The WHO classification of hematological malignancies (2016)

In 2001, the WHO classification of hematological malignancies was introduced and revised in 2008 and 2016.

While the FAB classification is primarily based on morphological and cytochemical criteria, the WHO classification includes immunological, cytogenetic, molecular biological and clinical criteria. The idea is to define entities that differ by natural course of the disease, prognosis and treatment response. According to the cell line, the WHO-classification differentiates the following groups of hematopoietic and lymphatic neoplasms (provisional entities are not listed):

Myeloproliferative neoplasms (MPN)

• Chronic myeloid leukemia (CML) BCR-ABL1 +
• Chronic neutrophilic leukemia (CNL)
• Polycythemia vera (PV)
• Primary myelofibrosis (PMF)
• Essential thrombocythemia (ET)
• Chronic eosinophilic leukemia, (CEL)
• MPN, unclassifiable

Mastocytosis

• Cutaneous mastocytosis
• Systemic mastocytosis
  • Indolent systemic mastocytosis (ISM)
  • Smoldering systemic mastocytosis (SSM)
  • Systemic mastocytosis with an associated (clonal) hematologic non–mast cell lineage disease (SM-AHN)
  • Aggressive systemic mastocytosis
  • Mast cell leukemia

Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2

• Myeloid/lymphoid neoplasms with PDGFRA rearrangement
• Myeloid/lymphoid neoplasms with PDGFRB rearrangement
• Myeloid/lymphoid neoplasms with FGFR1 rearrangement

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)

• Chronic myelomonocytic leukemia (CMML)
• Atypical chronic myeloid leukemia (aCML)
• Juvenile myelomonocytic leukemia (JMML)
• MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)
• MDS/MPN, unclassifiable

Myelodysplastic syndromes (MDS)

• MDS with single lineage dysplasia
• MDS with ringed sideroblasts (MDS-RS)
  • MDS-RS and single lineage dysplasia
  • MDS-RS and multilineage dysplasia
• MDS with multilineage dysplasia
• MDS with excess blasts (RAEB)
• MDS with isolated del(5q)
• MDS, unclassifiable

Acute myeloid leukemias (AML)

• AML with recurrent genetic abnormalities
  • AML with t(8;21)(q22;q22.1);RUNX1-RUNX1T1
  • AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22);CBFB-MYH11
  • Acute promyelocytic leukemia with PML-RARA
  • AML with t(9;11)(p21.3;q23.3);MLLT3-KMT2A
  • AML with t(6;9)(p23;q34.1);DEK-NUP214
  • AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM
  • AML (megakaryoblastic) with t(1;22)(p13.3;q13.3);RBM15-MKL1
  • AML with mutated NPM1
  • AML with biallelic mutations of CEBPA
• AML with myelodysplasia-related changes
• Therapy-related myeloid neoplasms
• AML, not otherwise specified (AML NOS)
  • AML with minimal differentiation (AML M0)
  • AML without maturation (AML M1)
  • AML with maturation (AML M2)
  • Acute myelomonocytic leukemia (AML M4)
  • Acute monoblastic/monocytic leukemia (AML M5a and M5b)
  • Pure erythroid leukemia (AML M6)
  • Acute megakaryoblastic leukemia (AML M7)
  • Acute basophilic leukemia
  • Acute panmyelosis with myelofibrosis
• Myeloid sarcoma
• Myeloid proliferations related to Down syndrome
  • Transient abnormal myelopoiesis (TAM)
    
  • Myeloid leukemia associated with Down syndrome

Acute leukemias of ambiguous lineage

• Acute undifferentiated leukemia
• Mixed phenotype acute leukemia (MPAL) with t(9;22)(q34.1;q11.2); BCR-ABL1
• MPAL with t(v;11q23.3); KMT2A rearranged
• MPAL, B/myeloid, NOS
• MPAL, T/myeloid, NOS

B-lymphoblastic leukemia/lymphoma

• B-lymphoblastic leukemia/lymphoma, NOS (B-ALL)
• B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities
  • with t(9;22)(q34.1;q11.2);BCR-ABL1
  • with t(v;11q23.3);KMT2A rearranged
  • with t(12;21)(p13.2;q22.1); ETV6-RUNX1
  • with hyperdiploidy
  • with hypodiploidy
  • with t(5;14)(q31.1;q32.3) IL3-IGH
  • with t(1;19)(q23;p13.3);TCF3-PBX1

T-lymphoblastic leukemia/lymphoma (T-ALL)

Mature B-cell neoplasms

• Chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL)
• Monoclonal B-cell lymphocytosis
• B-cell prolymphocytic leukemia (B-PLL)
• Splenic marginal zone lymphoma (SMZL)
• Hairy cell leukemia (HCL)
• Splenic B-cell lymphoma/leukemia, unclassifiable
  • Splenic diffuse red pulp small B-cell lymphoma
  • Hairy cell leukemia-variant
• Lymphoplasmacytic lymphoma (Waldenström macroglobulinemia)
• Monoclonal gammopathy of undetermined significance (MGUS), IgM
• μ heavy-chain disease
• γ heavy-chain disease
• α heavy-chain disease
• Monoclonal gammopathy of undetermined significance (MGUS), IgG/A
• Plasma cell myeloma
• Solitary plasmacytoma of bone
• Extraosseous plasmacytoma
• Monoclonal immunoglobulin deposition disease
• Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue
  (MALT lymphoma)
• Nodal marginal zone lymphoma
• Follicular lymphoma
• Pediatric-type follicular lymphoma
• Primary cutaneous follicle center lymphoma
• Mantle cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)
• T-cell/histiocyte-rich large B-cell lymphoma
• Primary DLBCL of the central nervous system
• DLBCL associated with chronic inflammation
• Lymphomatoid granulomatosis
• Primary mediastinal (thymic) large B-cell lymphoma
• Intravascular large B-cell lymphoma
• ALK1 large B-cell lymphoma
• Plasmablastic lymphoma
• Primary effusion lymphoma
• Burkitt lymphoma
• High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
• High-grade B-cell lymphoma, NOS
• B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma

Mature T and NK neoplasms

• T-cell prolymphocytic leukemia (T-PLL)
• T-cell large granular lymphocytic leukemia
• Chronic lymphoproliferative disorder of NK cells
• Aggressive NK-cell leukemia
• Systemic EBV⁺ T-cell lymphoma of childhood
• Hydroa vacciniforme–like lymphoproliferative disorder
• Adult T-cell leukemia/lymphoma (ATLL)
• Extranodal NK-/T-cell lymphoma, nasal type
• Enteropathy-associated T-cell lymphoma
• Monomorphic epitheliotropic intestinal T-cell lymphoma
• Hepatosplenic T-cell lymphoma
• Subcutaneous panniculitis-like T-cell lymphoma
• Mycosis fungoides
• Sézary syndrome
• Primary cutaneous CD30⁺ T-cell lymphoproliferative disorders
• Primary cutaneous γδ T-cell lymphoma
• Peripheral T-cell lymphoma, NOS
• Angioimmunoblastic T-cell lymphoma
• Anaplastic large-cell lymphoma, ALK⁺
• Anaplastic large-cell lymphoma, ALK^-

Hodgkin lymphoma

• Nodular lymphocyte predominant Hodgkin lymphoma
• Classical Hodgkin lymphoma
  • Nodular sclerosis classical Hodgkin lymphoma
  • Lymphocyte-rich classical Hodgkin lymphoma
  • Mixed cellularity classical Hodgkin lymphoma
  • Lymphocyte-depleted classical Hodgkin lymphoma

Posttransplant lymphoproliferative disorders (PTLD)

• Plasmacytic hyperplasia PTLD
• Infectious mononucleosis PTLD
• Florid follicular hyperplasia PTLD
• Polymorphic PTLD
• Monomorphic PTLD (B- and T-/NK-cell types)
• Classical Hodgkin lymphoma PTLD

Histiocytic and dendritic cell neoplasms

• Histiocytic sarcoma
• Langerhans cell histiocytosis
• Langerhans cell sarcoma
• Indeterminate dendritic cell tumor
• Interdigitating dendritic cell sarcoma
• Follicular dendritic cell sarcoma
• Fibroblastic reticular cell tumor
• Disseminated juvenile xanthogranuloma
• Erdheim-Chester disease