Diagnosis and classification of systemic mastocytosis

World Health Organistation 2008 criteria for systemic mastocytosis

1. Determine whether criteria for diagnosis of systemic mastocytosis are met

One major and one minor criterion, or three minor criteria are required.

Major criterionMinor criteria
Multifocal, dense infiltrates of mast cells (≥ 15 mast cells in aggregates) in sections of bone marrow and/or other extracutaneous tissues> 25% of mast cells are immature or spindle-shaped in tissue sections
cKit mutation at codon 816 (usually D816V)
Mast cells co-express CD117 with CD2 and/or CD25
Serum tryptase persistently > 20ng/mL

2. Determine presence of B and C criteria

B criteriaC criteria
> 30% infiltration of mast cells in bone marrow and/or serum total tryptase > 200ng/ml≥ 1 cytopenia (neutrophils < 1.0 x109/L, hemoglobin < 10g/dL, platelets < 100 x109/L
Signs of dysplasia or myeloproliferation in non-mast cell lineage cells but insufficient for the WHO criteria for other clonal hematologic malignanciesSkeletal involvement with large osteolytic lesion(s) and/or fractures
Hepatomegaly without impairment of liver function, and/or palpable splenomegaly without hypersplenism, and/or palpable visceral lymphadenopathyPalpable hepatomegaly with impairment of liver function, ascites, or portal hypertension
Palpable splenomegaly with hypersplenism
Malabsorption with weight loss due to gastointestinal mast cell infiltrates

3. Assign category according to B and C criteria and other features

CategoryFeatures
Indolent SM< 2 B criteria, and no C criteria
Smoldering SM≥ 2 B criteria, no C criteria
Aggressive SMAt least one C criterion
Mast cell leukemiaDiffuse bone marrow infiltration by atypical immature MCs; > 20% mast cells in bone marrow aspirate; mast cells in peripheral blood
SM with associated hematological non-mast cell disease (SM-AHNMD)SM with clonal hematological non-mast cell lineage disorder (e.g. myelodysplastic syndrome, acute myeloid leukemia, chronic myelomonocytic leukemia, chronic eosinophilic leukemia)

These World Health Organistation (WHO) criteria for the diagnosis of systemic mastocytosis (SM) were published in the fourth edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues in 2008.1