Malignant Peritoneal Mesothelioma

MONDO:0005512 Pathograph 10 Malignant Mesothelioma

Malignant peritoneal mesothelioma (MPeM) is a rare aggressive mesothelial cancer of the peritoneal lining characterized by locoregional abdominal progression, frequent BAP1 loss, and clinical management centered on cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in selected resectable patients. Compared with pleural mesothelioma, peritoneal disease shows less consistent asbestos attribution, relatively lower CDKN2A/CDKN2B/MTAP loss, and rare site-restricted ALK rearrangements.

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3
Mappings
5
Pathophys.
3
Histopath.
6
Phenotypes
10
Pathograph
5
Genes
4
Treatments
5
Subtypes
1
Deep Research
🔗

Mappings

MONDO
MONDO:0005512 malignant peritoneal mesothelioma
skos:exactMatch MONDO
Primary MONDO disease identifier for this curation.
NCIT
NCIT:C9350 Peritoneal Malignant Mesothelioma
skos:exactMatch NCIT
NCIT provides an exact oncology-specific concept for malignant mesothelioma arising from the peritoneum.
ICD-10-CM
ICD10CM:C45.1 Mesothelioma of peritoneum
skos:exactMatch ICD-10-CM
ICD-10-CM C45.1 is the direct topographic code for mesothelioma arising in the peritoneum.
NCIT
NCIT:C9350 Peritoneal Malignant Mesothelioma
skos:exactMatch NCIT
NCIT provides an exact oncology-specific concept for malignant mesothelioma arising from the peritoneum.
◆

Subtypes

5
histological
Epithelioid Malignant Peritoneal Mesothelioma NCIT:C162940
NCIT NCIT:C162940
Histologic subtype composed of epithelioid mesothelial cells, often with tubulopapillary, microglandular, or sheet-like architecture, and associated with better survival than nonepithelioid disease.
NCIT: Peritoneal Epithelioid Mesothelioma (skos:exactMatch) NCIT:C162940
Show evidence (1 reference)
PMID:33060816 SUPPORT Human Clinical
"absence of necrosis (P = 0.007), and epithelioid histotype (P < 0.0001)."
Large multi-institutional clinicopathologic analysis identifies epithelioid histotype as a favorable prognostic histologic subtype.
Biphasic Malignant Peritoneal Mesothelioma NCIT:C168805
NCIT NCIT:C168805
Histologic subtype containing both epithelioid and sarcomatoid components. Recent profiling studies group biphasic tumors with sarcomatoid tumors as nonepithelioid mesothelioma.
NCIT: Peritoneal Biphasic Mesothelioma (skos:exactMatch) NCIT:C168805
Show evidence (1 reference)
PMID:35704798 SUPPORT Human Clinical
"Compared with epithelioid MPM, nonepithelioid (ie, biphasic and sarcomatoid) MPM had identical tumor mutational burden (median 1.25 mut/Mb, P = .63), more commonly expressed PD-L1 (74% v 51%, P = .02), and was more likely to harbor MTAP, CDKN2A, and CDKN2B copy loss (P < .05)."
Molecular profiling explicitly groups biphasic peritoneal mesothelioma within the nonepithelioid class and distinguishes it from epithelioid tumors.
Sarcomatoid Malignant Peritoneal Mesothelioma NCIT:C168804
NCIT NCIT:C168804
Spindle-cell histologic subtype with aggressive behavior; grouped with biphasic tumors as nonepithelioid mesothelioma in modern molecular studies.
NCIT: Peritoneal Sarcomatoid Mesothelioma (skos:exactMatch) NCIT:C168804
Show evidence (1 reference)
PMID:35704798 SUPPORT Human Clinical
"Compared with epithelioid MPM, nonepithelioid (ie, biphasic and sarcomatoid) MPM had identical tumor mutational burden (median 1.25 mut/Mb, P = .63), more commonly expressed PD-L1 (74% v 51%, P = .02), and was more likely to harbor MTAP, CDKN2A, and CDKN2B copy loss (P < .05)."
Molecular profiling explicitly groups sarcomatoid peritoneal mesothelioma within the nonepithelioid class and distinguishes it from epithelioid tumors.
molecular
ALK-Rearranged Malignant Peritoneal Mesothelioma
ALK link
Rare molecular subtype defined by ALK rearrangement. Reported series suggest that ALK rearrangements are a site-restricted finding within peritoneal mesothelioma rather than pleural mesothelioma.
Show evidence (1 reference)
PMID:35704798 SUPPORT Human Clinical
"ALK rearrangements were only observed in MPeM."
Large-scale profiling identifies ALK rearrangements as a rare but site-restricted molecular subtype of peritoneal mesothelioma.
predisposition context
BAP1 Tumor Predisposition Syndrome-Associated Malignant Peritoneal Mesothelioma MONDO:0013692
MONDO MONDO:0013692
Predisposition-context subtype occurring in the setting of inherited BAP1-related tumor predisposition syndrome. This axis captures host susceptibility context rather than a separate disease-level causal program.
Show evidence (1 reference)
PMID:30001711 SUPPORT Human Clinical
"Germline mutations in the BRCA-1 associated tumor protein 1 (BAP1) increase susceptibility to mesothelioma and other cancers. We describe a patient with a family history of peritoneal mesothelioma, who developed malignant peritoneal mesothelioma at age 45 in the absence of known asbestos exposure."
Case-based clinical evidence supports a germline BAP1 predisposition context for a subset of malignant peritoneal mesothelioma cases.
⚙

Pathophysiology

5
BAP1 Tumor Suppressor Inactivation
BAP1 loss is the dominant recurrent genomic event in peritoneal mesothelioma, often occurring through biallelic inactivation and accompanied by loss of nuclear BAP1 expression.
BAP1 link
chromatin organization link ⚠ ABNORMAL
deubiquitinase activity link ↓ DECREASED
Downstream
Epigenetic Deregulation Loss of BAP1 disrupts chromatin-associated tumor suppressor programs.
Show evidence (2 references)
PMID:27813512 SUPPORT Human Clinical
"The most frequent genetic alteration was biallelic inactivation of the BAP1 gene, which occurred in 9/13 cases, with an additional two cases demonstrating monoallelic loss of BAP1."
Targeted sequencing identifies BAP1 loss as the most common recurrent driver lesion in malignant peritoneal mesothelioma.
PMID:28034829 SUPPORT Human Clinical
"Overall, 73% of the malignant peritoneal mesotheliomas analyzed carried at least one inactivated BAP1 allele, but only 57% had a complete loss of its protein nuclear expression."
Independent cohort data confirm that BAP1 inactivation is highly prevalent in malignant peritoneal mesothelioma.
Epigenetic Deregulation
Peritoneal mesothelioma recurrently alters epigenetic regulators including BAP1, SETD2, and DDX3X, supporting a transcriptionally deregulated disease program.
epigenetic regulation of gene expression link ⚠ ABNORMAL chromatin organization link ⚠ ABNORMAL
Downstream
Mesothelial Cell Proliferation Epigenetic deregulation supports malignant growth of transformed mesothelial cells.
Show evidence (1 reference)
PMID:27813512 SUPPORT Human Clinical
"Together, these findings demonstrate the importance of epigenetic modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis and suggest opportunities for targeted therapies."
Human tumor profiling supports epigenetic dysregulation as a core mechanistic layer in malignant peritoneal mesothelioma.
PI3K-AKT-mTOR Signaling Activation
Overactive PI3K-AKT-mTOR pathway signaling is a recurrent proliferative program in diffuse malignant peritoneal mesothelioma and provides a mechanistic rationale for targeted therapy development.
TOR signaling link ↑ INCREASED
Downstream
Mesothelial Cell Proliferation mTOR-pathway activation sustains malignant growth and survival.
Show evidence (1 reference)
PMID:36684194 SUPPORT Other
"The overexpression of the phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase 1 (AKT)/mammalian target of rapamycin (mTOR) signaling pathway drives the malignant phenotype of DMPM"
Review synthesis identifies PI3K-AKT-mTOR pathway activation as a recurring proliferative program in diffuse malignant peritoneal mesothelioma.
Mesothelial Cell Proliferation
Malignant peritoneal mesothelioma expands along the peritoneal surface through progressive proliferation of transformed mesothelial cells.
mesothelial cell link
positive regulation of cell population proliferation link ↑ INCREASED
peritoneum link
Downstream
Locoregional Peritoneal Tumor Expansion Progressive mesothelial proliferation produces diffuse serosal tumor burden.
Locoregional Peritoneal Tumor Expansion
Disease morbidity is dominated by progressive locoregional tumor effects within the abdomen rather than early distant metastasis.
abdominal cavity link
Downstream
Abdominal Distention Tumor burden and associated fluid accumulation increase abdominal girth.
Abdominal Pain Progressive serosal tumor involvement causes abdominal pain.
Early Satiety Intraperitoneal tumor burden reduces gastric accommodation.
Intestinal Obstruction Progressive locoregional spread compromises bowel transit.
Show evidence (1 reference)
PMID:32206577 SUPPORT Other
"Morbidity and mortality of the disease are related to progressive locoregional effects within the abdominal cavity, such as distention, pain, early satiety, and decreased oral intake that can ultimately lead to bowel obstruction and cachexia."
Review synthesis identifies locoregional intraperitoneal tumor expansion as the proximate cause of the dominant clinical phenotype set.
✶

Histopathology

3
Epithelioid Histotype
Epithelioid histology is the prognostically favored peritoneal mesothelioma subtype.
Show evidence (1 reference)
PMID:33060816 SUPPORT Human Clinical
"absence of necrosis (P = 0.007), and epithelioid histotype (P < 0.0001)."
Multi-institutional outcome analysis identifies epithelioid histotype as a favorable histopathologic subtype.
Composite Nuclear Grade
Composite nuclear grade is a validated prognostic histopathologic feature in epithelioid malignant peritoneal mesothelioma.
Show evidence (1 reference)
PMID:33060816 SUPPORT Human Clinical
"On multivariate analyses, the low composite nuclear grade was independently associated with longer overall and disease-free survival (P < 0.0001)."
Validates nuclear grade as a prognostically relevant histopathologic variable in epithelioid peritoneal mesothelioma.
Tumor Necrosis
Necrosis is an adverse histopathologic feature; its absence correlates with better survival.
Show evidence (1 reference)
PMID:33060816 SUPPORT Human Clinical
"absence of necrosis (P = 0.007), and epithelioid histotype (P < 0.0001)."
The inverse association of necrosis absence with survival supports necrosis as an adverse histopathologic feature.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Malignant Peritoneal Mesothelioma 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

6
Digestive 4
Ascites Ascites (HP:0001541)
Show evidence (1 reference)
PMID:22104079 SUPPORT Other
"Presenting symptoms in these patients include: ascites, abdominal pain, asthenia, weight loss, anorexia, abdominal mass, fever, diarrhea and vomiting."
Review-level clinical synthesis lists ascites among common presenting manifestations of diffuse malignant peritoneal mesothelioma.
Abdominal Distention Abdominal distention (HP:0003270)
Show evidence (1 reference)
PMID:36059360 SUPPORT Human Clinical
"Malignant peritoneal mesothelioma (MPM) is a rare and very aggressive malignancy of serosal membranes, which typically presents with abdominal pain, distension, and ascites."
Case-based clinical summary explicitly lists abdominal distension as a typical presenting manifestation of malignant peritoneal mesothelioma.
Early Satiety Early satiety (HP:0033842)
Show evidence (1 reference)
PMID:32206577 SUPPORT Other
"Morbidity and mortality of the disease are related to progressive locoregional effects within the abdominal cavity, such as distention, pain, early satiety, and decreased oral intake that can ultimately lead to bowel obstruction and cachexia."
Review-level clinical synthesis identifies early satiety as part of the dominant locoregional abdominal phenotype cluster.
Intestinal Obstruction Intestinal obstruction (HP:0005214)
Show evidence (1 reference)
PMID:32206577 SUPPORT Other
"Morbidity and mortality of the disease are related to progressive locoregional effects within the abdominal cavity, such as distention, pain, early satiety, and decreased oral intake that can ultimately lead to bowel obstruction and cachexia."
Review-level clinical synthesis identifies bowel obstruction as a late consequence of locoregional peritoneal tumor progression.
Constitutional 1
Abdominal Pain Abdominal pain (HP:0002027)
Show evidence (1 reference)
PMID:22104079 SUPPORT Other
"Presenting symptoms in these patients include: ascites, abdominal pain, asthenia, weight loss, anorexia, abdominal mass, fever, diarrhea and vomiting."
Review-level clinical synthesis lists abdominal pain among common presenting manifestations of diffuse malignant peritoneal mesothelioma.
Growth 1
Weight Loss Weight loss (HP:0001824)
Show evidence (1 reference)
PMID:22104079 SUPPORT Other
"Presenting symptoms in these patients include: ascites, abdominal pain, asthenia, weight loss, anorexia, abdominal mass, fever, diarrhea and vomiting."
Review-level clinical synthesis lists weight loss among common presenting manifestations of diffuse malignant peritoneal mesothelioma.
🧬

Genetic Associations

5
BAP1 (Recurrent Loss-of-Function Alteration)
Show evidence (1 reference)
PMID:28034829 SUPPORT Human Clinical
"Overall, 73% of the malignant peritoneal mesotheliomas analyzed carried at least one inactivated BAP1 allele"
Large peritoneal mesothelioma series confirms that BAP1 alteration is a dominant recurrent genetic event.
SETD2 (Recurrent Epigenetic Regulator Alteration)
Show evidence (1 reference)
PMID:27813512 SUPPORT Human Clinical
"Additional recurrently mutated genes in this cohort of malignant peritoneal mesotheliomas included NF2 (3/13), SETD2 (2/13), and DDX3X (2/13)."
Human tumor profiling identifies SETD2 as a recurrently mutated epigenetic regulator in malignant peritoneal mesothelioma.
PBRM1 (Site-Enriched Alteration)
Show evidence (1 reference)
PMID:35704798 SUPPORT Human Clinical
"The molecular profile of MPeM was similar to MPM, with the distinction that PBRM1 alterations occurred at higher frequency (16% v 7%, P < .01)."
Large-scale molecular profiling identifies PBRM1 alteration as a site-enriched genomic feature of peritoneal mesothelioma.
ALK (Rare Recurrent Rearrangement)
Show evidence (1 reference)
PMID:35704798 SUPPORT Human Clinical
"ALK rearrangements were only observed in MPeM."
Large-scale profiling identifies ALK rearrangement as a site-restricted molecular feature of malignant peritoneal mesothelioma.
CDKN2A (Less-Prevalent Copy-Number Loss than Pleural Disease)
Show evidence (1 reference)
PMID:26853494 SUPPORT Human Clinical
"Losses in 3p (BAP1 gene), 9p (CDKN2A) and 22q (NF2) were seen in tumors from both tumor sites, although CDKN2A and NF2 losses were seen at a higher rate in pleural disease (p<0.01)."
Comparative genomic profiling shows that CDKN2A loss occurs in peritoneal mesothelioma but is relatively less frequent than in pleural disease.
💊

Treatments

4
Cytoreductive Surgery
Action: cytoreductive surgery Ontology label: Cytoreductive Surgery NCIT:C132068
Upfront maximal cytoreduction is favored when complete or near-complete resection is achievable in carefully selected patients.
Show evidence (1 reference)
PMID:27472649 SUPPORT Human Clinical
"Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence."
Multi-institutional retrospective data support upfront cytoreductive surgery as part of curative-intent management when feasible.
Hyperthermic Intraperitoneal Chemotherapy
Action: hyperthermic intraperitoneal chemotherapy Ontology label: Hyperthermic Intraperitoneal Chemotherapy NCIT:C91835
HIPEC is paired with cytoreductive surgery in carefully selected resectable diffuse peritoneal mesothelioma and is part of the accepted locoregional standard-of-care strategy.
Show evidence (1 reference)
PMID:39609952 SUPPORT Other
"The panel unanimously recommended CRS-HIPEC for a carefully selected subset of DMPM patients, emphasizing that this approach offers the best potential for improved survival compared to systemic chemotherapy alone."
Multisocietal consensus recommends HIPEC as part of the preferred locoregional treatment strategy for selected patients with diffuse malignant peritoneal mesothelioma.
Pemetrexed Plus Cisplatin
Action: chemotherapy MAXO:0000647
Agent: pemetrexed ↗ cisplatin ↗
Platinum-antifolate chemotherapy is an active systemic option for unresectable disease and for patients who are not candidates for curative locoregional treatment.
Show evidence (1 reference)
PMID:28594258 SUPPORT Human Clinical
"Overall response rate and disease control rate were 45.8% and 91.7%, respectively. Median progression-free survival and median overall survival were 11.0 months and 15.8 months, respectively."
Retrospective first-line series demonstrates meaningful disease control with pemetrexed-cisplatin in malignant peritoneal mesothelioma.
Atezolizumab Plus Bevacizumab
Action: immunotherapy Ontology label: Immunotherapy NCIT:C15262
Agent: atezolizumab ↗ bevacizumab ↗
Combined PD-L1 and VEGF blockade has shown activity in advanced unresectable malignant peritoneal mesothelioma after prior platinum-pemetrexed chemotherapy.
Show evidence (1 reference)
PMID:34261675 SUPPORT Human Clinical
"AtezoBev showed promising and durable efficacy in patients with advanced MPeM with an acceptable safety profile."
Phase II trial data support atezolizumab-bevacizumab as an active systemic option in previously treated advanced malignant peritoneal mesothelioma.
🌍

Environmental Factors

1
Asbestos Exposure
exposure to asbestos link
Asbestos exposure is a recognized but less consistent risk factor for peritoneal mesothelioma than for pleural mesothelioma.
Show evidence (1 reference)
PMID:27813512 SUPPORT Human Clinical
"Most pleural mesotheliomas arise in patients with a history of asbestos exposure, whereas the association of peritoneal mesotheliomas with exposure to asbestos and other potential carcinogens is less clear"
Supports asbestos exposure as a relevant but less consistently attributable risk factor in the peritoneal disease site.
🔬

Biochemical Markers

2
Loss of Nuclear BAP1 Staining
Show evidence (2 references)
PMID:27813512 SUPPORT Human Clinical
"All 11 of these cases demonstrated loss of BAP1 nuclear staining by immunohistochemistry, whereas two tumors without BAP1 alteration and all 42 cases of histologic mimics in peritoneum"
Human tumor profiling supports BAP1 loss of nuclear expression as a diagnostically useful biomarker of malignant peritoneal mesothelioma.
PMID:36684194 SUPPORT Other
"with the advancements in the immunohistochemical analysis of BRCA1-Associated Protein 1 (BAP1) the lack of BAP1 expression shows the diagnosis of malignancy."
Review-level synthesis supports BAP1 loss as a marker that favors malignant over benign mesothelial proliferations.
WT1 Positive Immunostaining
Show evidence (1 reference)
PMID:36684194 SUPPORT Other
"In addition, the most sensitive immunohistochemical markers of DMPM include WT 1, D2-40, and calmodulin."
Review synthesis identifies WT1 among the most sensitive diagnostic immunohistochemical markers used in diffuse malignant peritoneal mesothelioma.
{ }

Source YAML

click to show 
name: Malignant Peritoneal Mesothelioma
creation_date: "2026-04-13T05:15:13Z"
updated_date: "2026-04-22T20:13:21Z"
description: >-
  Malignant peritoneal mesothelioma (MPeM) is a rare aggressive mesothelial
  cancer of the peritoneal lining characterized by locoregional abdominal
  progression, frequent BAP1 loss, and clinical management centered on
  cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in
  selected resectable patients. Compared with pleural mesothelioma, peritoneal
  disease shows less consistent asbestos attribution, relatively lower
  CDKN2A/CDKN2B/MTAP loss, and rare site-restricted ALK rearrangements.
categories:
- Rare Cancer
- Peritoneal Cancer
- Solid Tumor
parents:
- Malignant Mesothelioma
disease_term:
  preferred_term: malignant peritoneal mesothelioma
  term:
    id: MONDO:0005512
    label: malignant peritoneal mesothelioma
mappings:
  icd10cm_mappings:
  - term:
      id: ICD10CM:C45.1
      label: Mesothelioma of peritoneum
    mapping_predicate: skos:exactMatch
    mapping_source: ICD-10-CM
    mapping_justification: >-
      ICD-10-CM C45.1 is the direct topographic code for mesothelioma arising in
      the peritoneum.
  mondo_mappings:
  - term:
      id: MONDO:0005512
      label: malignant peritoneal mesothelioma
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: Primary MONDO disease identifier for this curation.
  ncit_mappings:
  - term:
      id: NCIT:C9350
      label: Peritoneal Malignant Mesothelioma
    mapping_predicate: skos:exactMatch
    mapping_source: NCIT
    mapping_justification: >-
      NCIT provides an exact oncology-specific concept for malignant mesothelioma
      arising from the peritoneum.
has_subtypes:
- name: Epithelioid
  display_name: Epithelioid Malignant Peritoneal Mesothelioma
  classification: histological
  description: >-
    Histologic subtype composed of epithelioid mesothelial cells, often with
    tubulopapillary, microglandular, or sheet-like architecture, and associated
    with better survival than nonepithelioid disease.
  evidence:
  - reference: PMID:33060816
    reference_title: >-
      Malignant peritoneal mesothelioma: prognostic significance of clinical and
      pathologic parameters and validation of a nuclear-grading system in a
      multi-institutional series of 225 cases.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      absence of necrosis (P = 0.007), and epithelioid histotype (P < 0.0001).
    explanation: >-
      Large multi-institutional clinicopathologic analysis identifies
      epithelioid histotype as a favorable prognostic histologic subtype.
  mappings:
    ncit_mappings:
    - term:
        id: NCIT:C162940
        label: Peritoneal Epithelioid Mesothelioma
      mapping_predicate: skos:exactMatch
      mapping_source: NCIT
      mapping_justification: Exact site-specific NCIT histologic subtype.
- name: Biphasic
  display_name: Biphasic Malignant Peritoneal Mesothelioma
  classification: histological
  description: >-
    Histologic subtype containing both epithelioid and sarcomatoid components.
    Recent profiling studies group biphasic tumors with sarcomatoid tumors as
    nonepithelioid mesothelioma.
  evidence:
  - reference: PMID:35704798
    reference_title: >-
      Molecular Characterization of Mesothelioma: Impact of Histologic Type and
      Site of Origin on Molecular Landscape.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Compared with epithelioid MPM, nonepithelioid (ie, biphasic and
      sarcomatoid) MPM had identical tumor mutational burden (median 1.25
      mut/Mb, P = .63), more commonly expressed PD-L1 (74% v 51%, P = .02), and
      was more likely to harbor MTAP, CDKN2A, and CDKN2B copy loss (P < .05).
    explanation: >-
      Molecular profiling explicitly groups biphasic peritoneal mesothelioma
      within the nonepithelioid class and distinguishes it from epithelioid
      tumors.
  mappings:
    ncit_mappings:
    - term:
        id: NCIT:C168805
        label: Peritoneal Biphasic Mesothelioma
      mapping_predicate: skos:exactMatch
      mapping_source: NCIT
      mapping_justification: Exact site-specific NCIT histologic subtype.
- name: Sarcomatoid
  display_name: Sarcomatoid Malignant Peritoneal Mesothelioma
  classification: histological
  description: >-
    Spindle-cell histologic subtype with aggressive behavior; grouped with
    biphasic tumors as nonepithelioid mesothelioma in modern molecular studies.
  evidence:
  - reference: PMID:35704798
    reference_title: >-
      Molecular Characterization of Mesothelioma: Impact of Histologic Type and
      Site of Origin on Molecular Landscape.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Compared with epithelioid MPM, nonepithelioid (ie, biphasic and
      sarcomatoid) MPM had identical tumor mutational burden (median 1.25
      mut/Mb, P = .63), more commonly expressed PD-L1 (74% v 51%, P = .02), and
      was more likely to harbor MTAP, CDKN2A, and CDKN2B copy loss (P < .05).
    explanation: >-
      Molecular profiling explicitly groups sarcomatoid peritoneal mesothelioma
      within the nonepithelioid class and distinguishes it from epithelioid
      tumors.
  mappings:
    ncit_mappings:
    - term:
        id: NCIT:C168804
        label: Peritoneal Sarcomatoid Mesothelioma
      mapping_predicate: skos:exactMatch
      mapping_source: NCIT
      mapping_justification: Exact site-specific NCIT histologic subtype.
- name: ALK-Rearranged
  display_name: ALK-Rearranged Malignant Peritoneal Mesothelioma
  classification: molecular
  description: >-
    Rare molecular subtype defined by ALK rearrangement. Reported series suggest
    that ALK rearrangements are a site-restricted finding within peritoneal
    mesothelioma rather than pleural mesothelioma.
  genes:
  - preferred_term: ALK
    term:
      id: hgnc:427
      label: ALK
  evidence:
  - reference: PMID:35704798
    reference_title: >-
      Molecular Characterization of Mesothelioma: Impact of Histologic Type and
      Site of Origin on Molecular Landscape.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: ALK rearrangements were only observed in MPeM.
    explanation: >-
      Large-scale profiling identifies ALK rearrangements as a rare but
      site-restricted molecular subtype of peritoneal mesothelioma.
- name: BAP1 Tumor Predisposition Syndrome-Associated
  display_name: BAP1 Tumor Predisposition Syndrome-Associated Malignant Peritoneal Mesothelioma
  classification: predisposition_context
  description: >-
    Predisposition-context subtype occurring in the setting of inherited
    BAP1-related tumor predisposition syndrome. This axis captures host
    susceptibility context rather than a separate disease-level causal program.
  evidence:
  - reference: PMID:30001711
    reference_title: >-
      Detecting germline BAP1 mutations in patients with peritoneal
      mesothelioma: benefits to patient and family members.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Germline mutations in the BRCA-1 associated tumor protein 1 (BAP1)
      increase susceptibility to mesothelioma and other cancers. We describe a
      patient with a family history of peritoneal mesothelioma, who developed
      malignant peritoneal mesothelioma at age 45 in the absence of known
      asbestos exposure.
    explanation: >-
      Case-based clinical evidence supports a germline BAP1 predisposition
      context for a subset of malignant peritoneal mesothelioma cases.
  mappings:
    mondo_mappings:
    - term:
        id: MONDO:0013692
        label: BAP1-related tumor predisposition syndrome
      mapping_predicate: skos:relatedMatch
      mapping_source: MONDO
      mapping_justification: >-
        Grounds the inherited predisposition context without implying a separate
        malignant peritoneal mesothelioma page.
environmental:
- name: Asbestos Exposure
  description: >-
    Asbestos exposure is a recognized but less consistent risk factor for
    peritoneal mesothelioma than for pleural mesothelioma.
  exposure_term:
    preferred_term: exposure to asbestos
    term:
      id: ECTO:9000033
      label: exposure to asbestos
  evidence:
  - reference: PMID:27813512
    reference_title: >-
      Genomic profiling of malignant peritoneal mesothelioma reveals recurrent
      alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Most pleural mesotheliomas arise in patients with a history of asbestos
      exposure, whereas the association of peritoneal mesotheliomas with
      exposure to asbestos and other potential carcinogens is less clear
    explanation: >-
      Supports asbestos exposure as a relevant but less consistently attributable
      risk factor in the peritoneal disease site.
pathophysiology:
- name: BAP1 Tumor Suppressor Inactivation
  description: >-
    BAP1 loss is the dominant recurrent genomic event in peritoneal mesothelioma,
    often occurring through biallelic inactivation and accompanied by loss of
    nuclear BAP1 expression.
  evidence:
  - reference: PMID:27813512
    reference_title: >-
      Genomic profiling of malignant peritoneal mesothelioma reveals recurrent
      alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most frequent genetic alteration was biallelic inactivation of the
      BAP1 gene, which occurred in 9/13 cases, with an additional two cases
      demonstrating monoallelic loss of BAP1.
    explanation: >-
      Targeted sequencing identifies BAP1 loss as the most common recurrent
      driver lesion in malignant peritoneal mesothelioma.
  - reference: PMID:28034829
    reference_title: >-
      BAP1 Is Altered by Copy Number Loss, Mutation, and/or Loss of Protein
      Expression in More Than 70% of Malignant Peritoneal Mesotheliomas.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Overall, 73% of the malignant peritoneal mesotheliomas analyzed carried at
      least one inactivated BAP1 allele, but only 57% had a complete loss of its
      protein nuclear expression.
    explanation: >-
      Independent cohort data confirm that BAP1 inactivation is highly prevalent
      in malignant peritoneal mesothelioma.
  genes:
  - preferred_term: BAP1
    term:
      id: hgnc:950
      label: BAP1
  molecular_functions:
  - preferred_term: deubiquitinase activity
    modifier: DECREASED
    term:
      id: GO:0101005
      label: deubiquitinase activity
  biological_processes:
  - preferred_term: chromatin organization
    modifier: ABNORMAL
    term:
      id: GO:0006325
      label: chromatin organization
  downstream:
  - target: Epigenetic Deregulation
    description: Loss of BAP1 disrupts chromatin-associated tumor suppressor programs.
- name: Epigenetic Deregulation
  description: >-
    Peritoneal mesothelioma recurrently alters epigenetic regulators including
    BAP1, SETD2, and DDX3X, supporting a transcriptionally deregulated disease
    program.
  evidence:
  - reference: PMID:27813512
    reference_title: >-
      Genomic profiling of malignant peritoneal mesothelioma reveals recurrent
      alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Together, these findings demonstrate the importance of epigenetic
      modifiers including BAP1, SETD2, and DDX3X in mesothelial tumorigenesis
      and suggest opportunities for targeted therapies.
    explanation: >-
      Human tumor profiling supports epigenetic dysregulation as a core
      mechanistic layer in malignant peritoneal mesothelioma.
  biological_processes:
  - preferred_term: epigenetic regulation of gene expression
    modifier: ABNORMAL
    term:
      id: GO:0040029
      label: epigenetic regulation of gene expression
  - preferred_term: chromatin organization
    modifier: ABNORMAL
    term:
      id: GO:0006325
      label: chromatin organization
  downstream:
  - target: Mesothelial Cell Proliferation
    description: Epigenetic deregulation supports malignant growth of transformed mesothelial cells.
- name: PI3K-AKT-mTOR Signaling Activation
  description: >-
    Overactive PI3K-AKT-mTOR pathway signaling is a recurrent proliferative
    program in diffuse malignant peritoneal mesothelioma and provides a
    mechanistic rationale for targeted therapy development.
  evidence:
  - reference: PMID:36684194
    reference_title: "Diffuse malignant peritoneal mesothelioma: A review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The overexpression of the phosphatidylinositol 3-kinase (PI3K)/AKT
      serine/threonine kinase 1 (AKT)/mammalian target of rapamycin (mTOR)
      signaling pathway drives the malignant phenotype of DMPM
    explanation: >-
      Review synthesis identifies PI3K-AKT-mTOR pathway activation as a
      recurring proliferative program in diffuse malignant peritoneal
      mesothelioma.
  biological_processes:
  - preferred_term: TOR signaling
    modifier: INCREASED
    term:
      id: GO:0031929
      label: TOR signaling
  downstream:
  - target: Mesothelial Cell Proliferation
    description: mTOR-pathway activation sustains malignant growth and survival.
- name: Mesothelial Cell Proliferation
  description: >-
    Malignant peritoneal mesothelioma expands along the peritoneal surface
    through progressive proliferation of transformed mesothelial cells.
  cell_types:
  - preferred_term: mesothelial cell
    term:
      id: CL:0000077
      label: mesothelial cell
  locations:
  - preferred_term: peritoneum
    term:
      id: UBERON:0002358
      label: peritoneum
  biological_processes:
  - preferred_term: positive regulation of cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
  downstream:
  - target: Locoregional Peritoneal Tumor Expansion
    description: Progressive mesothelial proliferation produces diffuse serosal tumor burden.
- name: Locoregional Peritoneal Tumor Expansion
  description: >-
    Disease morbidity is dominated by progressive locoregional tumor effects
    within the abdomen rather than early distant metastasis.
  locations:
  - preferred_term: abdominal cavity
    term:
      id: UBERON:0003684
      label: abdominal cavity
  evidence:
  - reference: PMID:32206577
    reference_title: "Peritoneal mesothelioma."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Morbidity and mortality of the disease are related to progressive
      locoregional effects within the abdominal cavity, such as distention,
      pain, early satiety, and decreased oral intake that can ultimately lead
      to bowel obstruction and cachexia.
    explanation: >-
      Review synthesis identifies locoregional intraperitoneal tumor expansion
      as the proximate cause of the dominant clinical phenotype set.
  downstream:
  - target: Abdominal Distention
    description: Tumor burden and associated fluid accumulation increase abdominal girth.
  - target: Abdominal Pain
    description: Progressive serosal tumor involvement causes abdominal pain.
  - target: Early Satiety
    description: Intraperitoneal tumor burden reduces gastric accommodation.
  - target: Intestinal Obstruction
    description: Progressive locoregional spread compromises bowel transit.
histopathology:
- name: Epithelioid Histotype
  subtype: Epithelioid
  finding_term:
    preferred_term: peritoneal epithelioid mesothelioma
    term:
      id: NCIT:C162940
      label: Peritoneal Epithelioid Mesothelioma
  diagnostic: true
  description: >-
    Epithelioid histology is the prognostically favored peritoneal mesothelioma
    subtype.
  evidence:
  - reference: PMID:33060816
    reference_title: >-
      Malignant peritoneal mesothelioma: prognostic significance of clinical and
      pathologic parameters and validation of a nuclear-grading system in a
      multi-institutional series of 225 cases.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      absence of necrosis (P = 0.007), and epithelioid histotype (P < 0.0001).
    explanation: >-
      Multi-institutional outcome analysis identifies epithelioid histotype as a
      favorable histopathologic subtype.
- name: Composite Nuclear Grade
  subtype: Epithelioid
  finding_term:
    preferred_term: nuclear grade
    term:
      id: NCIT:C18513
      label: Nuclear Grade
  description: >-
    Composite nuclear grade is a validated prognostic histopathologic feature in
    epithelioid malignant peritoneal mesothelioma.
  evidence:
  - reference: PMID:33060816
    reference_title: >-
      Malignant peritoneal mesothelioma: prognostic significance of clinical and
      pathologic parameters and validation of a nuclear-grading system in a
      multi-institutional series of 225 cases.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      On multivariate analyses, the low composite nuclear grade was
      independently associated with longer overall and disease-free survival
      (P < 0.0001).
    explanation: >-
      Validates nuclear grade as a prognostically relevant histopathologic
      variable in epithelioid peritoneal mesothelioma.
- name: Tumor Necrosis
  finding_term:
    preferred_term: necrosis
    term:
      id: NCIT:C36184
      label: Necrosis
  description: >-
    Necrosis is an adverse histopathologic feature; its absence correlates with
    better survival.
  evidence:
  - reference: PMID:33060816
    reference_title: >-
      Malignant peritoneal mesothelioma: prognostic significance of clinical and
      pathologic parameters and validation of a nuclear-grading system in a
      multi-institutional series of 225 cases.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      absence of necrosis (P = 0.007), and epithelioid histotype (P < 0.0001).
    explanation: >-
      The inverse association of necrosis absence with survival supports
      necrosis as an adverse histopathologic feature.
phenotypes:
- category: Abdominal
  name: Ascites
  description: Peritoneal tumor burden commonly presents with malignant ascites.
  phenotype_term:
    preferred_term: Ascites
    term:
      id: HP:0001541
      label: Ascites
  evidence:
  - reference: PMID:22104079
    reference_title: "Diffuse malignant peritoneal mesothelioma--an update on treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Presenting symptoms in these patients include: ascites, abdominal pain,
      asthenia, weight loss, anorexia, abdominal mass, fever, diarrhea and
      vomiting.
    explanation: >-
      Review-level clinical synthesis lists ascites among common presenting
      manifestations of diffuse malignant peritoneal mesothelioma.
- category: Abdominal
  name: Abdominal Pain
  description: Abdominal pain is a common presenting symptom of peritoneal disease.
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
  evidence:
  - reference: PMID:22104079
    reference_title: "Diffuse malignant peritoneal mesothelioma--an update on treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Presenting symptoms in these patients include: ascites, abdominal pain,
      asthenia, weight loss, anorexia, abdominal mass, fever, diarrhea and
      vomiting.
    explanation: >-
      Review-level clinical synthesis lists abdominal pain among common
      presenting manifestations of diffuse malignant peritoneal mesothelioma.
- category: Abdominal
  name: Abdominal Distention
  description: Progressive intraperitoneal tumor growth commonly causes abdominal distention.
  phenotype_term:
    preferred_term: Abdominal distention
    term:
      id: HP:0003270
      label: Abdominal distention
  evidence:
  - reference: PMID:36059360
    reference_title: "Malignant Peritoneal Mesothelioma: A Challenging Case for Palliative Care."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Malignant peritoneal mesothelioma (MPM) is a rare and very aggressive
      malignancy of serosal membranes, which typically presents with abdominal
      pain, distension, and ascites.
    explanation: >-
      Case-based clinical summary explicitly lists abdominal distension as a
      typical presenting manifestation of malignant peritoneal mesothelioma.
- category: Gastrointestinal
  name: Early Satiety
  description: Early satiety reflects locoregional abdominal tumor effects.
  phenotype_term:
    preferred_term: Early satiety
    term:
      id: HP:0033842
      label: Early satiety
  evidence:
  - reference: PMID:32206577
    reference_title: "Peritoneal mesothelioma."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Morbidity and mortality of the disease are related to progressive
      locoregional effects within the abdominal cavity, such as distention,
      pain, early satiety, and decreased oral intake that can ultimately lead
      to bowel obstruction and cachexia.
    explanation: >-
      Review-level clinical synthesis identifies early satiety as part of the
      dominant locoregional abdominal phenotype cluster.
- category: Gastrointestinal
  name: Intestinal Obstruction
  description: Advanced locoregional disease can culminate in bowel obstruction.
  phenotype_term:
    preferred_term: Intestinal obstruction
    term:
      id: HP:0005214
      label: Intestinal obstruction
  evidence:
  - reference: PMID:32206577
    reference_title: "Peritoneal mesothelioma."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Morbidity and mortality of the disease are related to progressive
      locoregional effects within the abdominal cavity, such as distention,
      pain, early satiety, and decreased oral intake that can ultimately lead
      to bowel obstruction and cachexia.
    explanation: >-
      Review-level clinical synthesis identifies bowel obstruction as a late
      consequence of locoregional peritoneal tumor progression.
- category: Constitutional
  name: Weight Loss
  description: Weight loss is a common constitutional manifestation of advanced disease.
  phenotype_term:
    preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
  evidence:
  - reference: PMID:22104079
    reference_title: "Diffuse malignant peritoneal mesothelioma--an update on treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Presenting symptoms in these patients include: ascites, abdominal pain,
      asthenia, weight loss, anorexia, abdominal mass, fever, diarrhea and
      vomiting.
    explanation: >-
      Review-level clinical synthesis lists weight loss among common presenting
      manifestations of diffuse malignant peritoneal mesothelioma.
biochemical:
- name: Loss of Nuclear BAP1 Staining
  biomarker_term:
    preferred_term: BAP1 negative
    term:
      id: NCIT:C179308
      label: BAP1 Negative
  notes: >-
    Loss of nuclear BAP1 staining is a useful adjunctive diagnostic marker for
    malignant peritoneal mesothelioma and reflects recurrent BAP1 pathway
    inactivation.
  evidence:
  - reference: PMID:27813512
    reference_title: >-
      Genomic profiling of malignant peritoneal mesothelioma reveals recurrent
      alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All 11 of these cases demonstrated loss of BAP1 nuclear staining by
      immunohistochemistry, whereas two tumors without BAP1 alteration and all
      42 cases of histologic mimics in peritoneum
    explanation: >-
      Human tumor profiling supports BAP1 loss of nuclear expression as a
      diagnostically useful biomarker of malignant peritoneal mesothelioma.
  - reference: PMID:36684194
    reference_title: "Diffuse malignant peritoneal mesothelioma: A review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      with the advancements in the immunohistochemical analysis of
      BRCA1-Associated Protein 1 (BAP1) the lack of BAP1 expression shows the
      diagnosis of malignancy.
    explanation: >-
      Review-level synthesis supports BAP1 loss as a marker that favors
      malignant over benign mesothelial proliferations.
- name: WT1 Positive Immunostaining
  biomarker_term:
    preferred_term: WT1 positive
    term:
      id: NCIT:C129453
      label: WT1 Positive
  notes: >-
    WT1 is part of the core immunohistochemical panel used to support the
    diagnosis of peritoneal mesothelioma.
  evidence:
  - reference: PMID:36684194
    reference_title: "Diffuse malignant peritoneal mesothelioma: A review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      In addition, the most sensitive immunohistochemical markers of DMPM
      include WT 1, D2-40, and calmodulin.
    explanation: >-
      Review synthesis identifies WT1 among the most sensitive diagnostic
      immunohistochemical markers used in diffuse malignant peritoneal
      mesothelioma.
genetic:
- name: BAP1
  association: Recurrent Loss-of-Function Alteration
  gene_term:
    preferred_term: BAP1
    term:
      id: hgnc:950
      label: BAP1
  notes: >-
    BAP1 is the dominant recurrently altered tumor suppressor in peritoneal
    mesothelioma and may be inactivated by mutation, copy-number loss, or both.
  evidence:
  - reference: PMID:28034829
    reference_title: >-
      BAP1 Is Altered by Copy Number Loss, Mutation, and/or Loss of Protein
      Expression in More Than 70% of Malignant Peritoneal Mesotheliomas.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Overall, 73% of the malignant peritoneal mesotheliomas analyzed carried at
      least one inactivated BAP1 allele
    explanation: >-
      Large peritoneal mesothelioma series confirms that BAP1 alteration is a
      dominant recurrent genetic event.
- name: SETD2
  association: Recurrent Epigenetic Regulator Alteration
  gene_term:
    preferred_term: SETD2
    term:
      id: hgnc:18420
      label: SETD2
  notes: >-
    SETD2 alteration identifies an epigenetic-regulator subset within
    peritoneal mesothelioma.
  evidence:
  - reference: PMID:27813512
    reference_title: >-
      Genomic profiling of malignant peritoneal mesothelioma reveals recurrent
      alterations in epigenetic regulatory genes BAP1, SETD2, and DDX3X.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Additional recurrently mutated genes in this cohort of malignant
      peritoneal mesotheliomas included NF2 (3/13), SETD2 (2/13), and DDX3X
      (2/13).
    explanation: >-
      Human tumor profiling identifies SETD2 as a recurrently mutated epigenetic
      regulator in malignant peritoneal mesothelioma.
- name: PBRM1
  association: Site-Enriched Alteration
  gene_term:
    preferred_term: PBRM1
    term:
      id: hgnc:30064
      label: PBRM1
  notes: >-
    PBRM1 alterations are enriched in peritoneal relative to pleural
    mesothelioma.
  evidence:
  - reference: PMID:35704798
    reference_title: >-
      Molecular Characterization of Mesothelioma: Impact of Histologic Type and
      Site of Origin on Molecular Landscape.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The molecular profile of MPeM was similar to MPM, with the distinction
      that PBRM1 alterations occurred at higher frequency (16% v 7%, P < .01).
    explanation: >-
      Large-scale molecular profiling identifies PBRM1 alteration as a
      site-enriched genomic feature of peritoneal mesothelioma.
- name: ALK
  subtype: ALK-Rearranged
  association: Rare Recurrent Rearrangement
  gene_term:
    preferred_term: ALK
    term:
      id: hgnc:427
      label: ALK
  notes: >-
    ALK rearrangements define a rare molecular subtype observed in peritoneal
    but not pleural mesothelioma in large profiling cohorts.
  evidence:
  - reference: PMID:35704798
    reference_title: >-
      Molecular Characterization of Mesothelioma: Impact of Histologic Type and
      Site of Origin on Molecular Landscape.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: ALK rearrangements were only observed in MPeM.
    explanation: >-
      Large-scale profiling identifies ALK rearrangement as a site-restricted
      molecular feature of malignant peritoneal mesothelioma.
- name: CDKN2A
  association: Less-Prevalent Copy-Number Loss than Pleural Disease
  gene_term:
    preferred_term: CDKN2A
    term:
      id: hgnc:1787
      label: CDKN2A
  notes: >-
    CDKN2A loss occurs in peritoneal mesothelioma but is less prevalent than in
    pleural mesothelioma and is enriched in nonepithelioid disease.
  evidence:
  - reference: PMID:26853494
    reference_title: >-
      Genome-wide analysis of abdominal and pleural malignant mesothelioma with
      DNA arrays reveals both common and distinct regions of copy number
      alteration.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Losses in 3p (BAP1 gene), 9p (CDKN2A) and 22q (NF2) were seen in tumors
      from both tumor sites, although CDKN2A and NF2 losses were seen at a
      higher rate in pleural disease (p<0.01).
    explanation: >-
      Comparative genomic profiling shows that CDKN2A loss occurs in peritoneal
      mesothelioma but is relatively less frequent than in pleural disease.
treatments:
- name: Cytoreductive Surgery
  description: >-
    Upfront maximal cytoreduction is favored when complete or near-complete
    resection is achievable in carefully selected patients.
  treatment_term:
    preferred_term: cytoreductive surgery
    term:
      id: NCIT:C132068
      label: Cytoreductive Surgery
  evidence:
  - reference: PMID:27472649
    reference_title: >-
      Diffuse malignant peritoneal mesothelioma: Evaluation of systemic
      chemotherapy with comprehensive treatment through the RENAPE Database:
      Multi-Institutional Retrospective Study.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Upfront CRS and HIPEC should be considered when achievable, waiting for
      stronger level of scientific evidence.
    explanation: >-
      Multi-institutional retrospective data support upfront cytoreductive
      surgery as part of curative-intent management when feasible.
- name: Hyperthermic Intraperitoneal Chemotherapy
  description: >-
    HIPEC is paired with cytoreductive surgery in carefully selected resectable
    diffuse peritoneal mesothelioma and is part of the accepted locoregional
    standard-of-care strategy.
  treatment_term:
    preferred_term: hyperthermic intraperitoneal chemotherapy
    term:
      id: NCIT:C91835
      label: Hyperthermic Intraperitoneal Chemotherapy
  evidence:
  - reference: PMID:39609952
    reference_title: >-
      Multisocietal Consensus on the Use of Cytoreductive Surgery and HIPEC for
      the Treatment of Diffuse Malignant Peritoneal Mesothelioma: A GRADE
      Approach for Evidence Evaluation and Recommendation.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The panel unanimously recommended CRS-HIPEC for a carefully selected
      subset of DMPM patients, emphasizing that this approach offers the best
      potential for improved survival compared to systemic chemotherapy alone.
    explanation: >-
      Multisocietal consensus recommends HIPEC as part of the preferred
      locoregional treatment strategy for selected patients with diffuse
      malignant peritoneal mesothelioma.
- name: Pemetrexed Plus Cisplatin
  description: >-
    Platinum-antifolate chemotherapy is an active systemic option for
    unresectable disease and for patients who are not candidates for curative
    locoregional treatment.
  treatment_term:
    preferred_term: chemotherapy
    term:
      id: MAXO:0000647
      label: chemotherapy
    therapeutic_agent:
    - preferred_term: pemetrexed
      term:
        id: CHEBI:63616
        label: pemetrexed
    - preferred_term: cisplatin
      term:
        id: CHEBI:27899
        label: cisplatin
  evidence:
  - reference: PMID:28594258
    reference_title: >-
      First-line chemotherapy with pemetrexed plus cisplatin for malignant
      peritoneal mesothelioma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Overall response rate and disease control rate were 45.8% and 91.7%,
      respectively. Median progression-free survival and median overall survival
      were 11.0 months and 15.8 months, respectively.
    explanation: >-
      Retrospective first-line series demonstrates meaningful disease control
      with pemetrexed-cisplatin in malignant peritoneal mesothelioma.
- name: Atezolizumab Plus Bevacizumab
  description: >-
    Combined PD-L1 and VEGF blockade has shown activity in advanced unresectable
    malignant peritoneal mesothelioma after prior platinum-pemetrexed
    chemotherapy.
  treatment_term:
    preferred_term: immunotherapy
    term:
      id: NCIT:C15262
      label: Immunotherapy
    therapeutic_agent:
    - preferred_term: atezolizumab
      term:
        id: NCIT:C106250
        label: Atezolizumab
    - preferred_term: bevacizumab
      term:
        id: NCIT:C2039
        label: Bevacizumab
  evidence:
  - reference: PMID:34261675
    reference_title: >-
      Efficacy, Safety, and Biomarker Analysis of Combined PD-L1 (Atezolizumab)
      and VEGF (Bevacizumab) Blockade in Advanced Malignant Peritoneal
      Mesothelioma.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      AtezoBev showed promising and durable efficacy in patients with advanced
      MPeM with an acceptable safety profile.
    explanation: >-
      Phase II trial data support atezolizumab-bevacizumab as an active systemic
      option in previously treated advanced malignant peritoneal mesothelioma.
📚

References & Deep Research

Deep Research

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Malignant Peritoneal Mesothelioma Research Notes
gpt-5.4 13 citations 2026-04-13T05:58:00Z

Malignant Peritoneal Mesothelioma Research Notes

Scope

This research note supports a disease-level dismech curation for malignant peritoneal mesothelioma (MPeM), anchored to MONDO:0005512. The entry is modeled as a single mechanism-graph unit, with subtype axes used for histology, molecular context, and inherited predisposition context rather than as separate dismech pages.

Disease Identity

MPeM is a rare aggressive mesothelial malignancy arising from the peritoneal lining. Compared with pleural mesothelioma, asbestos attribution is less consistent, while the disease remains strongly defined by locoregional intraperitoneal progression and a BAP1-dominant genomic landscape (PMID:27813512, PMID:32206577, PMID:35704798, PMID:36138075).

NCIT provides a useful exact disease mapping at the cancer-modeling level:

  • NCIT:C9350 Peritoneal Malignant Mesothelioma

Core Mechanistic Program

1. BAP1 tumor suppressor loss is the dominant recurrent driver

Multiple genomic series converge on BAP1 as the most frequent recurrent alteration in MPeM. In a targeted sequencing cohort, "The most frequent genetic alteration was biallelic inactivation of the BAP1 gene" (PMID:27813512). In an independent series, "Overall, 73% of the malignant peritoneal mesotheliomas analyzed carried at least one inactivated BAP1 allele" (PMID:28034829). This supports a core atomic mechanism node centered on BAP1 tumor suppressor inactivation rather than a generic omnibus "genomic instability" node.

2. Chromatin and epigenetic control are recurrently disrupted

MPeM is enriched for alterations affecting chromatin-associated regulators including BAP1, SETD2, DDX3X, and in larger profiling studies PBRM1 (PMID:27813512, PMID:35704798). The most useful disease-graph abstraction is an atomic chromatin/epigenetic dysregulation node downstream of BAP1 loss rather than a bundled multi-pathway node.

3. PI3K-AKT-mTOR signaling contributes to the malignant proliferative state

Review synthesis specific to diffuse malignant peritoneal mesothelioma states that "The overexpression of the phosphatidylinositol 3-kinase (PI3K)/AKT ... /mTOR signaling pathway drives the malignant phenotype of DMPM" (PMID:36684194). This supports a separate proliferative signaling node rather than collapsing signaling and proliferation into one step.

4. Clinical morbidity is driven by locoregional peritoneal expansion

MPeM morbidity is dominated by local abdominal progression. A concise disease-defining quote is: "Morbidity and mortality of the disease are related to progressive locoregional effects within the abdominal cavity" (PMID:32206577). This justifies a downstream node for locoregional peritoneal tumor expansion that explains major abdominal phenotypes.

Subtype Axes Used for Modeling

Histologic axis

Histology is the most important subtype axis and should remain flat rather than generating separate disease pages.

  • NCIT:C162940 Peritoneal Epithelioid Mesothelioma
  • NCIT:C168805 Peritoneal Biphasic Mesothelioma
  • NCIT:C168804 Peritoneal Sarcomatoid Mesothelioma

Large profiling data distinguish epithelioid from nonepithelioid tumors, with biphasic and sarcomatoid grouped together molecularly and clinically (PMID:35704798). Outcome data also support epithelioid histology and absence of necrosis as favorable features (PMID:33060816).

Molecular axis

ALK rearrangement is a rare but important molecular subtype axis. The key quote is: "ALK rearrangements were only observed in MPeM" (PMID:35704798). This is better modeled as a molecular subtype facet than as a separate disease page.

Predisposition-context axis

Inherited BAP1 predisposition is a host-context subtype axis rather than a distinct peritoneal mesothelioma disease entity. A relevant grounding term is:

  • MONDO:0013692 BAP1-related tumor predisposition syndrome

Case-based evidence directly links this syndrome to peritoneal mesothelioma susceptibility (PMID:30001711).

Histopathology and Biomarkers

Useful pathology-layer features for disease-level curation include:

  • Epithelioid histotype as the favorable histologic pattern (PMID:33060816)
  • Composite nuclear grade as a validated prognostic feature in epithelioid disease (PMID:33060816)
  • Tumor necrosis as an adverse feature (PMID:33060816)
  • Loss of nuclear BAP1 staining as a malignancy-supporting diagnostic biomarker (PMID:27813512, PMID:36684194)
  • WT1 positivity as part of the sensitive immunohistochemical panel for peritoneal mesothelioma (PMID:36684194)

Phenotype Layer

The dominant phenotype set is abdominal and locoregional rather than systemic-metastatic:

  • Ascites (PMID:22104079, PMID:36059360)
  • Abdominal pain (PMID:22104079, PMID:36059360)
  • Abdominal distention (PMID:32206577, PMID:36059360)
  • Early satiety (PMID:32206577)
  • Intestinal obstruction (PMID:32206577)
  • Weight loss (PMID:22104079)

Treatment Implications

The clearest treatment program for resectable disease is cytoreductive surgery plus HIPEC. Review and consensus support are consistent:

  • "The standard of care for patients with resectable disease remains cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC)" (PMID:32206577)
  • "The panel unanimously recommended CRS-HIPEC" for a carefully selected subset of DMPM patients (PMID:39609952)

For unresectable or previously treated disease, the structured entry should preserve systemic options with exact supporting studies:

  • Pemetrexed plus cisplatin showed meaningful disease control in first-line treatment (PMID:28594258)
  • Atezolizumab plus bevacizumab demonstrated activity in advanced previously treated MPeM (PMID:34261675)

Curation Takeaways

  • Keep the page at the disease level for MONDO:0005512.
  • Use NCIT mappings routinely for cancer-specific disease and histologic subtype grounding.
  • Treat histology, molecular status, and predisposition context as flat subtype axes.
  • Keep pathophysiology nodes atomic: BAP1 loss, chromatin dysregulation, PI3K-AKT-mTOR activation, transformed mesothelial proliferation, and locoregional abdominal expansion.
  • Avoid creating separate dismech pages for epithelioid, biphasic, sarcomatoid, ALK-rearranged, or BAP1-predisposition-context cases unless future evidence shows a genuinely distinct causal program.