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C H A P T E R 55

PROGRESS IN THE CLASSIFICATION OF HEMATOPOIETIC AND

LYMPHOID NEOPLASMS: CLINICAL IMPLICATIONS

Mohamed E. Salama and Ronald Hoffman

Defining and classifying tumors of the hematopoietic and lymphoid represent distinct entities, some categories are not as clearly defined
tissue accurately is a core requirement for providing optimal treat- and are regarded as provisional entities. In addition, borderline catego-
ment to patients with hematologic malignancies. Precise definitions ries have been created for cases that do not clearly fit into one category;
and terminologies are prerequisites for the precise classification of thus well-defined categories can remain homogeneous while border-
hematologic malignancies. A reproducible classification that is based line cases can be further studied and characterized. Furthermore, the
on consensus definitions and terminologies is fundamentally essential WHO classification stratifies hematologic neoplasms according to
for proper medical practice and the advancement of medical knowl- lineage into three main groups: myeloid, lymphoid, and histiocytic/
edge. Generally, such classifications should be based upon clinically dendritic cells. In this chapter we provide a summary of neoplasms
distinct, nonoverlapping disease entities that can be grouped together in these three groups, emphasizing changes that have had an effect
based on shared distinguishable clinical features, as well as phenotypic on practice guidelines.
and molecular markers which allow for reproducible laboratory
testing, clinical outcomes, and responses to therapeutic agents. Tra-
ditionally, preliminary attempts at disease classification are initiated PROGRESS IN THE DIAGNOSIS AND CLASSIFICATION OF
by the personal experience of experts, and then evolve after many MYELOID NEOPLASMS
years or even decades of controversy and exhaustive debate. Subse-
quently, classification schemes change when new scientific discoveries Clinical Implications
are validated.
Following many years of controversy, a collaborative project of The myeloid neoplasms are a heterogeneous group of diseases. In
members of the European Association for Haematopathology and the general terms, they are clonal hematopoietic malignancies that can
Society for Hematopathology, along with advice from clinical hema- arise in or affect a single myeloid lineage (e.g., monocytic). Alterna-
tologists and oncologists, resulted in the World Health Organization tively, they can be derived from a pluripotent progenitor cell and can
(WHO) Classification of Tumours of Haematopoietic and Lymphoid affect multiple or even all myeloid cell types (erythroid, megakaryo-
1,2
Tissues. This WHO classification, which is the first true worldwide cytic, monocytic, neutrophilic, basophilic, eosinophilic, and mast
consensus classification of hematologic malignancies, is based on the cells). The myeloid neoplasms include chronic and acute diseases,
principles initially defined in the “Revised European-American Clas- along with diseases that evolve from an indolent process to a more
sification of Lymphoid Neoplasms” (REAL) from the International aggressive state. As such, they can manifest as proliferative disorders,
3
Lymphoma Study Group (ILSG). The most recent WHO classifica- mostly involving primary mature hematopoietic elements; they can
tion (4th edition) was formulated in a series of meetings by two predominately affect immature or blastic cells; or sometimes they can
clinically advisory committees: one for myeloid neoplasms and other be a combination of these two manifestations. The diseases can result
4
acute leukemias, and one for lymphoid neoplasms. The current in excess production of blood cells, or they can proliferate in the bone
WHO classification, which addresses new developments related to marrow (BM) and exhibit ineffective hematopoiesis, resulting in
disease definitions, nomenclature, grading, and clinical relevance, peripheral cytopenias. Because the diseases range from indolent to
provides the basis for an approach to hematopoietic and lymphoid acute, they exhibit a wide variation in prognosis. Some disorders are
neoplasm classification that employs morphology, immune pheno- fairly indolent and require only supportive care and transfusional
4
type, genetic features, and clinical features to define diseases. The support; others slowly progress but have no successful treatment
relative importance of each of these components varies among diseases option. Acute and life-threatening disorders are often curable, even
and is dependent on the current state of knowledge. Morphologic within days or weeks after presentation, if appropriately managed.
assessment remains a key element of the diagnostic evaluation Accurate, timely diagnosis, and correct classification can have a tre-
and classification of hematologic malignancies, as many diseases mendous impact on outcome.
have characteristic diagnostic features. Morphologic evaluation also The diagnosis of the myeloid neoplasms typically requires a
remains a decisive step for prioritization of ancillary testing choices multifaceted team approach that relies on cooperation among the
that may include phenotyping, as well as molecular or genetic testing. clinician, laboratory personnel, and a skilled pathologist. The precise
Immunophenotypic studies such as flow cytometry and immunohis- diagnosis requires compiling accurate historical data, clinical infor-
tochemistry are used routinely to identify the lineage of the benign mation, general laboratory findings, and carefully interpreted obser-
or malignant process, and often are necessary to reach a definitive vations from the peripheral blood smear, bone core biopsy, and
diagnosis. In several lymphoid and myeloid neoplasms a specific aspirate merged with information from immunophenotyping, cyto-
diagnosis can be facilitated by genetic or molecular abnormalities genetic analysis, and molecular studies (Table 55.1). Although in
(e.g., CCND1 in suspected mantle cell lymphoma [MCL] or BCR/ some cases a diagnosis can be made with a quick examination of the
ABL for chronic myeloid leukemia [CML]). In addition, some blood smear, with a single molecular test, or with a simple immuno-
abnormalities can serve as prognostic markers in several diseases (e.g., phenotype, in general, careful assessment of the total clinical picture
TP53). However, many entities still lack defining genetic or molecular gives the most accurate and clinically relevant diagnosis. Future
abnormalities. routine diagnostic modalities may include next-generation sequenc-
In some conditions rendering an accurate diagnosis requires ing, single-nucleotide polymorphism array karyotyping, gene expres-
knowledge of clinical features such as a patient’s age and previous sion arrays, and genome-wide epigenetic studies.
therapy, as well as the anatomic site and/or extent of disease. Although The myeloid neoplasms are grouped as different categories of
most of the disease entities described in the WHO classification diseases. These categories seem to be changing constantly, both in

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