Analysis of immunohistochemical markers in bone marrow sections to evaluate for myelodysplastic syndromes and acute myeloid leukemias.
BACKGROUND
Accurate bone marrow (BM) blast counts (BCs) are essential for diagnosis (dx) of myelodysplasia (MDS), MDS/myeloproliferative (MDS/MPD) disease, or acute myeloid leukemia (AML), and may be difficult in hemodiluted bone marrow aspirates (BMAs). Erythroid precursors (EPs) may be indistinguishable from myeloblasts in BM sections (aspirate clots/cores). We compare the usefulness of immunohistochemistry (IHC) [ie, CD34, CD117, myeloperoxidase (MPO), Hemoglobin A1 (HbA1), and terminal deoxynucleotidyl transferase (TdT)] of BM sections (IHC-BM) with BMA, bone marrow touch preparation (BMTP), and flow cytometry (FC) BCs.


METHODS
The initial BC (48), percentage (%) of Eps (38) (both based on initial 100 to 600-cell counts), and FC expressions of CD34, CD117, Glycophorin A(GLY A), and TdT (44) were tabulated from 50 BMs (MDS, MDS/MPD, or AML). BMAs (48) and BMTPs (25) subsequently received 500-cell counts. IHC-BM was performed (45:formalin, 5:B5-fixed) [CD34 (46), CD117 (45), HbA1 (45), TdT (42), and MPO (45)].


RESULTS
Retrospective BMA BCs revealed a 31% (15/48) discrepant rate between the original/retrospective BMA BCs; 80% revealed an underestimated initial BC. There was a 28% discordance rate between the retrospective BMA and BMTP reviews; 77% showed a higher BMTP BC. IHC showed significantly higher BCs in 19% (9/47), resulting in a different dx (5). However, CD34 and CD117 IHCS revealed lower BCs in 38% and 48%, respectively. The CD34 IHC results were primarily due to CD34-negative blasts by FC. The CD117 IHC results were largely unexplained. EPs were CD34 and CD117-negative.


CONCLUSIONS
(1) Evaluation for MDS/AML requires 500-cell counts of BMAs and/or BMTPs. (2) CD34 and/or CD117 blasts by FC indicate IHC-BM may increase BC accuracy. (3) CD34 is more reliable than CD117 by IHC; however, in combination, they are most reliable and should be performed on BM clots/cores due to variable reactivity.
Dunphy
Cherie H
CH
Divisions of Hematopathology, Departments of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA. cdunphy@unch.unc.edu
O'Malley
Dennis P
DP
Perkins
Sherrie L
SL
Chang
Chung-Che
CC
D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D001772:Blood Cell Count; D001853:Bone Marrow / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D004253:DNA Nucleotidylexotransferase / Q000032:analysis; D005434:Flow Cytometry; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D009190:Myelodysplastic Syndromes / Q000201:enzymology / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D009195:Peroxidase / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D012189:Retrospective Studies
D018952:Antigens, CD34; D015415:Biomarkers; D004253:DNA Nucleotidylexotransferase; D006442:Glycated Hemoglobin; D009195:Peroxidase; D019009:Proto-Oncogene Proteins c-kit