Page 245 - Haematologica Atlas of Hematologic Cytology

CHAPTER 30 - Hypereosinophilic syndrome
Chapter 30. HYPEREOSINOPHILIC SYNDROME
Idiopathic hypereosinophilic syndrome (HES) is characterized by eosinophilia (≥1.5x109/L) of at least six mon- ths duration without any recognizable underlying cause. It is associated with signs of organ involvement and dysfunction. Tissue damage is due to infiltration by eosinophils and release of cytokines and humoral factors from the eosinophil granules; the heart, lungs, central nervous system, skin, and gastrointestinal tract are com- monly involved. The most serious clinical manifestation is endomyocardial fibrosis with consequent restrictive cardiomyopathy. When there is persistent eosinophilia without tissue damage, the term “idiopathic hypereosi- nophilia” is recommended (Bain et al., 2017).
In the peripheral blood, almost all eosinophils are mature with only occasional precursors, and various mor- phological abnormalities may be observed, such as nuclear hypo- or hypersegmentation, cytoplasmic hypogra- nulation, vacuolization, small size of the granules. Eosinophilia may be associated with neutrophilia, monocytosis or mild basophilia, but white blood cells other than eosinophils are morphologically normal. Bone marrow is hypercellular with hyperplasia of the eosinophilic lineage; erythropoiesis and megakaryopoiesis are normal, and there is no increase in blast cells. Marrow fibrosis is frequent, and Charcot-Leyden crystals are often found in macrophages.
All causes of reactive eosinophilia must be excluded by appropriate, thorough investigation. Conditions to be excluded include: parasitic infection, allergies, pulmonary diseases such as Loeffler s syndrome, skin diseases, and collagen vascular disorders. Hematologic malignancies such as T-cell lymphoma, Hodgkin lymphoma, acute lymphoblastic leukemia, myeloproliferative neoplasms, and systemic mastocytosis may also be associated with the release of cytokines (IL-2, IL-3, IL-5 or GM-CSF) and a reactive eosinophilia. Persistent eosinophilia is someti- mes due to the abnormal release of cytokines by a clonal or non-clonal immunophenotypically abnormal T-cell population; this condition must also be excluded. In such cases, the term “lymphocytic variant of HES” is used.
Finally, the differential diagnosis between HES or idiopathic hypereosinophilia and neoplastic eosinophil pro- liferation (chronic eosinophilic leukemia, myeloid/lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1) is based on genetic and molecular genetic studies to exclude eosinophil clonality, and/or on peripheral and bone marrow blast count (see Chapters “Myeloproliferative neoplasms” and “Myeloid/ lymphoid neoplasms with eosinophilia and gene rearrangement”). Patients with HES or idiopathic hypereosi- nophilia, however, should be carefully monitored since the evidence of the leukemic nature of the process may only emerge later.
Reference
Bain BJ, Horny H-P, Hasser ian RP, Orazi A. Chronic eosinophilic leukaemia, NOS. In: Swerdlow SH, Campo E, Harris NL et al (Eds). WHO Classification of Tumours of Hematopoietic and Lymphoid tissues (Revised 4th edition). IARC: Lyon; 2017. p. 54-56.
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