Mastocytosis Flashcards
How is childhood mastocytosis defined?
Onset prior to puberty
Almost 100% of children with mastocytosis experience resolution by adolescence
False - 50 - 70%
Age of onset for childhood mastocytosis
97% by age 2
73% occur in the first 6 months
Females have a higher rate of mastocytosis than men
Fale - M = F
Where do mast cells orginiate from?
From pleuropotent cd34+ precursor cells in the bone marrow
What receptors do mast cells have?
CD34
CD117 (KIT)
IgG (FcyRII)
Once in the tissue
IgE recptor (FceRI)
Describe the pathogenesis of mastocytosis
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
What are the subtypes of cutaneous mastocytosis?
Childhood
- Diffuse cutaneous
- Telangectasis macularis eruptive perstans (TMEP)
- Mastocytoma
- Maculopapular
Adulthood:
- maculopapular
- Telangectasis macularis eruptive perstans (TMEP)
- Nodular
- no skin lesions
What are the subtypes of childhood mastocytosis and their relative incidence?
1/ Mastocytoma (<3) = 15 - 50%
2/ Maculopapular = 45 - 75%
3/ Diffuse = <5 - 10%
Describe
Tan / Yellow / Brown plaque or nodule
Leathery texture
C - yellow / tan nodule on the wrist with a rim of erythema
D - Red/ brown plaque with a large bullae arising at one edge
What is diffuse mastocytosis in childhood?
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
Describe, what is the Dx?
Dx?
Maculopapular mastocytosis (Childhood)
What is the most common form of adult mastocytosis?
Maculopapular mastocytosis or urticaria pigmentosa
What is telangiectasia macularis eruptiva perstans?
A subtype of mastocytosis
characterized by macules and patches composed of telangiectasias without
significant hyperpigmentation
What is dariers sign?
Formation of an urticaria-like wheal upon firmly stroking or rubbing of skin lesions due to release of mast cell mediators
What are the systemic manifestations of mastocytosis?
- Skeletal
* pain
* radio-opaque or lucent lesions
* skull / spine / pelvis
* demineralisation or osteosclerosus - Bone Marrow
* Multifocal mast cell aggregates
* in perivascular and paratrabecular locations. - Splenomegaly
- Hepatomegaly
- GI
* Abdo pain / D / V / N
* Malnutrition - Brain
* Irritability
* Fatigue
* headache
* poor attention
What classification is used for mastocytosis? descirbe this
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
Which systemic subtypes of mastocytosis are likely to have cutaneous involvement?
1/ Indolent
2/ Smouldering
How is systemic mastocytosis diagnosed?
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
What are B findings, in regard to systemic mastocytosis?
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
What are C findings, in regard to systemic mastocytosis?
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
How do you differentiate indolent vs smouldering mastocytosis?
< 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)
In systemic mastocytosis, BM mast cells have what features?
Spindled
Hypogranulated
CD25 +
CD2 +
Significance of mature mast cells in the blood?
this is an abnormal finding, should raise suspicioun of a leukaemic form of mast cell leaukaemai
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
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.
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)
What cells are shown here?
Mast cells
What are mast cell degranulating agents?
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
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.
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
List mast cell mediators and symptoms?
Histamine
Heparin
Neutrophil chemotatic factors
Eosinophil chemotatic factors
tryptase / chymase
Platelet activating factor
PGD2
