The 2016 WHO diagnostic criteria for SM, SM variants, and B and C findings
| Diagnostic criteria . |
|---|
| SM diagnostic criteria* |
| Major |
| Multifocal, dense infiltrates of MCs (15 or more in aggregates) detected in sections of BM and/or another extracutaneous organ |
| Minor |
| In biopsy sections of BM or other extracutaneous organs, >25% of the MCs in the infiltrate are spindle shaped or have atypical morphology, or of all MCs in BM aspirate smears, >25% are immature or atypical MCs |
| Detection of an activating point mutation at codon 816 of KIT in BM, blood, or another extracutaneous organ |
| MCs in the BM, blood, or another extracutaneous organ express CD25, with or without CD2, in addition to normal MC markers |
| Serum total tryptase persistently >20 ng/mL in the absence of an associated clonal myeloid disorder |
| Variants of SM |
| Indolent SM† |
| No C findings |
| No evidence of an associated hematologic neoplasm |
| Low MC burden |
| Skin lesions are often present |
| Smoldering SM |
| ≥2 B findings; no C findings |
| No evidence of an associated hematologic neoplasm |
| Does not meet criteria for MC leukemia |
| SM with an associated hematologic neoplasm‡ |
| Meets the general criteria for SM as well as associated hematologic neoplasms classified as a distinct entity in the WHO classification |
| Aggressive SM§ |
| ≥1 C finding |
| Does not meet criteria for MC leukemia |
| MC leukemia‖ |
| BM aspirate smears show >20% MCs |
| BM biopsy shows diffuse infiltration (usually dense) by atypical, immature MCs |
| B and C findings |
| B findings indicate a high burden of MCs and expansion of the neoplastic process into multiple hematopoietic lineages without evidence of organ damage |
| High MC burden (shown on BM biopsy): >30% infiltration of cellularity by MCs and serum total tryptase >200 ng/mL |
| Signs of dysplasia or myeloproliferation in non-MC lineage(s), but criteria are not met for definitive diagnosis of an associated hematologic neoplasm, with normal or only slightly abnormal blood counts |
| Hepatomegaly without impairment of liver function, palpable splenomegaly without hypersplenism, and/or lymphadenopathy on palpation or imaging |
| C findings are indicative of organ damage produced by MC infiltration (should be confirmed by biopsy if possible) |
| BM dysfunction caused by neoplastic MC infiltration manifested by ≥1 cytopenia: absolute neutrophil count <1.0 × 109/L, hemoglobin level <10 g/dL, and/or platelet count <100 × 109/L |
| Palpable hepatomegaly with impairment of liver function, ascites, and/or portal hypertension |
| Skeletal involvement, with large osteolytic lesions with or without pathological fractures (pathological fractures caused by osteoporosis do not qualify as a C finding) |
| Palpable splenomegaly with hypersplenism |
| Malabsorption with weight loss due to gastrointestinal MC infiltrates |
| Diagnostic criteria . |
|---|
| SM diagnostic criteria* |
| Major |
| Multifocal, dense infiltrates of MCs (15 or more in aggregates) detected in sections of BM and/or another extracutaneous organ |
| Minor |
| In biopsy sections of BM or other extracutaneous organs, >25% of the MCs in the infiltrate are spindle shaped or have atypical morphology, or of all MCs in BM aspirate smears, >25% are immature or atypical MCs |
| Detection of an activating point mutation at codon 816 of KIT in BM, blood, or another extracutaneous organ |
| MCs in the BM, blood, or another extracutaneous organ express CD25, with or without CD2, in addition to normal MC markers |
| Serum total tryptase persistently >20 ng/mL in the absence of an associated clonal myeloid disorder |
| Variants of SM |
| Indolent SM† |
| No C findings |
| No evidence of an associated hematologic neoplasm |
| Low MC burden |
| Skin lesions are often present |
| Smoldering SM |
| ≥2 B findings; no C findings |
| No evidence of an associated hematologic neoplasm |
| Does not meet criteria for MC leukemia |
| SM with an associated hematologic neoplasm‡ |
| Meets the general criteria for SM as well as associated hematologic neoplasms classified as a distinct entity in the WHO classification |
| Aggressive SM§ |
| ≥1 C finding |
| Does not meet criteria for MC leukemia |
| MC leukemia‖ |
| BM aspirate smears show >20% MCs |
| BM biopsy shows diffuse infiltration (usually dense) by atypical, immature MCs |
| B and C findings |
| B findings indicate a high burden of MCs and expansion of the neoplastic process into multiple hematopoietic lineages without evidence of organ damage |
| High MC burden (shown on BM biopsy): >30% infiltration of cellularity by MCs and serum total tryptase >200 ng/mL |
| Signs of dysplasia or myeloproliferation in non-MC lineage(s), but criteria are not met for definitive diagnosis of an associated hematologic neoplasm, with normal or only slightly abnormal blood counts |
| Hepatomegaly without impairment of liver function, palpable splenomegaly without hypersplenism, and/or lymphadenopathy on palpation or imaging |
| C findings are indicative of organ damage produced by MC infiltration (should be confirmed by biopsy if possible) |
| BM dysfunction caused by neoplastic MC infiltration manifested by ≥1 cytopenia: absolute neutrophil count <1.0 × 109/L, hemoglobin level <10 g/dL, and/or platelet count <100 × 109/L |
| Palpable hepatomegaly with impairment of liver function, ascites, and/or portal hypertension |
| Skeletal involvement, with large osteolytic lesions with or without pathological fractures (pathological fractures caused by osteoporosis do not qualify as a C finding) |
| Palpable splenomegaly with hypersplenism |
| Malabsorption with weight loss due to gastrointestinal MC infiltrates |
A diagnosis of SM requires 1 major plus 1 minor criterion or ≥3 minor criteria.
BM mastocytosis is a subtype of indolent SM characterized by BM involvement and no skin lesions.
Usually, a myeloid neoplasm (ie, MDS, MPN, MDS/MPN, chronic eosinophilic leukemia, not otherwise specified, or acute myeloid leukemia). Lymphoid neoplasms (ie, multiple myeloma and chronic lymphocytic leukemia) constitute <10% of associated hematologic neoplasms.
Aggressive SM in transformation is a subvariant characterized by 5% to 19% MCs on BM aspirate smears and reflects evolution toward MC leukemia.
The aleukemic MC leukemia variant (in which MCs account for <10% of circulating white blood cells) is more common than cases with ≥10% circulating MCs, which are more aggressive; MC leukemia has also been divided into chronic (C findings absent) and acute (C findings present).