What is Epitheliod Mesothelioma?
Epithelioid mesothelioma is the most common and most treatable form of mesothelioma. It accounts for 60 to 70 percent of all mesothelioma cases and responds better to surgery, chemotherapy, and immunotherapy than the other major subtypes.
But "most treatable" does not mean easily treated. Epithelioid mesothelioma is still a serious cancer with a median survival measured in months at the population level. The prognosis for any individual patient depends on factors that a cell-type label alone cannot capture: the specific architectural pattern of the tumor, the nuclear grade, whether surgery is possible, which treatment regimen is chosen, and — critically — where care is received.
Understanding what "epithelioid" actually means, and what distinguishes high-risk from low-risk epithelioid disease, is essential for patients trying to make informed decisions about treatment and legal options.
Learn about all mesothelioma cell types and how they affect treatment.
What Epithelioid Cells Look Like and Why It Matters
Epithelioid mesothelioma cells are organized, cohesive, and relatively uniform in appearance. Under the microscope they form recognizable structures — sheets, nests, tubules, and papillary projections — that distinguish them from the disorganized, spindle-shaped cells of sarcomatoid mesothelioma.
This organization is not cosmetic. It reflects the underlying biology of the tumor. Epithelioid cells are better differentiated than sarcomatoid cells, which means they retain more of the original mesothelial cell's characteristics. That higher degree of differentiation is associated with slower growth, less aggressive invasion, and — most importantly for treatment — greater sensitivity to both chemotherapy and immunotherapy.
The 2021 World Health Organization classification formalized the relationship between architectural pattern, nuclear features, and prognosis within the epithelioid category. Not all epithelioid mesotheliomas behave the same way.
Architectural Patterns and Prognosis
The WHO classification identifies specific architectural patterns within epithelioid mesothelioma that carry prognostic significance:
Favorable patterns include tubulopapillary, trabecular, and adenomatoid architecture. Tumors with these predominant patterns tend to behave less aggressively and are associated with longer survival times.
Unfavorable patterns include solid architecture (when it comprises 50 percent or more of the tumor) and micropapillary architecture. Tumors with predominantly solid or micropapillary patterns behave more aggressively and are associated with shorter survival.
Within specific cell variants, the lymphohistiocytoid pattern — once thought to be a poor prognostic indicator — has been reclassified in recent work as carrying a more favorable prognosis within the epithelioid category, in part because of high PD-L1 expression that predicts immunotherapy response. Myxoid features (≥50% of the tumor) are similarly associated with better outcomes.
Unfavorable cellular features include rhabdoid and pleomorphic cells, and the presence of tumor necrosis. Any of these features can shift prognosis toward the lower end of the epithelioid range.
Nuclear Grading
The 2021 WHO classification introduced a nuclear grading system for epithelioid mesothelioma that provides prognostic granularity beyond architectural pattern alone. The system is based on nuclear atypia (how abnormal the cell nuclei appear) and the presence or absence of tumor necrosis:
Grade I (low grade, no necrosis): Median overall survival approximately 29 months
Low nuclear grade with necrosis, or high nuclear grade without necrosis: Median survival approximately 16 months
High nuclear grade with necrosis: Median survival approximately 10 months
Highest grade with severe atypia and extensive necrosis: Median survival approximately 8 months
These survival differences are substantial. A Grade I epithelioid mesothelioma patient has a fundamentally different clinical situation than a patient with high-grade epithelioid disease with necrosis, even if the cell type label is the same. Pathology reports should document nuclear grade explicitly, and treatment planning should account for it.
Immunohistochemistry and Diagnosis
Diagnosing epithelioid mesothelioma requires both confirming the mesothelial origin of the tumor and ruling out other cancers that can appear similar under the microscope — particularly pulmonary adenocarcinoma, which commonly spreads to the pleura.
The standard immunohistochemical panel for epithelioid mesothelioma uses a combination of positive markers (expressed in mesothelioma) and negative markers (absent in mesothelioma but present in other cancers):
Positive markers: Calretinin is the gold standard for epithelioid mesothelioma, positive in the vast majority of cases. WT-1, CK5/6, and D2-40 (podoplanin) provide supporting evidence of mesothelial origin.
Negative markers: CEA, MOC-31, BerEP4, and TTF-1 are typically absent in mesothelioma but present in pulmonary adenocarcinoma. Claudin-4 has emerged as particularly valuable — it is expressed in carcinomas with 77 to 100 percent sensitivity and 99 to 100 percent specificity, making it among the most reliable single negative markers for distinguishing mesothelioma from carcinoma.
Molecular markers: Loss of BAP1 expression, loss of MTAP expression, and homozygous deletion of CDKN2A detected by FISH all support a mesothelioma diagnosis. These markers are less frequently altered in epithelioid mesothelioma than in other subtypes, but when present they provide strong confirmation of malignancy over benign mesothelial proliferation.
Staging
Mesothelioma staging uses the TNM system, with the 9th edition (2024) representing the current standard. This revision updated the T-stage criteria to better reflect pleural thickness and fissure involvement, removed descriptors that could not be reliably assessed on imaging, and refined stage groupings from Stage I (T1N0) through Stage IV (any M1).
For epithelioid mesothelioma, staging carries meaningful prognostic information — more so than for sarcomatoid or biphasic disease. The SEER population analysis of 1,183 mesothelioma patients demonstrated that histological subtype was a stronger predictor of outcomes than TNM stage, but within the epithelioid category, stage provides clinically useful stratification.
An important implication: stage alone should never be used to rule out surgical consideration for an epithelioid patient. The interaction between stage and cell type means that a Stage II or even Stage III epithelioid patient may still benefit from lung-sparing surgical resection in a way that a Stage I sarcomatoid patient would not.
Treatment Options
Epithelioid mesothelioma offers the widest range of treatment options of any mesothelioma subtype. The combination of chemotherapy, immunotherapy, and surgery — when appropriate — produces the best outcomes for carefully selected patients.
Surgery. For epithelioid mesothelioma, lung-sparing surgery (pleurectomy/decortication, or P/D) is generally preferred over the more extensive extrapleural pneumonectomy (EPP). In the SEER analysis, cancer-directed surgery for epithelioid mesothelioma carried a hazard ratio of 0.72, representing a 28 percent reduction in risk of death. Among surgical patients, the median survival was approximately 19 months compared to 10 months for non-surgical patients — a significant difference.
The MARS2 trial (2024) tested extended P/D against chemotherapy alone and found that extended surgery did not improve survival overall (median 19.3 months for surgery versus 24.8 months for chemotherapy). However, post-hoc analyses suggest the trial's surgical arm had significant complications and that only about 34 percent of enrolled patients would have met modern surgical criteria. Centers that have rigorously applied patient selection have reported substantially better surgical outcomes.
Surgery should be evaluated at a high-volume mesothelioma center with a dedicated thoracic surgery program. The skill of the surgical team and the completeness of resection are among the strongest predictors of surgical outcomes.
Chemotherapy. The EMPHACIS trial established pemetrexed combined with cisplatin as standard first-line chemotherapy for mesothelioma. In the trial, pemetrexed plus cisplatin produced a median survival of approximately 12 months versus 9.3 months for cisplatin alone. Response rates were higher in epithelioid than in other subtypes. Bevacizumab added to chemotherapy (the MAPS trial) extended median survival to 18.8 months versus 16.1 months without bevacizumab in a predominantly epithelioid population.
Immunotherapy. The CheckMate 743 trial demonstrated that first-line nivolumab plus ipilimumab improved median overall survival to 18.1 months compared to 14.1 months with chemotherapy across all mesothelioma patients. In epithelioid patients specifically, the hazard ratio favored immunotherapy (HR 0.86). The IND.227 trial added pembrolizumab to pemetrexed plus platinum chemotherapy and showed an overall hazard ratio of 0.79 with particularly strong trends toward benefit in the epithelioid subgroup.
In the second-line setting, the CONFIRM trial demonstrated that nivolumab monotherapy extended progression-free and overall survival compared to placebo in relapsed mesothelioma, including in the epithelioid subgroup.
Peritoneal treatment. For patients with epithelioid peritoneal mesothelioma, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) offers outcomes substantially better than those achievable with systemic therapy alone. Median survival for epithelioid peritoneal mesothelioma treated at high-volume CRS-HIPEC centers reaches 39 months and beyond.
Learn more about pleural mesothelioma treatment. | Learn more about peritoneal mesothelioma treatment.
Prognosis
Epithelioid mesothelioma carries the best prognosis of the three major histological subtypes. The overall median survival across all epithelioid patients in population-based data is approximately 14 months — substantially better than the 10 months for biphasic and 4 months for sarcomatoid disease.
But population averages mask enormous individual variation. Grade I epithelioid patients without necrosis have a median survival of 29 months. Epithelioid peritoneal patients treated at high-volume CRS-HIPEC centers achieve median survivals in the range of 39 to 44 months, with 5-year survival rates of 40 to 70 percent in optimally selected patients. Even in pleural disease, the 5-year survival rate for surgical patients, though still only 2 to 3 percent in population-based data, likely underestimates outcomes for patients treated at specialized centers with current immunotherapy regimens.
Long-term survival is possible for epithelioid mesothelioma patients — it is rare, but it is not exceptional at experienced mesothelioma centers. The patients who achieve it share common characteristics: epithelioid histology, early nuclear grade, early-stage disease, complete or near-complete surgical resection, and care at a high-volume specialist program.
Asbestos and Epithelioid Mesothelioma
Epithelioid mesothelioma is caused by asbestos exposure. All six regulated asbestos fiber types can cause the disease. The 20- to 50-year latency between first exposure and diagnosis means that patients diagnosed today were typically exposed in the 1970s through the 1990s, during the peak industrial use of asbestos in American shipyards, refineries, construction trades, power plants, and manufacturing facilities.
Learn more about asbestos exposure by occupation. | Learn more about asbestos exposure by industry.
Legal Rights and Compensation
An epithelioid mesothelioma diagnosis creates the same legal rights as any other mesothelioma subtype. Every compensation pathway — asbestos trust fund claims, personal injury lawsuits, VA disability benefits, and SSDI — is available based on documented asbestos exposure and a confirmed mesothelioma diagnosis.
There are two aspects of epithelioid mesothelioma that have specific legal relevance.
First, epithelioid patients often retain the ability to provide a live deposition — recorded testimony about their work history, their exposure, and the impact of the disease on their lives. A deposition from a living plaintiff is among the most powerful pieces of evidence in an asbestos case. Acting early preserves that ability. Patients who wait until they are too ill to testify lose the evidentiary advantage that comes from being able to tell their own story.
Second, epithelioid disease typically involves longer treatment courses and higher cumulative medical costs than other subtypes. No state caps medical expense damages in asbestos litigation, which means the full documented cost of surgery, chemotherapy, immunotherapy, surveillance imaging, and supportive care is recoverable. The longer expected treatment duration in epithelioid mesothelioma can translate to higher total recoverable medical damages.
Our firm has recovered more than $400 million for asbestos victims. We maintain a database of over 200,000 verified exposure sites and can typically identify the responsible manufacturers within days of a consultation.
Explore all your legal options. | Learn how we build cases other firms can't.
Take the Next Step
If you have been diagnosed with epithelioid mesothelioma, you have more treatment options than patients with other subtypes — and you have the same legal rights to compensation from the companies whose products caused this disease.
The consultation is free. There's no obligation. You pay nothing unless we recover compensation for you.
Call 833-4-ASBESTOS (833-427-2378) or schedule your free consultation online.
References
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Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21(14):2636-2644. doi:10.1200/JCO.2003.11.136
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Peters S, Scherpereel A, Cornelissen R, et al. First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Ann Oncol. 2022;33(5):488-499. doi:10.1016/j.annonc.2022.01.074
Chu Q, Perrone F, Greillier L, et al. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet. 2023;402(10419):2295-2306. doi:10.1016/S0140-6736(23)01148-4
Fennell DA, Ewings S, Ottensmeier C, et al. Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised phase 3 trial. Lancet Oncol. 2021;22(11):1530-1540. doi:10.1016/S1470-2045(21)00471-X