CH.10 Non-neoplastic granulocytic and monocytic disorders Flashcards
(50 cards)
1
Q
What is the normal morphology
of a non-activated neutrophil ?
A
- 4-5 nuclear lobes separated by thin chromatin fibers
- clumbed chromatin
- orange cytoplasmic hue (Wright stain)
- due to many secondary granules
Note: ~50% of the neutrophils in circulation come from the marginated pool
2
Q
What are features that represent likely
reactive neutrophilia ?
A
- toxic changes
- WBC < 50 x 10^9/L
- known history of chemotherapy
- known history of G-CSF therapy
- known stressful condition/solid tumor
3
Q
What are features that favor a neoplastic
neutrophilia ?
A
- WBC > 50 x 10^9/L
- Basophilia
- Dysplasia
- persistent unexplained WBC > 20 x 10^9/L or monocytosis of >1000 (1 x10^9/L)
- Non-toxic left shift with blasts
- Blasts in the absence of left shift
- Auer rods
4
Q
What are some ancillary studies that can
be done on the PB if you have concern of
a myeloid malignancy with increased granulocytes ?
A
- BCR-ABL1 testing
- Cytogenetics if there are enough immature cells
5
Q
What are features that favor reactive monocytes ?
A
- known chronic infection or known chronic inflammatory state
- percent of monocytes <10%
- reactive morphologic features
6
Q
What are features that favor neoplastic monocytes ?
A
- circulating blasts
- immature monocytes
- eosinophilia
- dysplasia
- unexplained leukoerythroblastic reaction
7
Q
What additional testing on peripheral blood
can be performed if you are concerned
about neoplastic monocytes ?
A
- cytogenetics if sufficient immature cells
8
Q
What features favor a reactive eosinophilia ?
A
- reasonable explanation:
- drug
- infection
- allergy
9
Q
What features favor a neoplastic cause to
the eosinophilia ?
A
- circulating blasts (myeloid or lymphoid)
- basophilia
- circulating mast cells
- unexplained monocytosis
- eosinophils with dark granules (exclude rare Alder-Reily anomaly)
- dysplasia of granulocytes or platelets
10
Q
What ancillary studies should be performed
if suspecting a neoplastic cause to absolute eosinophilia ?
A
- T cell flow cytometry
- FISH for CHIC2 deletion
- cytogenetics if sufficient immature cells are present
- KIT D816V testing
11
Q
What features favor a reactive basophilia ?
A
- microcytic anemia (iron deficiency)
- minimal basophilia
- < 0.5 x 10^9/L
12
Q
What features favor a neoplastic cause
to the basophilia ?
A
- additional cytoses
- unexplained leukoerythroblastic reaction
- non-toxic left shift with blasts
13
Q
What additional testing on PB can be
done to evaluate absolute basophilia ?
A
- BCR-ABL1 testing
- JAK2/CALR/MPL testing
- Ferritin
- cytogenetics if sufficient immature cells are present
14
Q
What constitutional germline conditions
can have non-neoplastic absolute neutrophilia ?
A
- leukocyte adhesion factor deficiency
- CSF3R hereditary chronic neutrophilia
- familial cold urticaria
- chronic idiopathic neutrophilia (some cases)
- Down syndrome
15
Q
In the bone marrow, what are two conditions
that you can see increased, benign lymphoid aggregates ?
A
- viral infection
- autoimmune disorders
16
Q
What are morphologic features in neutrophils
that are suggestive of severe sepsis ?
A
- prominent cytoplasmic vacuoles
- toxic granules with dohle bodies
- howell-jolly body like inclusions
- also can be seen when someone is close to death
Note: cytoplasmic vacuoles are non-specific and can be seen in aged/an or degernated specimens. Also seen in:
- alcohol toxicity
17
Q
What are key things to remember when a patient
is receiving G-CSF therapy ?
A
- they can have PB and BM findings that are concerning for leukemia before the mature granulocytic forms develop
- Promyelocyte hyperplasia with reactive features can be seen early on in treatment -IMP
- rare histiocytic proliferations and bone necrosis can occur
- nuclear-cytoplasmic asynchrony
- binucleation of granulocyte precursors
- prominent paranuclear hof as well
- toxic granulation
- WBC count can be quite variable
- 13-100 x 10^9 /L
- morphologic effects of G-CSF therapy can last
- 3 days to 2 weeks post administration
18
Q
What is the morphology of any blasts that
are a result of G-CSF therapy ?
A
- they can rarely surpass 20%
- should have normal morphology
- no small blasts or Auer rods allowed
- phenotypically should be normal by flow cytometry
Note: promyelocytes should also have normal morphology, and not have:
- nuclear lobation, Auer rods or any significant lack of maturation
- typically G-CSF promyelocytes have paranuclear hofs and prominent granulation
19
Q
What can be seen on core biopsy
following G-CSF therapy ?
A
- clusters of immature/left shifted granulocytes, which can be highlighted by MPO
20
Q
Hantavirus infection can cause markedly
elevated WBC counts and specific findings on PB,
what are those ?
A
- WBC count >30 x 10^9 /L
- Key findings in PB in the florid/symptomatic phase:
- elevated hemoglobin (hemoconcentration)
- thrombocytopenia
- circulating immunoblasts that represent >10% of the lymphocytes
- neutrophilia with left shift and lack of toxic changes
21
Q
What neutrophilic disorders in kids mimic
overt neoplastic processes ?
A
- Transient abnormal myelopoiesis (clonal)
- Juvenile rheumatoid arthritis (reactive)
- Chronic EBV infection (reactive)
22
Q
What are the key findings in Transient abnormal
myelopoiesis in kids ?
A
- occurs in neonates/infants with Down Syndrome
- usually within the first 6 months of life
- transient leukocytosis with increased neutrophils and numberous blasts
- blast morphology is heterogeneous
- many megakaryoblasts as well as erythroblasts
- spontaneous recovery in 4-6 weeks, although it is clonal by molecular studies
- GATA1 mutation
- Mimics AML
23
Q
What are key PB findings in kids with juvenile
rheumatoid arthritis ?
A
- sustained leukocytosis with increased neutrophils and variable numbers of monocytes
- commonly see:
- hepatosplenomegaly
- lymphadenopathy
- often mimics Juvenile myelomonocytic leukemia
24
Q
What are the features identified in
chronic EBV infection ?
A
- usually there is an underlying immunodeficiency
- sustained leukocytosis with neutrophilia and marked monocytosis
- can see circulating immature forms
- increased LGLs are common
- anemia and thrombocytopenia are variable
- bone marrow is hypercellular and immature forms can be increased
- lymphocytosis of the bone marrow
- mimics JMML
Note: rarely can see these findings with chronic CMV infection
25
What is a Dohle-body composed of ?
* aggregates of rough endoplasmic reticulum
26
What non-neoplastic conditions are
associated with neutrophilic hyposegmentation ?
* def: nucleus with 1-2 lobes
* Conditions
* Pelger-Huet anomaly
* Acquired pseudo-Pelger-Huet (HIV, drugs, other infx)
* Major d/d consideration
* Myelodysplasia
27
What non-neoplastic conditions can cause
neutrophil hypersegmentation ?
* def: nucleus with \> 5 lobes
* Conditions
* Vitamin B12/Folate deficiency
* HIV
* Iron deficiency
* DNA inhibiting chemotherapy
* Myelokathexis (rare)
* Major d/d consideration
* Primary myeloid neoplasm
28
What non-neoplastic conditions can cause
Bytryoid/grape-like neutrophils ?
* Hyperthermia (heat stroke)
* Hemorrhagic shock and encephalopathy syndrome
29
What conditions can cause Dohle bodies
within neutrophils ?
* severe infection
* May-Hegglin disorder
* CSF effect
30
What are frequently associated with
Howell-Jolly body-like cytoplasmic
inclusions in neutrophils ?
* def: non-apoptotic nuclear fragments
* Conditions
* Immunosuppressive therapy
* Chemotherapy
* HIV
* Severe sepsis
31
What are frequent causes of cytoplasmic
vacuoles in neutrophils and monocytes ?
* bacteremia
* artifact (aged specimen)
* copper deficiency
* alcohol toxicity
* medium chain AcylCoA dehydrogenase deficiency
32
What are the findings and mutation associated
with Myelokathexis ?
* chronic marked neutropenia
* Neutrophils have thin interlobar strands, degenerative, pyknotic nuclei
* granulocytic hyperplasia and hypersegmentation can be seen in the PB and the BM
* hypercellular BM with granulocytic predominance but appropriate maturation
* Molecular defect
* WHIM syndrome (warts, hypogammaglobulinemia, infection and myelokathexis)
* CXCR4 mutation
33
What are the key findings and the mutation
in Pelger-Huet anomaly ?
* no hematologic parameters are different
* unsegmented or bilobed neutrophils are seen
* in the PB/BM they have hyposegmentation of the metamyelocytes, bands and neutrophils
* mutation:
* Lamin Beta-receptor mutation
* Autosomal dominant
* Neutrophils function normally
34
What are the key findings in
May-Hegglin ?
* macrothrombocytopenia
* neutrophils have cytoplasmic light-blue, Dohle-body like inclusions
* PB/BM may also see inclusions in eosinophils, basophils and monocytes
* mutation:
* MYH9 mutations
* Autosomal dominant
* accumulation of the myosin heavy chain that appears like dohle bodies
* Other features: thrombocytopenia, large platelets, occasional large platelets with diminished granulation
35
What are the key findings in the
Alder-Reilly phenomenon
(as a component of mucopolysaccharidosis)?
* hematologic parameters are variable and patients may have cytopenias
* Neutrophils have cytoplasmic, dark purple granules (uniform appearance)
* PB/BM findings
* inclusions in lymphocytes and monocytes
* intense cytoplasmic granulation of all myeloid cells
* eosinophils look like pseudobasophils
* Mutation
* Mucopolysaccharidosis
* typVII (Beta glucoronidase mutation)
* type VI (arylsulfatase B mutation)
36
What are the key findings of
Chediak-Higashi ?
* characterized by chronic neutropenia
* neutrophils have large azurophilic cytoplasmic inclusions
* PB/BM also see inclusions in the lymphoid cells, notably in the large granular lymphocytes
* Mutation
* LYST gene mutation
37
What is the normal morphology of
an eosinophil ?
* generally exhibits 2 nuclear lobes
* although occasionally 3 or more lobes can be seen
* minimal cytoplasmic, azurophilic granules are present
38
What is considered to be an
absolute eosinophil count for
all age groups ?
* 0.5 x 10^9/L
* there are further classifications for severity of increase
* see p. 182
39
What malignancies have been described
to present with increased eosinophils ?
* Hodgkin and non-Hodgkin lymphomas
* particularly T cells
* T cell clonality of undetermined significance
* B-ALL with t(5;14)
* Lung carcinoma
* Gastric carcinoma
40
What are causes of primary
neoplastic eosinophilias ?
* CML, BCR-ABL positive
* Myeloid/Lymphoid abnormalities with PDGFRA, PDGFRB, FGFR1 and PCM1-JAK2
* Systemic mastocytosis
* Chronic eosinophilic leukemia, NOS
* Chronic MPN (subset of them)
* MDS (subset)
* AML
* inv16 or t(16;16)
* CBFB-MYH11
41
What cytokines are thought to drive
reactive eosinophilias ?
* IL-3
* IL-5
42
What are morphologic clues of
chronic eosinophilic leukemia?
* difficult to differentiate from increased reactive eos
* Bone marrow morphology is a clue:
* increased granulopoiesis
* dysplastic megakaryocytes
* dyserythropoiesis
43
What is the normal basophil percentage
in the PB ?
* \<1 %
* It is thought, but not confirmed, that IL-3 produced by T cell activation plays a role in basophil development and maturation
44
What is the normal morphology of
a basophil ?
* contain large, deeply basophilic cytoplasmic granules that take up a large part of the cytoplasm
* frequently obscure the nucleus
* Contain
* histamine
* heparin
* chondroitin sulfate
* other molecules
45
What is the differential diagnosis of neoplastic
disorders that are associated with basophilia ?
* CML with BCR-ABL1
* BCR-ABL negative MPN
* MDS (\<10%)
* AML with t(6;9) (DEK-NUP214)
* AML with a basophil component
* ALL with basophil or eosinophil component
* Therapy related AML
* Acute basophilic leukemia
46
What cytochemical stains are positive in monocytes?
* monocytes usually comprise 2-10% of the peripheral blood monocytes
* (+) for cytochemical nonspecific esterase and negative for MPO
* stains do not differentiation the maturation level of the monocytes
47
What is the morphology of normal mature monocytes ?
* pale blue/ grey cytoplasm
* fine azuorphilic granules and cytoplasmic vacuoles
* granules collagenases, elastases and esterases
* nuclei show mild to moderate indentation
* ropey mature chromatin and no nucleoli
48
What is the definition of an absolute monocytosis ?
* adult: \>1 x 10^9 /L
* neonates: 3.5 x 10^9 /L
49
What are neoplastic conditions associated with monocytosis ?
* CMML
* advanced stage of an MPN
* Myeloid neoplasm with PDGFRB rearrangement
* AML with monocytic differentiation
* inv16
* KMT2A rearrangement
* mutated NPM1
50
What are the most common conditions associaated with
monocytopenia ?
* aplastic anemia
* glucocorticoid administration
* hemodialysis
* GATA2 deficiency syndrome
* sepsis
* Hairy cell leukemia
