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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Hematology

Understanding Your Pathology Report and Mayo Staging

At a Glance

In AL amyloidosis, pathology reports and Mayo Staging use specific blood markers like dFLC, NT-proBNP, and troponin to measure disease burden and heart stress. Understanding these numbers helps determine your disease stage and guides treatment decisions.

Your pathology and lab reports are the map your doctors use to understand the “load” of the disease and how it is affecting your organs. These reports contain complex terms, but they essentially boil down to two things: how many “bad” proteins are being made and how much stress those proteins are putting on your heart [1][2].

Decoding the Vocabulary

Before looking at staging, it helps to understand the markers your doctors are measuring in your blood:

  • Kappa/Lambda Free Light Chain Ratio: Free light chains (FLC) come in two types: kappa and lambda. In healthy individuals, they exist in a balanced ratio. In AL amyloidosis, the abnormal plasma cells produce far too much of one type, drastically skewing this ratio. A highly abnormal ratio is often the first red flag on a blood test [3][4].
  • dFLC (Difference in Free Light Chains): This is a critical number. It is the amount of the “involved” (bad) light chain minus the “uninvolved” (healthy) light chain. A higher dFLC usually means a higher disease burden [2][5]. Note on lab units: Labs may report this in mg/L or mg/dL. For example, 180 mg/L is exactly the same as 18 mg/dL.
  • NT-proBNP: This is a marker of heart “stretch.” When the heart is stiffened by amyloid, it releases more of this protein into the blood [6][7].
  • Cardiac Troponin (cTnT or cTnI): This protein is released when heart cells are under stress or damaged [1][8].

The Mayo Staging Systems

Doctors use these markers to assign a Stage, which helps them predict how the disease will behave and choose the right treatment.

The European Modification of Mayo 2004 System (Heart-Focused)

This system uses two markers: NT-proBNP and Troponin T to assign Stages I through III [9]. Doctors further divide Stage III to identify patients who need the most intensive care [10]:

  • Stage IIIA: Both markers are high, but NT-proBNP is below 8500 ng/L.
  • Stage IIIB: Both markers are high, and NT-proBNP is above 8500 ng/L. This indicates highly significant heart involvement [10][11].

The Mayo 2012 System (The “Full Picture”)

This updated system adds dFLC to the mix. It assigns 1 point for each factor that is high [12][13]:

  • NT-proBNP > 1800 ng/L

  • Troponin T > 0.025 µg/L

  • dFLC > 180 mg/L (or 18 mg/dL)

  • Stage I: 0 points

  • Stage II: 1 point

  • Stage III: 2 points

  • Stage IV: 3 points

The Bone Marrow Biopsy: Checking the “Factory”

Your report will also show the Bone Marrow Plasma Cell (BMPC) percentage. This tells you how much of your bone marrow is taken up by the plasma cells producing the toxic protein [14].

  • BMPC < 10%: Typical for most AL amyloidosis patients.
  • BMPC ≥ 10%: This is a “red flag” indicating a higher burden of disease. While it doesn’t always mean you have multiple myeloma (a related but different blood cancer), it is an independent risk factor that may lead your doctor to choose more aggressive therapy [15][16].

Understanding these numbers allows you to have a much more specific conversation with your hematologist about your individual risk and treatment goals [17].

Common questions in this guide

What does a high kappa/lambda ratio mean in AL amyloidosis?
A highly abnormal kappa/lambda free light chain ratio indicates that abnormal plasma cells are producing too much of one type of light chain protein. This skewed ratio is often the first warning sign of AL amyloidosis on a blood test.
What is dFLC and why is it important?
The dFLC, or difference in free light chains, measures the amount of abnormal disease-causing light chains minus the healthy ones. A higher number typically means a greater disease burden and is a key factor in calculating your Mayo stage.
What does the NT-proBNP marker measure?
NT-proBNP is a marker of heart stress or stretch. When the heart muscle becomes stiffened by amyloid protein buildup, it works harder and releases higher amounts of this protein into your bloodstream.
What is the difference between the Mayo 2004 and Mayo 2012 staging systems?
The Mayo 2004 system focuses primarily on heart involvement using NT-proBNP and Troponin T markers. The Mayo 2012 system provides a broader picture by also including the difference in free light chains (dFLC) to assign a stage from I to IV.
What does a high Bone Marrow Plasma Cell (BMPC) percentage mean?
A BMPC percentage of 10% or higher indicates a larger amount of abnormal plasma cells in your bone marrow. This higher disease burden is an independent risk factor that may lead your doctor to recommend more aggressive treatment.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is my current Mayo Stage, and does my report use the 2004 or 2012 staging system?
  2. 2.My NT-proBNP is quite high; does this put me into the 'IIIA' or 'IIIB' sub-category?
  3. 3.What was my Bone Marrow Plasma Cell (BMPC) percentage from my biopsy?
  4. 4.What is my target dFLC number, and do you prefer to measure it in mg/L or mg/dL?
  5. 5.How is my highly abnormal kappa/lambda ratio impacting my kidneys right now?

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 (17)
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    Immunoglobulin light chain amyloidosis: 2024 update on diagnosis, prognosis, and treatment.

    Gertz MA

    American journal of hematology 2024; (99(2)):309-324 doi:10.1002/ajh.27177.

    PMID: 38095141
  2. 2

    Immunoglobulin light chain amyloidosis: 2020 update on diagnosis, prognosis, and treatment.

    Gertz MA

    American journal of hematology 2020; (95(7)):848-860 doi:10.1002/ajh.25819.

    PMID: 32267020
  3. 3

    Warning values of serum total kappa/lambda ratio for M-proteinemia.

    Lu J, Zhu Y, Huang H, et al.

    BMC immunology 2024; (25(1)):73 doi:10.1186/s12865-024-00664-6.

    PMID: 39478462
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    [Free light chains assay: Indications and methods].

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    La Revue de medecine interne 2019; (40(5)):297-305 doi:10.1016/j.revmed.2019.01.005.

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    Relationship of tumor load parameters before and after autologous stem cell transplantation with clinical prognosis in transplant-eligible patients with multiple myeloma: A retrospective analysis.

    Minakata D, Fujiwara SI, Murahashi R, et al.

    Leukemia research 2022; (112()):106750 doi:10.1016/j.leukres.2021.106750.

    PMID: 34798568
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    Rapid hematologic responses improve outcomes in patients with very advanced (stage IIIb) cardiac immunoglobulin light chain amyloidosis.

    Manwani R, Foard D, Mahmood S, et al.

    Haematologica 2018; (103(4)):e165-e168 doi:10.3324/haematol.2017.178095.

    PMID: 29305414
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    Prognostic Value of Left Ventricular 18 F-Florbetapir Uptake in Systemic Light-Chain Amyloidosis.

    Clerc OF, Datar Y, Cuddy SA, et al.

    medRxiv : the preprint server for health sciences 2023; doi:10.1101/2023.09.13.23295520.

    PMID: 37745589
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    The cTnI/cTnT Ratio in Myocardial Injury: A Multicohort and Experimental Synthesis.

    Zimmermann T, Koechlin L, Walter J, et al.

    Journal of the American College of Cardiology 2026; (87(17)):2211-2230 doi:10.1016/j.jacc.2025.12.078.

    PMID: 41739020
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    Development and validation of a survival staging system incorporating BNP in patients with light chain amyloidosis.

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    Blood 2019; (133(3)):215-223 doi:10.1182/blood-2018-06-858951.

    PMID: 30333122
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    Cardiorenal AL amyloidosis: risk stratification and outcomes based upon cardiac and renal biomarkers.

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    British journal of haematology 2019; (186(3)):460-470 doi:10.1111/bjh.15955.

    PMID: 31124579
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    Anxious/Depressive Symptoms Alter the Subjective Perception of Heart Failure Severity in Transthyretin Cardiac Amyloidosis.

    Ponti L, Smorti M, Pozza F, et al.

    The American journal of cardiology 2023; (192()):1-6 doi:10.1016/j.amjcard.2023.01.007.

    PMID: 36689900
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    A risk stratification for systemic immunoglobulin light-chain amyloidosis with renal involvement.

    Li T, Huang X, Wang Q, et al.

    British journal of haematology 2019; (187(4)):459-469 doi:10.1111/bjh.16112.

    PMID: 31348519
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    Independent Prognostic Utility of 11C-Pittsburgh Compound B PET in Patients with Light-Chain Cardiac Amyloidosis.

    Choi YJ, Koh Y, Lee HJ, et al.

    Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2022; (63(7)):1064-1069 doi:10.2967/jnumed.121.263033.

    PMID: 34916248
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    Current applications of multiparameter flow cytometry in plasma cell disorders.

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    Prognostic Impact of Bone Marrow Plasma Cell Percentage in Patients With Systemic Light-Chain Amyloidosis: A Systematic Review and Meta-Analysis.

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    Diagnostic and Therapeutic Considerations in Concurrent Plasma Cell Dyscrasia and Amyloidosis.

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    Daratumumab-based therapy in patients with heavily-pretreated AL amyloidosis.

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    PMID: 30267007

This page explains AL amyloidosis pathology terminology and Mayo Staging for educational purposes only. Your hematologist and cardiologist are the best sources for interpreting your specific lab results and staging.

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