#HEMEPATH Navigating Change and Integrating WHO 5th/ ICC Classification Systems in the diagnosis …

Summary

In this lecture, Dr. Sanam Iwi, a hematopathology expert from MD Anderson Cancer Center, discusses the latest updates in hematopathology classifications for diagnosing AML and MDS. She highlights the 2022 classifications by WHO and ICC, focusing on their molecular-driven approaches and minor discrepancies. Dr. Iwi explains the hierarchical classification, genetic abnormalities, and the impact of mutations like TP53 and SF3B1 on prognosis and treatment. She also addresses questions on early detection, molecular advancements, and the practical implications of these classifications in clinical settings.

Takeaways

• 📅 The lecture was part of an ongoing series and took place on April 9th, 2024, focusing on updates in the field of hematopathology, specifically discussing the integration of WHO and ICC classifications in diagnosing AML and MDS.
• 👩‍⚕️ Dr. Sanam Loghavi is an associate professor of hematopathology at MD Anderson Cancer Center in Texas, known for her expertise in the field, and was the speaker for this lecture.
• 🔬 The WHO and ICC classifications, both published in 2022, are the newest standards in hematopathology, with changes mainly driven by molecular understanding of diseases.
• 🧬 The WHO classification has shifted to highlight the neoplastic nature of MDS by renaming it to 'MDS with dysplastic neoplasms' and emphasizes the importance of genetic abnormalities in defining the disease.
• 🧬.1 Isolated deletion 5q and SF3B1 mutations are considered disease-defining genetic abnormalities by the WHO, with specific criteria for diagnosis, including blast percentage limits.
• 🧬.2 The ICC classification system is also molecularly driven but has different thresholds and requirements for disease classification, such as a 10% blast threshold for MDS-AML.
• 🔬.1 The presence of TP53 mutations, particularly in a bi-allelic manner, is associated with a poor prognosis in MDS and AML, and is a significant factor in disease classification by both WHO and ICC.
• 🔬.2 SF3B1 mutated MDS is recognized as a distinct entity with specific morphologic features and prognosis, with the requirement of a certain variant allele frequency for classification.
• 💡 The lecture emphasized the importance of considering both classifications (WHO and ICC) in practice due to their implications on prognosis, treatment decisions, and clinical trial eligibility.
• 🛑 Dr. Loghavi stressed that classification does not always equate to prognostication and that pathologists should consider the whole clinical picture when diagnosing and reporting cases.

Q & A

What is the focus of Dr. Sanam Lwi's lecture?

Dr. Sanam Lwi's lecture focuses on the recent changes in the WHO and ICC classifications and their integration in the diagnosis of AML (Acute Myeloid Leukemia) and MDS (Myelodysplastic Syndromes).

What significant change did the WHO introduce regarding Myelodysplastic Syndromes (MDS)?

The WHO now refers to Myelodysplastic Syndromes as Myelodysplastic Neoplasms to highlight the neoplastic nature of the disease, although the abbreviation MDS remains the same.

How does the ICC classification differ from the WHO regarding MDS with SF3B1 mutation?

The ICC classification requires an SF3B1 variant allele frequency (VAF) of at least 10%, whereas the WHO requires a VAF of at least 5%.

What is the upper limit of blast count for MDS in the ICC classification?

The ICC classification considers up to 9% blasts in the bone marrow or peripheral blood for MDS, while more than 9% would classify as MDS/AML.

Why is the p53 mutation significant in both AML and MDS classifications?

The p53 mutation is significant because it indicates a poor prognosis in both AML and MDS. The ICC specifically considers any p53 mutation with a VAF over 10% as a defining feature for AML or MDS/AML.

What role does the variant allele frequency (VAF) play in diagnosing TP53 mutations?

VAF helps to determine the clonality and impact of TP53 mutations. A high VAF (>50%) may indicate copy-neutral loss of heterozygosity, which is used as a surrogate for determining biallelic inactivation.

What is the recommended approach when diagnosing MDS/AML using ICC and WHO classifications?

It is recommended to report both ICC and WHO classifications to ensure comprehensive clinical trial eligibility and appropriate treatment decisions.

How should pathology reports handle genetic abnormalities when resources for advanced diagnostics are limited?

Pathologists should rely on morphological features and immunohistochemistry to predict genetic abnormalities, which are essential for diagnosis and treatment decisions, especially when advanced diagnostic resources are limited.

What is the significance of erythroid and megakaryocytic differentiation in AML diagnosis?

Erythroid and megakaryocytic differentiation in AML diagnosis is significant because these features can inform therapy choices, such as the potential resistance to BCL-2 inhibitors like venetoclax.

How are therapy-related myeloid neoplasms classified in the WHO and ICC systems?

In the WHO system, therapy-related myeloid neoplasms are classified as a distinct category based on their post-cytotoxic therapy history. In the ICC system, therapy-related features are commented on, but the primary classification is based on genetic abnormalities.