Systemic Mastocytosis Flashcards
Most common neoplasm assoc with SM
CMML, followed by MDS/MPN-U; myeloma and lymphoid proliferations are rare
Mutation in SM
Most common is CKIT D816V
> CKIT variant mutations at codon 816 of KIT within the tyrosine kinase activation loop
SM WHO diagnostic criteria
The major criterion and at least 1 minor criterion must be present, or >=3 minor criteria must be present.
Major criterion :
- Multifocal dense infiltrates of mast cells (>=15 cells in aggregates) detected in sections of bone marrow and/or other extracutaneous organs
Minor criteria
-Atypical mast cell morphology, including spindle shape or immature morphology, present in > 25% of all mast cells on bone marrow smears or in other extracutaneous organ(s)a
- Mast cells aberrantly express one or more of the following antigens: CD2, CD25, CD30
- KIT p.D816V mutation or other activating KIT mutationb detected in peripheral blood, bone marrow, or other extracutaneous organ(s)
- Baseline serum tryptase concentration of > 20 ng/mL in the absence of an associated myeloid neoplasm;
Abberant Mast cell immunophenotype in SM
CD2, CD25 or CD30
B findings (“burden of disease”)
C findings (“cytoreduction-requiring”) in SM
(indicate organ involvement and organ dysfunction, respectively)
Clinical manifestations of SM
Symptoms of systemic mastocytosis are grouped into 4 categories:
- Constitutional
- Skin manifestations
- Mediator-related events (e.g. abdominal pain, diarrhoea, syncope, headache, hypotension, tachycardia, respiratory symptoms)
- Musculoskeletal symptoms (e.g. osteoporosis, fractures, bone pain, arthralgias, myalgias)
Clinical findings
- LAD, Hepatomegaly, splenomegaly
Haematological
- Anaemia
· Leukocytosis
· Eosinophilia (a common finding)
· Neutropenia and thrombocytopenia
· Bone marrow failuree
· Increased circulating mast cellsf
· Associated haematological neoplasm
Serum tryptase >20 ng/mL
Atypical Mast cell morphology
Spindling
Hypogranularity
Promastocytes: immature forms with bilobated or multilobated nuclei (a feature of aggressive disease)
NB in a few patients with SM, mast cells are mature and well-granulated, without atypia or aberrant CD25 expression; these are called ”well-differentiated systemic mastocytosis” and are not associated with KIT D816 mutations
Molecular testing in SM
VAF of KIT D816V mutations is prognostic of likelihood of progression to advanced systemic mastocytosis
Using high-sensitivity assays such as digital droplet polymerase chain reaction (PCR) and allele-specific PCR, KIT D816V can be detected in ~95% of patients with AdvSM
SRSF2, ASXL1, and RUNX1 (S/A/R panel) are high-risk mutations
KIT D816V allele-specific polymerase chain reaction (PCR) or digital droplet PCR are required/more specific, but can be detected on NGS with the benefit of picking up other high risk mutations
What is SM
Myeloid neoplasm characterized by clonal proliferation of mast cells, typically harbouring mutant KIT, involving at least one extracutaneous organ system, with or without evidence of skin lesions.
Presentation can be highly heterogenous
bone marrow is nearly always involved in SM
Subtypes of SM
- Indolent systemic mastocytosis (ISM);
- Bone marrow mastocytosis (BMM);
- Smouldering systemic mastocytosis (SSM);
- Aggressive systemic mastocytosis (ASM);
- Systemic mastocytosis with an associated haematological neoplasm (SM-AHN);
-Mast cell leukaemia (MCL)
