Your pathology report for atypical mesothelial proliferation

By Jason Wasserman MD PhD FRCPC
October 11, 2025

The term atypical mesothelial proliferation is used when a pathologist sees mesothelial cells—the cells that line the membranes covering the lungs (pleura), abdomen (peritoneum), heart (pericardium), or testis (tunica vaginalis)—that look abnormal (atypical) under the microscope.

This finding means that the pathologist sees some worrisome changes in how the mesothelial cells look or grow, but the tissue sample does not show enough clear features to make a definite diagnosis of either a benign (noncancerous) or malignant (cancerous) process.

Because the changes could represent either an early or limited form of mesothelioma (a cancer of mesothelial cells) or a reactive process (a noncancerous reaction to injury, infection, or inflammation), the phrase “atypical mesothelial proliferation” is used as a descriptive, cautious diagnosis until more information is available.

Does atypical mesothelial proliferation mean cancer?

No. Atypical mesothelial proliferation does not necessarily mean cancer.

This diagnosis means that the cells look unusual enough to raise concern, but not enough changes are seen to confirm mesothelioma or any other type of cancer. Many conditions that are not cancerous, such as infection, inflammation, prior surgery, or fluid buildup, can make mesothelial cells appear abnormal under the microscope.

However, because some of the features may overlap with early cancer, your pathologist uses this term to indicate uncertainty and the need for additional testing or follow-up. In some cases, a larger biopsy or special laboratory studies may be recommended to determine whether the atypical cells are part of a benign process or an early form of cancer.

When is this diagnosis made?

The diagnosis of atypical mesothelial proliferation is usually made after a biopsy when only a small amount of tissue is available for examination under the microscope.

This situation often occurs when a doctor removes a tiny piece of tissue or a small fragment from the lining around the lungs (pleura), the abdomen (peritoneum), the heart (pericardium), or the testis (tunica vaginalis). These thin membranes are covered by mesothelial cells, and sometimes the sample is too small to show whether the abnormal cells are simply reacting to irritation or inflammation (benign) or represent an early form of mesothelioma (cancer).

Because the sample is limited, the pathologist may see changes that raise concern but are not enough to make a definite diagnosis. In this situation, the descriptive phrase “atypical mesothelial proliferation” is used to indicate that more information—such as a larger biopsy or additional tests—may be needed to determine the exact cause.

What causes atypical mesothelial proliferation?

Atypical mesothelial proliferation can occur in response to many different conditions. Some are benign, while others are more serious.

Common causes include:

  • Inflammation or infection: Chronic inflammation of the pleura or peritoneum can cause reactive changes that mimic cancer.

  • Prior surgery or trauma: Healing after surgery or injury may produce atypical-appearing mesothelial cells.

  • Effusions (fluid buildup): Long-standing or bloody fluid collections can irritate mesothelial cells and cause them to grow abnormally.

  • Previous radiation or chemotherapy: Prior treatment can alter the appearance of cells.

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

Because of this overlap, additional testing and careful follow-up are usually needed to clarify the diagnosis.

What do atypical mesothelial proliferations look like under the microscope?

Under the microscope, the pathologist sees mesothelial cells that look different from normal. These changes may include:

  • Enlarged, irregular nuclei that are darker or more variable than usual

  • Cells arranged in clusters or sheets instead of a flat, even layer

  • Increased cell crowding and overlapping

  • Occasional mitotic figures (cells in the process of dividing)

  • Possible invasion or growth into surrounding tissue (although this may not be visible in small samples)

When these features are seen in a limited specimen, the pathologist may not have enough information to confidently determine whether the proliferation is reactive or malignant, leading to the diagnosis of atypical mesothelial proliferation.

What additional tests may be ordered?

To help clarify the nature of the proliferation, pathologists often perform immunohistochemistry or molecular tests. These tests look for proteins or genetic changes that are more typical of mesothelioma (cancer) or reactive mesothelial hyperplasia (noncancerous).

Common immunohistochemical and molecular markers include:

  • BAP1: Loss of BAP1 protein is seen in many cases of mesothelioma but not in reactive processes.

  • MTAP: Loss of MTAP often occurs with CDKN2A gene deletion, a change that supports a diagnosis of mesothelioma.

  • p16 (CDKN2A): A genetic test called FISH (fluorescence in situ hybridization) may be used to look for CDKN2A deletion, which also favors mesothelioma.

  • Ki-67: This marker helps measure how quickly cells are dividing.

  • Calretinin, WT1, and cytokeratin 5/6: These are positive in both reactive and malignant mesothelial cells and help confirm that the cells are mesothelial in origin.

The pathologist may recommend obtaining a larger biopsy to evaluate whether the atypical cells are invading nearby tissue, which is the most reliable way to diagnose mesothelioma.

What happens next?

If your pathology report says atypical mesothelial proliferation, your doctor will consider your clinical history, imaging studies, and other test results to decide what to do next.

Possible next steps include:

  • Repeat or larger biopsy: This may be recommended to obtain more tissue and allow for a more definitive diagnosis.

  • Special stains or molecular tests: Your pathologist may order these to look for changes associated with mesothelioma.

  • Follow-up imaging: CT scans or MRIs may help identify any mass or thickening of the pleura or peritoneum.

  • Clinical monitoring: If the atypia is mild and no cancer is suspected, your doctor may recommend close observation and repeat testing if symptoms persist or fluid reaccumulates.

Because atypical mesothelial proliferation can sometimes be an early sign of mesothelioma, ongoing communication between your pathologist, oncologist, and surgeon is essential to ensure appropriate follow-up.

What is the prognosis?

The prognosis depends on the underlying cause. Reactive or inflammatory proliferations are benign and often resolve once the underlying condition is treated. If further testing confirms mesothelioma, the outlook will depend on the stage, location, and type of mesothelioma identified.

When the report describes “atypical mesothelial proliferation”, it means that the diagnosis is inconclusive at this point, not that cancer is confirmed.

Questions to ask your doctor

  • What caused my sample to show atypical mesothelial proliferation?

  • Do I need additional biopsies or tests?

  • Were special stains or molecular tests such as BAP1 or p16 performed?

  • Is there any evidence of invasion or cancer?

  • Should I see a specialist in mesothelioma or thoracic oncology?

  • How will my condition be monitored over time?

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