A case of reactive erythrocytosis with CD34/CD61 dual positive megakaryocytes

Abstract

Dear Editors, Megakaryopoiesis has been studied in last few decades since the core regulation mechanism of platelet production was revealed together with advanced techniques like flow cytometry.1-4 Early megakaryocyte progenitor cells show cluster of differentiation (CD)34, CD38, and CD41 positivity, and megakaryocytes develop CD61 positivity while losing CD34 positivity during the maturation process.1-5 In normal bone marrow (BM), CD34/CD61 co-expression can be observed in small percent of megakaryocytes (polyploidy transitional immature megakaryocytes), comprising 1%-11% of megakaryocytes.1,6 CD34-positive mature megakaryocytes have been reported in some pathologic conditions like gray platelet syndrome and growth factor independent 1B (GFI1B) and RUNX1-related familial bleeding disorders, due to CD34-silencing processes in normal megakaryopoiesis.7,8 However, they have been reported mostly in cases with increased and/or dysplastic megakaryocytes, including myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN).9-12 A high level of CD34 expression on megakaryocytes, using 20% as a cutoff, was considered significant and associated with MDS; it was expected to predict poor prognosis in MDS patients.9,10 This phenomenon could be related to aberrant stem cells contributing to dysfunctional megakaryocyte maturation, as well as morphological dysplasia in MDS. Here, we report a case of reactive erythrocytosis, in which all observed megakaryocytes were positive for both CD34 and CD61. Although its clinical relevance is unclear, this case implies that all megakaryocytes may show CD34 and CD61 dual positivity in reactive BM, and 20% or higher proportion of such cells does not necessarily mean pathologic conditions including MDS and/or MPN. A 57-year-old man presented with erythrocytosis that lasted for two years. His past medical history and physical examination were unremarkable, except for hypertension and varicose veins. His complete blood counts were as follows: hemoglobin, 172 g/L; hematocrit, 50.4%; white blood cells, 6.4 × 109/L; and platelets, 272 × 109/L. In his BM, the estimated cellularity was 50%, and there was no evidence of panmyelosis, dyshematopoiesis, and increased blasts. Mature megakaryocytes with normal lobulation were observed in adequate number, and all of them (100/100 cells) showed CD34 and CD61 dual positivity on immunohistochemical staining (Figure 1). Fluorescence in situ hybridization (FISH) analyzes showed negative results of BCR/ABL1 rearrangement, RB1 (13q14.2) deletion, and D20S108 (20q12) deletion. Further, molecular studies showed negative results of JAK2 V617F, JAK2 exon 12, MPL W515, and MPL S505 mutations. The serum erythropoietin level was within the reference range. He was diagnosed as having reactive erythrocytosis of unknown origin, and MPNs including polycythemia vera were excluded.13 Table 1 summarizes previous cases with CD34+/CD61+ megakaryocytes and the present case. In the present case, we could not perform additional tests, including CALR mutation that can be found in MPNs and GFI1B or RUNX1 mutations to explore the abnormality of megakaryocytes. However, the patient was in a healthy condition with normal complete blood counts two weeks after the BM examination. Although long-term follow-up evaluation would be necessary, this case implies that megakaryocytes may show various level