CD34+ Megakaryocytes Associate with Myelodysplastic Syndromes and Related Cytogenetic Abnormalities, but Not Other Hematological Disorders

Background: CD34 is a transmembrane phosphoglycoprotein that is a marker of hematopoietic stem cells and is used clinically to aid in enumeration of blast cells for identification of advanced myeloid neoplasms. Megakaryocytes are differentiated cells from the myeloid lineage that reside in the bone marrow and generally stain negative for CD34 (CD34-). However, CD34 positive (CD34+) megakaryocytes have been observed in hematological disorders such as myelodysplastic syndrome, myeloproliferative neoplasms, and acute leukemias. CD34+ megakaryocytes are proposed to be relatively specific for malignant hematologic conditions and have been reported to associate with a worse prognosis. However, the general clinical, biochemical, and cytogenic characteristics for bone marrow cases of CD34+ megakaryocytes versus CD34- megakaryocytes remains unclear.

Objective: We sought to determine the clinical, biochemical, and cytogenetic characteristics associated with finding CD34+ megakaryocytes on bone marrow biopsies.

Methods: We identified 281 independent, index bone marrow biopsy cases between 2011-01-01 and 2017-12-31 from Vancouver General Hospital, Canada that underwent CD34 immunohistochemistry at clinical request. The clinical, biochemical, and cytogenetic characteristics of patients were compared based on megakaryocytes being CD34+ vs CD34- on immunohistochemistry. Cases of CD34+ megakaryocytes were defined as having >5% of megakaryocytes staining CD34+, but sensitivity analyses were performed using different percentage cut-offs of 10, 30, and 50%.

Results: Out of 281 cases, 134 had CD34+ megakaryocytes (58.2% male sex; mean age = 64.1 years [SD = 15.2 years]) and 147 had CD34- megakaryocytes (57.1% male sex; mean age = 60.0 years [SD = 16.6 years]). There was a significant difference in the distribution of diagnostic categories observed between cases of CD34+ versus CD34- megakaryocytes: myelodysplastic syndromes 35.1% (n=47) versus 21.8% (n=32), acute myeloid leukemias 20.9% (n=28) versus 21.1% (n=31), non-diagnostic etiology 17.9% (n=24) versus 14.3% (n=21), and myeloproliferative neoplasms 10.4% (n=14) versus 19.7% (n=29) (Figure A; Chi-square p-value=0.0004). Sensitivity analyses using different percentage cut-offs to define cases of CD34+ from CD34- megakaryocytes yielded similar results. The differences in biochemical characteristics between cases of CD34+ versus CD34- megakaryocytes were generally unremarkable. The median (IQR) for biochemical parameters between cases of CD34+ and CD34- megakaryocytes were hemoglobin 99 (28) versus 100 (34) g/L, mean corpuscular volume 94 (14) versus 93 (10) fL, neutrophil count 2.20 (3.68) versus 2.46 (3.63) x10 ⁹/L, platelet count 98 (158) versus 112 (194) x10 ⁹/L, and bone marrow blasts 7 (4) versus 3 (14)%. Lastly, there were notable trends in cytogenetic results associated with 90 cases with CD34+ versus 84 cases with CD34- megakaryocytes including: complex karyotypes for 15.6% (n=14) versus 6.0% (n=5), isolated deletion 5q for 7.8% (n=7) versus 1.2% (n=1), and/or isolated trisomy 8 for 5.6% (n=5) versus 2.4% (n=2). Similar cytogenetic results were observed when cases were restricted to only cases of CD34+ versus CD34- megakaryocytes with a diagnosis of myelodysplastic syndrome (Figure B).

Conclusion: The presence of CD34+ megakaryocytes is more common in cases of myelodysplastic syndrome relative to other neoplastic hematologic disorders, but does not appear to help with discriminating between neoplastic and non-neoplastic hematological disorders ( e.g. non-diagnostic etiology). Cases with CD34+ megakaryocytes tend to associate with complex karyotype and deletion 5q abnormalities relative to cases with CD34- megakaryocytes.