WHO Classification of Malignant Hematological Diseases

Classification of myeloid malignancies

Chronic myeloproliferative diseases Chronic myeloproliferative diseases
  Myelodysplastic/myeloproliferative diseases
Myelodysplastic syndromes Myelodysplastic syndromes
Acute myeloid leukamias Acute myeloid leukemias

The WHO classification system puts a few diseases that show characteristics of both myeloproliferative and myelodysplastic conditions into a new, separate group (myeloproliferative/myelodysplastic diseases).

Chronic myeloproliferative diseases (MPD)

Malignant stem cell disorder of clonal origin with a chronic course. It is characterized by splenomegaly and an elevated cell count in one or more cell lines. The marrow is hypercellular with signs of differentiation, there is no dysplasia.

Classification of chronic myeloproliferative diseases
Chronic myelogenous leukemia (CML) CML Ph+: t(9;22)(qq34;q11), BCR/ABL
  Chronic neutrophilic leukemia
Agnogenic myeloid metaplasia with myelofibrosis (MF)
(Idiopathic myelofibrosis)
Chronic eosinophilic leukemia/hypereosinophilic syndrome
Polycythemia vera (EV) Chronic idiopathic myelofibrosis
Essential thrombocytemia (ET) Polycythemia vera
  Essential thrombocytemia


The most important change is that only the Ph+ cases are called CML by the WHO. The Ph- cases (which show myelodysplastic signs and are known to have significantly worse prognosis) are called aCML (atypical CML) and belong to the newly created myelodysplastic/myeloproliferative group. The CML term is somewhat misleading, because it is not CML at all, but was kept having no better alternative.

Myelodysplastic/myeloproliferative diseases

WHO: myelodysplastic/myeloproliferative diseases
Atypical myelogenous leukemia (aCML)
Chronic myelomonocytic leukemia (CMML)
Juvenile myelomonocytic leukemia (JMML)

CMML belonged to the MDS in the FAB classification. About one half of the cases show proliferative, the other dysplastic signs, but it appears that these are just different forms of the same disease.

Myelodysplastic syndromes (MDS)

Myelodysplastic syndromes
FAB classification of MDS WHO classification of MDS
Refractory anemia (RA) Refractory anemia
Refractory anemia with ringed sideroblasts (RARS) with ringed sideroblasts (FAB: RARS)
  without ringed sideroblasts (FAB: RA)
Refractory anemia with excess blasts (RAEB) Refractory anemia with excess blasts (FAB: RAEB)
Refractory anemia with excess blasts in transformation (RAEB-T)  
Chronic myelomonocytic leukemia (CMML) Refractory cytopenia with multilineage dysplasia (new)
  5q- syndrome (new)
  unclassifiable (new)

Major changes: the RAEB-T of the FAB is now considered to be acute leukemia, not an MDS type.

CMML of the FAB was put into the new MPD/MDS group by the WHO.

A new group was formed from those cases previously classified as RA or RARS where the dysplasia affected more than one cell line, because the prognosis has been found worse for these cases (refractory cytopenia with multilineage dysplasia).

A new subgroup is 5q- syndrome (the loss of the long arm of chromosome 5).

Acute myeloid leukemias (AML)

AML classification
M0: minimally differentiated   AML with recurrent cytogenetic translocations
M1: myeloblastic leukemia without maturation   AML with t(8;21)(q22;q22) AML1/CBFalpha/ETO
M2: myeloblastic leukemia with maturation   Acute promyelocytic leukemia:
AML with t(15;17)(q22;q12) and variants PML/RARalpha
M3: hypergranular promyelocytic leukemia   AML with abnormal bone marrow eosinophils 
inv(16)(p13;q22) vagy t(16;16)(p13;q22) CBFbeta/MYH1
M4: myelomonocytic leukemia   AML with 11q23 MLL abnormalities
M4Eo: variant, increase in marrow eosinophils   AML with multilineage dysplasia
M5: monocytic leukemia   With prior MDS
M6: erythroleukemia (DiGuglielmo’s disease)   Without prior MDS
M7: megakaryoblastic leukemia   AML with myelodysplastic syndrome, therapy related
    Alkylating agent related
    Epipodophyllotoxin related
    Other types
    AML not otherwise categorized
    AML minimally differentiated
    AML without maturation
    AML with maturation
    Acute myelomonocytic leukemia
    Acute monocytic leukemia
    Acute erythroid leukemia
    Acute megakaryocytic leukemia
    Acute basophilic leukemia
    Acute panmyelosis with myelofibrosis

The changes are easily summarized: the leukemias with consistent cytogenetic abnormalitites and those that are MDS related were taken into separate groups, the rest of the old FAB classification was put under the “AML not otherwise categorized” entry.

“REAL” classification of lymphoid malignancies

WHO classification of lymphoid malignancies (part 1: non-Hodgkin types)
B cell   T cell
Precursor B cell neoplasm   Precursor T cell neoplasm
Precursor B lymphoblastic leukemia/lymphoma
(precursor B cell acute lymphoblastic leukemia)
  Precursor T lymphoblastic lymphoma/leukemia
(precursor T cell acute lymphoblastic leukemia)
Mature (peripheral) B cell neoplasms   Mature (peripheral) T cell neoplasms
B cell chronic lymphocytic leukemia/small lymphocytic lymphoma   T cell prolymphocytic leukemia
B cell prolymphocytic leukemia   T cell granular lymphocytic leukemia
Lymphoplasmacytic lymphoma   Aggressive NK cell leukemia
Splenic marginal zone B cell lymphoma  (villous lymphocytes)   Adult T cell lymphoma/leukemia (HTLV-I+)
Hairy cell leukemia   Extranodal NK/T cell lymphoma, nasal type
Plasma cell myeloma/plasmacytoma   Enteropathy-type T cell lymphoma
Extranodal marginal zone B cell lymphoma of MALT type   Hepatosplenic T cell lymphoma
Mantle cell lymphoma   Subcutaneous panniculitis-like T cell lymphoma
Follicular lymphoma   Mycosis fungoides/Sezary syndrome
Nodal marginal zone B cell lymphoma (monocytoid B cells)   Anaplastic large cell lymphoma, primary cutaneous type
Diffuse large B cell lymphoma   Peripheral T cell lymphoma, not otherwise specified (NOS)
Burkitt’s lymphoma/Burkitt cell leukemia   Angioimmunoblastic T cell lymphoma
    Anaplastic large cell lymphoma, primary systemic type
WHO classification of lymphoid malignancies (part 2: Hodgkin disease)
Nodular lymphocyte-predominant Hodgkin’s disease
Classical Hodgkin’s disease
Nodular sclerosis Hodgkin’s disease
Lymphocyte-rich classical Hodgkin’s disease
Mixed-cellularity Hodgkin’s disease
Lymphocyte-depletion Hodgkin’s disease