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PubMed This is a summary of 15 peer-reviewed journal articles Updated
Hematology

Navigating Your Diagnosis and Pathology Report

At a Glance

A bone marrow biopsy is essential for accurately diagnosing a myeloproliferative neoplasm (MPN). By examining cell shapes, mutation percentages (VAF), and marrow scarring (fibrosis grade), doctors can determine your exact MPN subtype and create the most effective treatment plan.

Navigating a diagnosis of a myeloproliferative neoplasm (MPN) requires looking at more than just a single blood test. Because MPNs can overlap in how they appear, doctors follow strict international standards—specifically the WHO 5th Edition and the ICC 2022 guidelines—to ensure you receive the correct diagnosis [1][2].

Why the Bone Marrow Biopsy is Essential

While blood tests (the “peripheral blood”) show that your cell counts are high, the bone marrow biopsy shows why [3]. It is the only way to see the “architecture” of your blood factory.

A critical part of the biopsy is looking at megakaryocytes—the large cells responsible for making platelets [4]. Their shape and how they cluster tell a story:

  • “Staghorn” shapes: Typically seen in Essential Thrombocythemia (ET) [5].
  • “Pleomorphic” (mixed sizes): Often found in Polycythemia Vera (PV) [5].
  • “Cloud-like” or “bulbous” shapes: A hallmark of Primary Myelofibrosis (PMF) [4].

Understanding the Technical Terms

Your pathology report may contain several complex terms that are vital for your care:

  • Reticulin Fibrosis Grade (0-3): This measures the amount of “scarring” in your marrow. Grade 0 or 1 is considered “pre-fibrotic,” while Grades 2 or 3 indicate “overt” fibrosis [3][6].
  • Variant Allele Frequency (VAF): This is a percentage that tells you how many of your cells carry the mutation (like JAK2). For example, a VAF of 25% means one-quarter of the cells tested have the “glitch” [7][8]. Note that your VAF can naturally fluctuate over time; “chasing zero” is not the goal for most patients, so small percentage shifts shouldn’t be an immediate cause for panic [7]. A significantly higher VAF can sometimes be linked to a higher risk of symptoms or blood clots [9].
  • Leukoerythroblastosis: This means that immature red and white blood cells, which should stay inside the marrow, have “leaked” out into your bloodstream. It is often a minor sign of marrow stress or scarring [1].
  • LDH (Lactate Dehydrogenase): This is a marker in your blood that shows how fast your cells are turning over. High levels are a “minor criterion” used to help confirm a diagnosis of PMF [10][11].

The “Completeness Checklist”

To ensure your diagnosis is thorough, your pathology and lab reports should ideally include these five elements:

  1. Hemoglobin and Hematocrit levels: To check for Polycythemia Vera (PV) [11].
  2. Driver Mutation Status: Confirmation of JAK2, CALR, or MPL status [2][12].
  3. Bone Marrow Cellularity: A description of how “crowded” your marrow is with cells [3].
  4. Fibrosis Grading: A specific number (0, 1, 2, or 3) for reticulin fibers [3].
  5. Minor Criteria: Results for Erythropoietin (EPO) levels (for PV) and LDH levels (for PMF) [13][11].

If your report is missing these, it is worth asking your doctor if more testing is needed to confirm your specific MPN subtype, especially to distinguish between “True ET” and “Pre-fibrotic PMF” [14][15]. Diagnosing these correctly from the start ensures your treatment plan is built on the right foundation.

Back to Home Page

Common questions in this guide

Why do I need a bone marrow biopsy to diagnose an MPN?
While blood tests show high cell counts, a bone marrow biopsy reveals why those counts are high by showing the architecture of your blood factory. It allows pathologists to examine cell shapes and clustering, which helps distinguish between different types of MPNs.
What are megakaryocytes and why does their shape matter?
Megakaryocytes are large cells in the bone marrow responsible for making platelets. Their shapes, such as staghorn, pleomorphic, or cloud-like, help doctors determine if you have Essential Thrombocythemia, Polycythemia Vera, or Primary Myelofibrosis.
What does reticulin fibrosis grade mean on my biopsy report?
Reticulin fibrosis grade measures the amount of scarring in your bone marrow on a scale of 0 to 3. Grades 0 or 1 are considered pre-fibrotic, while grades 2 or 3 indicate overt fibrosis or more advanced scarring.
What is Variant Allele Frequency (VAF) in my pathology report?
Variant Allele Frequency, or VAF, is a percentage showing how many of your cells carry a specific genetic mutation, like JAK2. This number can fluctuate over time, and small shifts are normal and not an immediate cause for concern.
What does leukoerythroblastosis mean?
Leukoerythroblastosis means that immature red and white blood cells have leaked out of your bone marrow into your bloodstream. It is often a minor sign of marrow stress or scarring that your doctor will monitor.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on the WHO 5th Edition and ICC 2022 criteria, does my biopsy report clearly distinguish between Essential Thrombocythemia and Pre-fibrotic Myelofibrosis?
  2. 2.What was my reticulin fibrosis grade (0, 1, 2, or 3), and how does that affect my monitoring schedule?
  3. 3.What is my Variant Allele Frequency (VAF), and will we be tracking this percentage over time to see if my treatment is working?
  4. 4.Were there any 'minor criteria' found, such as an elevated LDH or leukoerythroblastosis in my blood work?
  5. 5.If I am triple-negative, what other evidence of 'clonality' was found to confirm this is an MPN?

Questions For You

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References

References (15)
  1. 1

    Evolution of WHO diagnostic criteria in "Classical Myeloproliferative Neoplasms" compared with the International Consensus Classification.

    Thiele J, Kvasnicka HM, Gianelli U, et al.

    Blood cancer journal 2025; (15(1)):31 doi:10.1038/s41408-025-01235-7.

    PMID: 40038244
  2. 2

    The international consensus classification of myeloid neoplasms and acute Leukemias: myeloproliferative neoplasms.

    Thiele J, Kvasnicka HM, Orazi A, et al.

    American journal of hematology 2023; (98(1)):166-179 doi:10.1002/ajh.26751.

    PMID: 36200127
  3. 3

    Artificial intelligence-based quantitative bone marrow pathology analysis for myeloproliferative neoplasms.

    Yu D, Zhang H, Song Y, et al.

    Haematologica 2025; (110(11)) doi:10.3324/haematol.2024.286123.

    PMID: 40501395
  4. 4

    Megakaryocytic morphology in Janus kinase 2 V617F positive myeloproliferative neoplasm.

    Ghai S, Rai S

    South Asian journal of cancer 2017; (6(2)):75-78 doi:10.4103/2278-330X.208854.

    PMID: 28702412
  5. 5

    Myelofibrosis-type megakaryocyte dysplasia (MTMD) as a distinct category of BCR::ABL-negative myeloproliferative neoplasms. Challenges and perspectives.

    Barosi G, Rosti V, Gale RP

    Leukemia 2023; (37(4)):725-727 doi:10.1038/s41375-023-01861-9.

    PMID: 36871061
  6. 6

    Myeloproliferative disorders: A retrospective cohort study.

    Mhmed Ali R, Masoud V

    Annals of medicine and surgery (2012) 2021; (68()):102628 doi:10.1016/j.amsu.2021.102628.

    PMID: 34408865
  7. 7

    Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions.

    Gong B, Li D, Kusko R, et al.

    Genome biology 2021; (22(1)):109 doi:10.1186/s13059-021-02315-0.

    PMID: 33863344
  8. 8

    Tissue-based genomic profiling of 300,000 tumors highlights the detection of variants with low allele fraction.

    Sisoudiya SD, Tukachinsky H, Keller-Evans RB, et al.

    NPJ precision oncology 2025; (9(1)):190 doi:10.1038/s41698-025-00991-w.

    PMID: 40527927
  9. 9

    Association between JAK2V617F variable allele frequency and risk of thrombotic events in patients with myeloproliferative neoplasms.

    Brown R, Jasiakiewicz J, Greer V, et al.

    Irish journal of medical science 2024; (193(6)):2883-2888 doi:10.1007/s11845-024-03776-5.

    PMID: 39138783
  10. 10

    Clonogenic assays improve determination of variant allele frequency of driver mutations in myeloproliferative neoplasms.

    Kalmer M, Pannen K, Lemanzyk R, et al.

    Annals of hematology 2022; (101(12)):2655-2663 doi:10.1007/s00277-022-05000-9.

    PMID: 36269400
  11. 11

    Update from the latest WHO classification of MPNs: a user's manual.

    Passamonti F, Maffioli M

    Hematology. American Society of Hematology. Education Program 2016; (2016(1)):534-542 doi:10.1182/asheducation-2016.1.534.

    PMID: 27913526
  12. 12

    Clinical and Laboratory Features of JAK2 V617F, CALR, and MPL Mutations in Malaysian Patients with Classical Myeloproliferative Neoplasm (MPN).

    Zulkeflee RH, Zulkafli Z, Johan MF, et al.

    International journal of environmental research and public health 2021; (18(14)) doi:10.3390/ijerph18147582.

    PMID: 34300032
  13. 13

    The 2016 revision of WHO classification of myeloproliferative neoplasms: Clinical and molecular advances.

    Barbui T, Thiele J, Gisslinger H, et al.

    Blood reviews 2016; (30(6)):453-459 doi:10.1016/j.blre.2016.06.001.

    PMID: 27341755
  14. 14

    Quantification of JAK2V617F mutation load by droplet digital PCR can aid in diagnosis of myeloproliferative neoplasms.

    Zheng CF, Zhao XX, Chen XH, et al.

    International journal of laboratory hematology 2021; (43(4)):645-650 doi:10.1111/ijlh.13560.

    PMID: 33973741
  15. 15

    Towards a Personalized Definition of Prognosis in Philadelphia-Negative Myeloproliferative Neoplasms.

    Mora B, Passamonti F

    Current hematologic malignancy reports 2022; (17(5)):127-139 doi:10.1007/s11899-022-00672-6.

    PMID: 36048275

This page explains myeloproliferative neoplasm (MPN) pathology terminology for educational purposes. Always consult your hematologist or oncologist to interpret your specific bone marrow biopsy report and lab results.

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