Diagnostic complexities of eosinophilia

Arch Pathol Lab Med. 2013 Feb;137(2):259-69. doi: 10.5858/arpa.2011-0597-RA.


Context: The advent of molecular tools capable of subclassifying eosinophilia has changed the diagnostic and clinical approach to what was classically called hypereosinophilic syndrome.

Objectives: To review the etiologies of eosinophilia and to describe the current diagnostic approach to this abnormality.

Data sources: Literature review.

Conclusion: Eosinophilia is a common, hematologic abnormality with diverse etiologies. The underlying causes can be broadly divided into reactive, clonal, and idiopathic. Classically, many cases of eosinophilia were grouped together into the umbrella category of hypereosinophilic syndrome, a clinical diagnosis of exclusion. In recent years, an improved mechanistic understanding of many eosinophilias has revolutionized the way these disorders are understood, diagnosed, and treated. As a result, specific diagnoses can now be assigned in many cases that were previously defined as hypereosinophilic syndrome. Most notably, chromosomal rearrangements, such as FIP1L1-PDGFRA fusions caused by internal deletions in chromosome 4, are now known to be associated with many chronic eosinophilic leukemias. When present, these specific molecular abnormalities predict response to directed therapies. Although an improved molecular understanding is revolutionizing the treatment of patients with rare causes of eosinophilia, it has also complicated the approach to evaluating and treating eosinophilia. Here, we review causes of eosinophilia and present a framework by which the practicing pathologist may approach this diagnostic dilemma. Finally, we consider recent cases as clinical examples of eosinophilia from a single institution, demonstrating the diversity of etiologies that must be considered.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Adrenal Insufficiency / complications
  • Aged
  • Eosinophilia / classification
  • Eosinophilia / diagnosis*
  • Eosinophilia / etiology
  • Eosinophilia / therapy
  • Gene Rearrangement
  • Hematologic Neoplasms / complications
  • Hematologic Neoplasms / genetics
  • Humans
  • Hypereosinophilic Syndrome / diagnosis
  • Hypersensitivity / complications
  • Immunologic Deficiency Syndromes / complications
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Oncogene Proteins, Fusion / genetics
  • Parasitic Diseases / complications
  • Pulmonary Eosinophilia / diagnosis
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • mRNA Cleavage and Polyadenylation Factors / genetics


  • Oncogene Proteins, Fusion
  • mRNA Cleavage and Polyadenylation Factors
  • FGFR1 protein, human
  • FIP1L1-PDGFRA fusion protein, human
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta