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Classifications for all neoplasms have been reviewed and
updated in ICD-O-3, but the most extensive revision concerned
hematologic
malignancies.
Over the past 50 years, many classifications of leukemia
and lymphoma have been proposed. Some of these had a major
impact on clinical practice while others are now largely forgotten.
For most of this period, however, the distinction between
lymphoma and leukemia has been regarded as fundamental importance
and classifications have tended to evolve separately.
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Most lymphoma classifications can be grouped
into two major categories. Tumors may be subdivided
according to purely morphologic characteristics such
as cell size and shape and the pattern of tumor growth
within the lymph node or other tissue. In contrast,
the Kiel classification and the Lukes and Collins classification
were based on the ideas that the cells in a malignant
lymphoma have undergone maturational arrest and that
tumors could be classified by comparison with the normal
stages of lymphocyte differentiation. In the USA,
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the National Cancer Institute's Working Formulation was an
attempt to provide a tool for converting diagnostic data into
a common format for comparative purposes. In practice, the Working
Formulation became a primary classification based, like the
Rappaport classification, mainly on morphologic characteristics.
A grading system was used in most lymphoma classifications
to simplify the numerous tumor types into a few categories,
primarily for clinical use. It is important to recognize,
however, that grades were not strictly comparable between
different systems of classification. In the Kiel classification,
high and low grade referred to the size of cells in a tumor.
Grades used in the Working Formulation were derived from prognostic
data collected in the course of the original study that gave
rise to the classification; in clinical terms, high grade
came to mean an aggressive tumor potentially curable by chemotherapy,
while low-grade lymphomas were more indolent but often incurable.
The French-American-British (FAB)(7) system provided a parallel,
but distinct, system for the classification of lymphoid and
myeloid leukemias and myelodysplasia
based on traditionally stained specimens.
In the early 1990s, it was becoming apparent that there were
many problems with the existing classification systems for
leukemia and lymphoma. The introduction of immunophenotypic
and molecular biological techniques had shown that individual
categories were, in fact, heterogeneous. It was evident that
the use of lymphoma grades as the basis for clinical trials
or epidemiological studies was potentially highly misleading.
As definitions became clearer, it was increasingly obvious
that the distinction between lymphoid leukemias and lymphomas
was largely artificial; it reflected patterns of spread in
the individual patient rather than basic cellular or clinical
differences. The distinction between Hodgkin disease and non-Hodgkin
lymphoma was a cornerstone of lymphoma classification. However,
various investigations showed that the tumor cells in Hodgkin
disease were derived from germinal center B-cells and that
Hodgkin disease should therefore be regarded as a distinctive
form of B-cell lymphoma rather than as a completely separate
group of disorders. Cytogenetic studies revealed the importance
of chromosomal translocations with dysregulation of individual
genes in the pathogenesis and clinical behavior of several
types of leukemia and lymphoma, although achieving a complete
understanding of tumor pathogenesis is clearly going to be
a lengthy process.
These developments were the basis of the Revised European-American
Lymphoma (REAL) classification published in 1994 (6). Although
many of the terms used are similar to those used in the Kiel
classification, the underlying concepts are different. In
the REAL classification definitions of clinico-pathological
entities are based on a combination of morphology, immunophenotype,
genetic abnormalities, and clinical features. Despite the
vast number of possible combinations of these variables, there
are in fact relatively few disease entities, and more than
90% of lymphoid malignancies can be classified using this
approach. The WHO classification of hematologic malignancies
(21,22) is based on the same approach and the section on lymphoproliferative
disorders is broadly similar. The approach to subclassification
of acute myeloid leukemia (AML) recognizes the central importance
of cytogenetic abnormalities and the distinction between "de
novo" and myelodysplasia-associated AML.
The WHO classification cannot be regarded as definitive,
but it provides a sound basis for future developments. Many
of the major categories, such as diffuse large B-cell lymphoma,
are clearly heterogeneous in terms of clinical features and
response to treatment. In the future these will be further
subdivided according to cellular and molecular criteria, but
at present there is no consensus as to how this should be
done. It is likely that the differences in the hematologic
malignancy section of the next edition of ICD-O will be every
bit as great as the differences between the Second and Third
Editions.
Click here to view
Table 13 showing the WHO classification of Hematopoietic and
Lymphoid Neoplasms with ICD-O codes.
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