How Do WHO 2022 and ICC 2022 Classify MDS Differently?

If you are reading your pathology report, you might notice references to WHO 2022 or ICC 2022. It can be incredibly confusing to see different names or categories for your disease depending on which doctor or lab you consult.

In 2022, two different international groups of experts published updated classification systems for blood cancers. One group published the World Health Organization (WHO) 2022 (5th edition) classification, while another published the International Consensus Classification (ICC) 2022 ^[1].

Both systems agree on the underlying science and emphasize that diagnosing myelodysplastic syndromes (MDS) integrates your cell counts, how the cells look under a microscope (morphology), blast percentages, and genetic testing ^[1][2]. However, they use slightly different rulebooks for naming specific subtypes and setting thresholds.

Understanding these differences can help you make sense of your report and have more informed conversations with your care team.

Key Differences at a Glance

Note: This table is a simplified overview. Both systems have additional strict criteria and exclusions for diagnosis.

1. Blasts and the MDS/AML Overlap

Blasts are immature blood cells. Historically, having 20% or more blasts in the bone marrow or blood meant a diagnosis of Acute Myeloid Leukemia (AML), while having fewer than 20% meant MDS. However, this 20% rule is no longer absolute in either system ^[3]. Today, certain “AML-defining” genetic abnormalities can result in an AML diagnosis even if your blasts are below 20% ^[4][5].

For patients who do not have these specific AML-defining mutations but have 10% to 19% blasts, the two systems use different labels:

• WHO 2022: Calls this MDS-IB2 (MDS with increased blasts-2), keeping it under the MDS umbrella ^[3][2].
• ICC 2022: Calls this MDS/AML ^[3][2]. This blended name reflects that this blast range represents a biological continuum between MDS and AML ^[6]. It does not mean you have two separate diseases; it is simply a label for an overlapping, higher-risk presentation ^[7].

2. Genetically Defined Subtypes

While molecular testing is highly important, a mutation alone does not mean you have MDS. Your doctor must still assess your blood counts, morphology, and rule out other causes ^[2]. However, if you do have MDS, both systems define specific subtypes based on genetics.

When looking at genetic reports, you will often see VAF (Variant Allele Frequency). This refers to the proportion of DNA sequencing reads that carry a specific mutation, which helps doctors understand the mutation’s prominence ^[7].

SF3B1 Mutations

Both systems recognize a distinct subtype of MDS driven by a mutation in the SF3B1 gene.

• WHO 2022: Requires a 5% VAF for the SF3B1 mutation. Alternatively, if the mutation is not found, the diagnosis can still be made if 15% or more of your bone marrow cells are “ring sideroblasts” (a specific type of iron-loaded cell) ^[7][8].
• ICC 2022: Requires a 10% VAF for the SF3B1 mutation, regardless of how many ring sideroblasts you have ^[7][8].

In both systems, you cannot have certain other high-risk mutations (like a complex karyotype or RUNX1) to fit neatly into this category ^[7].

TP53 Mutations

Mutations in the TP53 gene require careful evaluation because they can indicate higher-risk disease.

• WHO 2022 uses the category MDS with biallelic TP53 inactivation.
• ICC 2022 uses the category MDS with mutated TP53.

While the names differ, both systems are looking for patients who have “multi-hit” or “biallelic” TP53 abnormalities—meaning both copies of the gene are mutated, deleted, or otherwise disabled ^[2][7]. Having only one mutated copy (monoallelic) does not place you into these specific high-risk categories, though a single mutation is still important for your doctor to monitor as it can still impact your prognosis ^[9].

Does the Classification System Change My Risk or Treatment?

It can be alarming if a second opinion changes your diagnosis from “MDS” to “MDS/AML” simply because a different rulebook was used. The WHO and ICC are nomenclature frameworks, not rigid treatment plans. A change in the label alone does not necessarily mean your disease has worsened.

However, the classification label and the underlying biology can influence your care in several ways:

• Your IPSS-M Score: The modern tool used to assess risk is the Molecular International Prognostic Scoring System (IPSS-M). IPSS-M combines your blood counts, blast percentage, cytogenetics (chromosome changes), and mutations across 31 specific genes to generate a personalized prognostic estimate ^[10][11]. The IPSS-M relies on your raw biological data, not the WHO or ICC label ^[12].
• Treatment Pathways and Transplant: Treatment is determined by your IPSS-M risk, fitness, transfusion needs, and transplant goals ^[13][14]. However, the label can sometimes influence whether your doctor recommends an MDS-directed treatment plan or an AML-directed treatment plan, particularly if you fall into the 10%–19% blast range ^[6].
• Clinical Trials: Historically, patients with 10% to 19% blasts were excluded from some AML trials. The ICC’s “MDS/AML” label may help facilitate access to clinical trials for both MDS and AML ^[15][6]. However, an MDS/AML label does not guarantee eligibility; trial access is determined strictly by the specific protocol of each study.

Because interpreting blasts, VAFs, and multi-hit mutations is highly complex, do not hesitate to ask your doctor to explain exactly which system they are using and how your specific biological data is guiding your treatment options. If your reports conflict or you are facing a major treatment decision, seeking a second pathology review from an MDS-focused hematopathologist can be very helpful.