Systemic Mastocytosis (SM)

CD2+, CD25+ Mast Cells

KIT D816V mutation (or other exon 17)

 

WHO Criteria (1 major + 1 minor, or 3 minor)

 

Major

Multifocal, dense infiltrates (>15 mast cells in aggregates) in marrow or extracutaneous organs.

 

Minor

>25% mast cells with spindled / atypical morphology

KIT point mutation at codon 816 (KIT D816V)

CD2 of CD25 expression in mast cells

Serum tryptase >20 ng/ml, unless there is an associated clonal myeloid disorder

 

2016 WHO Classification of Systemic Mastocytosis

 

ISM - Indolent SM

-       ISM-AHN

SSM - Smouldering SM

SM with AHN - with associated clonal, haematologic non-mast cell lineage disease

ASM - Aggressive SM

-       ASM-AHN

-       ASM-slow

-       ASM-rapid

-       ASM in transformation to MCL (ASM-t)

MCL - Mast cell leukaemia

-       Chronic MCL (cMCL)

-       Acute MCL (aMCL)

 

Clinical Presentation

 

Features of mast cell degranulation (‘mediator’ symptoms)

-       Anaphylaxis, flushing, itch, N&V, diarrhoea, lightheadedness, severe hypotension, bone paine, neuropsychiatric distrubance

-       Often no identifiable triggers

 

Staging Work-Up

 

Serum total tryptase

BM Biopsy

Relevant organ biopsy

KITD816V mutation (or other exon 17)

CD2 / CD25 Mast cell expression

If eosinophilia, screen for FIP1L1-PDGFRA

 

Indolent / Smouldering / Advanced

 

Indolent

-       No B or C findings

 

Smouldering: 2 or more B Findings

-       BM >30% mast cells + Tryptase >200 ng/ml

-       Signs of dysplasia or myeloproliferation without frank AHN, & normal FBC

-       Hepatomegaly without liver dysfunction and/or splenomegaly without hypersplenism

 

Advanced (ASM, MCL, SM-AHN with organ damage): C Findings, ie organ damage

-       One or more cytopenias

-       Hepatomegaly with liver dysfunction

-       Osteolytic lesions or fractures

-       Splenomegaly with hypersplenism

-       Malabsorption with weight loss due to GI infiltration

 

Management

 

Avoidance of triggers

 

Treatment of mediator symptoms

-       EpiPen

-       H1 anti-histamines (Cetirizine, Fexofenadine, Hydroxyzine)

-       H2 antagonists (Ranitidine, Cimetidine)

-       Leukotriene antagonists (Montelukast)

-       Bisphosphonates for osteoporosis / bone pain / fractures

-       Mast cell stabilisers (ketotifen, cromolyn)

-       PUVA light therapy

-       NSAID - Aspirin

 

Cytoreductive Therapy

-       Steroids

-       PEG Interferon alpha

-       Multi-agent chemotherapy

-       Cladribine (approx. 50% response rate)

-       Transplant

 

Target Therapies / Trials (Presence of KIT D816V confers resistance against many TKI’s)

-       Midostaurin (KIT inhibitor) (60% ORR)

-       Dasatinib / Nilotinib

-       Mastinib

-       Imatinib

-       Everolimus

-       Mabs – Daclizumab, Omalizumab

-       Other Mabs to consider based on pt’s immunophenotype – CD30, CD33, CD52, CD123

 

Mast Cell Activation Syndrome (MCAS)

 

Meeting only 1 or 2 of the minor diagnostic criteria

Lack the characteristic BM mast cell aggregates

Episodic symptoms of mast cell degranulation