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PubMed This is a summary of 12 peer-reviewed journal articles Updated
Pathology

The Pathology Report: Understanding the WHO Criteria

At a Glance

Diagnosing Systemic Mastocytosis requires meeting specific 2022 WHO criteria found in your pathology report. This involves finding large clusters of abnormal mast cells (the major criterion) or a combination of minor criteria like the KIT D816V mutation, atypical cell shapes, and elevated tryptase.

The pathology report is the most critical document in your diagnostic journey. It translates what a pathologist sees under the microscope into the clinical “proof” needed to confirm Systemic Mastocytosis (SM). To ensure accuracy and consistency worldwide, doctors use the 2022 WHO (World Health Organization) Criteria to make a diagnosis [1][2].

The Math of Diagnosis

Diagnosing SM is like solving a puzzle. To confirm you have the condition, your results must meet:

  • One Major Criterion + One Minor Criterion
  • OR
  • Three Minor Criteria [3][1]

The Major Criterion: Finding the Clusters

The major criterion focuses on the physical presence of “clumps” of mast cells in your bone marrow or other organs (excluding the skin) [4].

  • Definition: The pathologist must find multifocal dense aggregates of 15 or more mast cells [2][1]. Think of these as crowded “neighborhoods” of abnormal cells rather than cells scattered evenly throughout the tissue.

The Four Minor Criteria: Detailed Clues

If the clusters aren’t large enough, or to support the major finding, pathologists look for these four specific details:

  1. Atypical Shape (Morphology): More than 25% of the mast cells in your sample must be spindle-shaped (long and thin instead of round) or have atypical-looking nuclei [5][1].
  2. The KIT D816V Mutation: This is the genetic “stuck switch” discussed earlier. Finding this mutation in your bone marrow, blood, or other tissue counts as a minor criterion [6][7].
  3. Abnormal Surface Markers: Normal mast cells don’t usually carry certain “ID tags” on their surface. If your mast cells express CD25, CD2, and/or CD30, it is a sign they are neoplastic (abnormal) [1][2].
  4. Elevated Tryptase: Your baseline serum tryptase level must be consistently higher than 20 ng/mL [5][8]. (Note: This criterion may not apply if you have another related blood disorder) [5].

Pathology Checklist: Audit Your Report

When you receive your pathology report, use this checklist to see if the evaluation was complete. A thorough report should mention the following [8][9][3]:

What to Look For Why It Matters
CD117 & Tryptase Stains These stains act like “highlighters” to help the pathologist see and count the mast cells [9][10].
CD25, CD2, & CD30 These “aberrant markers” confirm the mast cells are part of a disease process rather than just reacting to an allergy [8][1].
KIT D816V Status This confirms the molecular driver of the disease. High-sensitivity tests like ddPCR are often better than standard sequencing [11][12].
Morphology Description Look for terms like “spindled,” “elongated,” or “atypical” to describe the mast cells [5].
Tryptase Level Ensure a recent blood test result (tryptase) is noted in the context of your bone marrow findings [8].

By understanding these criteria, you can engage in a more detailed conversation with your hematologist or oncologist about your specific subtype. To learn what comes next, proceed to The Subtypes & Risk: Understanding Your Diagnosis.

Common questions in this guide

What is the major diagnostic criterion for systemic mastocytosis?
The major criterion is the presence of multifocal dense aggregates, or clusters, of 15 or more mast cells in your bone marrow or other organs outside the skin.
What are the minor WHO criteria for mastocytosis?
Minor criteria include finding atypical spindle-shaped mast cells, the KIT D816V genetic mutation, abnormal cell surface markers like CD25 or CD30, and a baseline serum tryptase level consistently above 20 ng/mL.
Why does my pathology report mention surface markers like CD25 and CD30?
Normal mast cells do not typically have CD25, CD2, or CD30 markers on their surface. Finding these specific markers helps pathologists confirm that the mast cells are abnormal and related to a disease process rather than a standard allergic reaction.
How is the KIT D816V mutation tested in mastocytosis?
The KIT D816V mutation is ideally tested using highly sensitive molecular methods, such as digital droplet PCR (ddPCR). This genetic test checks your blood or bone marrow for the underlying mutation that drives abnormal mast cell growth.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does my bone marrow biopsy show the multifocal dense aggregates of 15 or more mast cells required for the major criterion?
  2. 2.Which minor criteria did I meet? Did my mast cells show atypical spindle shapes or express markers like CD25, CD2, or CD30?
  3. 3.What method was used to test for the KIT D816V mutation? Was it a highly sensitive test like ddPCR?
  4. 4.If my serum tryptase was over 20 ng/mL, do I have any other blood conditions that could explain that elevation?
  5. 5.Can we review the pathology report together to ensure all the 2022 WHO markers were checked?

Questions For You

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References

References (12)
  1. 1

    Diagnosing Systemic Mastocytosis: State of the Art.

    Rets A, George TI

    International journal of laboratory hematology 2025; doi:10.1111/ijlh.70011.

    PMID: 41058066
  2. 2

    The international consensus classification of eosinophilic disorders and systemic mastocytosis.

    Wang SA, Orazi A, Gotlib J, et al.

    American journal of hematology 2023; (98(8)):1286-1306 doi:10.1002/ajh.26966.

    PMID: 37283522
  3. 3

    NCCN Guidelines® Insights: Systemic Mastocytosis, Version 3.2024.

    Gotlib J, Gerds AT, Abdelmessieh P, et al.

    Journal of the National Comprehensive Cancer Network : JNCCN 2024; (22(2 D)).

    PMID: 38862005
  4. 4

    KIT D816V and the cytokine storm in mastocytosis: production and role of interleukin-6.

    Valent P

    Haematologica 2020; (105(1)):5-6 doi:10.3324/haematol.2019.234864.

    PMID: 31894094
  5. 5

    Systemic Mastocytosis and Other Entities Involving Mast Cells: A Practical Review and Update.

    El Hussein S, Chifotides HT, Khoury JD, et al.

    Cancers 2022; (14(14)) doi:10.3390/cancers14143474.

    PMID: 35884535
  6. 6

    Patient-reported outcomes among patients with systemic mastocytosis in routine clinical practice: Results of the TouchStone SM Patient Survey.

    Mesa RA, Sullivan EM, Dubinski D, et al.

    Cancer 2022; (128(20)):3691-3699 doi:10.1002/cncr.34420.

    PMID: 35996873
  7. 7

    Impact of Molecular Evaluations in the Biology, Diagnosis, and Prognostication of Patients With Mastocytosis.

    Hoermann G, Orfao A, Lyons JJ, et al.

    The journal of allergy and clinical immunology. In practice 2026; (14(1)):1-16 doi:10.1016/j.jaip.2025.07.055.

    PMID: 40846032
  8. 8

    Impact of centralized evaluation of bone marrow histology in systemic mastocytosis.

    Jawhar M, Schwaab J, Horny HP, et al.

    European journal of clinical investigation 2016; (46(5)):392-7 doi:10.1111/eci.12607.

    PMID: 26914980
  9. 9

    Morphologically occult systemic mastocytosis in bone marrow: clinicopathologic features and an algorithmic approach to diagnosis.

    Reichard KK, Chen D, Pardanani A, et al.

    American journal of clinical pathology 2015; (144(3)):493-502 doi:10.1309/AJCPSGQ71GJQQACL.

    PMID: 26276780
  10. 10

    Immunohistochemical Staining to Identify Concomitant Systemic Mastocytosis in Acute Myeloid Leukemia with RUNX1::RUNX1T1.

    Hwang SM, Kim BJ, Lee JS, et al.

    Annals of laboratory medicine 2022; (42(6)):678-682 doi:10.3343/alm.2022.42.6.678.

    PMID: 35765876
  11. 11

    High-sensitivity KIT D816V variation analysis by droplet digital polymerase chain reaction: The reference laboratory perspective.

    Shean RC, Hellwig S, Saadalla A, et al.

    American journal of clinical pathology 2025; (164(2)):145-149 doi:10.1093/ajcp/aqaf008.

    PMID: 40036308
  12. 12

    KIT Mutations and Other Genetic Defects in Mastocytosis: Implications for Disease Pathology and Targeted Therapies.

    Chantran Y, Valent P, Arock M

    Immunology and allergy clinics of North America 2023; (43(4)):651-664 doi:10.1016/j.iac.2023.04.008.

    PMID: 37758404

This page explains systemic mastocytosis pathology terminology for educational purposes only. Your hematologist or pathologist is the best source for interpreting your specific bone marrow biopsy report.

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