What is basophilia and how is it diagnosed and treated?

Definition of Basophilia

Basophilia is defined as an absolute basophil count ≥1000 per μL of peripheral blood, representing a persistent elevation that warrants investigation for underlying myeloid neoplasms. 1

Quantitative Thresholds

• Hyperbasophilia (HB) is the term used when the peripheral blood basophil count persistently exceeds 1000 cells per μL, which is highly indicative of an underlying myeloid malignancy and serves as a critical checkpoint requiring detailed hematologic investigation. 1

• In chronic myeloid leukemia (CML), basophilia exceeding 20% in peripheral blood is a specific criterion defining accelerated phase disease according to WHO and European LeukemiaNet criteria. 2

• Normal basophil counts typically represent <1-2% of white blood cells, making any persistent elevation clinically significant. 3

Clinical Significance and Associated Conditions

Myeloid Neoplasms (Primary Association)

• CML is the prototypical disease associated with basophilia, presenting classically with the combination of myeloid hyperplasia, splenomegaly, neutrophil leukocytosis, thrombocytosis, and basophilia. 4

• Basophilia is a typical feature of CML in the initial chronic phase, commonly found in bone marrow biopsies at diagnosis showing increased cellularity due to proliferation of myelopoiesis. 2

• The association between basophilia and myeloid neoplasms, especially chronic myeloid neoplasms, is well established and represents the most important diagnostic consideration. 3

• In primary myelofibrosis (PMF), persistent basophilia (>3 months) may suggest progression toward acute myeloid leukemia, particularly in CALR-positive patients. 5

Reactive Causes

• Basophils physiologically increase in allergic reactions, chronic inflammation, and parasitic infections, though these typically produce less marked elevations than myeloid neoplasms. 5

• Conflicting data exist regarding many benign medical conditions, and it remains unclear which specific reactive conditions reliably produce basophilia. 3

Diagnostic Approach

Step 1: Confirm True Basophilia

• Verify the basophil count by eliminating spurious basophilia, as the reliability of basophil counting is insufficient whether performed by microscopic slide examination or hematology analyzer. 3

• Perform peripheral blood smear examination to identify basophils morphologically and rule out technical artifacts. 4

Step 2: Assess for Myeloid Neoplasm

• Philadelphia chromosome testing via cytogenetics and/or BCR-ABL by RT-PCR or FISH should be obtained from peripheral blood or bone marrow when CML is suspected. 4, 2

• Evaluate for left shift, blast percentage, thrombocytosis, and degree of basophilia on complete blood count with differential. 4

• Assess for splenomegaly and hepatomegaly on physical examination, as approximately 50% of CML patients present with splenomegaly. 6, 4

• Consider bone marrow aspiration and biopsy for blast percentage and dysplasia assessment if acute leukemia is suspected. 4

Step 3: Investigate Reactive Causes

• Look for symptoms suggesting reactive basophilia including allergic symptoms, chronic inflammatory conditions, or parasitic infection exposure. 3

• In the absence of an identified reactive cause or with persistence of basophilia, proceed with investigations for myeloid neoplasm. 3

Common Pitfalls

• Do not rely solely on automated basophil counts without confirmatory peripheral smear review, as technical limitations affect accuracy. 3

• Rare manifestations of CML including upper gastrointestinal ulceration can occur from elevated histamine levels due to basophilia, which may be overlooked. 2

• Basophilia in lymphoid malignancies is extremely rare, though isolated case reports exist of CD5+ diffuse large B cell lymphoma with marked basophilia. 7