66 Basophils and Mast Cells and Their Disorders Flashcards
Mast cells and basophils express this receptor
high-affinity receptor for immunoglobulin (Ig) E (FcεRI)
The most common form of mastocytosis and typically presents with urticaria pigmentosa involving the skin
Indolent Systemic Mastocytosis
Most adult patients with mastocytosis has this mutation
Gain-of-function mutations affecting KIT
(kit ligand and mast cell growth factor)
The least common granulocyte in human blood
Basophil
0.5% to 0.6% of total leukocytes
0.3% of nucleated marrow cells
Basophil major growth factor
Interleukin (IL)-3
IL-3 is not necessary for the development of normal numbers of marrow or blood basophils but is important for the marrow and blood basophilia associated with certain T-helper (Th) 2 cell–associated immunologic responses
TRUE OR FALSE
Unlike basophils, mast cells can be longlived.
TRUE
Unlike basophils, mast cells can be longlived.
Mast cell major growth factor
Stem cell factor (SCF)
Promote mast cell mediator release and, at even lower concentrations, can augment mast cell mediator release in response to stimulation by IgE and antigen.
Basophil or Mast Cell
Represent the source of most (if not all) of the histamine present in normal human blood
Basophil
Basophil or Mast Cell
Origin of precursor cells is the marrow AND yolk sac
Mast Cell
Basophil: marrow
Difference of mast cell from basophil
- nonsegmented nucleus with moderate condensation
- smaller, more numerous
- more variable in appearance than in basophils
- covered by more uniformly distributed thin surface processes
- more cytoplasmic filaments and lacking cytoplasmic glycogen deposits
- contain numerous cytoplasmic lipid bodies
Site of maturation of mast cells
Connective Tissue
MAST CELL OR BASOPHIL
Responsible for virtually all of the vascular permeability changes and leukocyte infiltration associated with IgE-dependent cutaneous late-phase reactions and that TNF can importantly contribute to these responses
Mast Cell
HIV-derived protein that can induce mast cell or basophil mediator release (histamine and, in basophils, IL-4 and IL-13) by binding to and crosslinking cell surface–bound IgE
glycoprotein 120 (gp120)
Account for much or all of the protective effects against various venoms that were attributable to mast cells
CPA3 or mMCP-4 (the functional counterpart in the mouse to human chymase)
TRUE OR FALSE
Basophilopenia occurs in conditions that also are associated with eosinophilopenia
TRUE
Basophilopenia occurs in conditions that also are associated with eosinophilopenia
TRUE OR FALSE
A slight increase in the absolute monocyte count may be a useful early sign of a myeloproliferative neoplasm
FALSE
A slight increase in the absolute BASOPHIL count may be a useful early sign of a myeloproliferative neoplasm
TRUE OR FALSE
An increased absolute basophil count occurs in virtually all patients with CML.
TRUE
An increased absolute basophil count occurs in virtually all patients with CML.
TRUE OR FALSE
Exaggerated basophilia of this type is a poor prognostic sign and may herald transformation to the accelerated phase of CML.
TRUE
Exaggerated basophilia of this type is a poor prognostic sign and may herald transformation to the accelerated phase of CML.
Immunophenotype of Acute basophilic leukemia
CD123-positive, CD203cpositive, and CD117-negative blast cell
Gene mutation in Acute basophilic leukemia
t(X;6)(p11.2;q23.3)
Resulting in the fusion of MYB and GATA1
AML with marrow basophilia
t(9;22), t(6;9), t(3;6), or 12p
Other types of AML that have an associated increase in basophils are more prevalent than acute basophilic leukemia
t(6;9) AML : associated with erythroid hyperplasia and dysplasia, a high frequency of FLT3 mutations, and poor prognosis
Hyperbasophilia is defined as a basophil count of greater than or equal to ______ × 10 9 /L in the blood
1 × 10 9 /L
Human mast cells have been classified according to their content of neutral proteases
MC T: contain tryptase but not detectable chymase; predominates in lung and gastrointestinal (GI) mucosal tissues
MCTC: both enzymes; predominates in dermis and submucosal tissues
MCC: chymase but little or no tryptase
TRUE OR FALSE
No clinical disorder whose primary feature is a reduction in levels of tissue mast cells has been reported.
TRUE
No clinical disorder whose primary feature is a reduction in levels of tissue mast cells has been reported.
Skin lesions containing numerous mast cells
Usual presenting lesion of mastocytosis
Urticaria pigmentosa (UP) OR maculopapular cutaneous mastocytosis (MPCM)
Small yellowish-tan to reddish-brown macules or slightly raised papules
Compose the great majority of subjects with a clonal mast cell disorder
Can expect a normal lifespan
Indolent systemic mastocytosis (ISM)
Expected survival time of patients with aggressive systemic mastocytosis (ASM)
3- to 5-years
Most common mutation in clonal mastocytosis
Asp816Val
KIT, which encodes the SCF receptor
Results in ligand-independent activation of the KIT receptor
Result in the substitution of phenylalanine or tyrosine for aspartate
Believed to occur in more than 90% of adult patients with mastocytosis
Organs most frequently involved in systemic mastocytosis
Skin, lymph nodes, liver, spleen, marrow, and GI tract
Urticaria after mild friction of the skin
Darier sign
Areas of the skin that are free of lesions in mastocytosis
Palms, soles, face, and scalp
Lymphadenopathy is most prominent in patients with
SM-AHN or ASM
Marrow finding and major criterion in the diagnosis of systemic mastocytosis
Foci of spindle-shaped mast cells in a fibrotic background
Aggressive variants of mastocytosis, such as MCL, should be considered if the percentage of mast cells in the marrow aspirate film exceeds ____% of all nucleated cells.
20%
TRUE OR FALSE
Mast cells with bilobed nuclei may be seen in these lesions and is a finding associated with a poor prognosis.
TRUE
Mast cells with bilobed nuclei may be seen in these lesions and is a finding associated with a poor prognosis.
IHC of choice or visualizing mast cells
Tryptase
Others: chloracetate esterase and aminocaproate esterase
More specific mast cell markers in paraffin sections are
CD117 and mast cell tryptase
Strong CD117 membrane staining is equally sensitive for mast cells as tryptase but is less specific
Major diagnostic criteria for Systemic Mastocytosis
Multifocal, dense infiltrates of mast cells (≥15 mast cells in an aggregate) detected in sections of marrow or other extracutaneous organ(s)
Minor diagnostic criteria for Systemic Mastocytosis
a. In biopsy sections of marrow or other extracutaneous organs, >25% of the mast cells in the infiltrate are spindle shaped or have atypical morphology, or of all mast cells in marrow aspirate smears, >25% are immature or atypical mast cells
b. Detection of a point mutation in KIT at codon 816 in marrow, blood, or other extracutaneous organ
c. Mast cells in marrow, blood, or other extracutaneous organs express CD25 with or without CD2 in addition to normal mast cell markers
d. Serum total tryptase persistently >20 ng/mL unless there is an associated myeloid neoplasm, in which case this parameter is not valid
The diagnosis of systemic mastocytosis can be made if one major and one minor criterion are present or if three minor criteria are met.
TRUE OR FALSE
No single laboratory test showing an elevation in a mast cell mediator is diagnostic of mastocytosis; Rather, the demonstration of such mediators in blood or urine should prompt the clinician to investigate further for the presence of mastocytosis
TRUE
No single laboratory test showing an elevation in a mast cell mediator is diagnostic of mastocytosis; Rather, the demonstration of such mediators in blood or urine should prompt the clinician to investigate further for the presence of mastocytosis
TRUE OR FALSE
Mastocytosis can be cured
FALSE
Mastocytosis currently has no cure.
It is often considered to be a first-line drug of choice in Systemic Mastocytosis
Interferon-α or Cladribine
For many patients with advanced systemic mastocytosis, midostaurin may be considered the first-line therapy.
FDA-approved treatment for adult patients with ASM who do not have the KIT D816V mutation or with unknown KIT mutational status
Imatinib mesylate (Gleevec)
Inhibits ABL1, KIT, and PDGFR tyrosine kinases.
It does not inhibit KIT bearing codon 816 mutations associated with most common forms of systemic mastocytosis.
Inhibits both IgE-dependent release of histamine and the growth of neoplastic mast cells bearing various mutant forms of KIT
Midostaurin
FDA-approved for treatment of ASM, SM-AHN, and MCL
For many patients with advanced systemic mastocytosis, midostaurin may be considered the first-line therapy.
Primary toxicity of Midostaurin
GI side effects
Examples of KIT D816V inhibitors
Avapritinib
Masitinib
Most common adverse events for Avapritinib
Periorbital edema and myelosuppression
Most common adverse events for Masitinib
Diarrhea and rash
Term adopted for patients who have one or two minor diagnostic criteria for mastocytosis but lack the full diagnostic criteria for systemic disease.
Monoclonal Mast Cell Activation Syndrome
Patient with Monoclonal Mast Cell Activation Syndrome should e monitored every _________
Yearly
To determine if there is evidence of an expanding mast cell compartment
Term applied as a diagnosis for patients with episodic allergic-like signs and symptoms, including flushing, urticaria, diarrhea, and wheezing, involving two or more organ systems, when an extensive medical evaluation has failed to identify an etiology
Mast Cell Activation Disorder
Poor prognostic factors associated with mast cell disorders
- Elevated serum lactate dehydrogenase levels
- Late age of onset
- Patients with SM-AHN
- Presence of a significant hematologic abnormality
A major differential diagnosis to Mast Cell Leukemia
Myelomastocytic leukemia (MML)
Rare tumor characterized by nodules at various cutaneous and mucosal sites.
Mast Cell Sarcoma
Chronic basophilic leukemia should be distinguished from hyperbasophilia, defined as a basophil count of greater than or equal to ________in the blood.
1 × 10 9 /L
Hyperbasophilia is usually associated with an underlying myeloid neoplasm and presumably reactive.
