B-Cell Non-Hodgkin Lymphoma (Mature B-Cell NHL)

name: B-Cell Non-Hodgkin Lymphoma
display_name: B-Cell Non-Hodgkin Lymphoma (Mature B-Cell NHL)
creation_date: "2026-08-17T00:00:00Z"
description: >-
  B-cell non-Hodgkin lymphoma (B-NHL) is the large, clinically dominant family
  of non-Hodgkin lymphomas arising from mature (peripheral) B lymphocytes. Its
  members span indolent and aggressive entities that are defined by their
  cell-of-origin (germinal-center vs post-germinal-center / activated B cell),
  their recurrent driver genetics (characteristic immunoglobulin-locus
  translocations such as BCL2/t(14;18), MYC/t(8;14), CCND1/t(11;14), and
  activating BCR-NF-kB lesions), and their clinical behavior. They share a
  mature B-cell lineage and, in most members, a dependence on B-cell-receptor
  survival signaling — with constitutive NF-kB activation prominent in the
  activated-B-cell, marginal-zone and lymphoplasmacytic entities, but
  characteristically absent in Burkitt lymphoma, which depends on tonic
  BCR-PI3K signaling. Each is a genetically and clinically distinct disease with its
  own defining lesion, natural history, and therapy. This grouping is assembled
  below the level of the MONDO classification as an explicit, auditable union of
  the separately curated mature B-cell NHL Disease entries; it organizes and
  cross-references them rather than duplicating their content or blurring their
  distinct pathomechanisms into a single umbrella Disease graph.
grouping_basis:
- SHARED_PHENOTYPE
- CLINICAL_CONVENTION
grouping_rationale: >-
  Grouped on a shared cell-of-origin phenotype (a neoplasm of mature B
  lymphocytes) and long-standing clinical/WHO convention (the mature B-cell
  non-Hodgkin lymphomas as a diagnostic family). Members are deliberately kept
  as separate Disease entries — not folded into one umbrella Disease with
  has_subtypes — because they are genuinely distinct diseases: they differ in
  the causal driver gene and translocation (BCL2 in follicular lymphoma, MYC in
  Burkitt lymphoma, CCND1 in mantle cell lymphoma, MYD88 in Waldenstrom
  macroglobulinemia, MALT1/BCL10 in MALT lymphoma, NOTCH2 in splenic marginal
  zone lymphoma), in cell-of-origin (germinal-center vs activated post-GC B
  cell), in clinical tempo (indolent vs aggressive), and in treatment. What they
  share downstream — B-cell-receptor survival signaling (with constitutive NF-kB
  activation prominent in the activated-B-cell, marginal-zone and
  lymphoplasmacytic entities, but characteristically absent in Burkitt lymphoma,
  which depends on tonic BCR-PI3K signaling) and, in the germinal-center
  entities, aberrant somatic hypermutation and class-switch machinery — is a
  convergence point, not evidence that they are one disease.
  The grouping points DOWN at the real Disease entries with explicit membership
  criteria and per-member differentiators. The listed membership is
  incrementally curated: additional mature B-cell NHLs (e.g. nodal marginal zone
  lymphoma, primary CNS/mediastinal DLBCL, and the leukemic-presentation mature
  B-cell neoplasms) are candidate members as their entries are added — see the
  boundary note in the accompanying PR.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0015759
      label: B-cell non-Hodgkin lymphoma
    mapping_predicate: skos:closeMatch
    mapping_source: MONDO
    mapping_justification: >-
      This grouping corresponds closely to the MONDO B-cell non-Hodgkin lymphoma
      class but is deliberately narrower in intension, so closeMatch (rather than
      exactMatch) is used. MONDO:0015759 is logically defined as the intersection
      of "B-cell neoplasm" (MONDO:0004095) and "non-Hodgkin lymphoma"
      (MONDO:0018908), a definition that carries no maturity or
      clinical-presentation restriction; its is-a descendants therefore include
      entities this grouping intentionally excludes — chronic lymphocytic
      leukemia / small lymphocytic lymphoma (MONDO:0003864) and hairy cell
      leukemia (MONDO:0018935), which present as leukemias, and B-cell acute
      lymphoblastic leukemia (MONDO:0004947), which is a precursor
      (B-lymphoblastic), not mature, neoplasm. This grouping is scoped to the
      mature (peripheral) B-cell, non-leukemic-presentation lymphomas, so the
      concepts are close but not identical. Matching the Diabetes_Mellitus
      precedent, closeMatch keeps MONDO:0015759 in the curation queue rather than
      retiring it as fully covered.
    consistency:
    - reference: MONDO
      consistent: CONSISTENT
      notes: >-
        The divergence from MONDO:0015759 is intensional, not merely a coverage
        gap: MONDO's logical intersection (B-cell neoplasm AND non-Hodgkin
        lymphoma) places B-lymphoblastic (precursor) neoplasms and the
        leukemic-presentation mature B-cell neoplasms (CLL/SLL, hairy cell
        leukemia) inside the class, whereas this grouping's clinical concept —
        mature, non-leukemic-presentation B-cell NHL — sits strictly within that
        intersection and deliberately excludes them. MONDO's descendant list
        should therefore not be treated as an exhaustive set of dismech curation
        gaps for this grouping.
membership_criteria:
- description: >-
    A disorder is a member of this grouping if it is classified as a lymphoma of
    mature (peripheral) B lymphocytes that is not Hodgkin lymphoma — i.e. a
    B-cell non-Hodgkin lymphoma (the HPO analog is HP:0012191 "B-cell lymphoma",
    which itself sits under HP:0012539 "Non-Hodgkin lymphoma"). This both
    asserts the mature-B-cell lineage and, with the explicit exclusion of
    Hodgkin lymphoma, fixes the non-Hodgkin scope of the family. It does not by
    itself settle which specific entities are curated as members (that is the
    union listed below). The conjuncts use HAS_CLASSIFICATION because dismech
    has no single canonical nosology slot and the member entries carry the
    B-cell-neoplasm / non-Hodgkin-lymphoma nosology as free-text category and
    classification text rather than a structurally-resolvable annotation for
    the Hodgkin-exclusion conjunct; groupings.py therefore returns UNKNOWN for
    that conjunct, keeping the overall NECESSARY axiom partly auditable by hand
    rather than fully machine-satisfiable. The first conjunct is now stated as
    HAS_PHENOTYPE: each of the eight member Disease entries was annotated with
    its defining B-cell-lymphoma phenotype (HP:0012191, or the descendant
    HP:0033125 "Follicular lymphoma" for the Follicular Lymphoma entry) in
    PR #8770, so this conjunct is machine-evaluable via HP closure.
  criteria_semantics: NECESSARY
  logic:
    operator: AND
    operands:
    - criterion_predicate: HAS_PHENOTYPE
      phenotype_term:
        preferred_term: B-cell lymphoma
        term:
          id: HP:0012191
          label: B-cell lymphoma
      description: >-
        Classified as a neoplasm of mature B lymphocytes (a B-cell non-Hodgkin
        lymphoma); the corresponding HPO concept is HP:0012191 "B-cell
        lymphoma", a subtype of HP:0012539 "Non-Hodgkin lymphoma". Evaluated
        over the HP closure, so a member annotated with a descendant term
        (e.g. HP:0033125 "Follicular lymphoma") also satisfies this conjunct.
    - criterion_predicate: HAS_CLASSIFICATION
      classification: Hodgkin lymphoma
      negated: true
      description: >-
        Not Hodgkin lymphoma (HP:0012189) — excludes classic and
        nodular-lymphocyte-predominant Hodgkin lymphoma from the non-Hodgkin
        family.
members:
- member: Diffuse Large B-Cell Lymphoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      The most common aggressive B-NHL, resolved by cell-of-origin into
      germinal-center-B-cell (GCB) and activated-B-cell (ABC) types. ABC-type
      tumors depend on chronic active B-cell-receptor signaling and constitutive
      NF-kB activation, frequently driven by activating MYD88 (e.g. L265P) and
      CD79B mutations; GCB-type tumors carry BCL2 and EZH2 lesions. "Double-hit"
      cases combine MYC with BCL2 and/or BCL6 rearrangements.
    gene:
      preferred_term: BCL6
      term:
        id: hgnc:1001
        label: BCL6
- member: Follicular Lymphoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      The prototypical indolent germinal-center-derived B-NHL, defined by the
      t(14;18)(q32;q21) translocation juxtaposing BCL2 to the immunoglobulin
      heavy-chain enhancer, causing constitutive anti-apoptotic BCL2
      overexpression; a follicular growth pattern and CREBBP/EZH2 epigenetic
      lesions are characteristic.
    gene:
      preferred_term: BCL2
      term:
        id: hgnc:990
        label: BCL2
    module: resisting_cell_death
- member: Burkitt Lymphoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      A highly aggressive germinal-center B-NHL defined by MYC translocation to
      an immunoglobulin locus — classically t(8;14)(q24;q32) — driving
      unrestrained proliferation with a near-100% proliferation fraction; TCF3/ID3
      lesions cooperate. EBV-associated in the endemic form.
    gene:
      preferred_term: MYC
      term:
        id: hgnc:7553
        label: MYC
- member: Mantle Cell Lymphoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      A distinct, generally aggressive B-NHL of pre-germinal-center / naive
      mantle-zone B cells, defined by t(11;14)(q13;q32) juxtaposing CCND1 to the
      IGH locus, causing cyclin D1 overexpression and cell-cycle dysregulation;
      ATM loss and SOX11 expression are characteristic.
    gene:
      preferred_term: CCND1
      term:
        id: hgnc:1582
        label: CCND1
- member: MALT Lymphoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, an
      indolent B-NHL driven by chronic antigenic stimulation (e.g. Helicobacter
      pylori gastritis) and characterized by translocations that constitutively
      activate NF-kB, notably t(11;18)(q21;q21) creating the BIRC3-MALT1 fusion
      and t(1;14) deregulating BCL10.
    gene:
      preferred_term: MALT1
      term:
        id: hgnc:6819
        label: MALT1
- member: Splenic Marginal Zone Lymphoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      An indolent marginal-zone B-NHL primarily involving the spleen and bone
      marrow, distinguished from the extranodal (MALT) and nodal marginal zone
      lymphomas by recurrent NOTCH2 and KLF2 mutations and 7q deletion; often
      associated with hepatitis C virus infection.
    gene:
      preferred_term: NOTCH2
      term:
        id: hgnc:7882
        label: NOTCH2
- member: Waldenstrom Macroglobulinemia
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      The clinical manifestation of lymphoplasmacytic lymphoma, an indolent
      B-NHL of IgM-secreting lymphoplasmacytoid cells. It is defined at the
      molecular level by the recurrent activating MYD88 L265P mutation (NF-kB
      activation) with frequent CXCR4 mutations, and clinically by a serum IgM
      paraprotein producing hyperviscosity — features that separate it from the
      other mature B-cell lymphomas.
    gene:
      preferred_term: MYD88
      term:
        id: hgnc:7562
        label: MYD88
- member: Primary_Tonsillar_Lymphoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      An aggressive primary-site (Waldeyer's-ring) B-NHL, most often of
      diffuse-large-B-cell type. Germinal-center-type tumors carry BCL2 and EZH2
      lesions while activated-B-cell-type tumors depend on chronic BCR/NF-kB
      signaling (CD79B, MYD88); double-/triple-hit MYC-BCL2-BCL6 and IRF4
      rearrangements and EBV latency programs occur. It is distinguished by its
      anatomic site of origin rather than a single unique driver.
    gene:
      preferred_term: BCL6
      term:
        id: hgnc:1001
        label: BCL6