Can vacuolated neutrophils be suspected in patients with myeloproliferative (myelo proliferative) disorders?

Vacuolated Neutrophils in Myeloproliferative Disorders

Vacuolated neutrophils are not a characteristic feature of myeloproliferative disorders (MPDs) and should prompt evaluation for alternative diagnoses, particularly copper deficiency or myelodysplastic syndromes (MDS).

Key Diagnostic Distinction

• Vacuolation of myeloid precursors is specifically associated with copper deficiency, which can mimic MDS findings, rather than being a feature of MPDs 1
• Clinical features associated with copper deficiency include vacuolation of myeloid and/or erythroid precursors, prior gastrointestinal surgery, and a history of vitamin B12 deficiency 1
• When vacuolated neutrophils are observed, assessment of copper and ceruloplasmin levels should be performed as part of the diagnostic workup 1

Morphologic Features of Myeloproliferative Disorders

MPDs have distinct morphologic characteristics that do not include neutrophil vacuolation:

Polycythemia Vera (PV)

• Bone marrow shows hypercellularity with trilineage myeloproliferation and pleomorphic, mature megakaryocytes 1
• Increased number of megakaryocytes with cluster formation and giant megakaryocytes with pleomorphism 1
• Mild reticulin fibrosis may be present in 12% of patients 1

Essential Thrombocythemia (ET)

• Bone marrow demonstrates megakaryocyte proliferation with large and mature morphology 1
• No significant left-shift of neutrophil granulopoiesis or erythropoiesis 1

Primary Myelofibrosis (PMF)

• Megakaryocyte proliferation with small-to-large megakaryocytes showing aberrant nuclear/cytoplasmic ratio and hyperchromatic, irregularly folded nuclei 1
• Reticulin and/or collagen fibrosis in overt PMF 1

Chronic Neutrophilic Leukemia (CNL)

• Bone marrow shows expansion of neutrophilic granulopoiesis with mature neutrophils, without excess myeloblasts 2
• No mention of vacuolation as a characteristic feature 2

Functional Abnormalities in MPD Neutrophils

While neutrophils in MPDs show functional impairments, these are not morphologic vacuolation:

• Neutrophil chemotaxis is significantly impaired in PV and CML patients 3
• Superoxide anion release may be impaired in 25% of PV patients 3
• Increased neutrophil respiratory burst capacity is observed in MPDs when stimulated by receptor-mediated agonists 4
• These represent functional rather than morphologic abnormalities 3, 4

Critical Pitfall to Avoid

Do not attribute vacuolated neutrophils to MPDs. This morphologic finding should redirect your diagnostic evaluation toward:

1. Copper deficiency - the most important consideration when vacuolation is present 1
2. Myelodysplastic syndromes - where dysplastic changes including vacuolation may occur 1
3. Other metabolic or toxic causes affecting neutrophil morphology

The presence of vacuolated neutrophils in a patient with suspected MPD should prompt measurement of copper and ceruloplasmin levels and reconsideration of the diagnosis 1.