Paranasal Sinus Carcinoma (sinonasal carcinoma histologies)

name: Paranasal Sinus Carcinoma
display_name: Paranasal Sinus Carcinoma (sinonasal carcinoma histologies)
creation_date: "2026-08-27T00:00:00Z"
description: >-
  Malignant epithelial tumours of the maxillary, ethmoid, frontal and sphenoid
  sinuses. What holds these tumours together is anatomy and its clinical
  consequences, not a shared driver: the sinuses are air-filled cavities that
  accommodate a growing mass without producing early symptoms, so every histology
  in this group presents late, with nasal obstruction and epistaxis, and with
  local invasion toward the orbit and anterior skull base. The group is also the
  head and neck's classic occupational cancer — hardwood and leather dust, nickel
  and chromium compounds, and formaldehyde all carry established sinonasal
  risk (formaldehyde more weakly, and with wood-dust confounding still argued) —
  but the exposures partition by histology rather than acting on the group as a
  whole: hardwood and leather dust drive adenocarcinoma at pooled relative risks
  near 30, nickel compounds drive squamous carcinoma, and sinonasal
  undifferentiated carcinoma has no established occupational aetiology at all.
grouping_basis:
- SHARED_PHENOTYPE
- CLINICAL_CONVENTION
grouping_rationale: >-
  Grouped on shared anatomic origin and the shared clinical syndrome that origin
  produces (late presentation, nasal obstruction and epistaxis, orbital and
  anterior-skull-base invasion), plus the clinical convention that stages and
  manages sinonasal carcinomas as one problem with one AJCC staging system and one
  multidisciplinary team.

  Modeled as a Grouping rather than as a single Disease with `has_subtypes`
  because the member histologies do not share a pathograph. Their drivers are
  mutually exclusive and mechanistically unrelated: a neomorphic IDH2 R172 hotspot
  producing a DNA and H3K27 hypermethylator phenotype in sinonasal undifferentiated
  carcinoma; chronic dust-inflammation-associated TP53 mutagenesis followed by a
  wide spectrum of low-frequency Wnt/MAPK/PI3K lesions and an enteric CDX2/CK20
  phenotype switch in intestinal-type adenocarcinoma; and TP53/CDKN2A loss with an
  HPV-associated non-keratinizing subset in squamous cell carcinoma. Each member
  conforms to a different mechanism module — evading_growth_suppressors,
  genome_instability_mutation, and immune_checkpoint_blockade respectively — and
  none conforms to a module shared by the others. Collapsing them into one Disease
  entry would require a pathophysiology section whose nodes are true of a minority
  of the entity, which is exactly the blending a Grouping exists to avoid. The
  members are already distinct curated Disease entries with their own MONDO terms,
  so a union over them also reconciles the existing squamous entry rather than
  duplicating its content inside an umbrella.

  Note that this is a deliberate departure from the `CURATE_ROOT_WITH_SUBTYPES`
  priority hint carried on MONDO:0000380 by the curation dashboard. Per issue
  #8727 that hint is a prioritization signal, not a lump-versus-split ruling; the
  split is recorded here so the decision is auditable rather than implicit.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0000380
      label: paranasal sinus carcinoma
    mapping_predicate: skos:closeMatch
    mapping_source: MONDO
    mapping_justification: >-
      closeMatch, not exactMatch, because the extensions differ in both
      directions. MONDO:0000380 has descendants with no dismech entry yet
      (paranasal sinus adenoid cystic carcinoma MONDO:0006352, paranasal sinus
      mucoepidermoid carcinoma MONDO:0044956, and the per-subsite squamous and
      adenocarcinoma classes), so this grouping under-covers it. In the other
      direction, sinonasal undifferentiated carcinoma (MONDO:0006411) is a listed
      member on anatomic and clinical grounds but MONDO classifies it only under
      undifferentiated carcinoma (MONDO:0005617), not under the paranasal sinus
      branch, so the grouping is not a subset of the MONDO class either. Because
      the predicate is closeMatch, MONDO:0000380 is deliberately NOT retired from
      the curation queue by this entry.
    consistency:
    - reference: MONDO
      consistent: UNKNOWN
      notes: >-
        Two of three listed members (paranasal sinus squamous cell carcinoma
        MONDO:0044705, ethmoid sinus adenocarcinoma MONDO:0002418) are is-a
        descendants of MONDO:0000380. The third, sinonasal undifferentiated
        carcinoma, is not, for the reason given in the mapping justification.
membership_criteria:
- description: >-
    A member is a malignant epithelial neoplasm (carcinoma) whose site of origin
    is the paranasal sinuses or the immediately contiguous sinonasal tract.
  criteria_semantics: NECESSARY
  logic:
    criterion_predicate: OTHER
    description: >-
      Carcinoma arising in the paranasal sinuses (UBERON:0001825) or contiguous
      sinonasal tract. Expressed as an OTHER leaf because the criteria vocabulary
      has no anatomic-site predicate; the claim is checked by a curator against
      each member's disease_term and pathophysiology node locations, not
      automatically.
- description: >-
    A member presents with the sinonasal mass syndrome — nasal obstruction and/or
    epistaxis — which is the shared clinical consequence of a tumour expanding
    within an air-filled sinus.
  criteria_semantics: NECESSARY
  logic:
    operator: OR
    operands:
    - criterion_predicate: HAS_PHENOTYPE
      phenotype_term:
        preferred_term: Nasal congestion
        term:
          id: HP:0001742
          label: Nasal congestion
      description: Nasal obstruction from an expanding sinonasal mass.
    - criterion_predicate: HAS_PHENOTYPE
      phenotype_term:
        preferred_term: Epistaxis
        term:
          id: HP:0000421
          label: Epistaxis
      description: Epistaxis from a friable, vascular tumour surface.
members:
- member: Paranasal Sinus Squamous Cell Carcinoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      The majority histology. Malignant progression runs through TP53 and CDKN2A
      loss rather than through a positive driver, and a non-keratinizing subset is
      driven instead by transcriptionally active high-risk HPV. It is the member
      with an established immune-evasion arm — it is the only one conforming to
      the immune_checkpoint_blockade module — and correspondingly the only one for
      which checkpoint inhibition is an option. Among the occupational exposures,
      nickel compounds are the one preferentially tied to this histology, whereas
      wood dust confers only a slight excess squamous risk.
    gene:
      preferred_term: TP53
      term:
        id: hgnc:11998
        label: TP53
    module: immune_checkpoint_blockade
- member: Ethmoid Sinus Adenocarcinoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      The occupational member. Intestinal-type adenocarcinoma carries by far the
      strongest exposure-cancer association in the group (pooled relative risks
      near 29 for wood dust and 35 for leather dust, against 1.46 for squamous
      carcinoma from the same wood-dust exposure), and its route to TP53 mutation
      is indirect — chronic retained-dust inflammation generating reactive nitrogen
      species — rather than a direct carcinogen adduct. It is defined by a
      phenotype switch no other member shows, the adoption of an enteric CDX2 and
      cytokeratin-20 programme in an epithelium with no intestinal origin, and it
      kills by dural invasion and local recurrence rather than by metastasis.
    gene:
      preferred_term: TP53
      term:
        id: hgnc:11998
        label: TP53
    module: genome_instability_mutation
- member: Sinonasal Undifferentiated Carcinoma
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      The one member with a positive, near-defining molecular driver: a neomorphic
      IDH2 R172 hotspot mutation in 55% to 82% of cases, whose consequence is
      epigenetic rather than proliferative — a global DNA and H3K27 hypermethylator
      phenotype that clusters IDH2-mutant sinonasal tumours together irrespective
      of histology and separates them from SMARCB1-deficient carcinoma and
      olfactory neuroblastoma. It has no established occupational aetiology, and
      it is the only member whose treatment pathway uses response to induction
      chemotherapy as a biological test to choose between definitive
      chemoradiotherapy and surgery.
    gene:
      preferred_term: IDH2
      term:
        id: hgnc:5383
        label: IDH2
    module: evading_growth_suppressors
notes: >-
  Coverage is incomplete by design rather than by oversight. MONDO:0000380 and the
  sinonasal-oncology literature also recognize adenoid cystic carcinoma
  (MONDO:0006352, driven by MYB-NFIB fusion), mucoepidermoid carcinoma
  (MONDO:0044956, CRTC1-MAML2 fusion), and SMARCB1 (INI-1)-deficient sinonasal
  carcinoma (no MONDO class), none of which has a dismech Disease entry yet. Each
  would add a further mechanistically independent arm to this union and would
  strengthen, not weaken, the split rationale above. They are tracked as remaining
  work on issue #9036.

  The listed members are audited against the NECESSARY criteria only; because
  there are no SUFFICIENT criteria, `just check-groupings` will not propose
  candidate members from elsewhere in the knowledge base. That is intentional —
  the defining property of this group is anatomic site, and the criteria
  vocabulary has no site predicate that could support automatic discovery
  without also matching every non-neoplastic sinonasal entry.