Chronic Eosinophilic Leukemia, NOS Flashcards
What is the definition of
chronic eosinophilic leukemia ?
- autonomous clonal proliferation of eosinophil precursors
- persistently increased eosinophils in the PB, BM, and peripehral tissues
- eosinophilia is the dominant abnormality
- organ damage
- from leukemic infiltration
- release of cytokines
- enzymes and other proteins
What is necessary for the diagnosis
of CEL, NOS ?
- eosinophil count of 1.5 x10^9/L in the blood
- <20% blasts in the peripheral blood and bone marrow
- evidence of clonality in the myeloid cells or an increase in peripheral blood/bone marrow blasts
In cases where there is no clear
evidence of clonality or increased blasts
what diagnosis is rendered ?
- Idiopathic Hypereosinophilic Syndrome
- eosinophilia ( >1.5 x10^9/L) persisting for > 6 months
- No underlying cause for the eosinophilia has been discovered
- presence of associated signs and symptoms of organ involvement and dysfunction
- no evidence of clonality
- may be caused by unrecognized release of eosinophil cytokines:
- IL2, IL3, and IL5
When can the diagnosis of
Idiopathic Hypereosinophilia be rendered ?
- when the criteria for idiopathic hypereosinophilic syndrome are met with the exception:
- NO evidence of tissue damage
What is the epidemiology of
CEL, NOS ?
- true incidence of these rare diseases is unknown
- seems to be more common in men
- generally in 7th decade
What is the localization of
CEL, NOS ?
- multisystem disease
- PB and BM
- tissue infiltration with damage by eosinophils
- heart, lung, CNS
- skin, GI tract
- spleen and liver
What are the clinical features
of CEL, NOS ?
- eosinophilia is sometimes incidentally identified
- constitutional symptoms:
- most severe: endomyocardial fibrosis with CHF
- weight loss, night sweats, fever, fatigue, cough
- pruritis, diarrhea
- angio-edema
- symptoms to organ specific infiltration are frequently seen
- rheumatologic manifestations are common
What is the most common finding
in the peripheral blood ?
- mature eosinophils are predominant
- few immature myelocytes and promeylocyte eosinophils
- range of eosinophil abnormalities (can be seen in reactive conditions as well)
- sparse granulation (clear cytoplasm)
- cytoplasmic vacuolization
- nuclear hypersegmentation or hyposegmentation
- increased size
If present, what morphologic finding
supports the diagnosis of CEL, NOS ?
- the presence of dysplasia in cells of other myeloid lineages
- generally have a neutrophilia with mild monocytosis
- diagnostic criteria for CMML are NOT met
- mild basophilia can be present
- blasts can be seen but should be <20%
What are the morphologic
findings in the bone marrow of CEL, NOS ?
- hypercellular due to eosinophil infiltration
- eosinophil maturation is orderly
- charcot leyden crystals are seen
- erythroids and megas are normal
- increased blasts (>2% PB, 5-19% BM) support the diagnosis as long as there are no dysplastic features in other cells lines
- marrow fibrosis is in 1/3 of cases but severe fibrosis is rare
What is the differential diagnosis/
entities that must be excluded in order to
diagnose CEL, NOS ?
- myeloid neoplasms with PDGFRA, PDGFRB or FGFR1 or PCM-JAK2
- ETV6-JAK2
- BCR-JAK2 fusion
- reactive eosinophilia
- parasitic infection, allergies, pulmonary diseases like Loffler syndrome, cyclical eosinophilia, angiolymphoid hyperplasia, collagen vascular disorders and Kimura disease
What neoplastic disorders can present
with eosinophilia ?
- T cell lymphomas
- Hodgkin Lymphoma
- Systemic mastocytosis
- Lymphoblastic leukemia
- AML
- MPNS
release of eosinophil stimulating cytokines leads to eosinophilia:
- IL2, IL3, IL5 or G-CSF
When there is eosinophilia and the
presence of increased spindle shaped mast cells
what genetic abnormality should be considered ?
- rearrangement of PDGFRA or PDGFRB
When can the diagnosis of
Lymphocytic variant of Hypereosinophilic Syndrome
be used?
- when a neoplastic T cell population is driving the eosinophilia and organ damage
- If the monocyte count is high, a diagnosis of CMML with eosinophilia may be more appropriate
When should the consideration of a
diagnosis of atypical CML with
eosinophilia be made ?
- BCR-ABL1 negative
- eosinophilia
- >10% neutrophil precursors in the peripheral blood
- no monocytosis
What is the immunophenotype
of CEL, NOS ?
- No specific immunophenotypic abnormality has been described
What is the cell of origin
for CEL, NOS ?
- hematopoietic stem cell
- reports of T lymphoblastic transformation
What are the genetics of
CEL, NOS ?
- no single or specific cytogenetic or molecular abnormality has been identified
- even with a myeloid genetic abnormality hard to differentiate reactive eosinophils to the myeloid neoplasm
- BUT if recurrent karyotype abnormality often seen in myeloid neoplasms is present can call CEL, NOS
- gain of chromosome 8
- loss of chromosome 7
- isochromosome 17q
- also see ASLX1, TET2, EZH2 and rarely JAK2
- BUT if recurrent karyotype abnormality often seen in myeloid neoplasms is present can call CEL, NOS
What can be a molecular
pitfall in CEL, NOS?
- mutations in genes TET2, ASXL1 and DNMT3A have been reported in elderly people without myeloid neoplasms so if present with eosinophilia cannot definitivey say it is CEL, NOS.
What are the prognostic and predictive
factors for CEL-NOS ?
- survival is variable but acute transformation can occur
- prognosis overall is very poor (22 months)
- response to Imatinib is uncommon but has been reported
Unfavorable features in
CEL, NOS ?
- marked splenomegaly
- blasts in the blood or increased blasts in BM
- cytogenetic abnormalities
- dysplastic features in other myeloid lineages
