Thymoma

Neoplastic MONDO:0006456 Pathograph 10 thymic epithelial neoplasm

Thymoma is a thymic epithelial tumor of the anterior mediastinum that is best modeled in dismech as one disease-level mechanism graph with histologic and invasion-status subtype facets rather than separate disease pages. Thymomas have a lower mutational burden than thymic carcinoma, are enriched for GTF2I mutations in WHO type A and AB tumors, and uniquely perturb thymic selection programs so that impaired central tolerance drives autoimmune syndromes such as myasthenia gravis, pure red cell aplasia, and Good syndrome.

2
Mappings
0
Definitions
0
Inheritance
6
Pathophysiology
1
Histopathology
5
Phenotypes
10
Pathograph
2
Genes
4
Treatments
7
Subtypes
0
Differentials
0
Datasets
0
Trials
0
Models
1
Literature
🔗

Mappings

MONDO
MONDO:0006456 thymoma
skos:exactMatch MONDO
NCIT
NCIT:C3411 Thymoma
skos:exactMatch NCIT
NCIT
NCIT:C3411 Thymoma
skos:exactMatch NCIT
◆

Subtypes

7
histological pattern
Type A thymoma NCIT:C6454
Spindle-cell thymoma with relatively indolent clinical behavior and marked enrichment for GTF2I mutation.
Show evidence (1 reference)
PMID:24974848 SUPPORT Human Clinical
"We analyzed 28 thymic epithelial tumors (TETs) using next-generation sequencing and identified a missense mutation (chromosome 7 c.74146970T>A) in GTF2I at high frequency in type A thymomas, a relatively indolent subtype."
Human tumor sequencing links WHO type A thymoma to indolent biology and a strong GTF2I-mutant state.
Type AB thymoma NCIT:C6885
Mixed spindle-cell and lymphocyte-rich thymoma that shares much of the GTF2I-enriched molecular profile of type A thymoma.
Show evidence (1 reference)
PMID:24974848 SUPPORT Human Clinical
"In a series of 274 TETs, we detected the GTF2I mutation in 82% of type A and 74% of type AB thymomas but rarely in the aggressive subtypes, where recurrent mutations of known cancer genes have been identified."
Large human tumor series supports type AB thymoma as part of the GTF2I-enriched, less aggressive facet of thymoma.
Type B1 thymoma NCIT:C6887
Cortical-like thymoma rich in immature T lymphocytes, generally showing less invasion than type B3 thymoma.
Type B2 thymoma NCIT:C6888
Cortical thymoma with numerous lymphocytes and more conspicuous neoplastic epithelial cells; often associated with myasthenia gravis.
Type B3 thymoma NCIT:C7997
Epithelial-predominant thymoma with higher local invasiveness and worse disease-free survival than type A/AB and B1/B2 thymomas.
Show evidence (2 references)
PMID:15063231 SUPPORT Human Clinical
"The frequency of invasion to neighboring organs increased according to tumor subtype in the order A (0%), AB (6%), B1 (19%), B2 (25%), B3 (42%), and C (89%)."
Human surgical series supports higher invasive propensity in type B3 thymoma than in lower-grade WHO thymoma histotypes.
PMID:15063231 SUPPORT Human Clinical
"The disease-free survival rates were 100% for types A and AB, 83% for types B1 and B2, 36% for type B3, and 28% for type C thymoma at 10 years."
Long-term follow-up supports the prognostic distinction of type B3 within the thymoma histologic axis.
invasion status
Encapsulated thymoma NCIT:C7386
Organ-confined thymoma without gross invasion, generally corresponding to a more resectable and clinically indolent presentation.
Invasive thymoma NCIT:C7904
Thymoma that invades neighboring structures or disseminates intrathoracically and more often requires multimodal treatment.
Show evidence (1 reference)
PMID:20207296 SUPPORT Other
"Their clinical behaviour varies widely, from a relative indolence to the potential of lymph node and/or systematic metastases."
Review-level evidence supports an invasion-status facet within thymoma that is distinct from WHO histologic subtype.
⚙

Pathophysiology

6
GTF2I-driven thymic epithelial transformation
Recurrent GTF2I mutation defines a major molecular facet of type A and AB thymoma and promotes thymic epithelial proliferation and transformation.
epithelial cell of thymus link
cell population proliferation link ↑ INCREASED
thymus link
Show evidence (2 references)
PMID:24974848 SUPPORT Human Clinical
"In a series of 274 TETs, we detected the GTF2I mutation in 82% of type A and 74% of type AB thymomas but rarely in the aggressive subtypes, where recurrent mutations of known cancer genes have been identified."
Human tumor sequencing supports GTF2I mutation as the defining molecular driver of the indolent A/AB thymoma facet.
PMID:32034314 SUPPORT In Vitro
"Our findings identify GTF2I mutation as a new oncogenic driver that is responsible for transformation of thymic epithelial cells."
Cell-based functional evidence directly shows that mutant GTF2I can drive thymic epithelial transformation.
Metabolic stress survival program
Mutant GTF2I rewires glycolytic and stress-response programs, supporting tumor growth and survival under nutrient and DNA-damage stress.
glycolytic process link ↑ INCREASED
Show evidence (2 references)
PMID:32034314 SUPPORT In Vitro
"Gtf2i L424H knockin cells exhibited cell transformation, aneuploidy, and increase tumor growth and survival under glucose deprivation or DNA damage."
In vitro knock-in experiments support a stress-survival program downstream of mutant GTF2I.
PMID:32034314 SUPPORT In Vitro
"Gtf2i mutation also increased the expression of several glycolytic enzymes, cyclooxygenase-2, and caused modifications of lipid metabolism."
The same in vitro study supports metabolic rewiring as a distinct downstream consequence of mutant GTF2I.
Reduced MHC class II antigen presentation
Many thymomas, especially type A and AB tumors, show reduced MHC class II gene expression, weakening intrathymic antigen presentation.
epithelial cell of thymus link
antigen processing and presentation of peptide antigen via MHC class II link ↓ DECREASED
thymus link
Show evidence (1 reference)
PMID:18567864 SUPPORT Human Clinical
"We report here that a) expression levels of class II major histocompatibility complex (MHCII) genes are variably decreased in thymomas, most prominently in histological WHO types A and AB;"
Human thymoma tissue analysis supports reduced MHC class II expression as an atomic mechanism in A/AB thymoma.
AIRE loss in thymic epithelial cells
AIRE expression is absent from most thymomas, reducing tissue-restricted self-antigen display in the thymic epithelial compartment.
medullary thymic epithelial cell link
T cell differentiation in thymus link ⚠ ABNORMAL
Show evidence (1 reference)
PMID:18567864 SUPPORT Human Clinical
"Recently, we also found that expression of the autoimmune regulator (AIRE) gene is absent from approximately 95% of thymomas."
Human thymoma profiling supports AIRE loss as a distinct central-tolerance defect in thymoma.
Central tolerance failure in the thymic microenvironment
The cortex-dominant, medulla-poor thymoma microenvironment generates autoreactive effector T cells and underproduces regulatory T cells, allowing self-reactive T-cell escape.
epithelial cell of thymus link medullary thymic epithelial cell link regulatory T cell link
T cell differentiation in thymus link ⚠ ABNORMAL
thymus link
Show evidence (2 references)
PMID:41098393 SUPPORT Computational
"Since thymomas are mainly composed of the cortex, with few medullae, MG may be caused by immature thymoma-derived T cells that fail to undergo negative selection and have not yet acquired sufficient self-tolerance."
Transcriptomic and spatial analyses support negative-selection failure as a central mechanism linking thymoma to autoimmunity.
PMID:18567864 SUPPORT Human Clinical
"Generation of autoreactive CD4(+) effector T cells and defective production of regulatory CD4(+) T cells inside thymomas contribute to the development of myasthenia gravis (MG) in >90% of MG(+) thymomas."
Human thymoma studies support autoreactive effector-T-cell generation and deficient Treg production as distinct components of tolerance failure.
Neuromuscular autoantigen-expressing medullary epithelial niche
Myasthenia gravis-associated thymomas contain neuromuscular antigen-expressing medullary thymic epithelial populations that organize a local immune niche.
medullary thymic epithelial cell link
Show evidence (2 references)
PMID:41098393 SUPPORT Computational
"By analyzing bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) data from thymomas, we identified neuromuscular medullary thymic epithelial cells (nmTECs) as neuromuscular antigen-expressing cell populations."
Computational analysis of human thymoma transcriptomes supports a specialized neuromuscular autoantigen niche relevant to thymoma-associated MG.
PMID:41098393 SUPPORT Computational
"We observed spatial nmTEC colocalization and an immune niche, inferring an interaction and suggesting a pathological role of nmTECs in MG."
Spatial transcriptomic inference supports a local immune niche downstream of thymoma-associated thymic dysarchitecture.
✶

Histopathology

1
Thymoma OBLIGATE
Thymic epithelial neoplasm composed of neoplastic epithelial cells admixed with variable numbers of non-neoplastic immature T lymphocytes.
Show evidence (1 reference)
PMID:20207296 SUPPORT Other
"Epithelial tumours of the thymus include thymomas, thymic carcinomas and neuro-endocrine tumours."
Review abstract supports thymoma as a thymic epithelial neoplasm.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Thymoma Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

5
Blood 1
Pure red cell aplasia OCCASIONAL Pure red cell aplasia (HP:0012410)
Show evidence (1 reference)
PMID:40983285 SUPPORT Other
"Myasthenia gravis is the most common, followed by less frequent but notable conditions including pure red cell aplasia, Good's syndrome, and various neurologic, dermatologic, and systemic autoimmune disorders."
Contemporary review abstract supports pure red cell aplasia as a recurring thymoma-associated autoimmune phenotype.
Immune 1
Recurrent infections OCCASIONAL Recurrent infections (HP:0002719)
Show evidence (1 reference)
PMID:39180607 SUPPORT Human Clinical
"Good syndrome (GS), a rare acquired immunodeficiency disorder characterized by thymoma and hypogammaglobulinemia, predisposes individuals to recurrent infections."
Human clinical review data supports recurrent infections as a common downstream phenotype of thymoma-associated Good syndrome.
Other 3
Anterior mediastinal mass OBLIGATE Anterior mediastinal mass (HP:0033827)
Show evidence (1 reference)
PMID:37761349 SUPPORT Other
"Thymomas are considered one of the most prevalent types of mediastinal epithelial tumors, which frequently develop in the anterior mediastinum."
Review abstract supports the characteristic anterior mediastinal presentation of thymoma.
Myasthenia gravis FREQUENT myasthenia gravis (MONDO:0009688)
Show evidence (1 reference)
PMID:20207296 SUPPORT Other
"Thymomas, in particular, can be associated to auto-immune disorders, among which predominates myasthenia gravis."
Review abstract identifies myasthenia gravis as the leading autoimmune phenotype associated with thymoma.
Good syndrome OCCASIONAL Good syndrome (MONDO:0015696)
Show evidence (1 reference)
PMID:39180607 SUPPORT Human Clinical
"Good syndrome (GS), a rare acquired immunodeficiency disorder characterized by thymoma and hypogammaglobulinemia, predisposes individuals to recurrent infections."
Human case-review evidence supports Good syndrome as a bona fide thymoma-associated immunodeficiency phenotype.
🧬

Genetic Associations

2
GTF2I mutation (Recurrent somatic driver mutation)
Show evidence (1 reference)
PMID:24974848 SUPPORT Human Clinical
"In a series of 274 TETs, we detected the GTF2I mutation in 82% of type A and 74% of type AB thymomas but rarely in the aggressive subtypes, where recurrent mutations of known cancer genes have been identified."
Human tumor profiling establishes GTF2I as the dominant recurrent somatic alteration in indolent thymoma histotypes.
HRAS mutation (Recurrent somatic mutation)
Show evidence (1 reference)
PMID:38338833 SUPPORT Other
"Thymomas exhibit a limited mutational load, with prevalent GTF2I and HRAS mutations."
Review synthesis supports HRAS as one of the recurrent mutations in thymoma despite overall low tumor mutational burden.
💊

Treatments

4
Thymectomy
Action: thymectomy MAXO:0001079
Complete surgical resection is the central treatment for localized thymoma and can improve coexisting myasthenia gravis.
Show evidence (2 references)
PMID:20207296 SUPPORT Other
"The initial treatment, as well as that of the recurrence, is based mainly on a complete resection."
Review abstract supports complete surgical resection as the core treatment of thymoma.
PMID:40983285 SUPPORT Other
"Surgical intervention through thymectomy remains a cornerstone of treatment, particularly for myasthenia gravis, where it can lead to considerable symptomatic improvement."
Review abstract supports thymectomy as both oncologic and autoimmune disease management in thymoma.
Postoperative radiotherapy
Action: radiation therapy MAXO:0000014
Adjuvant radiotherapy is used for invasive thymoma, incomplete resection, or aggressive histologic subtypes.
Show evidence (1 reference)
PMID:20207296 SUPPORT Other
"Postoperative radiotherapy is systematically added to the treatment of invasive tumours and/or to those with an aggressive histological subtype."
Review abstract supports adjuvant radiotherapy for invasive or more aggressive thymoma facets.
Platinum-anthracycline chemotherapy
Action: chemotherapy MAXO:0000647
Agent: cisplatin ↗ doxorubicin ↗
Cisplatin-based multi-agent chemotherapy is used for unresectable, metastatic, or recurrent thymoma.
Show evidence (1 reference)
PMID:20207296 SUPPORT Other
"Inoperable or metastatic tumours require a cisplatine and anthracyclin-based chemotherapy, followed by radical surgery and/or radiotherapy."
Review abstract supports platinum-anthracycline chemotherapy as the standard systemic therapy for unresectable or metastatic thymoma.
Systemic immunosuppression
Action: immune suppressant agent therapy MAXO:0000297
Immunosuppressive therapy is often needed when thymoma-associated autoimmunity persists or emerges after thymectomy.
Show evidence (1 reference)
PMID:40983285 SUPPORT Other
"However, autoimmune conditions may persist or even develop after thymectomy, necessitating disease-specific approaches with systemic immunosuppression."
Review abstract supports systemic immunosuppression for thymoma-associated autoimmune complications that are not fully controlled by surgery.
📚

Literature Summaries

1
Manual Pubmed Review ▸
Thymoma: curation-oriented mechanistic summary
n/a 9 citations 2026-04-13T05:40:00Z

Thymoma: curation-oriented mechanistic summary

Modeling decisions applied from issue #1198

  • The dismech curation unit is the disease-level mechanism graph, not every oncology ontology subclass. Thymoma therefore remains one disease entry rather than separate pages for WHO types A, AB, B1, B2, B3, or invasion-status variants.
  • disease_term stays MONDO-first as MONDO:0006456 (thymoma).
  • The entry should also carry a disease-level NCIT mapping to NCIT:C3411 (Thymoma), because NCIT is the more oncology-native coding system for downstream cancer interoperability.
  • Subtypes are best represented as flat facet axes. For thymoma, the highest-yield axes are:
  • histological_pattern: Type A (NCIT:C6454), Type AB (NCIT:C6885), Type B1 (NCIT:C6887), Type B2 (NCIT:C6888), Type B3 (NCIT:C7997)
  • invasion_status: Encapsulated thymoma (NCIT:C7386), invasive thymoma (NCIT:C7904)
  • The NCIT-grounded subtype terms are ontology grounding only. They should not imply separate dismech pages or a “Not Yet Curated” renderer state.

Disease overview

Thymoma is a thymic epithelial tumor of the anterior mediastinum whose biology is unusual among solid tumors because the neoplasm also distorts thymic T-cell selection. The two dominant disease-level themes are therefore:

  1. Tumor-cell intrinsic oncogenesis, especially the GTF2I-enriched, low-mutation-burden program of indolent type A/AB thymoma.
  2. Tumor-microenvironment immune dysfunction, in which abnormal thymic epithelial architecture impairs central tolerance and promotes paraneoplastic autoimmunity.

Subtype biology

  • Type A / Type AB thymoma: indolent histotypes with the strongest GTF2I enrichment. PMID:24974848 reports that GTF2I mutation is detected in 82% of type A and 74% of type AB thymomas.
  • Type B1 / Type B2 thymoma: more cortical, lymphocyte-rich histotypes with increasing invasiveness and myasthenia gravis association.
  • Type B3 thymoma: epithelial-predominant thymoma with substantially greater local invasion and worse disease-free survival. PMID:15063231 reports a monotonic increase in neighboring-organ invasion across A → AB → B1 → B2 → B3.
  • Encapsulated vs invasive thymoma: a separate invasion-status axis is useful because clinical behavior spans indolent, organ-confined disease to locally invasive or metastatic disease even within the same broad disease entry (PMID:20207296).

Core mechanisms

1. GTF2I-driven thymic epithelial transformation

  • PMID:24974848: “We analyzed 28 thymic epithelial tumors (TETs) using next-generation sequencing and identified a missense mutation ... in GTF2I at high frequency in type A thymomas, a relatively indolent subtype.”
  • PMID:32034314: “Our findings identify GTF2I mutation as a new oncogenic driver that is responsible for transformation of thymic epithelial cells.”

Interpretation for YAML: this supports a disease node centered on thymic epithelial transformation, with subtype restriction to type A/AB thymoma and downstream linkage to proliferative and metabolic programs.

2. Metabolic stress adaptation downstream of mutant GTF2I

  • PMID:32034314: “Gtf2i L424H knockin cells exhibited cell transformation, aneuploidy, and increase tumor growth and survival under glucose deprivation or DNA damage.”
  • PMID:32034314: “Gtf2i mutation also increased the expression of several glycolytic enzymes, cyclooxygenase-2, and caused modifications of lipid metabolism.”

Interpretation for YAML: metabolic rewiring is worth its own atomic node rather than being bundled into the transformation node.

3. Reduced MHC class II antigen presentation

  • PMID:18567864: “expression levels of class II major histocompatibility complex (MHCII) genes are variably decreased in thymomas, most prominently in histological WHO types A and AB”

Interpretation for YAML: this directly supports an atomic node for reduced antigen presentation via MHC class II, especially in type A/AB thymoma.

4. AIRE loss in thymic epithelial cells

  • PMID:18567864: “expression of the autoimmune regulator (AIRE) gene is absent from approximately 95% of thymomas.”

Interpretation for YAML: AIRE loss should remain separate from reduced MHC II expression because both are central-tolerance defects but represent distinct molecular lesions.

5. Central tolerance failure with autoreactive T-cell escape

  • PMID:41098393: “Since thymomas are mainly composed of the cortex, with few medullae, MG may be caused by immature thymoma-derived T cells that fail to undergo negative selection and have not yet acquired sufficient self-tolerance.”
  • PMID:18567864: “Generation of autoreactive CD4(+) effector T cells and defective production of regulatory CD4(+) T cells inside thymomas contribute to the development of myasthenia gravis (MG) in >90% of MG(+) thymomas.”

Interpretation for YAML: negative-selection failure, autoreactive effector-T-cell generation, and defective Treg production belong in a linked but still atomic disease mechanism chain.

6. Neuromuscular autoantigen niche in MG-associated thymoma

  • PMID:41098393: “we identified neuromuscular medullary thymic epithelial cells (nmTECs) as neuromuscular antigen-expressing cell populations.”
  • PMID:41098393: “We observed spatial nmTEC colocalization and an immune niche, inferring an interaction and suggesting a pathological role of nmTECs in MG.”

Interpretation for YAML: this is a more specific downstream mechanism that helps explain why myasthenia gravis is the dominant autoimmune phenotype.

Hallmark phenotype profile

  • Anterior mediastinal mass: characteristic anatomic presentation (PMID:37761349).
  • Myasthenia gravis: dominant autoimmune phenotype (PMID:20207296).
  • Pure red cell aplasia: recurrent hematologic autoimmune complication (PMID:40983285).
  • Good syndrome and recurrent infections: thymoma-associated immunodeficiency phenotype with hypogammaglobulinemia and infection susceptibility (PMID:39180607).

Treatment implications

  • Complete resection / thymectomy remains the central intervention for localized disease (PMID:20207296; PMID:40983285).
  • Postoperative radiotherapy is mainly relevant for invasive disease or aggressive histology (PMID:20207296).
  • Platinum-anthracycline chemotherapy is the standard systemic approach for inoperable or metastatic thymoma (PMID:20207296).
  • Systemic immunosuppression remains necessary when autoimmune complications persist or newly arise after thymectomy (PMID:40983285).

Ontology grounding used in the YAML

  • Disease anchor: MONDO:0006456 thymoma
  • Disease-level NCIT mapping: NCIT:C3411 Thymoma
  • Histologic subtype grounding:
  • NCIT:C6454 Thymoma Type A
  • NCIT:C6885 Thymoma Type AB
  • NCIT:C6887 Thymoma Type B1
  • NCIT:C6888 Thymoma Type B2
  • NCIT:C7997 Thymoma Type B3
  • Invasion-status subtype grounding:
  • NCIT:C7386 Encapsulated Thymoma
  • NCIT:C7904 Invasive Malignant Thymoma

NCIT subtype identifiers were checked against the EVS neoplasm hierarchy page for thymoma subclasses while keeping the disease anchor MONDO-first in the dismech entry.

References

  • PMID:24974848
  • PMID:32034314
  • PMID:18567864
  • PMID:41098393
  • PMID:15063231
  • PMID:20207296
  • PMID:37761349
  • PMID:39180607
  • PMID:40983285
{ }

Source YAML

click to show 
name: Thymoma
creation_date: '2026-03-16T06:37:22Z'
updated_date: '2026-04-13T05:32:51Z'
description: >-
  Thymoma is a thymic epithelial tumor of the anterior mediastinum that is best
  modeled in dismech as one disease-level mechanism graph with histologic and
  invasion-status subtype facets rather than separate disease pages. Thymomas
  have a lower mutational burden than thymic carcinoma, are enriched for GTF2I
  mutations in WHO type A and AB tumors, and uniquely perturb thymic selection
  programs so that impaired central tolerance drives autoimmune syndromes such
  as myasthenia gravis, pure red cell aplasia, and Good syndrome.
category: Neoplastic
categories:
- Thymic epithelial tumor
- Mediastinal neoplasm
- Thoracic cancer
parents:
- thymic epithelial neoplasm
disease_term:
  preferred_term: thymoma
  term:
    id: MONDO:0006456
    label: thymoma
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0006456
      label: thymoma
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
  ncit_mappings:
  - term:
      id: NCIT:C3411
      label: Thymoma
    mapping_predicate: skos:exactMatch
    mapping_source: NCIT
notes: >-
  Following the cancer curation guidance from issue 1198, this entry treats
  thymoma as the disease-level mechanism-graph unit. WHO histotypes and
  invasion status are represented as flat subtype facets grounded to NCIT,
  rather than as separate dismech disease pages.
has_subtypes:
- name: Type A thymoma
  classification: histological_pattern
  subtype_term:
    preferred_term: Type A thymoma
    term:
      id: NCIT:C6454
      label: Thymoma Type A
  description: >-
    Spindle-cell thymoma with relatively indolent clinical behavior and marked
    enrichment for GTF2I mutation.
  evidence:
  - reference: PMID:24974848
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We analyzed 28 thymic epithelial tumors (TETs) using next-generation
      sequencing and identified a missense mutation (chromosome 7
      c.74146970T>A) in GTF2I at high frequency in type A thymomas, a
      relatively indolent subtype.
    explanation: >-
      Human tumor sequencing links WHO type A thymoma to indolent biology and a
      strong GTF2I-mutant state.
- name: Type AB thymoma
  classification: histological_pattern
  subtype_term:
    preferred_term: Type AB thymoma
    term:
      id: NCIT:C6885
      label: Thymoma Type AB
  description: >-
    Mixed spindle-cell and lymphocyte-rich thymoma that shares much of the
    GTF2I-enriched molecular profile of type A thymoma.
  evidence:
  - reference: PMID:24974848
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In a series of 274 TETs, we detected the GTF2I mutation in 82% of type A
      and 74% of type AB thymomas but rarely in the aggressive subtypes, where
      recurrent mutations of known cancer genes have been identified.
    explanation: >-
      Large human tumor series supports type AB thymoma as part of the
      GTF2I-enriched, less aggressive facet of thymoma.
- name: Type B1 thymoma
  classification: histological_pattern
  subtype_term:
    preferred_term: Type B1 thymoma
    term:
      id: NCIT:C6887
      label: Thymoma Type B1
  description: >-
    Cortical-like thymoma rich in immature T lymphocytes, generally showing less
    invasion than type B3 thymoma.
- name: Type B2 thymoma
  classification: histological_pattern
  subtype_term:
    preferred_term: Type B2 thymoma
    term:
      id: NCIT:C6888
      label: Thymoma Type B2
  description: >-
    Cortical thymoma with numerous lymphocytes and more conspicuous neoplastic
    epithelial cells; often associated with myasthenia gravis.
- name: Type B3 thymoma
  classification: histological_pattern
  subtype_term:
    preferred_term: Type B3 thymoma
    term:
      id: NCIT:C7997
      label: Thymoma Type B3
  description: >-
    Epithelial-predominant thymoma with higher local invasiveness and worse
    disease-free survival than type A/AB and B1/B2 thymomas.
  evidence:
  - reference: PMID:15063231
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The frequency of invasion to neighboring organs increased according to
      tumor subtype in the order A (0%), AB (6%), B1 (19%), B2 (25%), B3 (42%),
      and C (89%).
    explanation: >-
      Human surgical series supports higher invasive propensity in type B3
      thymoma than in lower-grade WHO thymoma histotypes.
  - reference: PMID:15063231
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The disease-free survival rates were 100% for types A and AB, 83% for
      types B1 and B2, 36% for type B3, and 28% for type C thymoma at 10 years.
    explanation: >-
      Long-term follow-up supports the prognostic distinction of type B3 within
      the thymoma histologic axis.
- name: Encapsulated thymoma
  classification: invasion_status
  subtype_term:
    preferred_term: encapsulated thymoma
    term:
      id: NCIT:C7386
      label: Encapsulated Thymoma
  description: >-
    Organ-confined thymoma without gross invasion, generally corresponding to a
    more resectable and clinically indolent presentation.
- name: Invasive thymoma
  classification: invasion_status
  subtype_term:
    preferred_term: invasive thymoma
    term:
      id: NCIT:C7904
      label: Invasive Malignant Thymoma
  description: >-
    Thymoma that invades neighboring structures or disseminates intrathoracically
    and more often requires multimodal treatment.
  evidence:
  - reference: PMID:20207296
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Their clinical behaviour varies widely, from a relative indolence to the
      potential of lymph node and/or systematic metastases.
    explanation: >-
      Review-level evidence supports an invasion-status facet within thymoma
      that is distinct from WHO histologic subtype.
pathophysiology:
- name: GTF2I-driven thymic epithelial transformation
  subtypes:
  - Type A thymoma
  - Type AB thymoma
  description: >-
    Recurrent GTF2I mutation defines a major molecular facet of type A and AB
    thymoma and promotes thymic epithelial proliferation and transformation.
  gene:
    preferred_term: GTF2I
    description: Recurrently mutated thymoma driver, usually p.L424H.
    modifier: ABNORMAL
    term:
      id: hgnc:4659
      label: GTF2I
  cell_types:
  - preferred_term: epithelial cell of thymus
    term:
      id: CL:0002293
      label: epithelial cell of thymus
  biological_processes:
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  locations:
  - preferred_term: thymus
    term:
      id: UBERON:0002370
      label: thymus
  evidence:
  - reference: PMID:24974848
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In a series of 274 TETs, we detected the GTF2I mutation in 82% of type A
      and 74% of type AB thymomas but rarely in the aggressive subtypes, where
      recurrent mutations of known cancer genes have been identified.
    explanation: >-
      Human tumor sequencing supports GTF2I mutation as the defining molecular
      driver of the indolent A/AB thymoma facet.
  - reference: PMID:32034314
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Our findings identify GTF2I mutation as a new oncogenic driver that is
      responsible for transformation of thymic epithelial cells.
    explanation: >-
      Cell-based functional evidence directly shows that mutant GTF2I can drive
      thymic epithelial transformation.
  downstream:
  - target: Metabolic stress survival program
    description: Mutant TFII-I supports stress-adapted growth states.
- name: Metabolic stress survival program
  subtypes:
  - Type A thymoma
  - Type AB thymoma
  description: >-
    Mutant GTF2I rewires glycolytic and stress-response programs, supporting
    tumor growth and survival under nutrient and DNA-damage stress.
  gene:
    preferred_term: GTF2I
    modifier: ABNORMAL
    term:
      id: hgnc:4659
      label: GTF2I
  biological_processes:
  - preferred_term: glycolytic process
    modifier: INCREASED
    term:
      id: GO:0006096
      label: glycolytic process
  evidence:
  - reference: PMID:32034314
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Gtf2i L424H knockin cells exhibited cell transformation, aneuploidy, and
      increase tumor growth and survival under glucose deprivation or DNA
      damage.
    explanation: >-
      In vitro knock-in experiments support a stress-survival program downstream
      of mutant GTF2I.
  - reference: PMID:32034314
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Gtf2i mutation also increased the expression of several glycolytic
      enzymes, cyclooxygenase-2, and caused modifications of lipid metabolism.
    explanation: >-
      The same in vitro study supports metabolic rewiring as a distinct
      downstream consequence of mutant GTF2I.
- name: Reduced MHC class II antigen presentation
  subtypes:
  - Type A thymoma
  - Type AB thymoma
  description: >-
    Many thymomas, especially type A and AB tumors, show reduced MHC class II
    gene expression, weakening intrathymic antigen presentation.
  cell_types:
  - preferred_term: epithelial cell of thymus
    term:
      id: CL:0002293
      label: epithelial cell of thymus
  biological_processes:
  - preferred_term: antigen processing and presentation of peptide antigen via MHC class II
    modifier: DECREASED
    term:
      id: GO:0002495
      label: antigen processing and presentation of peptide antigen via MHC class II
  locations:
  - preferred_term: thymus
    term:
      id: UBERON:0002370
      label: thymus
  evidence:
  - reference: PMID:18567864
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We report here that a) expression levels of class II major
      histocompatibility complex (MHCII) genes are variably decreased in
      thymomas, most prominently in histological WHO types A and AB;
    explanation: >-
      Human thymoma tissue analysis supports reduced MHC class II expression as
      an atomic mechanism in A/AB thymoma.
  downstream:
  - target: Central tolerance failure in the thymic microenvironment
    description: Poor self-antigen presentation impairs thymic selection.
- name: AIRE loss in thymic epithelial cells
  description: >-
    AIRE expression is absent from most thymomas, reducing tissue-restricted
    self-antigen display in the thymic epithelial compartment.
  gene:
    preferred_term: AIRE
    description: Autoimmune regulator required for central tolerance.
    modifier: ABNORMAL
    term:
      id: hgnc:360
      label: AIRE
  cell_types:
  - preferred_term: medullary thymic epithelial cell
    term:
      id: CL:0002365
      label: medullary thymic epithelial cell
  biological_processes:
  - preferred_term: T cell differentiation in thymus
    modifier: ABNORMAL
    term:
      id: GO:0033077
      label: T cell differentiation in thymus
  evidence:
  - reference: PMID:18567864
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Recently, we also found that expression of the autoimmune regulator
      (AIRE) gene is absent from approximately 95% of thymomas.
    explanation: >-
      Human thymoma profiling supports AIRE loss as a distinct central-tolerance
      defect in thymoma.
  downstream:
  - target: Central tolerance failure in the thymic microenvironment
    description: Loss of AIRE reduces self-antigen-guided thymocyte deletion.
- name: Central tolerance failure in the thymic microenvironment
  description: >-
    The cortex-dominant, medulla-poor thymoma microenvironment generates
    autoreactive effector T cells and underproduces regulatory T cells, allowing
    self-reactive T-cell escape.
  cell_types:
  - preferred_term: epithelial cell of thymus
    term:
      id: CL:0002293
      label: epithelial cell of thymus
  - preferred_term: medullary thymic epithelial cell
    term:
      id: CL:0002365
      label: medullary thymic epithelial cell
  - preferred_term: regulatory T cell
    term:
      id: CL:0000815
      label: regulatory T cell
  biological_processes:
  - preferred_term: T cell differentiation in thymus
    modifier: ABNORMAL
    term:
      id: GO:0033077
      label: T cell differentiation in thymus
  locations:
  - preferred_term: thymus
    term:
      id: UBERON:0002370
      label: thymus
  evidence:
  - reference: PMID:41098393
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: >-
      Since thymomas are mainly composed of the cortex, with few medullae, MG
      may be caused by immature thymoma-derived T cells that fail to undergo
      negative selection and have not yet acquired sufficient self-tolerance.
    explanation: >-
      Transcriptomic and spatial analyses support negative-selection failure as
      a central mechanism linking thymoma to autoimmunity.
  - reference: PMID:18567864
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Generation of autoreactive CD4(+) effector T cells and defective
      production of regulatory CD4(+) T cells inside thymomas contribute to the
      development of myasthenia gravis (MG) in >90% of MG(+) thymomas.
    explanation: >-
      Human thymoma studies support autoreactive effector-T-cell generation and
      deficient Treg production as distinct components of tolerance failure.
  downstream:
  - target: Neuromuscular autoantigen-expressing medullary epithelial niche
    description: Residual medullary-like niches can concentrate MG-relevant antigens.
  - target: Myasthenia gravis
    description: Autoreactive T-cell escape supports pathogenic neuromuscular autoimmunity.
  - target: Pure red cell aplasia
    description: Immune dysregulation can suppress erythroid precursors.
  - target: Good syndrome
    description: Immune dysregulation can coexist with thymoma-associated immunodeficiency.
- name: Neuromuscular autoantigen-expressing medullary epithelial niche
  description: >-
    Myasthenia gravis-associated thymomas contain neuromuscular antigen-expressing
    medullary thymic epithelial populations that organize a local immune niche.
  cell_types:
  - preferred_term: medullary thymic epithelial cell
    term:
      id: CL:0002365
      label: medullary thymic epithelial cell
  evidence:
  - reference: PMID:41098393
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: >-
      By analyzing bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq
      (scRNA-seq) data from thymomas, we identified neuromuscular medullary
      thymic epithelial cells (nmTECs) as neuromuscular antigen-expressing cell
      populations.
    explanation: >-
      Computational analysis of human thymoma transcriptomes supports a
      specialized neuromuscular autoantigen niche relevant to thymoma-associated
      MG.
  - reference: PMID:41098393
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: >-
      We observed spatial nmTEC colocalization and an immune niche, inferring
      an interaction and suggesting a pathological role of nmTECs in MG.
    explanation: >-
      Spatial transcriptomic inference supports a local immune niche downstream
      of thymoma-associated thymic dysarchitecture.
  downstream:
  - target: Myasthenia gravis
    description: Local neuromuscular autoantigen presentation helps focus MG autoimmunity.
histopathology:
- name: Thymoma
  finding_term:
    preferred_term: Thymoma
    term:
      id: NCIT:C3411
      label: Thymoma
  frequency: OBLIGATE
  diagnostic: true
  description: >-
    Thymic epithelial neoplasm composed of neoplastic epithelial cells admixed
    with variable numbers of non-neoplastic immature T lymphocytes.
  evidence:
  - reference: PMID:20207296
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Epithelial tumours of the thymus include thymomas, thymic carcinomas and
      neuro-endocrine tumours.
    explanation: >-
      Review abstract supports thymoma as a thymic epithelial neoplasm.
phenotypes:
- category: Thoracic
  name: Anterior mediastinal mass
  frequency: OBLIGATE
  diagnostic: true
  description: >-
    Thymoma classically presents as an anterior mediastinal epithelial mass on
    thoracic imaging.
  phenotype_term:
    preferred_term: anterior mediastinal mass
    term:
      id: HP:0033827
      label: Anterior mediastinal mass
  evidence:
  - reference: PMID:37761349
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Thymomas are considered one of the most prevalent types of mediastinal
      epithelial tumors, which frequently develop in the anterior mediastinum.
    explanation: >-
      Review abstract supports the characteristic anterior mediastinal
      presentation of thymoma.
- category: Neuromuscular
  name: Myasthenia gravis
  frequency: FREQUENT
  description: >-
    The dominant autoimmune complication of thymoma, reflecting failure of
    central tolerance and neuromuscular autoantigen presentation.
  phenotype_term:
    preferred_term: myasthenia gravis
    term:
      id: MONDO:0009688
      label: myasthenia gravis
  evidence:
  - reference: PMID:20207296
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Thymomas, in particular, can be associated to auto-immune disorders,
      among which predominates myasthenia gravis.
    explanation: >-
      Review abstract identifies myasthenia gravis as the leading autoimmune
      phenotype associated with thymoma.
- category: Hematologic
  name: Pure red cell aplasia
  frequency: OCCASIONAL
  description: >-
    Immune-mediated suppression of erythroid precursors causes severe anemia in
    a subset of thymoma patients.
  phenotype_term:
    preferred_term: pure red cell aplasia
    term:
      id: HP:0012410
      label: Pure red cell aplasia
  evidence:
  - reference: PMID:40983285
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Myasthenia gravis is the most common, followed by less frequent but
      notable conditions including pure red cell aplasia, Good's syndrome, and
      various neurologic, dermatologic, and systemic autoimmune disorders.
    explanation: >-
      Contemporary review abstract supports pure red cell aplasia as a recurring
      thymoma-associated autoimmune phenotype.
- category: Immunologic
  name: Good syndrome
  frequency: OCCASIONAL
  description: >-
    Thymoma-associated immunodeficiency with hypogammaglobulinemia and increased
    susceptibility to infection.
  phenotype_term:
    preferred_term: Good syndrome
    term:
      id: MONDO:0015696
      label: Good syndrome
  evidence:
  - reference: PMID:39180607
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Good syndrome (GS), a rare acquired immunodeficiency disorder characterized
      by thymoma and hypogammaglobulinemia, predisposes individuals to recurrent
      infections.
    explanation: >-
      Human case-review evidence supports Good syndrome as a bona fide
      thymoma-associated immunodeficiency phenotype.
- category: Immunologic
  name: Recurrent infections
  frequency: OCCASIONAL
  description: >-
    Recurrent bacterial, viral, or opportunistic infections can complicate
    thymoma-associated Good syndrome.
  phenotype_term:
    preferred_term: Recurrent infections
    term:
      id: HP:0002719
      label: Recurrent infections
  evidence:
  - reference: PMID:39180607
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Good syndrome (GS), a rare acquired immunodeficiency disorder characterized
      by thymoma and hypogammaglobulinemia, predisposes individuals to recurrent
      infections.
    explanation: >-
      Human clinical review data supports recurrent infections as a common
      downstream phenotype of thymoma-associated Good syndrome.
genetic:
- name: GTF2I mutation
  gene_term:
    preferred_term: GTF2I
    term:
      id: hgnc:4659
      label: GTF2I
  association: Recurrent somatic driver mutation
  notes: >-
    GTF2I mutation is highly enriched in type A and AB thymomas and tracks with
    more indolent biology.
  evidence:
  - reference: PMID:24974848
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In a series of 274 TETs, we detected the GTF2I mutation in 82% of type A
      and 74% of type AB thymomas but rarely in the aggressive subtypes, where
      recurrent mutations of known cancer genes have been identified.
    explanation: >-
      Human tumor profiling establishes GTF2I as the dominant recurrent somatic
      alteration in indolent thymoma histotypes.
- name: HRAS mutation
  gene_term:
    preferred_term: HRAS
    term:
      id: hgnc:5173
      label: HRAS
  association: Recurrent somatic mutation
  notes: >-
    HRAS mutations occur in a minority of thymomas and contribute to the
    low-mutation-burden but recurrently altered molecular landscape.
  evidence:
  - reference: PMID:38338833
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Thymomas exhibit a limited mutational load, with prevalent GTF2I and HRAS
      mutations.
    explanation: >-
      Review synthesis supports HRAS as one of the recurrent mutations in
      thymoma despite overall low tumor mutational burden.
treatments:
- name: Thymectomy
  description: >-
    Complete surgical resection is the central treatment for localized thymoma
    and can improve coexisting myasthenia gravis.
  treatment_term:
    preferred_term: thymectomy
    term:
      id: MAXO:0001079
      label: thymectomy
  evidence:
  - reference: PMID:20207296
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The initial treatment, as well as that of the recurrence, is based mainly
      on a complete resection.
    explanation: >-
      Review abstract supports complete surgical resection as the core
      treatment of thymoma.
  - reference: PMID:40983285
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Surgical intervention through thymectomy remains a cornerstone of
      treatment, particularly for myasthenia gravis, where it can lead to
      considerable symptomatic improvement.
    explanation: >-
      Review abstract supports thymectomy as both oncologic and autoimmune
      disease management in thymoma.
- name: Postoperative radiotherapy
  description: >-
    Adjuvant radiotherapy is used for invasive thymoma, incomplete resection,
    or aggressive histologic subtypes.
  treatment_term:
    preferred_term: radiation therapy
    term:
      id: MAXO:0000014
      label: radiation therapy
  evidence:
  - reference: PMID:20207296
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Postoperative radiotherapy is systematically added to the treatment of
      invasive tumours and/or to those with an aggressive histological subtype.
    explanation: >-
      Review abstract supports adjuvant radiotherapy for invasive or more
      aggressive thymoma facets.
- name: Platinum-anthracycline chemotherapy
  description: >-
    Cisplatin-based multi-agent chemotherapy is used for unresectable,
    metastatic, or recurrent thymoma.
  treatment_term:
    preferred_term: chemotherapy
    term:
      id: MAXO:0000647
      label: chemotherapy
    therapeutic_agent:
    - preferred_term: cisplatin
      term:
        id: CHEBI:27899
        label: cisplatin
    - preferred_term: doxorubicin
      term:
        id: CHEBI:28748
        label: doxorubicin
  evidence:
  - reference: PMID:20207296
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Inoperable or metastatic tumours require a cisplatine and
      anthracyclin-based chemotherapy, followed by radical surgery and/or
      radiotherapy.
    explanation: >-
      Review abstract supports platinum-anthracycline chemotherapy as the
      standard systemic therapy for unresectable or metastatic thymoma.
- name: Systemic immunosuppression
  description: >-
    Immunosuppressive therapy is often needed when thymoma-associated
    autoimmunity persists or emerges after thymectomy.
  treatment_term:
    preferred_term: immune suppressant agent therapy
    term:
      id: MAXO:0000297
      label: immune suppressant agent therapy
  evidence:
  - reference: PMID:40983285
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      However, autoimmune conditions may persist or even develop after
      thymectomy, necessitating disease-specific approaches with systemic
      immunosuppression.
    explanation: >-
      Review abstract supports systemic immunosuppression for thymoma-associated
      autoimmune complications that are not fully controlled by surgery.