Under the microscope, mesothelioma is classified into three cell types. The cell type is one of the most important factors in determining treatment options and prognosis, so it is always identified during biopsy.

Epithelioid Mesothelioma

The most common cell type, accounting for roughly 50-70% of cases. Epithelioid cells are more uniform and tend to cluster together, which makes the cancer less aggressive and more responsive to treatment than the other types. Patients with epithelioid mesothelioma generally have the most favorable prognosis and the widest range of treatment options, including surgery for eligible patients.

Sarcomatoid Mesothelioma

The least common and most aggressive cell type, making up about 10-20% of cases. Sarcomatoid cells are spindle-shaped and spread more readily, and the cancer tends to resist chemotherapy and radiation more than the epithelioid type. This gives it the most guarded prognosis, and patients are less often candidates for aggressive surgery. Sarcomatoid disease can be harder to diagnose because its cells can resemble other cancers.

Biphasic Mesothelioma

A mixture of both epithelioid and sarcomatoid cells, accounting for roughly 20-35% of cases. Prognosis and treatment response depend on the proportion of each cell type — tumors with a higher percentage of epithelioid cells tend to behave more like epithelioid mesothelioma and respond better, while those dominated by sarcomatoid cells behave more aggressively.

Why the Three Behave Differently

The subtypes are not grades of the same thing — they are structurally different tumours.

Epithelioid cells are cuboidal and adhere to one another, forming recognisable tubular and papillary patterns. That cohesion is part of why the disease spreads less diffusely and responds better to treatment.

Sarcomatoid cells are spindle-shaped and far less adherent, infiltrating surrounding tissue in a dispersed pattern that makes a clean surgical margin unrealistic and limits what any local treatment can achieve.

Biphasic tumours contain both populations. Because the proportions vary, the pathology report’s estimate of how much is epithelioid is genuinely informative — a predominantly epithelioid biphasic tumour tends to behave more like epithelioid disease.

How Cell Type Is Determined

Cell type is settled by a pathologist, not by imaging, and it requires tissue rather than fluid. Cytology from drained pleural fluid alone is frequently insufficient — it can suggest mesothelioma but often cannot reliably separate it from other cancers or establish the subtype.

The distinction relies on immunohistochemical staining rather than appearance under the microscope alone. Mesothelioma typically expresses markers such as calretinin, WT-1 and CK5/6 while lacking TTF-1, which lung adenocarcinoma usually expresses. A panel is used rather than any single marker, because no one stain is definitive.

This matters practically because mesothelioma is rare and the pathological distinction is genuinely difficult. A second pathology opinion from a centre that sees mesothelioma regularly is a reasonable thing to ask about, particularly where the original diagnosis was made somewhere that encounters few cases.

How Cell Type Changes Treatment

Subtype is not only prognostic — it affects what is offered:

  • Surgical eligibility. Aggressive surgery is far more readily offered for epithelioid disease. Sarcomatoid histology makes most centres reluctant, because the pattern of spread makes complete removal unlikely.
  • Expected response. Epithelioid disease responds better to chemotherapy and immunotherapy than sarcomatoid.
  • Trial eligibility. Many clinical trials either stratify by subtype or restrict entry to one, so the pathology report determines which studies are even open.

Why Cell Type Matters

Because cell type strongly influences how the cancer responds to surgery, chemotherapy, radiation, and immunotherapy, an accurate pathology diagnosis is essential to treatment planning. Determining cell type sometimes requires specialized testing (immunohistochemistry) and, in difficult cases, a second pathology opinion.

See also the stages guide and life expectancy and prognosis.

If you were diagnosed with any type of mesothelioma and were exposed to asbestos at work, in the military, or in a building, you may have a legal claim.

This information is educational, drawn from sources such as the American Cancer Society and National Cancer Institute, and is not medical advice. Consult your own physician about your diagnosis.