Eosinophilis and eosinophilia

1. SLIDE PRESENTATION
HEMATOLOGY
Sansar Babu Tiwari, MBBS, PGY I
Department of Pathology
TUTH
17th July 2019
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2. Single Wright-stained Peripheral Blood Smear
WBC MORPHOLOGY:
1. Neutrophils (15%)
Segmented nucleus with pink granules in cytoplasm
2. Lymphocytes(27%)
Deep purple nucleus almost covering cell and sky blue cytoplasm
3. Monocytes(5%)
Indented dark purple nucleus with blue-grey cytoplasm
SLIDE PRESENTATION
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3. WBC MORPHOLOGY:
4. Eosinophils (53%)
Segmented nucleus with orange granules in cytoplasm
 Mostly bilobed
 Few 3-4 lobed
 Occasional unilobed
 Blasts not seen
SLIDE PRESENTATION
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4. RBC MORPHOLOGY:
Normochromic Normocytic
Parasites not seen
PLATELET MORPHOLOGY:
Adequate
SLIDE PRESENTATION
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5. Olympus, 40x
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6. Olympus, 40x
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7. Olympus, 100x
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8. Olympus, 100x
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9. Olympus, 100x
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10. Peripheral Blood Eosinophilia
PROVISIONAL DIAGNOSIS
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11. EOSINOPHILS
Eosinophils are mobile, terminally differentiated
granulocytes that arise principally from the bone marrow.
8-10 µm in diameter (Wintrobes), 12-17 µm in diameter
(Dacie)
Large crystalloid (secondary/specific) granules  bright
red staining properties with acidic dye like eosin.
Eosin loving (Eosinophile) 11

12. Eosinophil is slightly larger than the neutrophil, much longer
lived, and unlike neutrophils, tissue eosinophils can recirculate
(Harrisons 20th Edition) [Once eosinophils enter target tissues, eosinophils
donot return to blood circulation; Wintrobe’s Clinical Hematology, 14th edition]
Nucleus is usually bilobed but occasional nuclei are trilobed,
average lobe count being 2.3
In females, eosinophils may have drum sticks
Eosinophil granules are spherical and considerably larger than
those of neutrophils; they pack the cytoplasm and are stained
reddish-orange
EOSINOPHIL
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13. Nuclei may show hypersegmentation (Megaloblastic
anemia, Down syndrome  Decrease eosinophil count),
hyposegmentation (Pelger-Huet anomaly) or ring-shaped
nuclei (not specific).
Abnormal eosinophilic granules: Chediak-Higashi
Syndrome  blue-grey; Alder-Reilly anomaly  grey-green
or purple; GM1 gangliosidosis type 1: vacuolation and
abnormal stain
Cytoplasmic Inclusions are present in the May-Hegglin
anomaly and Brandalise (actin inclusion) syndrome
EOSINOPHIL
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14. BIRTH of EOSINOPHILS
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15. BIRTH of EOSINOPHILS
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16. BIRTH of EOSINOPHILS
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17. EOSINOPHILS
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18. EOSINOPHILS
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19. Peripheral and tissue eosinophils are derived by
hemopoiesis from CD34+ myelocytic progenitors
found in bone marrow and inflamed tissues.
Approx 3% of the bone marrow
37% are fully differentiated
Remainder are pro(myelocytes) and metamyelocytes.
Newly matured cell occurs in blood approx 2.5
days from the time of last mitotic division.
EOSINOPHIL DIFFERENTIATION
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20. Extramedullary Recruitment of
EOSINOPHILS
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21. Tissue migration of EOSINOPHILS
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22. GRANULES of EOSINOPHILS
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23. 1. Crystalloid Granules: Electron dense core surr. by electron-
lucent matrix, can take up acidic dyes due to their cationic
nature. Mostly in mature Eo. MBP (Arginine-rich protein, has histaminase
activity  imp in parasite defense), EPX, ECP, EDN. About 200/Eo.
2. Primary Granules: CLC Proteins (Lyophospholipase) mostly
in immature Eo.
3. Small Granules: Acid Phosphatase, Arylsulfatase B, Catalase
and Cyt b558
4. Lipid Bodies: About 5/mature eosinophils, may be increased
in HE….. AA  GlyPLs
5. Secretory Vesicles: DUMBBELL SHAPED IN CROSS SECTION
GRANULES of EOSINOPHILS
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24. GRANULES of EOSINOPHILS
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25. Degranulation of EOSINOPHILS
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26. Eosinophils form phagosome (phagocytic)
Helminth releases granules
Immediate-type Hypersensitivity reactions
Neutralized histamine and downregulates allergic reactions
When in excessive levels, tissue damage and
endomyocardial fibrosis
Function of EOSINOPHILS
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27. EOSINOPHILIA
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28. Eosinophilia is defined as an Absolute eosinophilic count (AEC) more
than 0.5 x 109 /L independent of age
Peripheral Blood Eosinophilia, Wintrobe’s
Hematology 14th edition, 2019:
• Mild: 0.5-1.5 x 109 /L
• Moderate: 1.5-5.0 x 109 /L
• Marked: >5.0 x 109 /L
Transient, Episodic and
Persistent (chronic)
Persistent eosinophilia is defined as PB eosinophilia recorded on at
least two occasions with a minimum time interval of 4 weeks
SOME TERMINOLOGIES
Williams Hematology 9th edition:
Mild: < 1.0 x 109 /L
Moderate: 1.0-5.0 x 109 /L
High: >5.0 x 109 /L
Wintrobe’s Atlas of Hematology
2nd edition, 2018:
Mild 0.5 – 1.5 x 109 /L
Marked >1.5 x 109 /L
Massive >5.0 x 109 /L
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29. Hypereosinophilia in PB is defined as an AEC >1.5 x 109 /L and is
usually persistent.
Hypereosinophilic syndrome is defined by the presence of HE
for atleast 6 months, with eosinophil-mediated organ damage
and/or dysfunction with no other etiology for eosinophilia.
For every 1 eosinophil in blood there are hundreds in the
tissues.
Diurnal variation reciprocally with serum cortisol level. Morning
 Increased cortisol  Decreased eosinophil count (40 %
variation)
SOME TERMINOLOGIES
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30. EOSINOPHILIA
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31. Non-neoplastic or Reactive
Most frequent cause of eosinophilia
Tissue invasive helminthes
Allergic/vasculitis disease
Drugs
Metastatic cancers
SECONDARY EOSINOPHILIA
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32. Clonal: Diagnosis requires morphologic,
cytogenetic, or molecular evidence of a myeloid
neoplasm.
Eosinophilia a/w AML, MDS, CML, mastocytosis,
MDS/MPN overlap
Idiopathic: When both secondary and clonal
eosinophilias have been ruled out
PRIMARY EOSINOPHILIA
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33. PRIMARY EOSINOPHILIA
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34. PRIMARY EOSINOPHILIA
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35. CAUSES OF EOSINOPHILIA
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36. CAUSES OF EOSINOPHILIA
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37. CAUSES OF EOSINOPHILIA
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38. RARE CAUSES OF EOSINOPHILIA
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39. ORGAN EFFECTS of EOSINOPHILIA
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40. IL-5, The Main Culprit
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41. PARASITIC INFESTATIONS
Studies have suggested that eosinophils may have a protective role in
Strongyloides and Filariasis but not in Schistosoma, Nippostrongylus,
and Trichuris infections
Trichenella spiralis: Primary infection  ↑IL-10  decreased
intracellular NO-mediated larval killing, Secondary infection 
Eosinophils are protective for host
Mechanism of eosinophilia in parasitic disease is thought to be similar
to allergic disease, with a Th2-type response mediated by both
adaptive Th2 cells and innate lymphoid Type 2 cells to helminthic
antigens resulting in increased production of eosinophil GF, in
particular IL-5. Recruitment of Eo to the site of parasitic infection may
involve nematode induced production of LTB4 by Eo.
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42. PARASITIC INFESTATIONS
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43. PARASITIC INFESTATIONS
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44. Peripheral blood eosinophilia (5000-9000/µL) is the
most characteristic finding
Levels over 1500cells/µL (or >10% of TLC) should
prompt suspicion of EGPA
Corticosteroid treatment may sometimes obscure
eosinophilia
Asthma, Mononeuopathy and Paranasal sinus
abnormality are frequently present 44
EGPA

45. ASTHMA
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46. HYPEREOSINOPHILIC SYNDROME
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47. HODGKINS LYMPHOMA
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48. HODGKINS LYMPHOMA
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49. ADRENAL INSUFFICIENCY
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50. OLMSTED SYNDROME
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51. OMENN SYNDROME
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52. JOBBS SYNDROME
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53. GLEICH SYNDROME
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54. WELLS SYNDROME
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55. KIMURA vs ALHE
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56. Acute Eosinophilic Leukemia 1912
AML M4 (myelomonocytic) with bone marrow eosinophilia
[Inv16/Translocation 16] is a different entity
AEL can arise denovo as AML, with 50-80% of eosinophilic
cells in the bone and marrow
Anemia, thrombocytopenia and blast cells in blood and
marrow
Eosinophilic cells are dysmorphic and the cytoplasm
hypogranulated with smaller than normal eosinophilic
granules
AES may develop in patients having the chronic form of HES
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57. Acute Eosinophilic Leukemia 1912
Patients with AEL donot usually develop bronchospastic
signs, neurological signs and heart failure from
endomyocardial fibrosis as seen in CEL, probabaly
because those tissue changes are the result of release
of toxins in the granule crystalloid, absent in most
eosinophils in AEL and shorter duration of survival.
Hepatomegaly, splenomegaly and lymphadenopathy
are more common than in other variants of AML.
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58. Chronic Eosinophilic Leukemia
Eosinophilic variant of Chronic Myelomonocytic leukemia
(PDGFR-β) is a distinct entity
Cytological findings in CEL are different and some cases
involve PDGFR-α (2 orders of magnitude more
responsive to imatinib than BCR-ABL1)
Serum IgE, vitamin B12 and tryptase levels are usually
elevated
Patients with normal tryptase level are more prone to
eosinophilic dermatitis and GI complaints. 58

59. REFERENCES:
1. Wintrobe’s Clinical Hematology, 14th edition, 2019
2. Wintrobe’s Atlas of Hematology, 2nd edition, 2018
3. William’s Hematology, 9th edition, 2016
4. Dacie Practical Hematology, 12th edition, 2017
5. Eosinophils in Health and Disease, 1st edition, 2013
6. Blood cells A Practical Guide, 5th edition, 2015
7. Post Graduate Hematology, 6th edition, 2011
8. Harrisons Principle of Internal Medicine, 20th Edition,
2018
9. Robbins and Cotran Pathological Basis of Disease, 9th
edition, 2015
10. www.ncbi.nlm.nih.gov/pubmed
11. www.pathologyoutlines.com
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