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CD34-positive dwarf megakaryocytes in chronic myeloid leukemia are not indicators of disease progression


1 Department of Medical Oncology/Hematology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

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Date of Submission14-Jun-2021
Date of Decision06-Dec-2021
Date of Acceptance09-Dec-2021
Date of Web Publication26-May-2022
 


How to cite this URL:
Bhuyan B, Padhi S. CD34-positive dwarf megakaryocytes in chronic myeloid leukemia are not indicators of disease progression. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Feb 5]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=345887




Dear Editor,

A twenty-one-year-old male with p210 KD BCR-ABL positive chronic phase chronic myeloid leukemia (CML) underwent baseline bone marrow aspiration (BMA) and trephine biopsy which demonstrated florid myelomegakaryocytic hyperplasia with 5% myeloid blasts and 6% basophils along with clustering of dwarf megakaryocytes (MK). Immunohistochemistry (IHC) using CD34, CD117, and terminal deoxy transferase (TdT) demonstrated no localized blast collection, although 30% of the dwarf megakaryocytes showed intermediate to strong cytoplasmic granular positivity for CD34 only [Figure 1]a, [Figure 1]b and [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. Flowcytometry analysis of BMA revealed 6% myeloid blasts positive for CD34 and CD117.
Figure 1: Peripheral blood smear (a) from the case demonstrating marked leukocytosis, myeloid left shift with circulating blasts, and basophilia suggestive of chronic phase chronic myeloid leukemia (CML). Stained bone marrow aspirate smear (b) demonstrating florid myeloid hyperplasia along with increased and clustered dwarf megakaryocytes giving a bunch-of-grapes appearance from the same case (Leishman-Giemsa stain, ×400).

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Figure 2: Decalcified bone marrow trephine biopsy sections demonstrating a markedly hypercellular marrow, florid myeloid and megakaryocytic hyperplasia in the case of CML in chronic phase. Note the presence of increased number of dwarf megakaryocytes showing loose interstitial clustering (a) and at places, paratrabecular localization (b) (Hematoxylin and eosin, ×400). Representative sections from the same areas showing intermediate to strong diffuse, granular cytoplasmic CD34 positivity in 30% of dwarf megakaryocytes (c and d). Also note the scattered CD34 negative megakaryocytes in the background and increased angiogenesis (black arrow) (Peroxidase-antiperoxidase) (c; ×200, d; ×400). There was no evidence of localized nodule of myeloid or lymphoid blasts in this case. T is trabecular bone

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Aberrant CD34 positivity (+) MK in trephine sections has been reported in both reactive as well as neoplastic conditions such as myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPNs), and MDS/MPN cases.[1],[2],[3],[4],[5] While the prognostic and/or diagnostic utility of CD34 + MK is not fully known, previous studies have reported that ≥ 10% to 20% cut off positivity was more likely to be associated with significant thrombocytopenia, aggressive clinical course, and poorer outcome in subjects with MDS.[1],[3] In contrast, percentage of CD34 + MK did not correlate with MDS subtypes in another study by Torlakovic et al.[4]

Giovanni et al.[6] studied the significance of CD34 + MK in a large series comprising of 120 non-neoplastic cases including 12 megaloblastic anemias (MBA), 17 non-megaloblastic anemias, 43 immune thrombocytopenia (ITP), 25 autoimmune conditions, and 23 staging marrows, and 180 cases of non-AML myeloid neoplasms (69 MDS, 79 MPN, and 32 MDS/MPN). A ≥30% cut off CD34 positivity in MK (on IHC) was strongly associated with MBA (8/12, average; 45%, range; 1-84%) compared to non-megaloblastic cases (P < 0.0001), though no significant difference was noted in regard to pattern of intensity and cellular distribution between two subgroups. CD34 cut off positivity did not significantly alter the platelet count among MBA cases (P = 0.15). Thirteen MDS cases (six refractory cytopenia with multilineage dysplasia, five MDS-excess blast, one RCUD, and one MDS-U); nine MPN (six CML (1 accelerated phase), two MPN-unclassified, one primary myelofibrosis); and two MDS/MPN cases showed ≥ 30% CD34 + MK on trephine biopsy. CML cases (n = 21) showed statistically significant CD34 positivity when compared with non-CML cases (n = 58) (P = 0.0091). MDS cases with ≥ 30% CD34 + MKs (n = 13) had significantly lower platelet counts than those with <30% (n = 56) (38 ± 18 × 109 / L vs. 162 ± 150 × 109 / L, P = 0.03). Cases of MPN and MDS / MPN with ≥30% CD34 + MKs tended to have lower platelet counts (P = 0.15). The MBA cases demonstrated consistent stronger CD34 positivity (membranous, cytoplasmic and Golgi zone) compared to predominantly weaker staining in non-MBA reactive cases. In contrast, the majority of neoplastic megakaryocytes exhibited a cytoplasmic pattern of staining, with membranous and Golgi zone pattern was distinctly rare.[6] The mechanism CD34 expression in dwarf megakaryocytes in CML is poorly understood, and may possibly be linked to secondary/acquired dysplastic changes seen in such cases. Though our observation needs to be validated by a larger cohort of cases, we do suggest that aberrant CD34 positivity in dwarf megakaryocytes should not be misinterpreted as evidence of megakaryoblastic transformation or disease progression in CML.

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Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Machhi J, Bunyi-Teopengco E, Chang C. CD34 expression in megakaryocytes favours myelodysplasia. Mod Pathol 2001;14:171.  Back to cited text no. 1
    
2.
Pellegrini W, Facchetti F, Marocolo D, Pelizzari AM, Capucci A, Rossi G. Expression of CD34 by megakaryocytes in myelodysplastic syndromes. Haematologica 2000;85:1117-8.  Back to cited text no. 2
    
3.
Tang G, Wang SA, Menon M, Dresser K, Woda BA, Hao S. High-level CD34 expression on megakaryocytes independently predicts an adverse outcome in patients with myelodysplastic syndromes. Leuk Res 2011;35:766-70.  Back to cited text no. 3
    
4.
Torlakovic G, Langholm R, Torlakovic E. CD34 / QBEND10 immunohistochemistry in the bone marrow trephine biopsy: A study of CD34-positive mononuclear cells and megakaryocytes. Arch Pathol Lab Med 2002;126:823-8.  Back to cited text no. 4
    
5.
Chen Y, Chang H. CD34+megakaryocytes and megakaryocytic fragments in myelodysplastic syndrome. Blood 2017;129:2818.  Back to cited text no. 5
    
6.
Insuasti-Beltran G, Steidler NL, Kang H, Reichard KK. CD34+megakaryocytes (≥30%) are associated with megaloblastic anaemia and non-acute myeloid neoplasia. Histopathology 2012;61:694-701.  Back to cited text no. 6
    

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Correspondence Address:
Somanath Padhi,
Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_601_21



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