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Foucar > CH.10 Non-neoplastic granulocytic and monocytic disorders > Flashcards

CH.10 Non-neoplastic granulocytic and monocytic disorders Flashcards

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

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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
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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
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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
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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
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6
Q

What are features that favor neoplastic monocytes ?

A
  • circulating blasts
  • immature monocytes
  • eosinophilia
  • dysplasia
  • unexplained leukoerythroblastic reaction
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7
Q

What additional testing on peripheral blood

can be performed if you are concerned

about neoplastic monocytes ?

A
  • cytogenetics if sufficient immature cells
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8
Q

What features favor a reactive eosinophilia ?

A
  • reasonable explanation:
    • drug
    • infection
    • allergy
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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
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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
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11
Q

What features favor a reactive basophilia ?

A
  • microcytic anemia (iron deficiency)
  • minimal basophilia
    • < 0.5 x 10^9/L
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12
Q

What features favor a neoplastic cause

to the basophilia ?

A
  • additional cytoses
  • unexplained leukoerythroblastic reaction
  • non-toxic left shift with blasts
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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
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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
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15
Q

In the bone marrow, what are two conditions

that you can see increased, benign lymphoid aggregates ?

A
  • viral infection
  • autoimmune disorders
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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
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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
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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
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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
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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
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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
Q

What is a Dohle-body composed of ?

A
  • aggregates of rough endoplasmic reticulum
26
Q

What non-neoplastic conditions are

associated with neutrophilic hyposegmentation ?

A
  • def: nucleus with 1-2 lobes
  • Conditions
    • Pelger-Huet anomaly
    • Acquired pseudo-Pelger-Huet (HIV, drugs, other infx)
  • Major d/d consideration
    • Myelodysplasia
27
Q

What non-neoplastic conditions can cause

neutrophil hypersegmentation ?

A
  • 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
Q

What non-neoplastic conditions can cause

Bytryoid/grape-like neutrophils ?

A
  • Hyperthermia (heat stroke)
  • Hemorrhagic shock and encephalopathy syndrome
29
Q

What conditions can cause Dohle bodies

within neutrophils ?

A
  • severe infection
  • May-Hegglin disorder
  • CSF effect
30
Q

What are frequently associated with

Howell-Jolly body-like cytoplasmic

inclusions in neutrophils ?

A
  • def: non-apoptotic nuclear fragments
  • Conditions
    • Immunosuppressive therapy
    • Chemotherapy
    • HIV
    • Severe sepsis
31
Q

What are frequent causes of cytoplasmic

vacuoles in neutrophils and monocytes ?

A
  • bacteremia
  • artifact (aged specimen)
  • copper deficiency
  • alcohol toxicity
  • medium chain AcylCoA dehydrogenase deficiency
32
Q

What are the findings and mutation associated

with Myelokathexis ?

A
  • 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
Q

What are the key findings and the mutation

in Pelger-Huet anomaly ?

A
  • 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
Q

What are the key findings in

May-Hegglin ?

A
  • 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
Q

What are the key findings in the

Alder-Reilly phenomenon

(as a component of mucopolysaccharidosis)?

A
  • 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
Q

What are the key findings of

Chediak-Higashi ?

A
  • 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
Q

What is the normal morphology of

an eosinophil ?

A
  • generally exhibits 2 nuclear lobes
    • although occasionally 3 or more lobes can be seen
  • minimal cytoplasmic, azurophilic granules are present
38
Q

What is considered to be an

absolute eosinophil count for

all age groups ?

A
  • 0.5 x 10^9/L
  • there are further classifications for severity of increase
    • see p. 182
39
Q

What malignancies have been described

to present with increased eosinophils ?

A
  • 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
Q

What are causes of primary

neoplastic eosinophilias ?

A
  • 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
Q

What cytokines are thought to drive

reactive eosinophilias ?

A
  • IL-3
  • IL-5
42
Q

What are morphologic clues of

chronic eosinophilic leukemia?

A
  • difficult to differentiate from increased reactive eos
  • Bone marrow morphology is a clue:
    • increased granulopoiesis
    • dysplastic megakaryocytes
    • dyserythropoiesis
43
Q

What is the normal basophil percentage

in the PB ?

A
  • <1 %
  • It is thought, but not confirmed, that IL-3 produced by T cell activation plays a role in basophil development and maturation
44
Q

What is the normal morphology of

a basophil ?

A
  • 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
Q

What is the differential diagnosis of neoplastic

disorders that are associated with basophilia ?

A
  • 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
Q

What cytochemical stains are positive in monocytes?

A
  • 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
Q

What is the morphology of normal mature monocytes ?

A
  • 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
Q

What is the definition of an absolute monocytosis ?

A
  • adult: >1 x 10^9 /L
  • neonates: 3.5 x 10^9 /L
49
Q

What are neoplastic conditions associated with monocytosis ?

A
  • CMML
  • advanced stage of an MPN
  • Myeloid neoplasm with PDGFRB rearrangement
  • AML with monocytic differentiation
    • inv16
    • KMT2A rearrangement
    • mutated NPM1
50
Q

What are the most common conditions associaated with

monocytopenia ?

A
  • aplastic anemia
  • glucocorticoid administration
  • hemodialysis
  • GATA2 deficiency syndrome
  • sepsis
  • Hairy cell leukemia

Foucar (2 decks)

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