65 Eosinophils and Their Disorders Flashcards
Most specific eosinophilopoietic growth factor
IL-5
Eosinophils persist in the circulation for ______ hours
25 hours
Granular proteins uniquely expressed by eosinophils
EPX and MBP-2
Majority of mature eosinophilic granules are
Secondary (specific) large granules
The smaller primary granules of eosinophils contain
Charcot-Leyden Crystal protein (Galectin-10)
Cell surface markers of eosinophils using flow cytometry
EMR-1, Siglec-8, and CCR3 (CD193)
In tissues, eosinophils can be detected by immunohistochemistry using
MBP, ECP, and EPX stains
Eosinophilia is defined as
Exceeding the upper limit of normal and an absolute eosinophil count (AEC) of 0.35–0.5 ×10 9 /L
Severity of eosinophilia
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)
Hypereosinophilia (HE) is defined as
Persistent eosinophilia greater than 1.5 × 10 9 /L
Divided into primary (clonal or neoplastic), secondary (reactive), hereditary (familial), or HE of undetermined significance
Hypereosinophilic syndrome (HES)
(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
Idiopathic HE or HE of undetermined significance
Patients with an absolute eosinophil greater than 1.5 × 10 9 /L are asymptomatic with no end-organ damage
Gene rearrangement associated with myeloid/lymphoid neoplasms with eosinophilia
PDGFRA, PDGFRB, and fibroblast growth factor receptor (FGFR) 1, PCM1-JAK2
Incidence of FIP1L1–PDGFRA fusion with idiopathic HE or HES
10%
Most common clinical manifestations at presentation of HES
Skin (37%)
Lungs (25%)
GI tract (14%)
At table: Hematopoetic, heart, skin, nervous system
Rare HES-like hereditary immune deficiencies characterized by an elevated IgE level, eczema-like skin rashes, characteristic facial and dental abnormalities, and recurrent infections
Hyper IgE syndromes
Mutations in Hyper IgE syndromes
Autosomal dominant mutations- STAT3 (Job syndrome)
Autosomal recessive mutations- DOCK8, PGM3, SPINK5, or TYK2
An elevated serum vitamin B12 level is commonly seen in primary HES/CEL, NOS, caused by __________
Increased production of the haptocorrins
Useful screening test in patients with HE
Tryptase
Useful in the diagnosis of lymphocyte-variant HE/HES
Testing for clonal T lymphocytes by flow cytometry and polymerase chain reaction (PCR)/next-generation sequencing (NGS)
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.
TRUE
In using FISH in the diagnosis of primary HES, this is a surrogate for FIP1L1-PDGFRA fusion gene
CHIC2 deletion
Interstitial submicroscopic microdeletion on the long arm of chromosome 4
Immunohistochemical staining to identify increased numbers of neoplastic mast cells
CD117, tryptase, and CD25
Translocations that warrants FISH testing for PDGFRA, PDGFRB, FGFR1, JAK2, or FLT3
4q12, 5q31~33, 8p11~12, 9p24, or 13q12
In patients with elevated tryptase, testing should be undertaken for________
KIT D816V mutation
Most common gene partner of:
PDGFRA: _________
PDGFRB: _________
FGFR1: __________
JAK2: _________
ABL1: _________
FLT3: _________
PDGFRA: FIP1L1
PDGFRB: ETV6
FGFR1: ZMYM2
JAK2: PCM1
ABL1: ETV6
FLT3: ETV6
There is a remarkable ________ predominance in patients with FIP1L1PDGFRA, PDGFRB, and JAK2 fusions for unknown reason
male predominance
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
TRUE OR FALSE
Higher standard doses of imatinib being required for patients with PDGFRA and PDGFRB rearrangements than patients with CML
FALSE
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
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
Most common mutation in patients with primary or secondary resistance to imatinib in patients with PDGFRA/PDGFRB rearrangements
T674I (most commonly) and D842V
TKI with partial activity against the FGFR1 tyrosine kinase
Ponatinib
FGFR1 inhibitor
Pemigatinib
TRUE OR FALSE
AHSCT is recommended following TKI inhibition in PDGFRA and PDGFRB
FALSE
This fusion gene is cryptic and not detected by routine cytogenetics unless alternatve gene partners present
FIP1L1
Preferred or Potential TKI in JAK2
Ruxolitinib
Preferred or Potential TKI in ABL1
Imatinib
Nilotinib
Dasatinib
Preferred or Potential TKI in FLT3
Sorafenib
Sunitinib
Midostaurin
Second generation FLT3 inhibitors
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
Treatment options for CEL, NOS
Hydroxyurea
Interferon (INF)-α
Imatinib
Allogeneic HSCT
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–
Patients with lymphocyte variant HE or HES are at a slightly increased risk of _______________
Lymphomas, mainly T-cell lymphoma and Sézary syndrome
Treatment for lymphocyte variant HE or HES
Glucocorticoids
Glucocorticoid-sparing agent such as INF-α, cyclosporine, or anti–IL-5–directed therapy
A humanized monoclonal IgG1 antibody that binds free IL-5
Mepolizumab
A humanized afucosylated monoclonal antibody against the IL-5Rα chain
Benralizumab
Mainstay of treatment for idiopathic HES
Glucocorticoids
Mainstay of treatment for organ-restricted HES
Glucocorticoids
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)
Treatment for eosinophilic esophagitis
Reslizumab
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.
Mutation in AML with increased marrow eosinophils
Core binding factor (CBF)
In MDS patients, eosinophilia greater than ___________ predicts significantly reduced survival and marrow eosinophilia is associated with complex karyotype
0.35 × 10 9 /L
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
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
Rare benign chronic inflammatory disease characterized by lymphadenopathy, elevated IgE levels, and eosinophilia
Kimura disease
Toxic oil:________
Eosinophilia–myalgia syndromes: __________
Toxic oil:contaminated rapeseed oil
Eosinophilia–myalgia syndromes: tryptophan supplements
Mature eosinophils are normally present in the gastrointestinal (GI) tract except in the
Esophagus
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)
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
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
Patients with neurologic symptoms should undergo brain imaging (with or without cerebral angiography), with preference for
Magnetic resonance imaging
Mixed lineage (eg, undifferentiated or biphenotypic leukemia) presentation is more common with ____________ fusions
FGFR1 fusions
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
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
In patients presenting with eosinophilic fasciitis, evaluation of underlying_______ is recommended.
MDS
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
