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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Pathology

Decoding Your Pathology Report

At a Glance

A pleural mesothelioma pathology report uses a 2+2 panel of cell markers and checks for the loss of BAP1 and MTAP proteins to definitively diagnose cancer. It also identifies your tumor's histologic subtype—epithelioid, sarcomatoid, or biphasic—which directly guides treatment.

Your pathology report is the most important document in your medical file. It is the “gold standard” evidence that confirms whether a growth is malignant pleural mesothelioma (cancer) or a benign, reactive mesothelial proliferation (scarring or inflammation) [1][2].

The “2+2” Panel: Confirming the Identity

Because mesothelioma can look like other cancers—especially lung adenocarcinoma—under a microscope, pathologists use a technique called Immunohistochemistry (IHC) [3]. They apply specific antibodies to your tissue sample to see which proteins are present.

To be confident in a diagnosis, experts recommend a 2+2 panel: the tumor must be “positive” for at least two mesothelial markers and “negative” for at least two carcinoma markers [4].

Panel Category Common Markers Used Expected Result for Mesothelioma
Mesothelial Markers Calretinin, WT1, CK5/6, D2-40 Positive [5][6]
Carcinoma Markers MOC-31, TTF-1, Ber-EP4, CEA Negative [5][7]

If your report shows the tumor is positive for TTF-1 or claudin-4, it is much more likely to be lung cancer rather than mesothelioma [8][7].

Critical Diagnostic Markers: BAP1 and MTAP

Traditional markers show what the cell is (a mesothelial cell), but they don’t always show if it is cancerous. Two specific markers have revolutionized this process because their loss is nearly 100% specific for malignancy [9][10].

  • BAP1 Loss: BAP1 is a normal protein that protects your DNA. In malignant mesothelioma, this protein is often “lost” [11]. If your report says “BAP1: Nuclear loss” or “BAP1: Negative,” it means the protein is missing from the nucleus (the center) of the cell [12]. (Note: “Nuclear” here has nothing to do with radiation; it simply refers to the cell’s nucleus.) This is a very strong indicator that the growth is cancerous [13].
  • MTAP Loss: The loss of MTAP is often used as a sign that a specific gene (CDKN2A) has been deleted [14]. This deletion is a major driver of mesothelioma growth. Like BAP1, if MTAP is missing, it confirms the diagnosis of cancer [10][1].

Pathology Report Completeness Checklist

A complete report should provide your care team with everything they need to build a treatment plan. Ensure your report includes these elements [15]:

  1. Histologic Subtype: Is it Epithelioid (most common, generally better prognosis), Sarcomatoid (more aggressive), or Biphasic (a mix of both)? [16][17]
  2. Invasion: Does the report explicitly state that the cells have invaded the pleural fat or lung tissue? Invasion is the defining proof of malignancy [1].
  3. Marker List: A detailed list of all IHC stains performed (the 2+2 markers) [4].
  4. BAP1/MTAP Status: Results for these definitive cancer markers [11][10].

Common questions in this guide

What is a 2+2 panel in a mesothelioma diagnosis?
A 2+2 panel is a tissue test that uses specific antibodies to identify proteins in your biopsy sample. To confirm mesothelioma, pathologists look for at least two positive mesothelial markers and at least two negative carcinoma markers.
What does BAP1 or MTAP loss mean on my pathology report?
When a pathology report notes the loss of BAP1 or MTAP proteins in the cells, it is a very strong indicator that the growth is cancerous. This loss helps doctors distinguish malignant pleural mesothelioma from harmless inflammation or scarring.
What are the main subtypes of pleural mesothelioma?
The three main histologic subtypes of mesothelioma are epithelioid, sarcomatoid, and biphasic. Epithelioid is the most common and generally has a better prognosis, sarcomatoid is more aggressive, and biphasic is a combination of both types.
Why does my report need to mention tissue invasion?
Tissue invasion is the defining proof of cancer. To confirm a diagnosis of malignant pleural mesothelioma rather than benign scarring, the pathology report needs to explicitly state that abnormal cells have grown into the pleural fat or lung tissue.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.My report shows these markers were used—does this meet the '2+2' guideline for confirming mesothelioma?
  2. 2.What is the 'histologic subtype' of my tumor (epithelioid, sarcomatoid, or biphasic), and how does that influence my treatment plan?
  3. 3.If BAP1 and MTAP markers were not tested, can we add them to help confirm this is a malignancy rather than reactive inflammation?
  4. 4.Does the report indicate any invasion into nearby tissues like the fat, ribs, or chest wall?
  5. 5.Was this report reviewed by a pathologist who specializes specifically in thoracic or pleural cancers?

Questions For You

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References

References (17)
  1. 1

    Diagnostic Challenges in the Pathological Approach to Pleural Mesothelioma.

    Lucà S, Pignata G, Cioce A, et al.

    Cancers 2025; (17(3)) doi:10.3390/cancers17030481.

    PMID: 39941848
  2. 2

    Diagnostic performance of immunohistochemistry markers for malignant pleural mesothelioma diagnosis and subtypes. A systematic review and meta-analysis.

    Parra-Medina R, Castañeda-González JP, Chaves-Cabezas V, et al.

    Pathology, research and practice 2024; (257()):155276 doi:10.1016/j.prp.2024.155276.

    PMID: 38603842
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    Diagnosis and management of pleural mesothelioma: three unique cases and review of the literature.

    Al Achkar Z, Gaspard D, Iskandar M

    BMC pulmonary medicine 2026; (26(1)).

    PMID: 42026555
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    Differential Diagnosis of Epithelioid Malignant Mesothelioma With Lung and Breast Pleural Metastasis: A Systematic Review Compared With a Standardized Panel of Antibodies-A New Proposal That May Influence Pathologic Practice.

    Le Stang N, Burke L, Blaizot G, et al.

    Archives of pathology & laboratory medicine 2020; (144(4)):446-456 doi:10.5858/arpa.2018-0457-OA.

    PMID: 31389715
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    Application of immunohistochemistry in diagnosis and management of malignant mesothelioma.

    Chapel DB, Schulte JJ, Husain AN, Krausz T

    Translational lung cancer research 2020; (9(Suppl 1)):S3-S27 doi:10.21037/tlcr.2019.11.29.

    PMID: 32206567
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    Malignant Mesothelioma Diagnosis.

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    Archives of pathology & laboratory medicine 2015; (139(8)):978-80 doi:10.5858/arpa.2013-0381-RA.

    PMID: 26230591
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    Clinical utility and prognostic value of GATA3 in epithelioid malignant mesothelioma: a practical and cost-effective approach for resource-limited settings.

    Thabit DM, Thabet DM

    Journal of clinical pathology 2026; (79(7)):475-485 doi:10.1136/jcp-2026-210673.

    PMID: 42135065
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    New developments in mesothelial pathology.

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    Histopathology 2024; (84(1)):136-152 doi:10.1111/his.15007.

    PMID: 37694811
  9. 9

    BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations.

    Cigognetti M, Lonardi S, Fisogni S, et al.

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2015; (28(8)):1043-57 doi:10.1038/modpathol.2015.65.

    PMID: 26022455
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    Utility of Methylthioadenosine Phosphorylase Compared With BAP1 Immunohistochemistry, and CDKN2A and NF2 Fluorescence In Situ Hybridization in Separating Reactive Mesothelial Proliferations From Epithelioid Malignant Mesotheliomas.

    Berg KB, Dacic S, Miller C, et al.

    Archives of pathology & laboratory medicine 2018; (142(12)):1549-1553 doi:10.5858/arpa.2018-0273-OA.

    PMID: 30059257
  11. 11

    Mediastinal undifferentiated pleomorphic sarcoma with pleural effusion cytopathologically misdiagnosed as epithelial malignant pleural mesothelioma: An autopsy case report.

    Matsumoto K, Nakamura Y, Inagaki Y, et al.

    Thoracic cancer 2021; (12(7)):1137-1140 doi:10.1111/1759-7714.13898.

    PMID: 33605078
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    Evidence-based diagnostic performance of novel biomarkers for the diagnosis of malignant mesothelioma in effusion cytology.

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    Cancer cytopathology 2022; (130(2)):96-109 doi:10.1002/cncy.22509.

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    A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma.

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    Cancer cytopathology 2018; (126(1)):54-63 doi:10.1002/cncy.21928.

    PMID: 29053210
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    Loss of Methylthioadenosine Phosphorylase by Immunohistochemistry Is Common in Pulmonary Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma.

    Terra S, Roden AC, Yi ES, et al.

    American journal of clinical pathology 2022; (157(1)):33-39 doi:10.1093/ajcp/aqab091.

    PMID: 34463336
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    Treatment of Pleural Mesothelioma: ASCO Guideline Update.

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    Prognostic factors and the prognostic role of inflammation indices in malignant pleural mesothelioma.

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    Update on Diagnosing and Reporting Malignant Pleural Mesothelioma.

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This page explains pleural mesothelioma pathology terminology for educational purposes only. Always discuss your specific pathology report and diagnosis with your pathologist and oncologist.

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