65 Eosinophils and Their Disorders Flashcards

(66 cards)

1
Q

Most specific eosinophilopoietic growth factor

A

IL-5

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2
Q

Eosinophils persist in the circulation for ______ hours

A

25 hours

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3
Q

Granular proteins uniquely expressed by eosinophils

A

EPX and MBP-2

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4
Q

Majority of mature eosinophilic granules are

A

Secondary (specific) large granules

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5
Q

The smaller primary granules of eosinophils contain

A

Charcot-Leyden Crystal protein (Galectin-10)

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6
Q

Cell surface markers of eosinophils using flow cytometry

A

EMR-1, Siglec-8, and CCR3 (CD193)

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7
Q

In tissues, eosinophils can be detected by immunohistochemistry using

A

MBP, ECP, and EPX stains

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8
Q

Eosinophilia is defined as

A

Exceeding the upper limit of normal and an absolute eosinophil count (AEC) of 0.35–0.5 ×10 9 /L

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8
Q

Severity of eosinophilia

A

Mild (AEC <1.5 ×10 9 /L)
Moderate or marked (AEC 1.5–5 × 10 9 /L)
Severe or massive (AEC >5 × 10 9 /L)

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9
Q

Hypereosinophilia (HE) is defined as

A

Persistent eosinophilia greater than 1.5 × 10 9 /L

Divided into primary (clonal or neoplastic), secondary (reactive), hereditary (familial), or HE of undetermined significance

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10
Q

Hypereosinophilic syndrome (HES)

A

(a) a persistent eosinophilia of greater than 1.5× 10 9 /L for longer than 6 months or death before 6 months associated with the signs and symptoms of hypereosinophilic disease

(b) a lack of evidence for parasitic, allergic, or other known causes of eosinophilia; and

(c) presumptive signs and symptoms of organ involvement

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11
Q

Idiopathic HE or HE of undetermined significance

A

Patients with an absolute eosinophil greater than 1.5 × 10 9 /L are asymptomatic with no end-organ damage

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12
Q

Gene rearrangement associated with myeloid/lymphoid neoplasms with eosinophilia

A

PDGFRA, PDGFRB, and fibroblast growth factor receptor (FGFR) 1, PCM1-JAK2

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13
Q

Incidence of FIP1L1–PDGFRA fusion with idiopathic HE or HES

A

10%

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14
Q

Most common clinical manifestations at presentation of HES

A

Skin (37%)
Lungs (25%)
GI tract (14%)

At table: Hematopoetic, heart, skin, nervous system

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15
Q

Rare HES-like hereditary immune deficiencies characterized by an elevated IgE level, eczema-like skin rashes, characteristic facial and dental abnormalities, and recurrent infections

A

Hyper IgE syndromes

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16
Q

Mutations in Hyper IgE syndromes

A

Autosomal dominant mutations- STAT3 (Job syndrome)

Autosomal recessive mutations- DOCK8, PGM3, SPINK5, or TYK2

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17
Q

An elevated serum vitamin B12 level is commonly seen in primary HES/CEL, NOS, caused by __________

A

Increased production of the haptocorrins

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18
Q

Useful screening test in patients with HE

A

Tryptase

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19
Q

Useful in the diagnosis of lymphocyte-variant HE/HES

A

Testing for clonal T lymphocytes by flow cytometry and polymerase chain reaction (PCR)/next-generation sequencing (NGS)

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20
Q

TRUE OR FALSE

Given its dire consequences, all patients with HE and HES should be screened for cardiac involvement with troponin (T or I) looking for myocarditis and an echocardiogram (+/- N-terminal pro B-type natriuretic peptide [NT-BNP]) to evaluate the presence of cardiomyopathy.

A

TRUE

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21
Q

In using FISH in the diagnosis of primary HES, this is a surrogate for FIP1L1-PDGFRA fusion gene

A

CHIC2 deletion

Interstitial submicroscopic microdeletion on the long arm of chromosome 4

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22
Q

Immunohistochemical staining to identify increased numbers of neoplastic mast cells

A

CD117, tryptase, and CD25

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23
Q

Translocations that warrants FISH testing for PDGFRA, PDGFRB, FGFR1, JAK2, or FLT3

A

4q12, 5q31~33, 8p11~12, 9p24, or 13q12

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24
In patients with elevated tryptase, testing should be undertaken for________
KIT D816V mutation
25
Most common gene partner of: PDGFRA: _________ PDGFRB: _________ FGFR1: __________ JAK2: _________ ABL1: _________ FLT3: _________
PDGFRA: FIP1L1 PDGFRB: ETV6 FGFR1: ZMYM2 JAK2: PCM1 ABL1: ETV6 FLT3: ETV6
26
There is a remarkable ________ predominance in patients with FIP1L1PDGFRA, PDGFRB, and JAK2 fusions for unknown reason
male predominance
27
Treatment of choice for patients with PDGFRA and PDGFRB rearrangements
**Imatinib** PDGFRA: starting dose of **100 mg/day** with dose increase to 400 mg PDGFRB: initially with **400 mg/day**, and the dose is then lowered to 100 mg/day
28
TRUE OR FALSE Higher standard doses of imatinib being required for patients with PDGFRA and PDGFRB rearrangements than patients with CML
FALSE ## Footnote **LOWER** standard doses of imatinib being required for patients with PDGFRA and PDGFRB rearrangements than patients with CML who present with chronic phase disease since in vitro, PDGFRA and PDGFRB rearrangements are **MORE SENSITIVE to imatinib** compared with BCR-ABL1
29
Drug added to Imatinib to **dampen the immune response** and **lessen the risk of myocardial injury** from degranulation of eosinophils
Prophylactic **glucocorticoids** during the initial **1 to 2 weeks** of imatinib therapy
30
Most common mutation in patients with primary or secondary resistance to imatinib in patients with PDGFRA/PDGFRB rearrangements
**T674I** (most commonly) and D842V
31
TKI with partial activity against the **FGFR1** tyrosine kinase
Ponatinib
32
FGFR1 inhibitor
Pemigatinib
33
TRUE OR FALSE AHSCT is recommended following TKI inhibition in PDGFRA and PDGFRB
FALSE
34
This fusion gene is cryptic and not detected by routine cytogenetics unless alternatve gene partners present
FIP1L1
35
Preferred or Potential TKI in JAK2
Ruxolitinib
36
Preferred or Potential TKI in ABL1
Imatinib Nilotinib Dasatinib
37
Preferred or Potential TKI in FLT3
Sorafenib Sunitinib Midostaurin Second generation FLT3 inhibitors
38
HE with concomitant evidence of a clonal cytogenetic or molecular abnormality OR An increase in myeloblast percentage in the marrow or blood (≥5% and 2%, respectively but <20% to exclude acute leukemia)
CHRONIC EOSINOPHILIC LEUKEMIA, NOT OTHERWISE SPECIFIED
39
Treatment options for CEL, NOS
Hydroxyurea Interferon (INF)-α Imatinib Allogeneic HSCT
40
Flow immunophenotypic abnormalities in lymphocyte variant HE or HES
**Absence of CD3** from the T-cell receptor complex **(CD3 CD4+)** **Double-negative immature T cells (CD3+ CD4– CD8–)** **CD3+ CD4+ CD7–**
41
Patients with lymphocyte variant HE or HES are at a slightly increased risk of _______________
Lymphomas, mainly **T-cell lymphoma and Sézary syndrome**
42
Treatment for lymphocyte variant HE or HES
**Glucocorticoids** ## Footnote Glucocorticoid-sparing agent such as **INF-α, cyclosporine**, or **anti–IL-5–directed therapy**
43
A humanized monoclonal IgG1 antibody that binds free IL-5
Mepolizumab
44
A humanized afucosylated monoclonal antibody against the IL-5Rα chain
Benralizumab
45
Mainstay of treatment for idiopathic HES
Glucocorticoids
46
Mainstay of treatment for organ-restricted HES
Glucocorticoids
46
Treatment for eosinophilic asthma
**Mepolizumab** (100 mg subcutaneously every 4 weeks) **Reslizumab** (anti–IL-5 antibody dosed at 3 mg/kg intravenously every 4 weeks) **Benralizumab** (30 mg subcutaneously every 4 weeks)
47
Treatment for eosinophilic esophagitis
Reslizumab
48
TRUE OR FALSE Eosinophilia can be seen in patients with several WHO-defined myeloid and lymphoid neoplasms, but it is common to have eosinophil-mediated organ damage in these patients.
FALSE Eosinophilia can be seen in patients with several WHO-defined myeloid and lymphoid neoplasms, but it is UNCOMMON to have eosinophil-mediated organ damage in these patients.
49
Mutation in AML with increased marrow eosinophils
Core binding factor (CBF)
50
In MDS patients, eosinophilia greater than ___________ predicts significantly reduced survival and marrow eosinophilia is associated with complex karyotype
0.35 × 10 9 /L
51
TRUE OR FALSE The presence of eosinophilia in MDS and SM carries prognostic significance
TRUE The presence of eosinophilia in MDS and SM carries prognostic significance
52
Rare disease characterized by **cyclic eosinophilia**, **angioedema, fever, weight gain, polyclonal IgM**, and **aberrant CD3 - clonal T cells** that occur every 3–4 weeks and self-resolves with spontaneous diuresis
Gleich syndrome
53
Rare benign chronic inflammatory disease characterized by **lymphadenopathy, elevated IgE levels,** and **eosinophilia**
Kimura disease
54
Toxic oil:________ Eosinophilia–myalgia syndromes: __________
Toxic oil:contaminated rapeseed oil Eosinophilia–myalgia syndromes: tryptophan supplements
55
Mature eosinophils are normally present in the gastrointestinal (GI) tract except in the
Esophagus
56
Eosinophil's granular contents
Proteins (eg, major basic proteins [MBP], eosinophil peroxidase [EPX], eosinophil cationic protein [ECP], and eosinophil derived neurotoxin) Enzymes (eg, nonspecific esterase and catalase) Inflammatory mediators/cytokines (eg, eotaxin, ILs, and leukotriene C4)
57
TRUE OR FALSE The workup of patients presenting with HE starts with excluding secondary (reactive) causes and screening for end-organ involvement
TRUE The workup of patients presenting with HE starts with excluding secondary (reactive) causes and screening for end-organ involvement
58
TRUE OR FALSE Elevated immunoglobulin (Ig) E levels is a nonspecific finding that is mostly seen in reactive conditions (infectious, allergic, vasculitis, and lymphocytevariant HES)
TRUE Elevated immunoglobulin (Ig) E levels is a nonspecific finding that is mostly seen in reactive conditions (infectious, allergic, vasculitis, and lymphocytevariant HES) But its elevation is variable in patients with primary HES/CEL, NOS
59
Patients with neurologic symptoms should undergo brain imaging (with or without cerebral angiography), with preference for
Magnetic resonance imaging
60
Mixed lineage (eg, undifferentiated or biphenotypic leukemia) presentation is more common with ____________ fusions
FGFR1 fusions
61
TRUE OR FALSE The presence of T-cell receptor rearrangements without phenotypic abnormality on flow cytometry is not considered sufficient for the diagnosis of lymphocyte-variant HES and should be interpreted with caution
TRUE The presence of T-cell receptor rearrangements without phenotypic abnormality on flow cytometry is not considered sufficient for the diagnosis of lymphocyte-variant HES and should be interpreted with caution
62
TRUE OR FALSE Patients with idiopathic HES who have marrow findings similar to CEL, NOS (discussed earlier) but do not meet its diagnostic criteria have a worse prognosis than those without such marrow abnormalities
TRUE Patients with idiopathic HES who have marrow findings similar to CEL, NOS (discussed earlier) but do not meet its diagnostic criteria have a worse prognosis than those without such marrow abnormalities
63
In patients presenting with eosinophilic fasciitis, evaluation of underlying_______ is recommended.
MDS
64
TRUE OR FALSE Acute and chronic graft-versus-host disease can present with eosinophilia and is probably a poor prognostic biomarker in these patients
FALSE Acute and chronic graft-versus-host disease can present with **eosinophilia** and is probably a **good prognostic biomarker** in these patients