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Malignant Peritoneal Mesothelioma

Malignant Peritoneal Mesothelioma Research Notes

2026-04-13
Codex MONDO:0005512 Model: gpt-5.4 13 citations

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:

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.