Institution: Hematopathology Unit,Pathology Department, Hospital Clínic, IDIBAPS, University of Barcelona
Additional authors:Neus Villamor, Dolors Costa, Marta Aymerich, Jordi Esteve, Dolors Colomer, Ivan Dlouhy. Hematopathology Unit, Pathology Department, and Hematology Department, IDIBAPS, Hospital Clínic, Barcelona
Session: Erythroleukemia and megakaryoblastic AML and mimics
HISTORY
A 75 year old female consulted due to malaise for the last week. She had no previous relevant medical history. On examination only paleness was found. The laboratory tests showed severe pancytopenia: Hb 61 g/L, MCV 86 fL, WBC 3.09 x 10^9/L, Platelets 37 x 10^9/L.
DETAILS
Bone marrow aspirate smears stained with May-Grunwald Giemsa, and cytochemistry (MPO and PAS).
The bone marrow aspirate was hypercellular, with 18% erythroid precursors, 38% granulocytic precursors, 29% blasts and 13% other cells (lymphocytes, plasma cells, macrophages). The megakaryocytes were quantitatively normal but 70% of them were dysplastic (micromegakaryocytes, hypolobated nuclei). Dyserythropoiesis was present in 100% of the erythtoid cells (nuclear budding, karyorhexis, multinuclearity, cytoplasmic basophilic stippling). Dysgranulopoiesis (cytoplasmic hypogranularity, bizarrely-segmented nuclei) was also present.The blasts had a round nucleus with finely dispersed chromatin, prominent nucleoli and cytoplasmic vacuoles, some of which were coalescent. The MPO was negative and the PAS showed intense cytoplasmic globular staining.Bone marrow biopsy was not performed.IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY
Flow cytometry:
The sample contained 17% lymphocytes, 18% erythroid series (FSC/SSC small, CD45-), 46% granulocytic series, 6% monocytes, and 0.7% immature precursors (CD34+). There was a 6% - 8% of elements with intermediate FSC/SSC and phenotypically CD117++, CD45 weak, CD33 weak, CD13+ weak, HLA-DR+, CD71+++, MPO-, lysozyme -, and negative for neutrophilic and monocytic maturation markers except for the expression of CD36. This population also co-expressed CD2, CD4 and CD7. Immunocytochemistry (glycophorin, MPO and CD61):The vast majority of the blasts expressed glycophorin. Very occasional CD61 or MPO positive blasts were seen.CYTOGENETIC FINDINGS
45-47,XX,add(2)(q37)[7],-5[3],del(5)(q13q33)[12],-7[3],r(7)(p22q36)[8],+mar1[2],+mar2[2][cp18]/46,XX[7]
MOLECULAR FINDINGS
FLT3-ITD was negative.
INTERESTING FEATURES
Although the striking morphology of the blasts, the present case does not fulfill criteria for acute erythroid leukemia, both erythroid/myeloid subtype (there is <50% erythroid series even if the blasts are included) and pure erythroid subtype (<80% erythroid blasts). The presence of multilineage dysplasia and the cytogenetic findings are consistent with the proposed diagnosis.
PROPOSED DIAGNOSIS
Acute myeloid leukemia with myelodysplasia-related changes
CONSENSUS GROUP: ADDITIONAL INFORMATION/STUDIES
Due to the patient's age, no bone marrow core biopsy was obtained at the time of diagnosis. A second bone marrow aspirate was performed two days later, and the findings were identical. The patient was treated with 6 courses of azacitidine, he achieved a normal hemogram, but bone marrow still showed 5% blasts. After another two courses of azacitidine, disease relapsed. Bone marrow aspirate showed 28% blasts with the same erythroblast morphology. She died two months later. No molecular studies were performed.
CONSENSUS DIAGNOSIS
High grade myeloid neoplasm: Acute myeloid leukemia with erythroid differentiation versus high-grade myelodysplastic syndrome with prominent left-shifted erythroid maturation