How Mesothelioma Is Diagnosed

Mesothelioma Diagnosis at a Glance

Why Mesothelioma Can Be Difficult to Diagnose

Mesothelioma is rare, and its symptoms and imaging findings often mimic more common conditions. In the chest, pleural thickening and pleural effusion on imaging, as well as symptoms such as pain and breathlessness, have many possible causes. Microscopically, mesothelioma can resemble metastatic carcinoma or a reactive mesothelial proliferation. Therefore, diagnosis typically requires multiple sources of evidence.

If symptoms are the starting point, see Mesothelioma Symptoms. For the main risk-factor discussion, see Mesothelioma Causes.

Medical History and Physical Examination

Clinicians will ask about symptom onset and progression, asbestos exposure, and occupational history. They also review prior cancer diagnoses, prior radiation therapy, family history, and other medical conditions. Physical examination may reveal reduced breath sounds, signs related to fluid accumulation, or abdominal distension.

Imaging Tests Used in Diagnosis

Imaging identifies abnormalities, assesses their distribution, and guides further testing. While imaging may strongly suggest mesothelioma, pathologic confirmation is generally required.

For more detail about each modality, see Imaging Tests.

Chest X-ray

A chest X-ray is often an initial test for chest symptoms. It may reveal pleural effusion, thickening, or other abnormalities, but these findings are nonspecific and cannot confirm mesothelioma.

CT Scan

Computed tomography (CT) offers detailed cross-sectional images. In pleural disease, CT can reveal pleural thickening, masses, fluid, chest wall or diaphragmatic involvement, lymph-node abnormalities, and subdiaphragmatic disease. A CT scan of the chest and upper abdomen with IV contrast is recommended for initial staging of pleural mesothelioma.

PET/CT

FDG PET/CT assesses metabolically active disease and can identify nodal or distant spread. It may also help select biopsy targets. However, increased FDG uptake is not specific to mesothelioma, because inflammation and other cancers can also be PET-avid. ASCO recommends FDG PET/CT for initial staging of pleural mesothelioma; it may be omitted in patients who are not being considered for definitive surgical resection.

MRI and Ultrasound

MRI provides detailed information about local invasion, including the diaphragm, chest wall, or mediastinal structures, and assists in planning certain procedures. Ultrasound helps assess pleural or abdominal fluid and guides procedures such as thoracentesis or paracentesis. Neither test alone can confirm mesothelioma.

Fluid Sampling and Cytology

When fluid accumulates around the lung or abdomen, clinicians may remove it for symptom relief and laboratory analysis. Fluid is examined for malignant cells, and cytology can aid diagnosis. However, sensitivity varies based on tumor type, site, sample quality, and available tests.

Pleural Fluid and Thoracentesis

For suspected pleural mesothelioma with a symptomatic pleural effusion, ASCO recommends initial thoracentesis with cytologic examination. Cytology can establish the diagnosis in selected cases when the morphologic findings and ancillary studies are sufficient; however, a negative or nondiagnostic result does not rule out mesothelioma.

Peritoneal and Other Fluid Samples

Paracentesis provides ascitic fluid for cytologic evaluation when peritoneal disease is suspected. Pericardial fluid may be sampled in patients with pericardial effusion. Diagnostic performance of fluid cytology varies by site, so pleural data should not be applied to peritoneal or pericardial disease.

Biopsy and Tissue Diagnosis

A biopsy removes tissue for pathologic evaluation of tumor architecture and cells. Adequate tissue is important for confirming mesothelioma, determining histologic subtype, and performing ancillary tests. The optimal biopsy method depends on lesion location, the presence of an effusion, the patient’s overall health, and the treatment plan.

For procedural details, see Tests and Biopsy.

Thoracoscopic Biopsy

For pleural mesothelioma, thoracoscopy enables direct inspection of the pleural space and collection of multiple tissue samples. ASCO recommends thoracoscopic biopsy when antineoplastic treatment is planned, as it provides histologic confirmation, improves subtype assessment, and supplies material for further studies. Thoracoscopy is not suitable for all patients; decisions are individualized.

Core Needle Biopsy vs. Fine-Needle Aspiration

Image-guided core needle biopsy removes a small tissue cylinder and is used when a lesion is accessible and safe to sample, especially if thoracoscopy or open biopsy is unsuitable. Fine-needle aspiration generally retrieves a smaller sample, often composed primarily of cells rather than a tissue core. While cytology and small samples can be useful, they may not provide enough material to assess tumor architecture or heterogeneity. ‘Needle biopsy’ and ‘fine-needle aspiration’ are not interchangeable.

Open or Surgical Biopsy

Open surgical biopsy is not routinely used as a first test. It is considered when less invasive methods cannot provide adequate tissue or are not feasible.

Diagnosing Peritoneal Mesothelioma

The diagnostic approach for peritoneal mesothelioma differs from the pleural pathway. CT or other abdominal imaging may reveal ascites, peritoneal thickening, nodules, or omental abnormalities. Fluid cytology may be used when ascites is present, but tissue sampling is often necessary for a definitive diagnosis. Image-guided core biopsy or laparoscopy may be selected based on disease distribution and clinical context.

See the dedicated Peritoneal Mesothelioma guide for site-specific information.

Diagnosing Pericardial and Tunica Vaginalis Mesothelioma

Pericardial Mesothelioma

Primary pericardial mesothelioma is extremely rare, and no standardized diagnostic algorithm exists. Echocardiography, CT, or MRI may detect a pericardial effusion, pericardial thickening, or a mass. Pericardial fluid can be analyzed, but nondiagnostic cytology does not exclude the disease. When clinically feasible, tissue sampling and pathologic examination may be required to establish the diagnosis.

See Pericardial Mesothelioma.

Mesothelioma of the Tunica Vaginalis

Mesothelioma of the tunica vaginalis is also rare. It may present as a hydrocele or scrotal/paratesticular mass. Ultrasound can identify an abnormality, but the diagnosis is often established by pathologic examination of tissue obtained during surgery or another procedure. Because the published evidence is limited, no universal diagnostic pathway can be established.

For anatomical classification, see Types of Mesothelioma.

How Pathologists Diagnose Mesothelioma

Pathology involves more than identifying a single ‘mesothelioma marker.’ Pathologists assess cell shape, growth patterns, the tumor’s relationship to surrounding tissue, immunohistochemical stains, and, when needed, ancillary tests. These findings are integrated with clinical and radiologic information.

Histologic Subtypes

Mesothelioma is classified as epithelioid, sarcomatoid, or biphasic. Histologic subtype can influence treatment discussions and prognosis. Biphasic tumors contain both epithelioid and sarcomatoid components, and small biopsies may not capture the full tumor heterogeneity. Adequate sampling is therefore important.

Immunohistochemistry Uses a Panel, Not One Marker

Immunohistochemistry (IHC) uses antibodies to identify proteins in tissue. In suspected mesothelioma, pathologists select a panel based on the tumor’s appearance, anatomical site, and the diagnoses being considered. Markers that can support mesothelial lineage include calretinin, WT1, D2-40, and CK5/6 in appropriate contexts, while other markers are chosen to evaluate competing diagnoses such as metastatic carcinoma.

BAP1, MTAP, and CDKN2A/FISH

When a pathologist needs help distinguishing a malignant mesothelial proliferation from a benign or reactive process, selected ancillary tests may provide additional evidence. Loss of BAP1 expression by immunohistochemistry, loss of MTAP expression in appropriate settings, and homozygous deletion of CDKN2A detected by fluorescence in situ hybridization (FISH) are among the tools discussed in current International Mesothelioma Interest Group guidance.

In an appropriate mesothelial proliferation, findings such as BAP1 loss, MTAP loss, or CDKN2A homozygous deletion can strongly support malignancy, but these tests are not sufficiently sensitive to exclude mesothelioma when the abnormality is absent. Retained BAP1 or MTAP expression, or the absence of CDKN2A homozygous deletion, therefore does not rule out mesothelioma. Test performance and interpretation vary by anatomical site, histologic pattern, and specimen type.

Tumor BAP1 Testing Is Not the Same as Germline Testing

BAP1 immunohistochemistry on tumor tissue assesses protein expression in the tumor. Germline testing detects inherited DNA variants, typically from blood or saliva. These tests serve different purposes and are not interchangeable.

Can Blood Tests Diagnose Mesothelioma?

No routine blood test can independently confirm or exclude mesothelioma. Biomarkers such as mesothelin have been studied and may provide adjunctive information in selected contexts, but their sensitivity and specificity are insufficient to replace imaging, tissue assessment, and pathology. A normal biomarker result does not rule out mesothelioma.

Diagnosis Is Different From Staging

Diagnosis determines whether the tumor is mesothelioma and, if possible, its histologic subtype. Staging assesses disease extent. Some imaging tests inform both, but staging scans do not replace pathologic confirmation.

The validated AJCC/IASLC TNM staging system applies to pleural mesothelioma. Other anatomical sites should not be staged by simply applying the pleural system. See Mesothelioma Stages for a dedicated explanation.

Why Specialist Pathology Review May Matter

Diagnosing mesothelioma can be challenging, particularly with small biopsies, unusual tumor patterns, or complex differential diagnoses. In such cases, review by a pathologist experienced in mesothelial tumors can help confirm findings and determine the need for additional stains or molecular tests.

Patients seeking a second opinion should ask how to obtain their pathology report, slides, and imaging. The NCI notes that a second-opinion clinician may review these materials before confirming or revising the original interpretation. The Find a Mesothelioma Specialist resource can help identify specialist care options.

What Happens After a Diagnosis?

After confirming mesothelioma, the care team assesses disease extent, reviews histologic subtype and the patient’s overall health, and discusses treatment options. Next steps depend on the anatomical site and the individual clinical circumstances.

Continue with Mesothelioma Treatment, Mesothelioma Prognosis, or Mesothelioma Stages.

Questions to Ask Your Medical Team

1. What findings make mesothelioma a concern, and what other diagnoses are being considered?
2. Which imaging study is most useful in my situation?
3. If fluid cytology is negative or nondiagnostic, what would the next step be?
4. What type of biopsy would provide adequate tissue while balancing diagnostic yield and procedural risk?
5. Will my sample be reviewed by a pathologist experienced in mesothelioma?
6. Were immunohistochemical stains or ancillary tests used to support the diagnosis?
7. Has my tumor been assigned a histologic subtype?
8. Which tests are being used for diagnosis, and which are being used for staging?

Frequently Asked Questions

References

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6. Grogg JB, Fronzaroli JN, Oliveira P, et al. Clinicopathological characteristics and outcomes in men with mesothelioma of the tunica vaginalis testis: analysis of published case-series data. Journal of Cancer Research and Clinical Oncology. 2021;147(9):2671–2679. PMID: 33559739. doi:10.1007/s00432-021-03533-6.
7. Scherpereel A, Opitz I, Berghmans T, et al. ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma. European Respiratory Journal. 2020;55(6):1900953. PMID: 32451346. doi:10.1183/13993003.00953-2019.
8. Hollevoet K, Reitsma JB, Creaney J, et al. Serum Mesothelin for Diagnosing Malignant Pleural Mesothelioma: An Individual Patient Data Meta-analysis. Journal of Clinical Oncology. 2012;30(13):1541–1549. PMID: 22412141. doi:10.1200/JCO.2011.39.6671.
9. Wolf AS, Eisele M, Giroux DJ, et al. The International Association for the Study of Lung Cancer Pleural Mesothelioma Staging Project: Expanded Database to Inform Revisions in the Ninth Edition of the TNM Classification of Pleural Mesothelioma. Journal of Thoracic Oncology. 2024;19(8):1242–1252. PMID: 38309456. doi:10.1016/j.jtho.2024.01.018.