Mesothelioma: Understanding Your Pathology Report

By Jason Wasserman MD PhD FRCPC and Matt Cecchini MD PhD FRCPC
April 29, 2026

Mesothelioma is a cancer that starts in mesothelial cells — the specialized cells that form a thin lining around internal organs. This lining, called the mesothelium, is found around the lungs (the pleura), around the abdominal organs (the peritoneum), and around the heart (the pericardium). The large majority of mesotheliomas — roughly 75–80% — arise in the pleura and are called pleural mesothelioma. About 15–20% arise in the peritoneum. Pericardial mesothelioma, affecting the lining around the heart, is very rare. This article focuses primarily on pleural mesothelioma but covers features shared across all types. This article will help you understand the findings in your pathology report — what each term means and why it matters for your care.

What causes mesothelioma?

Asbestos exposure is by far the most common cause of mesothelioma, responsible for the majority of cases. Asbestos is a group of naturally occurring minerals that were widely used in construction materials, shipbuilding, and industrial insulation for much of the twentieth century. When asbestos fibers are inhaled, they can travel deep into the lungs and become permanently lodged in the lining of the lung or abdomen. Over decades, these fibers cause ongoing irritation and damage to cells in the mesothelium, eventually triggering the genetic changes that lead to cancer. The time between first asbestos exposure and the development of mesothelioma is typically 20 to 50 years, which is why many patients are diagnosed later in life, long after the original exposure.

Other contributing factors include:

• Erionite exposure — Erionite is a naturally occurring mineral with a fiber structure similar to asbestos, found in volcanic rock in certain parts of the world. Prolonged exposure is associated with a high risk of mesothelioma.
• Prior radiation therapy — People who received radiation to the chest or abdomen for a previous cancer have a small but recognized increased risk of developing mesothelioma years later.
• Inherited genetic changes — Some people carry an inherited change in a gene called BAP1 that significantly increases the risk of developing mesothelioma, even after relatively minimal asbestos exposure. This is discussed further in the biomarker section below.

Mesothelioma can occasionally develop in people with no identifiable history of asbestos exposure or known genetic risk factors, in which case the underlying cause is unclear.

What are the symptoms of mesothelioma?

Symptoms depend on where the mesothelioma has developed and on its stage. Because mesothelioma grows along the surface of the pleura or peritoneum rather than forming a single localized mass, it often causes symptoms related to fluid buildup or pressure on nearby structures before it is detected.

Common symptoms of pleural mesothelioma (affecting the lung lining) include:

• Shortness of breath — often caused by fluid building up between the two layers of the pleura (called a pleural effusion), which compresses the lung.
• Chest pain or a persistent dull ache on one side of the chest.
• A persistent cough.
• Unexplained weight loss and fatigue.
• Night sweats or low-grade fever.

Common symptoms of peritoneal mesothelioma (affecting the abdominal lining) include:

• Abdominal swelling or discomfort, often caused by fluid collecting in the abdomen (called ascites).
• A feeling of fullness or bloating after eating very little.
• Nausea or changes in bowel habits.
• Unexplained weight loss.

Symptoms tend to develop slowly and worsen over time. Because they overlap with many other, less serious conditions, mesothelioma is often not suspected until imaging reveals an abnormality in the chest or abdomen. Anyone with a known history of asbestos exposure who develops any of these symptoms should discuss them with their doctor promptly.

How is the diagnosis made?

Mesothelioma is typically diagnosed from a tissue sample obtained by biopsy. For pleural mesothelioma, the biopsy is most often obtained by thoracoscopy — a minimally invasive procedure in which a camera and biopsy instruments are inserted through small cuts in the chest wall to sample the pleural lining directly. CT-guided needle biopsy is an alternative for some patients. For peritoneal mesothelioma, laparoscopy or image-guided needle biopsy is used to obtain tissue from the abdominal lining. Because mesothelioma grows as a diffuse sheet rather than a single lump, obtaining an adequate tissue sample is important — a small or poorly representative sample can make the diagnosis difficult to establish with certainty.

Under the microscope, a pathologist examines the tumor cells and their growth pattern. Mesothelioma cells typically grow along the pleural or peritoneal surface in a spreading, coating pattern rather than forming a discrete localized mass. Depending on the histologic type (see section below), the cells may appear rounded and gland-like, long and spindle-shaped, or a mixture of both. This is one of the key features the pathologist assesses when making the diagnosis.

Confirming the diagnosis of mesothelioma is one of the most challenging tasks in surgical pathology, because mesothelioma can look very similar to other conditions under the microscope — particularly other cancers that have spread to the pleura (such as lung adenocarcinoma or breast cancer) and, crucially, to benign (non-cancerous) reactive changes of the mesothelium that can occur after infection, inflammation, or prior surgery. To distinguish mesothelioma from these other conditions, the pathologist uses two main types of additional testing.

The first is immunohistochemistry (IHC) — a technique that uses antibodies linked to colored dyes to detect specific proteins inside the cells. Mesothelioma cells typically show strong positive staining for proteins called calretinin, WT-1, D2-40, and cytokeratin 5/6, which are characteristic of mesothelial cells. At the same time, they typically show negative staining for proteins that mark other cancer types — such as claudin-4, MOC-31, BerEP4, and TTF-1, which are found in lung adenocarcinoma. This pattern of positive and negative staining helps the pathologist confirm that the tumor is of mesothelial origin rather than a cancer that has spread from another organ. Two additional IHC markers are particularly useful for distinguishing mesothelioma from benign mesothelial conditions: loss of BAP1 protein staining (meaning the BAP1 protein is absent from the tumor cell nuclei) and loss of MTAP protein staining (which reflects a genetic change discussed below) are both strongly associated with malignant mesothelioma and are rarely seen in benign reactive conditions.

The second test is fluorescence in situ hybridization (FISH) — a laboratory technique that uses fluorescent probes to detect whether a specific piece of DNA is present or missing in the tumor cells. In mesothelioma, FISH is most commonly used to detect deletion of the CDKN2A gene — a tumor suppressor gene that is lost in approximately 70% of mesotheliomas. Because benign mesothelial conditions almost never lose this gene, the finding of CDKN2A deletion is strong evidence that mesothelial proliferation is malignant rather than reactive.

Once the diagnosis is confirmed, imaging — including CT of the chest and abdomen, and increasingly PET scan — is used to determine how far the mesothelioma has spread and to guide treatment planning.

Histologic types of mesothelioma

Mesothelioma is divided into three main types based on the tumor cells’ appearance under the microscope. The histologic type is one of the most important pieces of information in the pathology report, because it strongly influences prognosis and treatment decisions.

• Epithelioid mesothelioma — The most common type, accounting for approximately 50–60% of cases. The tumor cells are rounded or polygonal, with well-defined edges, and tend to form organized structures such as glands, tubules, or papillary clusters. This type is associated with the best prognosis among the three.
• Sarcomatoid mesothelioma — Accounts for approximately 10–15% of cases. The tumor cells are elongated and spindle-shaped, resembling the cells of a sarcoma (a cancer of connective tissue). This type tends to grow and spread more rapidly than epithelioid mesothelioma and is associated with the worst prognosis. A specific subtype, desmoplastic mesothelioma, belongs to this category: the tumor is dominated by dense, scar-like tissue and can be particularly difficult to distinguish from benign scar tissue under the microscope.
• Biphasic mesothelioma — Accounts for approximately 25–35% of cases. The tumor contains a mixture of epithelioid and sarcomatoid cells, each accounting for at least 10% of the tumor. Prognosis depends on the proportion of each component — tumors with a higher sarcomatoid component generally behave more aggressively.

Histologic grade

Mesothelioma is not assigned a histologic grade as many other cancers are. The grading systems used for other tumors — such as well, moderately, and poorly differentiated — have not been formally established for mesothelioma. Instead, the most important prognostic indicator of tumor aggressiveness is the histologic type described above: epithelioid, sarcomatoid, or biphasic. The histologic type effectively functions as a proxy for grade in clinical practice. All mesotheliomas are treated as aggressive cancers regardless of type, and this distinction does not lead to a “low-grade” or “benign-acting” category.

Within epithelioid mesothelioma specifically, pathologists sometimes note the mitotic count (how many cells are actively dividing) and the nuclear grade (how abnormal the cell nuclei appear), as higher values are associated with a worse prognosis even within the epithelioid category. Your pathology report may describe these features if they were formally assessed.

Lymphovascular invasion

Lymphovascular invasion (LVI) means that tumor cells have been found within blood or lymphatic vessels — the small channels that carry lymph — in or near the tumor. These vessels can act as pathways for tumor cells to travel to lymph nodes or other parts of the body.

• Lymphovascular invasion not identified — No tumor cells are seen within vessels near the tumor. This is the more favorable finding.
• Lymphovascular invasion present — Tumor cells are found within vessels. This finding is associated with a higher risk of spread beyond the pleura and may influence treatment planning.

Surgical margins

Surgical margins are the cut edges of the tissue removed during an operation. The pathologist examines all margins to determine whether the tumor was completely removed. Because mesothelioma grows as a diffuse coating of the pleural surface rather than a discrete lump, achieving completely clear margins is technically challenging — and in many cases, the goal of surgery is disease control rather than complete microscopic clearance.

• Negative margin — No tumor cells are seen at the cut edge. This is the most favorable result.
• Close margin — Tumor cells are present very near the cut edge but do not reach it. Further treatment may be recommended depending on the clinical context.
• Positive margin — Tumor cells are present at the cut edge. This raises concern that some tumor remains and typically leads to a recommendation for additional radiation therapy or other treatment.

Lymph nodes

Lymph nodes are small immune organs distributed throughout the chest. During surgery for mesothelioma, the surgeon may remove lymph nodes from locations within the chest and send them to the pathologist for examination. The pathology report will describe the total number of lymph nodes examined, where they came from, and whether any contain tumor cells.

Lymph node involvement is common in mesothelioma, particularly as the disease advances, and is one of the features used to stage the disease (N stage). Finding tumor cells in lymph nodes indicates that the cancer has begun to spread beyond the pleural surface and is associated with a higher risk of recurrence and worse outcomes. The nodal stage also influences whether surgery is likely to be beneficial and whether additional treatment, such as chemotherapy or radiation, is recommended.

Biomarker and molecular testing

Biomarker testing plays a growing role in the management of mesothelioma. Some tests are used to help confirm the diagnosis, while others guide treatment decisions or have important implications for the patient’s family members.

BAP1

BAP1 is a protein that normally acts as a brake on uncontrolled cell growth. In many mesothelioma tumors, the gene that produces BAP1 is lost or inactivated, and the BAP1 protein disappears from the cell nucleus. This loss of BAP1 protein — detected by immunohistochemistry — is a helpful marker of malignancy, because benign mesothelial conditions almost never show BAP1 loss.

Importantly, BAP1 loss in a mesothelioma can sometimes reflect an inherited change in the BAP1 gene rather than a change that occurred only in the tumor itself. People who carry an inherited (germline) BAP1 mutation have a condition called BAP1 tumor predisposition syndrome, which significantly increases the risk of mesothelioma, uveal melanoma (a type of eye cancer), skin melanoma, and clear cell kidney cancer, among others. Family members of someone with a germline BAP1 mutation may also be at increased risk. If your tumor shows loss of BAP1 staining, your doctor may recommend referral to a genetic counselor to determine whether further testing for a germline mutation is appropriate.

CDKN2A and MTAP

CDKN2A is a gene that helps control cell division. When this gene is deleted from tumor cells — a change detected by the FISH test — it is a strong signal that a mesothelial growth is malignant. CDKN2A deletion is found in approximately 70% of mesotheliomas and is rarely seen in benign reactive conditions, making it one of the most useful diagnostic tests for confirming the diagnosis when the picture is uncertain.

MTAP is a protein encoded by a gene that sits physically next to CDKN2A on the same chromosome. When CDKN2A is deleted, the neighboring MTAP gene is often deleted as well. Loss of MTAP protein staining on immunohistochemistry is therefore a practical surrogate marker for CDKN2A deletion — it provides the pathologist with the same diagnostic information without requiring FISH in all cases. MTAP loss may also have emerging treatment implications, as drugs targeting this vulnerability are under investigation in clinical trials.

PD-L1

PD-L1 (programmed death-ligand 1) is a protein that some cancer cells display on their surface to avoid being attacked by the immune system. Drugs called checkpoint inhibitors work by blocking this mechanism, allowing the immune system to recognize and attack the cancer. PD-L1 expression in mesothelioma is variable — some tumors express it strongly, others weakly or not at all. While PD-L1 expression does not reliably predict who will respond to immunotherapy in mesothelioma (as it does more consistently in some other cancers), it is often measured as part of the overall tumor profile and may be considered alongside other factors when making treatment decisions.

Checkpoint immunotherapy — nivolumab and ipilimumab

The CheckMate-743 clinical trial showed that the combination of two checkpoint inhibitors — nivolumab (Opdivo) and ipilimumab (Yervoy) — improved survival compared to standard chemotherapy when used as the first treatment for unresectable pleural mesothelioma. The median overall survival with nivolumab plus ipilimumab was approximately 18 months compared to 14 months with chemotherapy, and the benefit was particularly pronounced in patients with non-epithelioid (sarcomatoid or biphasic) tumors. Based on this trial, nivolumab plus ipilimumab is now approved as a first-line treatment option for unresectable pleural mesothelioma. This is one of the most important advances in mesothelioma treatment in recent years.

For more information about biomarker testing in cancer, visit the Biomarkers and Molecular Testing section of MyPathologyReport.

Pathologic stage (pTNM)

Pleural mesothelioma is staged using a TNM system developed specifically for this cancer, based on AJCC 8th edition criteria. This system differs from the one used for lung cancers such as adenocarcinoma and squamous cell carcinoma. The T category describes how far the tumor has grown along the pleural surface and into nearby structures. The N category indicates whether the cancer has spread to nearby lymph nodes. The M category — which describes spread to distant organs — is determined by imaging rather than the pathology specimen and is typically not reported in the surgical pathology report.

Tumor stage (pT)

• pT1 — The tumor is limited to the lining on one side of the chest. It may involve the outer pleural layer (parietal pleura), the pleura covering the lung surface (visceral pleura), the pleura lining the diaphragm, or the pleura lining the inside of the chest cavity — but has not grown through into the diaphragm muscle or into the lung tissue itself.
• pT2 — The tumor involves all of the pleural surfaces on one side and has grown into at least one of: the muscle of the diaphragm, or the lung tissue beneath the visceral pleura.
• pT3 — The tumor is locally advanced but may still be surgically removable. In addition to involving all pleural surfaces, the tumor has grown into at least one of: the layer of connective tissue lining the inside of the chest wall (endothoracic fascia), the fat in the center of the chest (mediastinal fat), a single focus in the soft tissue of the chest wall, or the outer layer of the pericardium (the sac around the heart) without going through it.
• pT4 — The tumor is locally advanced and is not surgically removable. It has spread diffusely through the chest wall, grown through the diaphragm into the abdominal cavity, spread to the other side of the chest, invaded the spine, grown through the pericardium into the heart, or involved major blood vessels or the nerves of the arm (brachial plexus).

Nodal stage (pN)

• pN0 — No tumor cells found in any lymph nodes examined.
• pN1 — Tumor cells found in regional lymph nodes on the same side as the tumor — including lymph nodes within the lung, near the airways, in the center of the chest, along the internal mammary vessels, or near the diaphragm.

What is the prognosis?

The prognosis for mesothelioma is challenging overall, though outcomes vary considerably depending on the histologic type, stage, and the treatment received. Mesothelioma is generally diagnosed at an advanced stage because symptoms develop slowly and are non-specific, which limits the proportion of patients who are candidates for surgery.

The histologic type is the single strongest predictor of outcome:

• Epithelioid mesothelioma — The most favorable prognosis. Median overall survival with modern treatment is approximately 18–24 months for patients with early-stage disease treated with surgery and systemic therapy, and approximately 18 months for patients with advanced unresectable disease treated with nivolumab plus ipilimumab.
• Biphasic mesothelioma — Intermediate prognosis, strongly influenced by the proportion of sarcomatoid cells. Median overall survival is typically 12–16 months.
• Sarcomatoid mesothelioma — The most aggressive type, with a median overall survival of approximately 8–12 months. This group shows the greatest relative benefit from nivolumab plus ipilimumab compared with chemotherapy, according to the CheckMate-743 trial.

Other factors that influence prognosis include:

• Stage — Earlier-stage disease (T1–T2, N0) that can be fully resected has a better prognosis than advanced or unresectable disease.
• Lymph node involvement — The presence of tumor in lymph nodes (N1) is associated with a higher risk of recurrence and worse survival.
• Performance status — Patients who are in good overall health and can tolerate aggressive treatment tend to have better outcomes.
• CDKN2A deletion — Loss of this gene is associated with more aggressive tumor behavior, even within the epithelioid type.

Treatment advances — particularly the introduction of checkpoint immunotherapy — have meaningfully improved outcomes for some patients in recent years, and ongoing clinical trials are investigating new approaches.

What happens after the diagnosis?

After the pathology report is finalized, your doctor will review the findings along with your imaging results and overall health to develop a treatment plan. Mesothelioma is managed by a multidisciplinary team including a thoracic surgeon, medical oncologist, radiation oncologist, and pathologist. Because mesothelioma is a relatively rare cancer, treatment at a specialist center with experience in this disease is strongly recommended.

For patients with early-stage, resectable pleural mesothelioma who are fit for surgery, the surgical options include two main procedures. The first is pleurectomy/decortication (P/D), in which the tumor lining the pleura, visible to the pathologist, is stripped away while preserving the lung. The second is extrapleural pneumonectomy (EPP), a more extensive operation in which the entire pleura, the lung on the affected side, part of the diaphragm, and the pericardium are removed together. P/D is generally preferred when it can achieve adequate tumor removal, as it preserves lung function. Surgery is typically combined with chemotherapy and sometimes radiation to reduce the risk of recurrence. Not all patients are candidates for surgery — the extent of disease, the histologic type, and the patient’s lung function and general health all factor into this decision.

For patients with unresectable disease, systemic treatment is the mainstay. Two main options are used as first-line treatment:

• Checkpoint immunotherapy — nivolumab plus ipilimumab — Approved as a first-line option for unresectable pleural mesothelioma based on the CheckMate-743 trial. This combination is particularly favored for non-epithelioid tumors (sarcomatoid and biphasic), where the benefit over chemotherapy is largest.
• Chemotherapy — pemetrexed plus cisplatin — The established chemotherapy backbone for mesothelioma. Bevacizumab (a drug that blocks new blood vessel formation) is sometimes added to this regimen in eligible patients. This approach may be preferred for some patients with epithelioid tumors or when immunotherapy is not suitable.

For peritoneal mesothelioma, a specialized treatment approach called cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) — in which heated chemotherapy is delivered directly into the abdominal cavity during surgery — has shown significant survival benefit in selected patients with epithelioid peritoneal mesothelioma. This is performed at specialized centers.

Radiation therapy may be used after surgery to reduce the risk of local recurrence at the surgical site, or to treat specific areas of disease-causing symptoms such as pain.

Follow-up after treatment includes regular chest and abdominal CT imaging and clinical assessment to monitor for signs of recurrence. Given the known association between mesothelioma and inherited BAP1 mutations, referral to a genetic counselor may be recommended based on BAP1 test results.

Questions to ask your doctor

• What histologic type of mesothelioma do I have — epithelioid, sarcomatoid, or biphasic — and what does that mean for my prognosis?
• What is my pathologic stage, and what does it mean for my treatment options?
• Was BAP1 protein staining lost in my tumor, and should I be referred to a genetic counselor?
• Was CDKN2A deletion found on the FISH test, and what does it mean for my prognosis?
• Was MTAP protein staining assessed, and what were the results?
• Am I a candidate for surgery, and if so, which operation — P/D or EPP — would be recommended?
• Is first-line immunotherapy (nivolumab plus ipilimumab) or chemotherapy recommended for me, and why?
• Were any lymph nodes removed and examined, and did any contain tumor cells?
• Were the surgical margins clear, and does that affect my need for additional treatment?
• What follow-up schedule is recommended after treatment?
• What symptoms should prompt me to contact you between appointments?
• Are there clinical trials I might be eligible for?
• What support resources are available for mesothelioma patients and their families?