In June 2016 the World Health Organization (WHO) updated its 2008 classification of tumors of the hematopoietic and lymphoid tissues. The revised myeloid disorders classification was published in Blood.1
“This 2016 classification is not a major overhaul of the disease categories. Rather, it is intended to incorporate new knowledge of these disorders obtained since the 2008 publication and is a revision of that classification,” the authors, led by Daniel A. Arber, MD, from Stanford University in California, explained.
The inclusion of many novel molecular findings with diagnostic and/or prognostic importance “represents the efforts of pathologists working closely with clinicians and geneticists,” Mario Cazzola, MD, a co-author and associate editor of Blood, wrote in an editorial accompanying the updated classification.2 “In the next few years, we should continue this collaboration to further improve the integration of clinical features, morphology, and genetics.”
Dr. Arber and co-authors explained that several advances necessitated a revised classification, including “discoveries in diagnostic and prognostic markers; improved characterization and standardization of morphologic features; and the clinical-pathologic studies that call for an integrated approach incorporating hematologic, morphologic, cytogenetic, and molecular genetic findings.”
To develop this updated classification system, the WHO convened a clinical advisory committee in early 2014 comprising nearly 100 pathologists, hematologists, oncologists, and geneticists to propose revisions to the 2008 classification.
Read below for some of the major and proposed changes. For the full updated classification, visit bloodjournal.org.
Myeloproliferative Neoplasms (MPNs)
The categories of MPNs have not significantly changed since the 2008 edition, the authors noted, “but discoveries of new mutations and improved understanding of the morphologic features of some entities have impacted the diagnostic criteria for the disease entities.”
Discoveries of new genetic mutations associated with these diseases have changed their diagnostic criteria. Mastocytosis is no longer considered a subgroup of the MPNs because of its unique clinical and pathologic features and is now considered a separate disease category by the WHO. Recognized mastocytosis subtypes include:
- cutaneous mastocytosis
- systemic mastocytosis, including:
- indolent systemic mastocytosis
- smoldering systemic mastocytosis
- systemic mastocytosis with an associated hematologic neoplasm
- aggressive systemic mastocytosis
- mast cell leukemia
- mast cell sarcoma
Myelodysplastic Syndromes (MDS)/MPN
The MDS/MPN category was introduced in the third edition of the WHO classification to include MPNs with clinical, laboratory, and morphologic features that overlap with MDS and MPN, the authors explained.
MDS/MPN with ring sideroblasts and thrombocytosis has been converted from a provisional to a full entity.
Chronic myelomonocytic leukemia (CMML): Targeted sequencing can detect a high proportion of cases with mutated genes, with SRSF2, TET2, and ASXL1 as the most commonly mutated genes. CMML is separated into two subtypes: Proliferative type (white blood cell [WBC] count ≥13×109/L) and dysplastic type (WBC count <13 x 109/L) with differences related in part to aberrancies in the RAS/MAPK signaling pathways.
The updated guidelines removed “refractory anemia” and “refractory cytopenia” from the terminology for adult MDS and adjusted terminology. For example, the former MDS subtype refractory anemia with excess blasts type 1 is now simply MDS with excess blasts type 1. No changes were made for childhood MDS.
The new classification includes a section on myeloid neoplasms with germline predisposition, including the following:
- myeloid neoplasms with germline predisposition without a preexisting disorder or organ dysfunction
- myeloid neoplasms with germline predisposition and preexisting platelet disorders
- myeloid neoplasm with germline predisposition and other organ dysfunction
Acute Myeloid Leukemia (AML)
A new provisional category of AML with BCR-ABL1 has been established to recognize rare de novo AML cases that may benefit from treatment with tyrosine kinase inhibitor (TKI) therapy.
In addition, a provisional category of AML with mutated RUNX1 has been added to the classification for de novo AML.
Under the classification for AML, not otherwise specified, the subcategory of acute erythroid leukemia, erythroid/myeloid type (previously defined as having ≥50% bone marrow erythroid precursors and ≥20% myeloblasts among non-erythroid cells) has been removed. Myeloblasts are always counted as a percentage of total marrow cells, with the majority of these cases having less than 20 percent total blast cells, thus classified as MDS.
Acute Leukemias of Ambiguous Lineage
New provisions have been added for B-cell lymphoblastic leukemia/lymphoma (B-ALL) and T-cell lymphoblastic leukemia/lymphoma (T-ALL). For B-ALL, two provisional entities with recurrent genetic abnormalities have been recognized:
- B-ALL with intrachromosomal amplification of chromosome 21
- amplification of a portion of chromosome 21
- occurs in about 2% of children with ALL, especially older children with low WBC counts
- associated with an adverse prognosis, which, to some extent, can be overcome with more aggressive therapy
- B-ALL with translocations involving tyrosine kinases or cytokine receptors
- associated with an adverse prognosis and responses of some cases to TKIs
- difficult to define in the clinical setting
Though studies have investigated the genetic mechanisms of T-ALL, assays have not yet been standardized and prognostic implications are still controversial, so no major changes were made to the T-ALL classification.
- Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391-405.
- Cazzola M. Introduction to a review series: the 2016 revision of the WHO classification of tumors of hematopoietic and lymphoid tissues. Blood. 2016;127:2361-4.