World Health Organization Classification
- Mastocytosis was classified by the WHO as a myeloproliferative neoplasm for a number of years. In 2016, the WHO placed mastocytosis into its own category, separate from myeloproliferative neoplasms.
- In a paper summarizing changes to WHO classification of myeloid neoplasms and acute leukemias, the author stated that “mastocytosis…is no longer considered a subgroup of the MPNs due to its unique clinical and pathologic features, ranging from indolent cutaneous disease to aggressive systemic disease, and is now a separate disease category in the classification[i].”
Table 1: WHO Classification of Mastocytosisi | |
Category | Subtype |
Cutaneous mastocytosis (CM) | Cutaneous mastocytosis (CM), including maculopapular cutaneous mastocytosis (MPCM, previously called urticaria pigmentosa); solitary mastocytoma of the skin; diffuse cutaneous mastocytosis*Author’s note: Telangiectasia macularis eruptiva perstans (TMEP) is considered a variant of maculopapular cutaneous mastocytosis (MPCM, previously called urticaria pigmentosa) |
Systemic mastocytosis (SM) | Indolent systemic mastocytosis (ISM) |
Smoldering systemic mastocytosis (SSM) | |
Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) | |
Aggressive systemic mastocytosis (ASM) | |
Mast cell leukemia (MCL) | |
Mast cell sarcoma (MCS) | Mast cell sarcoma (MCS) |
Diagnostic criteria for subvariants of systemic mastocytosis
Table 2: Diagnostic criteria for indolent systemic mastocytosis[ii] 1 major and 1 minor criterion; or 3 minor criteria | ||||
Major | Multifocal dense infiltrates of mast cells (15 or more in aggregate) detected in sections of bone marrow and/or extracutaneous organ | |||
Minor | In biopsy sections, more than 25% of mast cells in infiltrated space are spindle-shaped or otherwise morphologically abnormal; or, of all mast cells in bone marrow aspirate smears, more than 25% mast cells are immature or abnormal. | Detection of CKIT mutation at codon 816 in bone marrow, blood or extracutaneous organ | Mast cells in bone marrow, blood or other extracutaneous organ that co-expresses CD-117 with CD2 and/or CD25 | Baseline serum tryptase of 20 ng/ml or higher. |
Table 3: Examples that meet minimum criteria for indolent systemic mastocytosis | |||
Scenario 1:
1 major criterion, 1 minor criterion |
Major criterion: Multifocal dense infiltrates of mast cells (15 or more in aggregate) detected in sections of bone marrow and/or extracutaneous organ | Minor criterion: Baseline serum tryptase of 20 ng/ml or higher. | |
Scenario 2:
1 major criterion, 1 minor criterion |
Major criterion: Multifocal dense infiltrates of mast cells (15 or more in aggregate) detected in sections of bone marrow and/or extracutaneous. | Minor criterion: In biopsy sections, more than 25% of mast cells in infiltrated space are spindle-shaped or otherwise morphologically abnormal; or, of all mast cells in bone marrow aspirate smears, more than 25% mast cells are immature or abnormal | |
Scenario 3:
1 major criterion, 1 minor criterion |
Major criterion: Multifocal dense infiltrates of mast cells (15 or more in aggregate) detected in sections of bone marrow and/or extracutaneous | Minor criterion: Detection of CKIT mutation at codon 816 in bone marrow, blood or extracutaneous organ | |
Scenario 4:
1 major criterion, 1 minor criterion |
Major criterion: Multifocal dense infiltrates of mast cells (15 or more in aggregate) detected in sections of bone marrow and/or extracutaneous | Minor criterion: Mast cells in bone marrow, blood or other extracutaneous organ that co-expresses CD-117 with CD2 and/or CD25 | |
Scenario 5:
3 minor criteria |
Minor criterion: Mast cells in bone marrow, blood or other extracutaneous organ that co-expresses CD-117 with CD2 and/or CD25 | Minor criterion: Detection of CKIT mutation at codon 816 in bone marrow, blood or extracutaneous organ | Minor criterion: Baseline serum tryptase of 20 ng/ml or higher. |
Scenario 6:
3 minor criteria |
Minor criterion: Mast cells in bone marrow, blood or other extracutaneous organ that co-expresses CD-117 with CD2 and/or CD25 | Minor criterion: Detection of CKIT mutation at codon 816 in bone marrow, blood or extracutaneous organ | Minor criterion: In biopsy sections, more than 25% of mast cells in infiltrated space are spindle-shaped or otherwise morphologically abnormal; or, of all mast cells in bone marrow aspirate smears, more than 25% mast cells are immature or abnormal |
Scenario 7:
3 minor criteria |
Minor criterion: Mast cells in bone marrow, blood or other extracutaneous organ that co-expresses CD-117 with CD2 and/or CD25 | Minor criterion:Baseline serum tryptase of 20 ng/ml or higher. | Minor criterion: In biopsy sections, more than 25% of mast cells in infiltrated space are spindle-shaped or otherwise morphologically abnormal; or, of all mast cells in bone marrow aspirate smears, more than 25% mast cells are immature or abnormal |
Scenario 8:
3 minor criteria |
Minor criterion: In biopsy sections, more than 25% of mast cells in infiltrated space are spindle-shaped or otherwise morphologically abnormal; or, of all mast cells in bone marrow aspirate smears, more than 25% mast cells are immature or abnormal | Minor criterion:Baseline serum tryptase of 20 ng/ml or higher. | Minor criterion: Detection of CKIT mutation at codon 816 in bone marrow, blood or extracutaneous organ |
Systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) is essentially treated as two separate condition: systemic mastocytosis and an associated hematologic neoplastic condition. Accordingly, the diagnostic criteria for the systemic mastocytosis aspect of this diagnosis is the same as described here.
Table 4: Diagnostic criteria for smoldering systemic mastocytosis (2 or 3 B findings)[ii] | |||
B findings | Increased mast cell burden (>30% mast cell aggregates on bone marrow biopsy and/or serum tryptase >200 ng/mL) | Hypercellular marrow, signs of myelodysplasia or myeloproliferation in absence of MDS or MPN | Organ swelling without deficit of organ function (hepatomegaly without ascites, palpable splenomegaly, lymphadenopathy >2 cm) |
Table 5: Examples that meet the criteria for smoldering systemic mastocytosis (2 or 3 B findings) | ||||
Scenario 1:
2 B findings |
Meets criteria for systemic mastocytosis | Increased mast cell burden (>30% mast cell aggregates on bone marrow biopsy and/or serum tryptase >200 ng/mL) | Hypercellular marrow, signs of myelodysplasia or myeloproliferation in absence of MDS or MPN | |
Scenario 2:
2 B findings |
Meets criteria for systemic mastocytosis | Increased mast cell burden (>30% mast cell aggregates on bone marrow biopsy and/or serum tryptase >200 ng/mL) | Organ swelling without deficit of organ function (hepatomegaly without ascites, palpable splenomegaly, lymphadenopathy >2 cm) | |
Scenario 3:
2 B findings |
Meets criteria for systemic mastocytosis | Hypercellular marrow, signs of myelodysplasia or myeloproliferation in absence of MDS or MPN | Organ swelling without deficit of organ function (hepatomegaly without ascites, palpable splenomegaly, lymphadenopathy >2 cm) | |
Scenario 4:
3 B findings |
Meets criteria for systemic mastocytosis | Increased mast cell burden (>30% mast cell aggregates on bone marrow biopsy and/or serum tryptase >200 ng/mL) | Hypercellular marrow, signs of myelodysplasia or myeloproliferation in absence of MDS or MPN | Organ swelling without deficit of organ function (hepatomegaly without ascites, palpable splenomegaly, lymphadenopathy >2 cm) |
Table 6: Diagnostic criteria for aggressive systemic mastocytosis (1 or more C finding)[ii] | |||||
C findings | One or more cytopenias (absolute neutrophil count <1000/µl; Hemoglobin <10g/dl; platelets <100000/µl) | Hepatomegaly with ascites, elevated liver enzymes with or without portal hypertension | Splenomegaly with hypersplenism | Malabsorption evidenced by low albumin and weight loss | Large osteolysis and/or severe osteoporosis and pathologic fractures (2 or more fractures as direct result of mast cell activity) |
Table 7: Examples that meet the minimum criteria for aggressive systemic mastocytosis (1 or more C finding) | |||
Scenario 1:
1 C finding |
Meets criteria for systemic mastocytosis | 1 or more B findings may be present, not a requirement | One or more cytopenias (absolute neutrophil count <1000/µl; Hemoglobin <10g/dl; platelets <100000/µl) |
Scenario 2:
1 C finding |
Meets criteria for systemic mastocytosis | 1 or more B findings may be present, not a requirement | Malabsorption evidenced by low albumin and weight loss |
Scenario 3:
1 C finding |
Meets criteria for systemic mastocytosis | 1 or more B findings may be present, not a requirement | Large osteolysis and/or severe osteoporosis and pathologic fractures (2 or more fractures as direct result of mast cell activity) |
Scenario 4:
1 C finding |
Meets criteria for systemic mastocytosis | 1 or more B findings may be present, not a requirement | Hepatomegaly with ascites, elevated liver enzymes with or without portal hypertension |
Scenario 5:
1 C finding |
Meets criteria for systemic mastocytosis | 1 or more B findings may be present, not a requirement | Splenomegaly with hypersplenism |
Table 8: Diagnostic criteria for mast cell leukemia[iii] | |
Meets criteria for systemic mastocytosis | Mast cells compromise 20% of all nucleated cells in blood smears |
Table 9: Examples that meet the minimum criteria for mast cell leukemia | ||||
Scenario 1 | Meets criteria for systemic mastocytosis | B findings may be present but are not required | C findings may be present but are not required | Mast cells compromise 20% of all nucleated cells in blood smears |
[i] Arber DA, et al. (2016). The 2016 revisioin to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 127(20), 2391-2405.
[ii] Molderings GJ, et al. (2011). Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. Journal of Hematology & Oncology, 4(10), 10.1186/1756-8722-4-10
[iii] Valent P, et al. (2014). Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal. Ann Oncol, 25(9), 1691-1700.