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768 Part VII Hematologic Malignancies

TABLE Evolving Classifications of the Myelodysplastic TABLE The Myelodysplastic/Myeloproliferative Neoplasms
55.5 Syndromes (MDS) 55.6
FAB 1982 WHO 2001 WHO 2008 WHO 2016 • CMML
• “aCML,” BCR-ABL1 negative
RA RA RCUD MDS with single lineage • JMML
RA dysplasia (MDS-SLD) • RARS-T (provisional)
RN
RT aCML, “Atypical” chronic myeloid leukemia; CMML, chronic myelomonocytic
leukemia; JMML, juvenile myelomonocytic leukemia; RARS-T, refractory anemia
RARS RARS RARS MDS-RS with single lineage with ring sideroblasts and thrombocytosis.
dysplasia (MDS-RS-SLD)
RCMD RCMD (-RS) MDS with multilineage
RCMD-RS dysplasia (MDS-MLD)
MDS-RS with multilineage however, its use will not be required in the diagnostic workup
dysplasia (MDS-RS-MLD) 22
of MDS.
RAEB RAEB-1 RAEB-1 MDS with excess blasts
(MDS-EB-1)
RAEB-2 RAEB-2 MDS with excess blasts The Overlap Myelodysplastic/
(MDS-EB2) Myeloproliferative Neoplasms
MDS-U MDS, unclassifiable
(MDS-U) In 2001 WHO introduced the overlap syndromes—that is, the
MDS with 5q- MDS with isolated del(5q) MDS/MPNs (Table 55.6)—because at the time there was disagree-
RCC (provisional) Refractory cytopenia of ment among committee members as to whether CMML was an
childhood MDS, as the FAB suggested, or an MPN, as a number of investigators
RAEB-T suggested. This group of diseases was defined to include disorders
that share features of the MPNs and of MDS at the time of initial
CMML
presentation, but that do not fit well into either group. Some of the
AML, Acute myeloid leukemia; AR, Auer rods; BM, bone marrow; entities in the MPD/MPN category still are not well understood and
CMML, chronic myelomonocytic leukemia; FAB, French–American–British may represent a disease in transition from MDS or MPN, although
classification; MDS-U, myelodysplastic syndrome, unclassified; PB, peripheral
blood; RA, refractory anemia; RARS, refractory anemia with ring sideroblasts; a case should not be placed in this category if initially diagnosed as
RAEB, refractory anemia with excess blasts; RAEB-T, refractory anemia with MDS or MPN. However, without complete knowledge of the histori-
excess blasts in transformation; RCC, refractory cytopenia of childhood; cal pathology of each individual patient, it is useful to have this
RCMD, refractory cytopenia with multilineage dysplasia; RCUD, refractory category in order to construct a more reasonable classification. The
cytopenia with unilineage dysplasia; RS, ring sideroblasts (% indicates percent
RS of total nucleated erythroid precursors); WHO, World Health Organization overlap syndromes include CMML, including the juvenile type and
classification. juvenile myelomonocytic leukemia (JMML; see Chapter 63), in
addition to “atypical” CML (atypical CML, BCR-ABL1 negative) and
an “unclassifiable” category that includes refractory anemia with ring
sideroblasts and thrombocytosis (RARS-T). The MDS/MPNs share
proliferative features in some cell lineages but also have dysplastic
affected. The 2008 WHO classification scheme also emphasized the features, including ineffective hematopoiesis, in others. Similar to the
key role of cytogenetic analysis in the diagnosis of MDS, particularly MPNs, the overlap syndromes require a full evaluation of clinical and
in cases with otherwise insufficient morphologic evidence to substan- morphologic findings and evaluation of ancillary studies before a firm
tiate a diagnosis of MDS. This is reflected in the inclusion of the diagnosis can be rendered.
subtype MDS unclassified (MDS-U), defined by the presence of
cytopenias, less than 1% peripheral blasts, less than 10% dysplastic
cells in any lineage, and less than 5% BM blasts with the presence of EVOLVING CONCEPTS IN CLASSIFICATION OF
specific cytogenetic abnormalities commonly associated with MDS. LYMPHOID NEOPLASMS
In addition, the WHO 2008 classification now includes “MDS with
an isolated del(5q)” including the “5q minus syndrome.” This syn- Hodgkin lymphoma was first described by Thomas Hodgkin in 1932
drome had been recognized for some time and is characterized typi- and is a distinct entity (Table 55.7) that can be distinguished from
cally by its presentation in middle-aged women with macrocytic the majority of lymphomas that are designated non-Hodgkin lym-
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anemia, splenomegaly, normal-to-elevated platelet counts, hypolo- phomas (NHL). Historically, different classification systems have
bated megakaryocytes in the BM, and an isolated del(5q). The specific been proposed for NHL (Table 55.8). Henry Rappaport utilized the
types of MDS have been increased and there are more than 10 dif- histologic features and the architectural arrangement of the neoplastic
ferent entities. cells and their cytology when developing a classification system in
Although the basic diagnostic principles of the 2008 WHO 1956, which became widely accepted. This system was created prior
classification of MDS are expected to remain unchanged in the to the advent of modern immunology; as such, the Lukes–Collins
2016 WHO classification system, several changes to the classifica- classification in 1975 attempted to relate cell morphology to immu-
tion are proposed. The proposed nomenclature changes include nologic function. Subsequently in 1982, the Working Formulation
replacement of the terminology “refractory anemia” and “refractory for classifying NHL replaced the Rappaport and Lukes–Collins clas-
cytopenia” with “myelodysplastic syndrome with single lineage sification. This system had three groups based on patient prognosis:
dysplasia.” In addition, the proposed changes will incorporate low, intermediate, and high grade. In 1994, the REAL classification
considerations of the prognostic significance of gene mutations in implemented a new approach for classifying NHL, taking into
MDS, revising the diagnostic criteria for MDS entities with ring account immunologic, genetic, and clinical features, and not solely
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sideroblasts based on the detection of SF3B1 mutations, slightly relying on histopathologic characteristics of the tumor cells. In 2001,
modifying the cytogenetic criteria for MDS with isolated del(5q), the WHO classification successfully provided a common language
reclassifying most cases of the erythroid/myeloid type of acute and was adopted as the standard for clinicians and investigators
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erythroleukemia, and recognizing the familial link in some cases worldwide. The modifications made in the 2008 classification are
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of MDS. Flow cytometry immunophenotyping will be recog- the result of a successful coordination between pathologists, clini-
nized as a useful ancillary technique in the evaluation of MDS, cians, and biologists. 4