Breast Implant-Associated Anaplastic Large Cell Lymphoma

Cancer MONDO:0850112 Pathograph 7 Show in embeddings browser Mature T-cell and NK-cell non-Hodgkin lymphoma

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare mature T-cell lymphoma arising in the peri-implant capsule, usually after textured breast-implant exposure. It is represented separately from the MONDO:0020325 ALCL branch because MONDO assigns it the distinct identifier MONDO:0850112 under mature T-cell and NK-cell non-Hodgkin lymphoma.

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1
Mappings
1
Definitions
2
Pathophys.
1
Histopath.
2
Phenotypes
1
Hypotheses
1
Gaps
7
Pathograph
2
Genes
1
Medical Actions
1
Differentials
1
Datasets
🔗

Mappings

MONDO
MONDO:0850112 breast implant-associated anaplastic large cell lymphoma
skos:exactMatch MONDO
Primary MONDO identifier for the exposure-associated BIA-ALCL entity.
📘

Definitions

1
Capsule-associated clinical definition
BIA-ALCL arises as a delayed peri-implant seroma or a capsule-based mass surrounding a textured breast implant.
CASE_DEFINITION Clinical and anatomic definition of BIA-ALCL
Show evidence (1 reference)
PMID:38102324 SUPPORT Human Clinical
"Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a subtype of ALCL that arises as a seroma or a mass in the capsule surrounding textured breast implants."
This cohort provides the capsule, implant, seroma, and mass boundaries used for this disorder entry.
◈

Mechanistic Hypotheses

1
JAK/STAT-driven BIA-ALCL model
bia_jak_stat_genomic_model EMERGING
Evidence balance 1 support
Recurrent somatic variants converge on JAK/STAT activation in BIA-ALCL; this pathway is modeled as a tumor-cell driver while the upstream bridge from implant exposure to acquisition or selection of these lesions remains unresolved.
Pathograph links
JAK/STAT Activation in BIA-ALCL -> Periprosthetic CD30-Positive Malignant T-Cell Expansion INDIRECT KNOWN INTERMEDIATES Activated JAK/STAT signaling supports the survival and expansion of the peri-implant malignant T-cell clone. Intermediates: transcriptional programs supporting malignant-cell survival and proliferation
Periprosthetic CD30-Positive Malignant T-Cell Expansion -> Delayed Peri-Implant Seroma INDIRECT KNOWN INTERMEDIATES Fluid-dominant capsule disease produces a clinically evident delayed peri-implant effusion. Intermediates: local tumor and capsule inflammatory fluid accumulation
Periprosthetic CD30-Positive Malignant T-Cell Expansion -> Capsular Mass INDIRECT KNOWN INTERMEDIATES Mass-forming growth in the peri-implant capsule produces a palpable or imaging-detectable breast mass. Intermediates: localized solid tumor accumulation in the capsule
Show evidence (1 reference)
PMID:30546832 SUPPORT Human Clinical
"We observed sequence variants leading to JAK/STAT activation in 10 out of 11 patients."
Patient-tumor sequencing shows frequent genomic convergence on JAK/STAT activation.
?

Discussions and Knowledge Gaps

1
Which peri-implant processes connect textured-surface exposure to selection or acquisition of JAK/STAT-activating lesions in BIA-ALCL?
KNOWLEDGE GAP OPEN gap_bia_implant_exposure_to_jak_stat_driver
Attached to
environmental#Textured Breast Implant Exposure pathophysiology#JAK/STAT Activation in BIA-ALCL
Human cohorts establish the textured-implant context and tumor sequencing establishes frequent JAK/STAT activation, but these observations do not identify a direct causal bridge. Keeping that bridge open prevents an exposure association from being promoted to an unsupported molecular edge.
Posed 2026-07-21T02:53:02Z
Show evidence (2 references)
PMID:38102324 SUPPORT Human Clinical
"All known implants were macrotextured with the proprietary Biocell macrotexturing pattern from salt-loss technique."
The cohort establishes the exposure side of the unresolved bridge.
PMID:30546832 SUPPORT Human Clinical
"We observed sequence variants leading to JAK/STAT activation in 10 out of 11 patients."
Tumor sequencing establishes the downstream genomic side of the bridge.
⚙

Pathophysiology

2
JAK/STAT Activation in BIA-ALCL
Somatic sequence variants frequently activate JAK/STAT signaling in BIA-ALCL tumor cells, with recurrent involvement of STAT3 and JAK-family genes.
JAK/STAT-driven BIA-ALCL model
JAK1 hgnc:6190 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves JAK1 (hgnc:6190). hgnc:6190 is a gene from the HUGO Gene Nomenclature Committee. STAT3 hgnc:11364 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves STAT3 (hgnc:11364). hgnc:11364 is a gene from the HUGO Gene Nomenclature Committee.
cell surface receptor signaling pathway via JAK-STAT GO:0007259 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased cell surface receptor signaling pathway via JAK-STAT (GO:0007259). GO:0007259 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Periprosthetic CD30-Positive Malignant T-Cell Expansion Activated JAK/STAT signaling supports the survival and expansion of the peri-implant malignant T-cell clone. JAK/STAT-driven BIA-ALCL model
Show evidence (2 references)
PMID:30546832 SUPPORT Human Clinical
"We observed sequence variants leading to JAK/STAT activation in 10 out of 11 patients."
Sequencing of eleven patient tumors directly supports frequent JAK/STAT pathway activation in BIA-ALCL.
PMID:34572893 SUPPORT Other
"The JAK1/3 and STAT3 mutations have also been identified in BIA-ALCL but not in pc-ALCL."
This review identifies JAK-family and STAT3 mutations specifically in BIA-ALCL.
Periprosthetic CD30-Positive Malignant T-Cell Expansion
A malignant T-cell clone expands within the peri-implant effusion and capsule, producing either fluid-dominant or mass-forming disease.
JAK/STAT-driven BIA-ALCL model
cell population proliferation GO:0008283 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased cell population proliferation (GO:0008283). GO:0008283 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Delayed Peri-Implant Seroma Fluid-dominant capsule disease produces a clinically evident delayed peri-implant effusion. JAK/STAT-driven BIA-ALCL model
Capsular Mass Mass-forming growth in the peri-implant capsule produces a palpable or imaging-detectable breast mass. JAK/STAT-driven BIA-ALCL model
Show evidence (1 reference)
PMID:38102324 SUPPORT Human Clinical
"Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a subtype of ALCL that arises as a seroma or a mass in the capsule surrounding textured breast implants."
The cohort localizes BIA-ALCL to the implant capsule and its seroma or mass presentations.
✶

Histopathology

1
CD30-Positive Neoplastic Cells in Peri-Implant Effusion and Capsule
Diagnostic material may be present in the peri-implant effusion and in the capsule. Cytologic preparations and cell-block sections permit morphologic and immunohistochemical assessment, while systematic capsule mapping assesses microscopic tumor and invasion.
Show evidence (3 references)
PMID:40565334 SUPPORT Other
"Anaplastic Large Cell Lymphoma (ALCL) represents a diverse group of mature T-Cell Lymphomas unified by strong CD30 expression but with different molecular and clinical subtypes."
The review directly supports strong CD30 expression as the shared immunophenotype of the ALCL family that includes BIA-ALCL.
PMID:32045544 SUPPORT Other
"Preparation of a cell block is desirable to allow for hematoxylin and eosin staining and immunohistochemical analysis of formalin-fixed, paraffin-embedded histologic sections."
The best-practices guideline supports cell-block morphology and immunohistochemistry for peri-implant effusion material.
PMID:32045544 SUPPORT Other
"Fixation and mapping of the capsulectomy specimen to select multiple representative sections are advised to assess for microscopic tumor involvement and capsular invasion."
The guideline directly supports mapped microscopic assessment of the capsule for tumor and invasion.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Breast Implant-Associated Anaplastic Large Cell Lymphoma 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

2
Breast 1
Capsular Mass OCCASIONAL Breast mass HP:0032408 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Breast mass (HP:0032408). HP:0032408 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:38102324 SUPPORT Human Clinical
"Patients presented with clinically evident effusion in 78% of cases and a mass in 17% of cases, and 83% of patients presented with stage 1 BIA-ALCL."
The 17% cohort frequency places mass presentation in the OCCASIONAL band.
Other 1
Delayed Peri-Implant Seroma FREQUENT
Show evidence (1 reference)
PMID:38102324 SUPPORT Human Clinical
"Patients presented with clinically evident effusion in 78% of cases and a mass in 17% of cases, and 83% of patients presented with stage 1 BIA-ALCL."
The 78% cohort frequency places delayed effusion in the FREQUENT band.
🧬

Genetic Associations

2
JAK1 Mutation (Somatic JAK/STAT-pathway driver alteration)
Gene: JAK1 hgnc:6190 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is JAK1 (hgnc:6190). hgnc:6190 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SOMATIC_DRIVER variant_origin: SOMATIC
Show evidence (1 reference)
PMID:34572893 SUPPORT Other
"The JAK1/3 and STAT3 mutations have also been identified in BIA-ALCL but not in pc-ALCL."
This review directly identifies JAK-family mutations in BIA-ALCL.
STAT3 Mutation (Somatic JAK/STAT-pathway driver alteration)
Gene: STAT3 hgnc:11364 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is STAT3 (hgnc:11364). hgnc:11364 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SOMATIC_DRIVER variant_origin: SOMATIC
Show evidence (2 references)
PMID:30546832 SUPPORT Human Clinical
"We observed sequence variants leading to JAK/STAT activation in 10 out of 11 patients."
Patient-tumor sequencing supports recurrent somatic variants that activate the pathway containing STAT3.
PMID:34572893 SUPPORT Other
"The JAK1/3 and STAT3 mutations have also been identified in BIA-ALCL but not in pc-ALCL."
This review directly identifies STAT3 mutations in BIA-ALCL.
💊

Medical Actions

1
Complete Surgical Excision with Implant Removal
Category: Therapeutic Action: surgical procedureNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is surgical procedure (NCIT:C15329). NCIT:C15329 is a clinical intervention from the NCI Thesaurus. Ontology label: Surgical Procedure NCIT:C15329
Complete surgical excision, including total capsulectomy and implant removal, is the principal treatment for localized capsule-confined BIA-ALCL.
Mechanism Target:
INHIBITS Periprosthetic CD30-Positive Malignant T-Cell Expansion — Total capsulectomy and implant removal physically excise the capsule-localized malignant compartment.
Show evidence (1 reference)
PMID:26628470 SUPPORT Human Clinical
"Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014)"
The cohort links complete removal of the implant and capsule to improved outcomes, supporting excision of the capsule-localized tumor mechanism.
Show evidence (1 reference)
PMID:26628470 SUPPORT Human Clinical
"Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014)"
The multi-institutional cohort directly supports total capsulectomy with implant removal as the key localized-disease treatment.
🌍

Environmental Factors

1
Textured Breast Implant Exposure
BIA-ALCL occurs in the capsule around breast implants; in the cited cohort, every implant with known surface type was macrotextured. This is modeled as an exposure association, not as a proven direct cause of a particular somatic driver.
Show evidence (1 reference)
PMID:38102324 SUPPORT Human Clinical
"Median age at diagnosis was 57 (range 35-77) years following a median implant exposure of 11 (range 7-33) years. All known implants were macrotextured with the proprietary Biocell macrotexturing pattern from salt-loss technique."
The cohort directly documents long implant exposure and macrotextured surfaces among implants whose surface was known.
🔬

Biochemical Markers

2
CD30/TNFRSF8 Expression (strong tumor-cell expression)
Show evidence (1 reference)
PMID:40565334 SUPPORT Other
"Anaplastic Large Cell Lymphoma (ALCL) represents a diverse group of mature T-Cell Lymphomas unified by strong CD30 expression but with different molecular and clinical subtypes."
The review identifies strong CD30 expression as the shared ALCL-family biomarker.
ALK Protein Expression (ABSENT)
Show evidence (1 reference)
PMID:34572893 SUPPORT Other
"Based on the presence/absence of the rearrangement and expression of anaplastic lymphoma kinase (ALK), ALCL is divided into ALK+ and ALK-, and both differ clinically and prognostically. This review focuses on the historical points, clinical features, histopathology, differential diagnosis, and..."
The review classifies BIA-ALCL as an ALK-negative ALCL subtype and ties that classification to absent ALK rearrangement and expression.
🔬

Diagnosis

3
Cytologic Evaluation of Peri-Implant Effusion
Fresh peri-implant effusion fluid should be processed promptly for cytomorphology; cytocentrifugation and filtration are prioritized because fluid-dominant disease is the common presentation.
clinical cytological testing NCIT:C16490 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:32045544 SUPPORT Other
"The first priority is cytocentrifugation and filtration of fresh, unfixed effusion fluid to produce air-dried smears that are stained with Wright-Giemsa or other Romanowsky-type stains."
The guideline directly specifies first-priority processing of fresh effusion fluid for cytologic diagnosis.
Cell Block Immunohistochemistry and T-Cell Clonality Testing
A cell block supports hematoxylin-eosin morphology and immunohistochemistry; polymerase-chain-reaction testing of T-cell receptor rearrangement can assess clonality.
molecular genetic testing NCIT:C19770 NCI Thesaurus (NCIT)
Markers: CD30, T-cell receptor gene rearrangement
Show evidence (1 reference)
PMID:32045544 SUPPORT Other
"Cell block sections can be used for polymerase chain reaction-based investigation of T-cell receptor gene rearrangement to detect clonality."
The guideline directly supports cell-block-based molecular clonality testing.
Mapped Capsulectomy Specimen Evaluation
When a capsulectomy is performed, fixation and mapped representative sections determine microscopic involvement and capsular invasion.
diagnostic procedure NCIT:C18020 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:32045544 SUPPORT Other
"Fixation and mapping of the capsulectomy specimen to select multiple representative sections are advised to assess for microscopic tumor involvement and capsular invasion."
The guideline directly specifies mapped evaluation of the capsulectomy specimen.
🩻

Imaging Findings

1
Peri-Implant Fluid Collection on Breast Ultrasound
Breast ultrasound can identify the peri-implant fluid collection that prompts diagnostic aspiration; the finding is not itself diagnostic because the effusion requires cytologic evaluation.
Ultrasound
Peri-implant fluid collection
Show evidence (1 reference)
PMID:32045544 SUPPORT Other
"Because the most common presentation of BIA-ALCL is swelling of the breast with fluid collection, an accurate diagnosis requires cytologic evaluation of the effusion fluid surrounding the affected implant."
The guideline supports peri-implant fluid collection as the finding that triggers aspiration and establishes that imaging alone is insufficient; the cached abstract does not quantify ultrasound performance.
🔀

Differential Diagnoses

1

Conditions with similar clinical presentations that must be differentiated from Breast Implant-Associated Anaplastic Large Cell Lymphoma:

Reactive Late Peri-Implant Seroma
Overlapping Features Benign peri-implant fluid can produce the same breast-swelling presentation as fluid-dominant BIA-ALCL.
Distinguishing Features
  • Cytologic evaluation of the effusion is required to identify or exclude lymphoma cells.
  • Cell-block immunohistochemistry and, when needed, T-cell clonality testing refine the distinction.
Show evidence (1 reference)
PMID:32045544 SUPPORT Other
"Because the most common presentation of BIA-ALCL is swelling of the breast with fluid collection, an accurate diagnosis requires cytologic evaluation of the effusion fluid surrounding the affected implant."
The guideline establishes that a fluid collection cannot be classified as BIA-ALCL without cytologic evaluation.
📊

Related Datasets

1
Breast implant-associated anaplastic large cell lymphoma shallow whole genome sequencing for copy number analysis and Whole exome sequencing data. ega:EGAS00001003962
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) shallow whole genome sequencing of 29 BIA-ALCL patients for copy number analysis and 24 Alk-negative ALCL samples as control cohort. 7 Whole exome sequencing BIA-ALCL samples.
human
PMID:32898861
European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Breast Implant-Associated Anaplastic Large Cell Lymphoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.
{ }

Source YAML

click to show 
name: Breast Implant-Associated Anaplastic Large Cell Lymphoma
creation_date: "2026-07-21T02:53:02Z"
category: Cancer
categories:
- Hematologic Malignancy
- T-cell Neoplasm
- Non-Hodgkin Lymphoma
- Exposure-Associated Neoplasm
synonyms:
- BIA-ALCL
- breast implant-associated ALCL
description: >-
  Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare
  mature T-cell lymphoma arising in the peri-implant capsule, usually after
  textured breast-implant exposure. It is represented separately from the
  MONDO:0020325 ALCL branch because MONDO assigns it the distinct identifier
  MONDO:0850112 under mature T-cell and NK-cell non-Hodgkin lymphoma.
definitions:
- name: Capsule-associated clinical definition
  definition_type: CASE_DEFINITION
  description: >-
    BIA-ALCL arises as a delayed peri-implant seroma or a capsule-based mass
    surrounding a textured breast implant.
  scope: Clinical and anatomic definition of BIA-ALCL
  evidence:
  - reference: PMID:38102324
    reference_title: "Surgical Management and Long-Term Outcomes of BIA-ALCL: A Multidisciplinary Approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a
      subtype of ALCL that arises as a seroma or a mass in the capsule
      surrounding textured breast implants.
    explanation: >-
      This cohort provides the capsule, implant, seroma, and mass boundaries
      used for this disorder entry.
disease_term:
  preferred_term: breast implant-associated anaplastic large cell lymphoma
  term:
    id: MONDO:0850112
    label: breast implant-associated anaplastic large cell lymphoma
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0850112
      label: breast implant-associated anaplastic large cell lymphoma
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: >-
      Primary MONDO identifier for the exposure-associated BIA-ALCL entity.
parents:
- Mature T-cell and NK-cell non-Hodgkin lymphoma
mechanistic_hypotheses:
- hypothesis_group_id: bia_jak_stat_genomic_model
  hypothesis_label: JAK/STAT-driven BIA-ALCL model
  status: EMERGING
  description: >-
    Recurrent somatic variants converge on JAK/STAT activation in BIA-ALCL;
    this pathway is modeled as a tumor-cell driver while the upstream bridge
    from implant exposure to acquisition or selection of these lesions remains
    unresolved.
  evidence:
  - reference: PMID:30546832
    reference_title: Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We observed sequence variants leading to JAK/STAT activation in 10 out
      of 11 patients.
    explanation: >-
      Patient-tumor sequencing shows frequent genomic convergence on JAK/STAT
      activation.
environmental:
- name: Textured Breast Implant Exposure
  presence: Positive
  description: >-
    BIA-ALCL occurs in the capsule around breast implants; in the cited cohort,
    every implant with known surface type was macrotextured. This is modeled as
    an exposure association, not as a proven direct cause of a particular
    somatic driver.
  effect: Associated peri-implant context for capsule-based lymphoma
  evidence:
  - reference: PMID:38102324
    reference_title: "Surgical Management and Long-Term Outcomes of BIA-ALCL: A Multidisciplinary Approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Median age at diagnosis was 57 (range 35-77) years following a median
      implant exposure of 11 (range 7-33) years. All known implants were
      macrotextured with the proprietary Biocell macrotexturing pattern from
      salt-loss technique.
    explanation: >-
      The cohort directly documents long implant exposure and macrotextured
      surfaces among implants whose surface was known.
pathophysiology:
- name: JAK/STAT Activation in BIA-ALCL
  conforms_to: "jak_stat_pathway_activation#Constitutive STAT Activation and Nuclear Translocation"
  description: >-
    Somatic sequence variants frequently activate JAK/STAT signaling in
    BIA-ALCL tumor cells, with recurrent involvement of STAT3 and JAK-family
    genes.
  genes:
  - preferred_term: JAK1
    term:
      id: hgnc:6190
      label: JAK1
  - preferred_term: STAT3
    term:
      id: hgnc:11364
      label: STAT3
  biological_processes:
  - preferred_term: cell surface receptor signaling pathway via JAK-STAT
    modifier: INCREASED
    term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
  evidence:
  - reference: PMID:30546832
    reference_title: Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We observed sequence variants leading to JAK/STAT activation in 10 out
      of 11 patients.
    explanation: >-
      Sequencing of eleven patient tumors directly supports frequent JAK/STAT
      pathway activation in BIA-ALCL.
  - reference: PMID:34572893
    reference_title: "ALK-Negative Anaplastic Large Cell Lymphoma: Current Concepts and Molecular Pathogenesis of a Heterogeneous Group of Large T-Cell Lymphomas."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The JAK1/3 and STAT3 mutations have also been identified in BIA-ALCL but
      not in pc-ALCL.
    explanation: >-
      This review identifies JAK-family and STAT3 mutations specifically in
      BIA-ALCL.
  downstream:
  - target: Periprosthetic CD30-Positive Malignant T-Cell Expansion
    description: >-
      Activated JAK/STAT signaling supports the survival and expansion of the
      peri-implant malignant T-cell clone.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - transcriptional programs supporting malignant-cell survival and proliferation
    hypothesis_groups:
    - bia_jak_stat_genomic_model
    evidence:
    - reference: PMID:30546832
      reference_title: Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        In summary, our comprehensive genomic characterisation of 11 cases of
        BIA-ALCL has provided insight into potential pathobiological mechanisms
        (JAK/STAT, MYC and TP53) as well as identifying targets for future
        therapeutic intervention (TNFRSF11A, PDGFRA) in this rare entity.
      explanation: >-
        The patient genomic series supports JAK/STAT as a pathobiological
        mechanism; the intervening survival and proliferation program is
        intentionally represented as an omitted intermediate.
- name: Periprosthetic CD30-Positive Malignant T-Cell Expansion
  description: >-
    A malignant T-cell clone expands within the peri-implant effusion and
    capsule, producing either fluid-dominant or mass-forming disease.
  biological_processes:
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  evidence:
  - reference: PMID:38102324
    reference_title: "Surgical Management and Long-Term Outcomes of BIA-ALCL: A Multidisciplinary Approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a
      subtype of ALCL that arises as a seroma or a mass in the capsule
      surrounding textured breast implants.
    explanation: >-
      The cohort localizes BIA-ALCL to the implant capsule and its seroma or
      mass presentations.
  downstream:
  - target: Delayed Peri-Implant Seroma
    description: >-
      Fluid-dominant capsule disease produces a clinically evident delayed
      peri-implant effusion.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - local tumor and capsule inflammatory fluid accumulation
    hypothesis_groups:
    - bia_jak_stat_genomic_model
    evidence:
    - reference: PMID:38102324
      reference_title: "Surgical Management and Long-Term Outcomes of BIA-ALCL: A Multidisciplinary Approach."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Patients presented with clinically evident effusion in 78% of cases and
        a mass in 17% of cases, and 83% of patients presented with stage 1
        BIA-ALCL.
      explanation: >-
        This cohort directly supports effusion as the common clinical output of
        capsule-localized BIA-ALCL.
  - target: Capsular Mass
    description: >-
      Mass-forming growth in the peri-implant capsule produces a palpable or
      imaging-detectable breast mass.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - localized solid tumor accumulation in the capsule
    hypothesis_groups:
    - bia_jak_stat_genomic_model
    evidence:
    - reference: PMID:38102324
      reference_title: "Surgical Management and Long-Term Outcomes of BIA-ALCL: A Multidisciplinary Approach."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Patients presented with clinically evident effusion in 78% of cases and
        a mass in 17% of cases, and 83% of patients presented with stage 1
        BIA-ALCL.
      explanation: >-
        This cohort directly supports a capsule-based mass as the less-common
        presentation of BIA-ALCL.
histopathology:
- name: CD30-Positive Neoplastic Cells in Peri-Implant Effusion and Capsule
  finding_term:
    preferred_term: CD30-positive neoplastic cells in peri-implant effusion or capsule
    term:
      id: NCIT:C39715
      label: CD30-Positive Neoplastic Cells Present
  description: >-
    Diagnostic material may be present in the peri-implant effusion and in the
    capsule. Cytologic preparations and cell-block sections permit morphologic
    and immunohistochemical assessment, while systematic capsule mapping
    assesses microscopic tumor and invasion.
  diagnostic: true
  evidence:
  - reference: PMID:40565334
    reference_title: "Molecular Insights into the Diagnosis of Anaplastic Large Cell Lymphoma: Beyond Morphology and Immunophenotype."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Anaplastic Large Cell Lymphoma (ALCL) represents a diverse group of mature
      T-Cell Lymphomas unified by strong CD30 expression but with different
      molecular and clinical subtypes.
    explanation: >-
      The review directly supports strong CD30 expression as the shared
      immunophenotype of the ALCL family that includes BIA-ALCL.
  - reference: PMID:32045544
    reference_title: Best Practices Guideline for the Pathologic Diagnosis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Preparation of a cell block is desirable to allow for hematoxylin and
      eosin staining and immunohistochemical analysis of formalin-fixed,
      paraffin-embedded histologic sections.
    explanation: >-
      The best-practices guideline supports cell-block morphology and
      immunohistochemistry for peri-implant effusion material.
  - reference: PMID:32045544
    reference_title: Best Practices Guideline for the Pathologic Diagnosis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Fixation and mapping of the capsulectomy specimen to select multiple
      representative sections are advised to assess for microscopic tumor
      involvement and capsular invasion.
    explanation: >-
      The guideline directly supports mapped microscopic assessment of the
      capsule for tumor and invasion.
phenotypes:
- category: Breast
  name: Delayed Peri-Implant Seroma
  frequency: FREQUENT
  description: >-
    Delayed breast swelling with peri-implant fluid is the most common
    presentation; the cited cohort observed clinically evident effusion in 78%
    of cases.
  phenotype_term:
    preferred_term: Delayed peri-implant seroma
  evidence:
  - reference: PMID:38102324
    reference_title: "Surgical Management and Long-Term Outcomes of BIA-ALCL: A Multidisciplinary Approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients presented with clinically evident effusion in 78% of cases and a
      mass in 17% of cases, and 83% of patients presented with stage 1 BIA-ALCL.
    explanation: >-
      The 78% cohort frequency places delayed effusion in the FREQUENT band.
- category: Breast
  name: Capsular Mass
  frequency: OCCASIONAL
  description: >-
    A minority of patients have a solid capsule-based breast mass, observed in
    17% of the cited cohort.
  phenotype_term:
    preferred_term: Breast mass
    term:
      id: HP:0032408
      label: Breast mass
  evidence:
  - reference: PMID:38102324
    reference_title: "Surgical Management and Long-Term Outcomes of BIA-ALCL: A Multidisciplinary Approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients presented with clinically evident effusion in 78% of cases and a
      mass in 17% of cases, and 83% of patients presented with stage 1 BIA-ALCL.
    explanation: >-
      The 17% cohort frequency places mass presentation in the OCCASIONAL band.
imaging_findings:
- name: Peri-Implant Fluid Collection on Breast Ultrasound
  modality: ULTRASOUND
  imaging_finding_term:
    preferred_term: Peri-implant fluid collection
  diagnostic: false
  description: >-
    Breast ultrasound can identify the peri-implant fluid collection that
    prompts diagnostic aspiration; the finding is not itself diagnostic because
    the effusion requires cytologic evaluation.
  evidence:
  - reference: PMID:32045544
    reference_title: Best Practices Guideline for the Pathologic Diagnosis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Because the most common presentation of BIA-ALCL is swelling of the breast
      with fluid collection, an accurate diagnosis requires cytologic evaluation
      of the effusion fluid surrounding the affected implant.
    explanation: >-
      The guideline supports peri-implant fluid collection as the finding that
      triggers aspiration and establishes that imaging alone is insufficient;
      the cached abstract does not quantify ultrasound performance.
biochemical:
- name: CD30/TNFRSF8 Expression
  biomarker_term:
    preferred_term: Tumor Necrosis Factor Receptor Superfamily Member 8
    term:
      id: NCIT:C38906
      label: Tumor Necrosis Factor Receptor Superfamily Member 8
  presence: strong tumor-cell expression
  notes: >-
    BIA-ALCL shares the strong CD30 expression that defines the ALCL family and
    enables CD30-directed immunophenotypic confirmation.
  evidence:
  - reference: PMID:40565334
    reference_title: "Molecular Insights into the Diagnosis of Anaplastic Large Cell Lymphoma: Beyond Morphology and Immunophenotype."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Anaplastic Large Cell Lymphoma (ALCL) represents a diverse group of mature
      T-Cell Lymphomas unified by strong CD30 expression but with different
      molecular and clinical subtypes.
    explanation: >-
      The review identifies strong CD30 expression as the shared ALCL-family
      biomarker.
- name: ALK Protein Expression
  biomarker_term:
    preferred_term: ALK tyrosine kinase receptor
    term:
      id: NCIT:C27032
      label: ALK Tyrosine Kinase Receptor
  presence: ABSENT
  notes: >-
    BIA-ALCL belongs to the ALK-negative ALCL group; absence of ALK expression
    helps distinguish it from systemic ALK-positive ALCL.
  evidence:
  - reference: PMID:34572893
    reference_title: "ALK-Negative Anaplastic Large Cell Lymphoma: Current Concepts and Molecular Pathogenesis of a Heterogeneous Group of Large T-Cell Lymphomas."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Based on the presence/absence of the rearrangement and expression of
      anaplastic lymphoma kinase (ALK), ALCL is divided into ALK+ and ALK-, and
      both differ clinically and prognostically. This review focuses on the
      historical points, clinical features, histopathology, differential diagnosis,
      and relevant cytogenetic and molecular alterations of ALK- ALCL and its
      subtypes: systemic, primary cutaneous (pc-ALCL), and breast
      implant-associated (BIA-ALCL).
    explanation: >-
      The review classifies BIA-ALCL as an ALK-negative ALCL subtype and ties
      that classification to absent ALK rearrangement and expression.
genetic:
- name: JAK1 Mutation
  association: Somatic JAK/STAT-pathway driver alteration
  relationship_type: SOMATIC_DRIVER
  variant_origin: SOMATIC
  gene_term:
    preferred_term: JAK1
    term:
      id: hgnc:6190
      label: JAK1
  notes: >-
    JAK1 mutation is one documented route to pathway activation in BIA-ALCL;
    it is not asserted to occur in every tumor.
  evidence:
  - reference: PMID:34572893
    reference_title: "ALK-Negative Anaplastic Large Cell Lymphoma: Current Concepts and Molecular Pathogenesis of a Heterogeneous Group of Large T-Cell Lymphomas."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The JAK1/3 and STAT3 mutations have also been identified in BIA-ALCL but
      not in pc-ALCL.
    explanation: >-
      This review directly identifies JAK-family mutations in BIA-ALCL.
- name: STAT3 Mutation
  association: Somatic JAK/STAT-pathway driver alteration
  relationship_type: SOMATIC_DRIVER
  variant_origin: SOMATIC
  gene_term:
    preferred_term: STAT3
    term:
      id: hgnc:11364
      label: STAT3
  notes: >-
    Activating STAT3 mutation is a recurrent route to JAK/STAT signaling in
    BIA-ALCL, but no universal case frequency is asserted.
  evidence:
  - reference: PMID:30546832
    reference_title: Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We observed sequence variants leading to JAK/STAT activation in 10 out
      of 11 patients.
    explanation: >-
      Patient-tumor sequencing supports recurrent somatic variants that activate
      the pathway containing STAT3.
  - reference: PMID:34572893
    reference_title: "ALK-Negative Anaplastic Large Cell Lymphoma: Current Concepts and Molecular Pathogenesis of a Heterogeneous Group of Large T-Cell Lymphomas."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The JAK1/3 and STAT3 mutations have also been identified in BIA-ALCL but
      not in pc-ALCL.
    explanation: >-
      This review directly identifies STAT3 mutations in BIA-ALCL.
diagnosis:
- name: Cytologic Evaluation of Peri-Implant Effusion
  description: >-
    Fresh peri-implant effusion fluid should be processed promptly for
    cytomorphology; cytocentrifugation and filtration are prioritized because
    fluid-dominant disease is the common presentation.
  diagnosis_term:
    preferred_term: clinical cytological testing
    term:
      id: NCIT:C16490
      label: Cytological Procedure
  evidence:
  - reference: PMID:32045544
    reference_title: Best Practices Guideline for the Pathologic Diagnosis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The first priority is cytocentrifugation and filtration of fresh, unfixed
      effusion fluid to produce air-dried smears that are stained with
      Wright-Giemsa or other Romanowsky-type stains.
    explanation: >-
      The guideline directly specifies first-priority processing of fresh
      effusion fluid for cytologic diagnosis.
- name: Cell Block Immunohistochemistry and T-Cell Clonality Testing
  description: >-
    A cell block supports hematoxylin-eosin morphology and
    immunohistochemistry; polymerase-chain-reaction testing of T-cell receptor
    rearrangement can assess clonality.
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: NCIT:C19770
      label: Molecular Analysis
  markers: CD30, T-cell receptor gene rearrangement
  evidence:
  - reference: PMID:32045544
    reference_title: Best Practices Guideline for the Pathologic Diagnosis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Cell block sections can be used for polymerase chain reaction-based
      investigation of T-cell receptor gene rearrangement to detect clonality.
    explanation: >-
      The guideline directly supports cell-block-based molecular clonality
      testing.
- name: Mapped Capsulectomy Specimen Evaluation
  description: >-
    When a capsulectomy is performed, fixation and mapped representative
    sections determine microscopic involvement and capsular invasion.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  evidence:
  - reference: PMID:32045544
    reference_title: Best Practices Guideline for the Pathologic Diagnosis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Fixation and mapping of the capsulectomy specimen to select multiple
      representative sections are advised to assess for microscopic tumor
      involvement and capsular invasion.
    explanation: >-
      The guideline directly specifies mapped evaluation of the capsulectomy
      specimen.
differential_diagnoses:
- name: Reactive Late Peri-Implant Seroma
  description: >-
    Benign peri-implant fluid can produce the same breast-swelling presentation
    as fluid-dominant BIA-ALCL.
  distinguishing_features:
  - Cytologic evaluation of the effusion is required to identify or exclude lymphoma cells.
  - Cell-block immunohistochemistry and, when needed, T-cell clonality testing refine the distinction.
  evidence:
  - reference: PMID:32045544
    reference_title: Best Practices Guideline for the Pathologic Diagnosis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Because the most common presentation of BIA-ALCL is swelling of the breast
      with fluid collection, an accurate diagnosis requires cytologic evaluation
      of the effusion fluid surrounding the affected implant.
    explanation: >-
      The guideline establishes that a fluid collection cannot be classified as
      BIA-ALCL without cytologic evaluation.
treatments:
- name: Complete Surgical Excision with Implant Removal
  action_category: THERAPEUTIC
  description: >-
    Complete surgical excision, including total capsulectomy and implant
    removal, is the principal treatment for localized capsule-confined
    BIA-ALCL.
  context: Localized capsule-confined BIA-ALCL
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: NCIT:C15329
      label: Surgical Procedure
  target_mechanisms:
  - target: Periprosthetic CD30-Positive Malignant T-Cell Expansion
    treatment_effect: INHIBITS
    description: >-
      Total capsulectomy and implant removal physically excise the
      capsule-localized malignant compartment.
    evidence:
    - reference: PMID:26628470
      reference_title: Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant-Associated Anaplastic Large-Cell Lymphoma.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Patients who underwent a complete surgical excision that consisted of
        total capsulectomy with breast implant removal had better OS (P = .022)
        and EFS (P = .014)
      explanation: >-
        The cohort links complete removal of the implant and capsule to improved
        outcomes, supporting excision of the capsule-localized tumor mechanism.
  evidence:
  - reference: PMID:26628470
    reference_title: Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant-Associated Anaplastic Large-Cell Lymphoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients who underwent a complete surgical excision that consisted of
      total capsulectomy with breast implant removal had better OS (P = .022)
      and EFS (P = .014)
    explanation: >-
      The multi-institutional cohort directly supports total capsulectomy with
      implant removal as the key localized-disease treatment.
discussions:
- discussion_id: gap_bia_implant_exposure_to_jak_stat_driver
  prompt: >-
    Which peri-implant processes connect textured-surface exposure to selection
    or acquisition of JAK/STAT-activating lesions in BIA-ALCL?
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - environmental#Textured Breast Implant Exposure
  - pathophysiology#JAK/STAT Activation in BIA-ALCL
  rationale: >-
    Human cohorts establish the textured-implant context and tumor sequencing
    establishes frequent JAK/STAT activation, but these observations do not
    identify a direct causal bridge. Keeping that bridge open prevents an
    exposure association from being promoted to an unsupported molecular edge.
  evidence:
  - reference: PMID:38102324
    reference_title: "Surgical Management and Long-Term Outcomes of BIA-ALCL: A Multidisciplinary Approach."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All known implants were macrotextured with the proprietary Biocell
      macrotexturing pattern from salt-loss technique.
    explanation: >-
      The cohort establishes the exposure side of the unresolved bridge.
  - reference: PMID:30546832
    reference_title: Frequent activating STAT3 mutations and novel recurrent genomic abnormalities detected in breast implant-associated anaplastic large cell lymphoma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We observed sequence variants leading to JAK/STAT activation in 10 out
      of 11 patients.
    explanation: >-
      Tumor sequencing establishes the downstream genomic side of the bridge.
  posed_date: "2026-07-21T02:53:02Z"
datasets:
- accession: ega:EGAS00001003962
  title: Breast implant-associated anaplastic large cell lymphoma shallow whole genome sequencing for copy number analysis and Whole exome sequencing data.
  description: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) shallow whole genome sequencing of 29 BIA-ALCL patients for copy number analysis and 24 Alk-negative ALCL samples as control cohort. 7 Whole exome sequencing BIA-ALCL samples.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  publication: PMID:32898861
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Breast Implant-Associated Anaplastic Large Cell Lymphoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'