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PubMed This is a summary of 13 peer-reviewed journal articles Updated
Pathology

Understanding Your Pathology Report in Systemic Mastocytosis

At a Glance

A systemic mastocytosis (SM) pathology report diagnoses the disease by identifying clusters of abnormal mast cells (multifocal dense aggregates), atypical spindle shapes, aberrant surface markers like CD25, and the KIT D816V mutation in bone marrow.

Your pathology report is a technical document that “translates” the findings from your blood and bone marrow samples into a diagnosis. For systemic mastocytosis (SM), this report is complex because it must combine visual findings under a microscope with molecular genetic data [1][2].

Decoding the Microscopic Language

When a pathologist looks at your bone marrow sample, they are searching for specific visual markers of the disease.

  • Multifocal Dense Aggregates: This is a key phrase. It refers to “clumps” of 15 or more mast cells clustered together [1][3]. Finding these clusters is the “Major Criterion” for an SM diagnosis [2].
  • Spindle-Shaped Mast Cells: Normal mast cells are round. In SM, many cells become elongated or “atypical,” looking like thin spindles [4][5]. If more than 25% of the mast cells are spindle-shaped, it counts as a diagnostic marker [2].

Key Markers: The Flow Cytometry and IHC

Immunohistochemistry (IHC) and flow cytometry are tests that use special dyes to identify proteins on the surface of your cells.

  • CD117: This is the “ID tag” for mast cells. It helps the pathologist find them in the first place [6][7].
  • CD25 and CD2: These are “aberrant” markers. Healthy mast cells do not usually have these. Their presence is a strong signal that the mast cells are neoplastic (part of a disease process) [7][8].
  • CD30: This is an additional marker often found in more active or advanced forms of the disease [9][6].

Understanding the KIT D816V VAF

Your report will likely include molecular testing for the KIT D816V mutation. Increasingly, doctors look at the Variant Allele Frequency (VAF) [10].

What is VAF? Think of it as a measurement of the “volume” of the disease. It tells you what percentage of the cells in your sample carry the mutation [10][11].

  • Low VAF (<2%): Often seen in indolent (slow-moving) forms of the disease [10].
  • High VAF (>10%): May suggest a higher “burden” of mast cells and is more common in advanced subtypes [10][12].

This is usually measured using highly sensitive tests like ddPCR (Droplet Digital PCR), which can find the mutation even if only a tiny fraction of cells are affected [13][12].

High-Quality Report: The Completeness Checklist

A comprehensive pathology report for SM should ideally contain the following data points to ensure an accurate classification according to WHO 2022 guidelines [1][4]:

  1. [ ] Major Criterion Check: Presence or absence of multifocal dense aggregates (clusters of ≥15 mast cells).
  2. [ ] Morphological Assessment: Percentage of mast cells that are spindle-shaped or atypical (Target: >25%).
  3. [ ] IHC Marker Panel: Results for CD117, CD25, and ideally CD2 or CD30.
  4. [ ] Mutation Status: Confirmation of the KIT D816V mutation status.
  5. [ ] Quantitative Burden: The Variant Allele Frequency (VAF) percentage.
  6. [ ] Bone Marrow Cellularity: The total percentage of the bone marrow area occupied by mast cells (Target for “B-finding”: ≥30%).
  7. [ ] AHN Screening: A statement on whether any “Associated Hematologic Neoplasm” (a second blood disorder) was found.

Common questions in this guide

What are multifocal dense aggregates in systemic mastocytosis?
Multifocal dense aggregates are clumps of 15 or more mast cells found clustered together in a bone marrow sample. Finding these clusters is the major criterion for diagnosing systemic mastocytosis.
What does KIT D816V VAF mean on my pathology report?
VAF stands for Variant Allele Frequency, which measures the percentage of cells in your sample that carry the KIT D816V mutation. A higher VAF often suggests a larger burden of mast cells and is more common in advanced subtypes of the disease.
Why are CD25 and CD2 markers important in mast cell testing?
CD25 and CD2 are aberrant markers, meaning they are not typically found on healthy mast cells. If your lab tests show these proteins are present, it is a strong signal that the mast cells are part of a disease process.
What are spindle-shaped mast cells?
Normal mast cells are usually round, but in systemic mastocytosis, they often become elongated and look like thin spindles. If more than 25 percent of the mast cells in your sample are spindle-shaped, it counts as a diagnostic marker for the condition.
What is an Associated Hematologic Neoplasm (AHN)?
An Associated Hematologic Neoplasm (AHN) is a second blood disorder that can sometimes occur alongside systemic mastocytosis. A comprehensive pathology report will include a screening section to state whether an additional blood condition was found.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What was the exact percentage of mast cell infiltration in my bone marrow trephine biopsy?
  2. 2.Can you walk me through the immunohistochemistry (IHC) markers—did my mast cells test positive for CD25 and CD30?
  3. 3.What is my KIT D816V Variant Allele Frequency (VAF), and how does this number compare to the average for my subtype?
  4. 4.Does the pathologist's report mention any 'atypical' or 'spindle-shaped' cells, and what does that mean for my diagnosis?
  5. 5.Was a highly sensitive test like ddPCR used to detect the KIT mutation, or was it a standard NGS panel?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (13)
  1. 1

    How I diagnose systemic mastocytosis.

    Rets AV, George TI

    American journal of clinical pathology 2024; (162(4)):332-348 doi:10.1093/ajcp/aqae047.

    PMID: 38683762
  2. 2

    Diagnosing Systemic Mastocytosis: State of the Art.

    Rets A, George TI

    International journal of laboratory hematology 2026; (48(3)):551-560 doi:10.1111/ijlh.70011.

    PMID: 41058066
  3. 3

    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
  4. 4

    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
  5. 5

    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
  6. 6

    Review and Updates on Systemic Mastocytosis and Related Entities.

    Li JY, Ryder CB, Zhang H, et al.

    Cancers 2023; (15(23)) doi:10.3390/cancers15235626.

    PMID: 38067330
  7. 7

    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
  8. 8

    CD30 expression in cutaneous lesions of systemic mastocytosis: clinical, biological and histopathological analysis of 27 patients.

    Poirier E, Fraitag S, Tezenas du Montcel S, et al.

    Journal of the European Academy of Dermatology and Venereology : JEADV 2019; (33(9)):e344-e347 doi:10.1111/jdv.15633.

    PMID: 30989735
  9. 9

    Treatment of CD30-positive systemic mastocytosis with brentuximab vedotin.

    Borate U, Mehta A, Reddy V, et al.

    Leukemia research 2016; (44()):25-31.

    PMID: 26994848
  10. 10

    Accurate Diagnosis and Prognosis in Systemic Mastocytosis: The Role of Mutational Analysis.

    Weiler CR, Akin C

    The journal of allergy and clinical immunology. In practice 2020; (8(9)):3128-3129 doi:10.1016/j.jaip.2020.06.030.

    PMID: 33039016
  11. 11

    Molecular quantification of tissue disease burden is a new biomarker and independent predictor of survival in mastocytosis.

    Greiner G, Gurbisz M, Ratzinger F, et al.

    Haematologica 2020; (105(2)):366-374 doi:10.3324/haematol.2019.217950.

    PMID: 31018976
  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
  13. 13

    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

This page explains systemic mastocytosis pathology terminology for educational purposes. Your hematologist and pathologist are the best sources for interpreting your specific biopsy results.

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