WHO diagnostic criteria for systemic mastocytosis
| Major criterion . | Comments . |
|---|---|
| Multifocal compact infiltrates of mast cells (>15 cells per infiltrate) in a tissue biopsy other than skin (such as bone marrow). | Mast cells are best visualized by tryptase or CD117 immunohistochemical stains in biopsy sections. These infiltrates are generally found in perivascular and paratrabecular locations. |
| Minor criteria | |
| Mast cells co-express CD25, CD2, and CD30. | CD25 is the most specific neoplastic mast cell marker. CD2 may be absent in some advanced SM cases. CD30 has been recently added as a marker in the latest WHO document. These markers can be assessed by serial sections by immunohistochemistry or by flow cytometry. However, mast cell flow cytometry should be treated as a rare event analysis with acquisition of ideally 1 million or more events. Typical leukemia/lymphoma FC panels do not contain enough cells to gate on mast cells. |
| Morphological abnormalities in mast cells, such as spindle-shaped, elongated mast cells with hypogranulation, cytoplasmic projection, and an off-centric or multilobated nucleus. | More than 25% of mast cells in the infiltrate should be morphologically aberrant. A bone marrow aspirate smear is the best sample to evaluate for these aberrant mast cell forms. Mast cells are usually found embedded in or in close proximity to spicules. There is insufficient data on other tissue biopsies to assess mast cell morphology. A detailed photographic guide to these abnormalities is presented in Sperr et al.42 |
| Detection of KIT D816V mutation or another gain of function KIT mutation in blood, bone marrow, or another noncutaneous tissue. | Mutation detection should be done by a high-sensitivity test such as allele specific PCR or droplet digital PCR with a sensitivity to detect mutated allele frequency of <0.1%. NGS panels or sequencing-based assays lack this sensitivity and are often falsely negative. |
| Baseline serum or plasma tryptase level of >20 ng/ml. | Tryptase is a highly specific marker for mast cell burden and activation. It should be measured when the patient is at baseline and not after an anaphylactic or mast cell activation event, during which it may be found elevated regardless of mastocytosis. This criterion is not valid if the patient has another myeloid neoplasm as tryptase can be found in smaller quantities in myeloid progenitor cells. |
| Major criterion . | Comments . |
|---|---|
| Multifocal compact infiltrates of mast cells (>15 cells per infiltrate) in a tissue biopsy other than skin (such as bone marrow). | Mast cells are best visualized by tryptase or CD117 immunohistochemical stains in biopsy sections. These infiltrates are generally found in perivascular and paratrabecular locations. |
| Minor criteria | |
| Mast cells co-express CD25, CD2, and CD30. | CD25 is the most specific neoplastic mast cell marker. CD2 may be absent in some advanced SM cases. CD30 has been recently added as a marker in the latest WHO document. These markers can be assessed by serial sections by immunohistochemistry or by flow cytometry. However, mast cell flow cytometry should be treated as a rare event analysis with acquisition of ideally 1 million or more events. Typical leukemia/lymphoma FC panels do not contain enough cells to gate on mast cells. |
| Morphological abnormalities in mast cells, such as spindle-shaped, elongated mast cells with hypogranulation, cytoplasmic projection, and an off-centric or multilobated nucleus. | More than 25% of mast cells in the infiltrate should be morphologically aberrant. A bone marrow aspirate smear is the best sample to evaluate for these aberrant mast cell forms. Mast cells are usually found embedded in or in close proximity to spicules. There is insufficient data on other tissue biopsies to assess mast cell morphology. A detailed photographic guide to these abnormalities is presented in Sperr et al.42 |
| Detection of KIT D816V mutation or another gain of function KIT mutation in blood, bone marrow, or another noncutaneous tissue. | Mutation detection should be done by a high-sensitivity test such as allele specific PCR or droplet digital PCR with a sensitivity to detect mutated allele frequency of <0.1%. NGS panels or sequencing-based assays lack this sensitivity and are often falsely negative. |
| Baseline serum or plasma tryptase level of >20 ng/ml. | Tryptase is a highly specific marker for mast cell burden and activation. It should be measured when the patient is at baseline and not after an anaphylactic or mast cell activation event, during which it may be found elevated regardless of mastocytosis. This criterion is not valid if the patient has another myeloid neoplasm as tryptase can be found in smaller quantities in myeloid progenitor cells. |