66 Basophils and Mast Cells and Their Disorders

Question 1

Mast cells and basophils express this receptor

Answer 1

high-affinity receptor for immunoglobulin (Ig) E (FcεRI)

Question 2

The most common form of mastocytosis and typically presents with urticaria pigmentosa involving the skin

Answer 2

Indolent Systemic Mastocytosis

Question 3

Most adult patients with mastocytosis has this mutation

Answer 3

Gain-of-function mutations affecting KIT
(kit ligand and mast cell growth factor)

Question 4

The least common granulocyte in human blood

Answer 4

Basophil

0.5% to 0.6% of total leukocytes
0.3% of nucleated marrow cells

Question 5

Basophil major growth factor

Answer 5

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

Question 6

TRUE OR FALSE

Unlike basophils, mast cells can be longlived.

Answer 6

TRUE

Unlike basophils, mast cells can be longlived.

Question 7

Mast cell major growth factor

Answer 7

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.

Question 8

Basophil or Mast Cell

Represent the source of most (if not all) of the histamine present in normal human blood

Answer 8

Basophil

Question 9

Basophil or Mast Cell

Origin of precursor cells is the marrow AND yolk sac

Answer 9

Mast Cell

Basophil: marrow

Question 10

Difference of mast cell from basophil

Answer 10

• 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

Question 11

Site of maturation of mast cells

Answer 11

Connective Tissue

Question 12

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

Answer 12

Mast Cell

Question 13

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

Answer 13

glycoprotein 120 (gp120)

Question 14

Account for much or all of the protective effects against various venoms that were attributable to mast cells

Answer 14

CPA3 or mMCP-4 (the functional counterpart in the mouse to human chymase)

Question 15

TRUE OR FALSE

Basophilopenia occurs in conditions that also are associated with eosinophilopenia

Answer 15

TRUE

Basophilopenia occurs in conditions that also are associated with eosinophilopenia

Question 16

TRUE OR FALSE

A slight increase in the absolute monocyte count may be a useful early sign of a myeloproliferative neoplasm

Answer 16

FALSE

A slight increase in the absolute BASOPHIL count may be a useful early sign of a myeloproliferative neoplasm

Question 17

TRUE OR FALSE

An increased absolute basophil count occurs in virtually all patients with CML.

Answer 17

TRUE

An increased absolute basophil count occurs in virtually all patients with CML.

Question 18

TRUE OR FALSE

Exaggerated basophilia of this type is a poor prognostic sign and may herald transformation to the accelerated phase of CML.

Answer 18

TRUE

Exaggerated basophilia of this type is a poor prognostic sign and may herald transformation to the accelerated phase of CML.

Question 19

Immunophenotype of Acute basophilic leukemia

Answer 19

CD123-positive, CD203cpositive, and CD117-negative blast cell

Question 20

Gene mutation in Acute basophilic leukemia

Answer 20

t(X;6)(p11.2;q23.3)

Resulting in the fusion of MYB and GATA1

Question 21

AML with marrow basophilia

Answer 21

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

Question 22

Hyperbasophilia is defined as a basophil count of greater than or equal to ______ × 10 9 /L in the blood

Answer 22

1 × 10 9 /L

Question 23

Human mast cells have been classified according to their content of neutral proteases

Answer 23

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

Question 24

TRUE OR FALSE

No clinical disorder whose primary feature is a reduction in levels of tissue mast cells has been reported.

Answer 24

TRUE

No clinical disorder whose primary feature is a reduction in levels of tissue mast cells has been reported.

Question 25

Skin lesions containing numerous mast cells Usual presenting lesion of mastocytosis

Answer 25

Urticaria pigmentosa (UP) OR maculopapular cutaneous mastocytosis (MPCM) ## Footnote Small yellowish-tan to reddish-brown macules or slightly raised papules

Question 26

Compose the great majority of subjects with a clonal mast cell disorder Can expect a normal lifespan

Answer 26

Indolent systemic mastocytosis (ISM)

Question 27

Expected survival time of patients with aggressive systemic mastocytosis (ASM)

Answer 27

3- to 5-years

Question 28

Most common mutation in clonal mastocytosis

Answer 28

Asp816Val **KIT**, which encodes the SCF receptor ## Footnote 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

Question 29

Organs most frequently involved in systemic mastocytosis

Answer 29

Skin, lymph nodes, liver, spleen, marrow, and GI tract

Question 30

Urticaria after mild friction of the skin

Answer 30

Darier sign

Question 31

Areas of the skin that are free of lesions in mastocytosis

Answer 31

Palms, soles, face, and scalp

Question 32

Lymphadenopathy is most prominent in patients with

Answer 32

SM-AHN or ASM

Question 33

Marrow finding and major criterion in the diagnosis of systemic mastocytosis

Answer 33

Foci of spindle-shaped mast cells in a fibrotic background

Question 34

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.

Answer 34

20%

Question 35

TRUE OR FALSE Mast cells with bilobed nuclei may be seen in these lesions and is a finding associated with a poor prognosis.

Answer 35

TRUE Mast cells with bilobed nuclei may be seen in these lesions and is a finding associated with a poor prognosis.

Question 36

IHC of choice or visualizing mast cells

Answer 36

Tryptase Others: chloracetate esterase and aminocaproate esterase

Question 37

More specific mast cell markers in paraffin sections are

Answer 37

CD117 and mast cell tryptase ## Footnote Strong CD117 membrane staining is equally sensitive for mast cells as tryptase but is less specific

Question 38

Major diagnostic criteria for Systemic Mastocytosis

Answer 38

Multifocal, dense infiltrates of mast cells (≥15 mast cells in an aggregate) detected in sections of marrow or other extracutaneous organ(s)

Question 39

Minor diagnostic criteria for Systemic Mastocytosis

Answer 39

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 ## Footnote The diagnosis of systemic mastocytosis can be made if **one major and one minor** criterion are present or if **three minor criteria** are met.

Question 40

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

Answer 40

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

Question 41

TRUE OR FALSE Mastocytosis can be cured

Answer 41

FALSE Mastocytosis currently has no cure.

Question 42

It is often considered to be a first-line drug of choice in Systemic Mastocytosis

Answer 42

Interferon-α or Cladribine ## Footnote For many patients with advanced systemic mastocytosis, **midostaurin** may be considered the first-line therapy.

Question 43

FDA-approved treatment for adult patients with ASM who **do not have the KIT D816V mutation** or **with unknown KIT mutational status**

Answer 43

Imatinib mesylate (Gleevec) ## Footnote Inhibits ABL1, KIT, and PDGFR tyrosine kinases. **It does not inhibit KIT bearing codon 816 mutations** associated with most common forms of systemic mastocytosis.

Question 44

Inhibits both IgE-dependent release of histamine and the growth of neoplastic mast cells bearing various mutant forms of KIT

Answer 44

Midostaurin ## Footnote 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.

Question 45

Primary toxicity of Midostaurin

Answer 45

GI side effects

Question 46

Examples of KIT D816V inhibitors

Answer 46

Avapritinib Masitinib

Question 47

Most common adverse events for Avapritinib

Answer 47

Periorbital edema and myelosuppression

Question 48

Most common adverse events for Masitinib

Answer 48

Diarrhea and rash

Question 49

Term adopted for patients who have **one or two minor diagnostic criteria for mastocytosis** but lack the full diagnostic criteria for systemic disease.

Answer 49

Monoclonal Mast Cell Activation Syndrome

Question 50

Patient with Monoclonal Mast Cell Activation Syndrome should e monitored every _________

Answer 50

Yearly ## Footnote To determine if there is evidence of an expanding mast cell compartment

Question 51

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

Answer 51

Mast Cell Activation Disorder

Question 52

Poor prognostic factors associated with mast cell disorders

Answer 52

- Elevated serum lactate dehydrogenase levels - Late age of onset - Patients with SM-AHN - Presence of a significant hematologic abnormality

Question 53

A major differential diagnosis to Mast Cell Leukemia

Answer 53

Myelomastocytic leukemia (MML)

Question 54

Rare tumor characterized by nodules at various cutaneous and mucosal sites.

Answer 54

Mast Cell Sarcoma

Question 55

Chronic basophilic leukemia should be distinguished from hyperbasophilia, defined as a basophil count of greater than or equal to ________in the blood.

Answer 55

1 × 10 9 /L ## Footnote Hyperbasophilia is usually associated with an underlying myeloid neoplasm and presumably reactive.