What is mesothelial proliferation?

Mesothelial proliferation is a term used by pathologists to describe an increase in the number of mesothelial cells. Mesothelial cells form a thin layer that lines the membranes around the lungs (pleura), abdomen (peritoneum), heart (pericardium), and testis (tunica vaginalis).

A mesothelial proliferation can be benign (noncancerous) or, less commonly, part of a malignant (cancerous) process such as mesothelioma. When the pathologist uses this term, it means that mesothelial cells are growing more than usual. Still, additional features or tests are often needed to determine whether the proliferation is reactive (a normal response to irritation) or malignant (caused by cancer).

What causes mesothelial proliferation?

Mesothelial proliferation can develop for two main reasons. It may be a reactive process, which means the cells are responding to irritation, inflammation, or injury, or it may be part of an abnormal growth, such as a tumor or an early stage of mesothelioma. Because both can look similar under the microscope, your pathologist may recommend more tests to determine the exact cause.

Reactive (noncancerous) causes:

• Inflammation or infection: Conditions that irritate the lining of the lungs or abdomen can cause the mesothelial cells to multiply.

• Fluid buildup (effusion): Long-standing or bloody fluid in the chest or abdomen can stimulate the mesothelial lining to grow.

• Recent surgery or injury: Healing after surgery or trauma can cause a temporary increase in mesothelial cells.

• Radiation or certain medications: Previous cancer treatments can make mesothelial cells grow more actively.

• Nearby noncancerous growths: Cysts or benign tumors can irritate the lining and trigger cell growth.

Abnormal growth (neoplastic) causes:

• Tumors near the mesothelial surface: A proliferation may form at the edge of another tumor growing close to the pleura or peritoneum.

• Early or limited mesothelioma: In some cases, mesothelial proliferation represents an early stage of mesothelioma that cannot yet be confirmed without more tissue.

Because there are many possible causes, mesothelial proliferation is a descriptive finding rather than a final diagnosis. Further testing or a larger biopsy may be needed to determine whether the process is reactive (noncancerous) or malignant (cancerous).

What does mesothelial proliferation look like under the microscope?

Under the microscope, mesothelial proliferation appears as thickened layers or clusters of mesothelial cells. Normally, the mesothelium consists of a single layer of flat cells. In proliferation, these cells may look more crowded or form small papillary (finger-like) projections.

The cells themselves may look normal, as in reactive mesothelial proliferation, or they may show atypia (mild abnormalities in size or shape). However, in benign proliferations, the cells do not invade the underlying tissue.

Pathologists may describe the process using terms such as:

• Reactive mesothelial proliferation: A benign, noncancerous reaction to irritation or injury.

• Atypical mesothelial proliferation: A term used when some concerning changes are seen, but not enough to confirm cancer.

• Malignant mesothelial proliferation: This term is used when definite signs of cancer, such as invasion, are present.

How do pathologists distinguish between benign and malignant mesothelial proliferation?

Distinguishing between a benign (noncancerous) proliferation and a malignant (cancerous) proliferation can be difficult, especially when the biopsy sample is small. Pathologists use several tools to help make this distinction, including the microscopic features, immunohistochemistry, molecular tests, and clinical correlation.

Microscopic features

Benign proliferations show organized, smooth layers of cells without invasion into surrounding tissue. Malignant proliferations show irregular growth patterns and evidence of invasion.

Immunohistochemistry

This special laboratory test uses antibodies to highlight specific proteins in the cells.

• BAP1: Retained (normal) staining supports a reactive process, while loss of BAP1 supports mesothelioma.

• MTAP and p16 (CDKN2A): Normal results favor hyperplasia or reactive proliferation. Loss or deletion supports mesothelioma.

• Calretinin, WT1, cytokeratin 5/6: Positive in both reactive and malignant mesothelial cells, confirming their origin.

Molecular tests

Some laboratories use genetic tests (such as FISH) to look for deletions in genes like CDKN2A, which are common in mesothelioma but not in reactive proliferations.

Clinical correlation

Pathologists consider the patient’s history, symptoms, imaging results, and the appearance of the tissue sample to determine whether additional testing or a larger biopsy is needed.

Is mesothelial proliferation dangerous?

Mesothelial proliferation by itself is not a diagnosis of cancer. In many cases, it represents a benign and reversible response to irritation or inflammation. However, because mesothelial proliferation can sometimes look similar to early mesothelioma, your pathologist may recommend additional testing or a repeat biopsy to ensure that no malignancy is present.

If the proliferation is confirmed to be reactive, it usually resolves once the underlying cause—such as infection, inflammation, or fluid buildup—is treated.

How is mesothelial proliferation described in a pathology report?

If your pathology report mentions mesothelial proliferation, it means that the mesothelial cells are growing more than usual.

Your pathology report may include additional words to describe the process:

• Reactive mesothelial proliferation: Noncancerous changes due to irritation or inflammation.

• Atypical mesothelial proliferation: The cells in an atypical mesothelial proliferation appear abnormal, but the diagnosis is uncertain.

• Malignant mesothelial proliferation – A cancerous growth showing invasion, consistent with mesothelioma.

The report may also mention the results of immunohistochemistry or molecular tests that help clarify whether the proliferation is benign or malignant.

What is the prognosis for mesothelial proliferation?

The prognosis depends on the underlying cause. Reactive or benign proliferations are harmless and usually disappear once the cause of irritation is treated. If further testing shows mesothelioma, the prognosis will depend on the cancer’s stage and type.

Most patients with mesothelial proliferation do not have cancer, but careful follow-up is important to ensure an accurate diagnosis.

Questions to ask your doctor

• What caused the mesothelial proliferation in my sample?

• Did the pathologist describe it as reactive, atypical, or malignant?

• Were special stains or genetic tests (such as BAP1 or p16) performed?

• Is there any sign of invasion or mesothelioma?

• Will I need additional testing, a larger biopsy, or imaging studies?

• How will my condition be monitored over time?