Mastocytosis Flashcards

1
Q

How is childhood mastocytosis defined?

A

Onset prior to puberty

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2
Q

Almost 100% of children with mastocytosis experience resolution by adolescence

A

False - 50 - 70%

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3
Q

Age of onset for childhood mastocytosis

A

97% by age 2
73% occur in the first 6 months

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4
Q

Females have a higher rate of mastocytosis than men

A

Fale - M = F

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5
Q

Where do mast cells orginiate from?

A

From pleuropotent cd34+ precursor cells in the bone marrow

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6
Q

What receptors do mast cells have?

A

CD34
CD117 (KIT)
IgG (FcyRII)

Once in the tissue
IgE recptor (FceRI)

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7
Q

Describe the pathogenesis of mastocytosis

A

Somatic activating mutation in **KIT **

Results in a substitution of aspartic acid (D) with Valine (V) - D816V

Leads to ligand independant activation of the recptor

Results in mast cell growth, maturation, and prevents apoptosis

*Nb this is the most common, there are other genetic mutations see image

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8
Q

What are the subtypes of cutaneous mastocytosis?

A

Childhood
- Diffuse cutaneous
- Telangectasis macularis eruptive perstans (TMEP)
- Mastocytoma
- Maculopapular

Adulthood:
- maculopapular
- Telangectasis macularis eruptive perstans (TMEP)
- Nodular
- no skin lesions

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9
Q

What are the subtypes of childhood mastocytosis and their relative incidence?

A

1/ Mastocytoma (<3) = 15 - 50%

2/ Maculopapular = 45 - 75%

3/ Diffuse = <5 - 10%

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10
Q

Describe

A

Tan / Yellow / Brown plaque or nodule

Leathery texture

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11
Q
A

C - yellow / tan nodule on the wrist with a rim of erythema

D - Red/ brown plaque with a large bullae arising at one edge

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12
Q

What is diffuse mastocytosis in childhood?

A

Rare variant

Presents in the first few months of life

Thickened skin with a leathery texture and varibale hyperpigmentation in a generalised distribution

Systemic disease = absent

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13
Q

Describe, what is the Dx?

A
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14
Q

Dx?

A

Maculopapular mastocytosis (Childhood)

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15
Q

What is the most common form of adult mastocytosis?

A

Maculopapular mastocytosis or urticaria pigmentosa

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16
Q

What is telangiectasia macularis eruptiva perstans?

A

A subtype of mastocytosis

characterized by macules and patches composed of telangiectasias without
significant hyperpigmentation

17
Q

What is dariers sign?

A

Formation of an urticaria-like wheal upon firmly stroking or rubbing of skin lesions due to release of mast cell mediators

18
Q

What are the systemic manifestations of mastocytosis?

A
  1. Skeletal
    * pain
    * radio-opaque or lucent lesions
    * skull / spine / pelvis
    * demineralisation or osteosclerosus
  2. Bone Marrow
    * Multifocal mast cell aggregates
    * in perivascular and paratrabecular locations.
  3. Splenomegaly
  4. Hepatomegaly
  5. GI
    * Abdo pain / D / V / N
    * Malnutrition
  6. Brain
    * Irritability
    * Fatigue
    * headache
    * poor attention
19
Q

What classification is used for mastocytosis? descirbe this

A

WHO 2016 classification

Cutaneous mastocyosis (CM)
- diffuse
- maculopapular
- mastocytoma

Systemic mastocyosis (SM)
- indolent SM
- smouldering SM
- SM with ass haematological neoplasm
- Aggressive SM
- Mast cell leukaemia

20
Q

Which systemic subtypes of mastocytosis are likely to have cutaneous involvement?

A

1/ Indolent
2/ Smouldering

21
Q

How is systemic mastocytosis diagnosed?

A

WHO criteria: 1 major and 1 minor or 3 minor

**Major: **
* Multifocal, dense infiltrate of Mast Cells in BM biopsies or extracutaneous organs

Minor:
* In BM smear >25% of all Mast cells are atypical OR >25% of MCs are spindle shaped in extracutaneous organs
* KIT point mutation at codon 816
* Mast cell in BM, Blood, extracutaneous tissue express CD2 or CD25
* Baseline serum tryptase >20 ng/ml

22
Q

What are B findings, in regard to systemic mastocytosis?

A

As per WHO criteria:

B findings = indicate a high burden of mast cells and / or expansion of the neoplastic process into multiple haematopoetic lineages WITHOUT organ impairment

Criteria:
* Mast cell infiltrate of the BM >30%
* Basal serum Tryptase >200ng/ml
* Hypercellular BM with loss of fat cells, signs of dysmyelopoesis without cytopaenias
* Organomegaly (spleen, liver, LNs) without organ dysfunction

23
Q

What are C findings, in regard to systemic mastocytosis?

A

As per WHO criteria

C findings = organ damage produced by Mast Cell infiltration

  • **Cytopenia(s) **caused by MCs: absolute neutrophil count <1000/mcl,
    hemoglobin <10 g/dl, or platelet count <100 000/mcl
  • Hepatomegaly with abnormal liver function, ascites, and/or portal
    hypertension
  • Splenomegaly with associated hypersplenism
  • Skeletal osteolytic lesions with pathologic fractures (fractures from osteoporosis alone is not a C finding)
  • Malabsorption with hypoalbuminemia and weight loss due to gastrointestinal MCs
24
Q

How do you differentiate indolent vs smouldering mastocytosis?

A

< 2 B findings and no C findings = Indolent

> 2 B findings, no C findings = smouldering

> 1 C finding = Aggressive SM (<20% MC in BM smears) or MC leukaemia (>20% MCs in BM smears)

25
In systemic mastocytosis, BM mast cells have what features?
Spindled Hypogranulated CD25 + CD2 +
26
Significance of mature mast cells in the blood?
this is an abnormal finding, should raise suspicioun of a leukaemic form of mast cell leaukaemai
27
Investigations for a child with mastocytosis?
This is a clinical diagnosis and investigations are usually not required to confirm the diagnosis Not ass. with systemic disease --> no investigations for disease extend are required If there is doubt re Dx: - skin bioopsy can be performed
28
What do you expect to see on skin biopsy of masto?
increased numbers of mast cells and/or the presence of an activating KIT mutation.
29
What investigations are required for an adult with cutaneous masto?
To confrirm dx: - skin biopsy is normally not required but can be perforemd if any uncertanty on the Dx To determine extent of disease: - FBC - LFT - serum tryptase - DEXA scan / bone scan - +/- BM biopsy (controversion if always needed, defintely if B or C symptoms)
30
What cells are shown here?
Mast cells
31
What are mast cell degranulating agents?
32
Management of mastocytosis?
Avoid environmental triggers and degranulating agents Antihistamines * Second generation (loratadine, citirizine) Nbuvb Potent TCS Referral to immunology for consideration of an epipen Referral to haematology for consideration of BM Bx
33
Management option for patients with GI symptoms of masto?
Oral cromolyn sodium (disodium cromoglycate; 400–800 mg/day), a mast cell stabilizer with poor oral absorption, may alleviate GI manifes- tations and (to a lesser degree) cutaneous and CNS symptoms associated with mastocytosis.
34
What are the expected histo findings of mastocytosis?
Normal epidermis (unless blistering) Mast cell infiltrate (fried egg appearance) Scattered Eos Stain positive for - KIT (CD117) - Mast cell tryptase - Giemsa (mast cell granules) Negative for s100 and CD1a
35
List mast cell mediators and symptoms?
Histamine Heparin Neutrophil chemotatic factors Eosinophil chemotatic factors tryptase / chymase Platelet activating factor PGD2