli (Right image). An intrasinusoidal growth pattern was also seen, highlighted by CD34 staining. Immunohistochemical staining showed the blastoid cells to be positive for CD117 but negative for CD34, myeloperoxidase, and terminal deoxynucleotidyl transferase. CD45 was weakly positive. All other routine stains for lymphoid, megakaryocytic, mast cell, plasma cell, and NK cell lineages were negative as were stains for non-hematopoietic malignancies. After an extensive work-up, we suspected a diagnosis of pure erythroid leukemia. E-cadherin staining was strongly positive in the blasts (Top image) while glycophorin A was negative (Bottom image). Retrospective analysis of the immunophenotyping plots revealed a population of CD117-positive cells found within the monocyte region on the CD45/side scatter plot. These cells were positive for CD13, CD33, and CD71. A periodic acid-Schiff stain was then performed on a trephine biopsy imprint, showing block positivity. A diagnosis of pure erythroid leukemia was made. Chromosomal analysis revealed a complex karyotype with near-diploid and near-tetraploid cell lines. Pure erythroid leukemia is a rare subtype of acute myeloid leukemia associated with an aggressive clinical course. The diagnosis can be made when >80% of bone marrow cells are erythroid and at least 30% are proerythroblasts, without a significant myeloblastic component. In some cases the blasts can be identified morphologically as proerythroblasts, while in other cases they appear undifferentiated. When there is no cytological evidence of erythroid maturation, the diagnosis can be challenging. The blasts are typically negative for CD34 and HLA-DR; they may express CD36 and CD71 but neither is lineage specific. The differential diagnosis includes acute megakaryoblastic leukemia, acute lymphoblastic leukemia, lymphoma, and metastatic tumors. In bone marrow samples, glycophorin A is specific for erythroblasts but is a poor marker of the early stages of erythroid maturation and is thus negative in some cases of erythroid leukemia with no maturation beyond the early proerythroblast stage. In these cases staining for E-cadherin can be very important in confirming the erythroid lineage. The authors have no conflict of interest to report.