The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms

Abstract

The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.

The WHO Classification of Haematolymphoid Tumours

“…The outcome of this effort is another classification in the series that will help move the field forward by being based on a forwardlooking multidisciplinary effort grounded in genetic advances, with an eye on worldwide applicability. An overview of the classification and its salient features are provided in the two excellent companion manuscripts, which cover the classification of myeloid and histiocytic/dendritic neoplasms [12] and the classification of lymphoid neoplasms [13].…”

Clinical Significance of Clonal Hematopoiesis of Indeterminate Potential in Hematology and Cardiovascular Disease

“…Only an increase of red cell distribution width (RDW) is consistently associated with CHIP [ 7 ]. In some individuals, CHIP is accompanied by unexplained cytopenia (anemia, neutropenia, and/or thrombocytopenia) which is defined as clonal cytopenia of unknown significance (CCUS) [ 11 , 12 , 28 ]. Per definition, CCUS patients do not meet the diagnostic criteria of a hematologic neoplasm.…”

“…The definition also includes a minimal variant allele fraction (VAF) of 2% in the peripheral blood (corresponding to ~4% of leukocytes harboring a heterozygous mutation) to discriminate CHIP from nearly ubiquitous extremely small hematopoietic clones [ 11 ]. CHIP will also be included as an entity in the 5th edition of the World Health Organization Classification of Hematolymphoid Tumors where it will be defined similarly by the presence of somatic mutations of myeloid malignancy-associated genes detected in the blood or bone marrow with a VAF ≥ 2% (≥4% for X-linked gene mutations in males) in individuals without a diagnosed hematologic disorder or unexplained cytopenia [ 12 ].…”

“…Table 1 lists the genes typically mutated in individuals with CHIP [ 12 ]. While some of the CHIP mutations are specific for hematopoietic clones and neoplasms, others are also frequently found in solid cancers.…”

When Ring Sideroblasts on Bone Marrow Smears Are Inconsistent with the Diagnosis of Myelodysplastic Neoplasms

“…Hemoglobin synthesis is then impaired, resulting in the development of anemia [ 6 ]. The detection of RS is required in myelodysplastic neoplasms (MDSs) or myelodysplastic/myeloproliferative neoplasms (MDS/MPNs), allowing a more accurate classification of these acquired clonal conditions according to WHO recommendations [ 7 , 8 , 9 , 10 ].…”