Epithelioid mesothelioma is the most common histological subtype of malignant mesothelioma, accounting for approximately 50–60% of all cases. This subtype is characterized by its distinct cellular structure, clinical behavior, and response to treatment, making it a critical focus for both diagnosis and management of mesothelioma.

Cellular and Histological Characteristics
Epithelioid mesothelioma is defined by its uniform, cube-like cells that often form tubular or papillary structures. These cells closely resemble normal epithelial cells, which can make differentiation from other cancers, such as adenocarcinomas, challenging. Key features include:

Cell Shape: Round or polygonal cells with a uniform appearance.
Growth Pattern: Cells often grow in clusters or sheets, forming gland-like structures.
Immunohistochemical Markers: Epithelioid mesothelioma cells typically express mesothelial markers such as:
Calretinin
WT-1 (Wilms Tumor 1)
Cytokeratin 5/6
D2-40 (Podoplanin)
These markers are critical in distinguishing epithelioid mesothelioma from other malignancies, particularly metastatic adenocarcinomas, which may present similarly under a microscope.

Diagnostic Challenges
While epithelioid mesothelioma is easier to diagnose compared to other subtypes, challenges remain due to its phenotypic overlap with other cancers. Diagnostic methods include:

Histopathology: Examination of tissue samples under a microscope remains the gold standard.
Immunohistochemistry (IHC): A panel of two positive mesothelial markers (e.g., calretinin, WT-1) and two negative carcinoma markers (e.g., CEA, TTF-1) is recommended for accurate diagnosis.
Cytology: In cases where tissue samples are limited, cytological analysis of pleural effusions can provide clues, though it is less definitive for epithelioid mesothelioma.
Prognosis and Survival
Epithelioid mesothelioma is associated with the most favorable prognosis among mesothelioma subtypes. Key prognostic factors include:

Median Survival: Patients with epithelioid mesothelioma typically have a median survival of 12–24 months, compared to 7–9 months for sarcomatoid mesothelioma.
Treatment Response: This subtype responds better to multimodal treatments, including surgery, chemotherapy, and radiation therapy.
Age and Gender: Younger patients and females tend to have better outcomes.
Treatment Approaches
The treatment of epithelioid mesothelioma often involves a multimodal approach, tailored to the stage of the disease and the patient’s overall health. Common strategies include:

1. Surgery
Extrapleural Pneumonectomy (EPP): Removal of the affected lung, pleura, diaphragm, and pericardium. This is typically reserved for early-stage disease.
Pleurectomy/Decortication (P/D): A lung-sparing surgery that removes the pleura and visible tumor masses. It is less invasive than EPP and is often preferred for epithelioid mesothelioma.
2. Chemotherapy
Standard Regimen: A combination of pemetrexed and cisplatin is the first-line treatment for unresectable mesothelioma.
Emerging Therapies: Newer agents, such as immunotherapy drugs (e.g., nivolumab, ipilimumab), are showing promise in clinical trials.
3. Radiation Therapy
Used primarily for palliative purposes or as part of a trimodal approach to reduce the risk of recurrence after surgery.
4. Immunotherapy
Recent studies have shown that immune checkpoint inhibitors, such as PD-1/PD-L1 inhibitors, may improve outcomes in epithelioid mesothelioma.
Research and Future Directions
Ongoing research is focused on improving the diagnosis and treatment of epithelioid mesothelioma. Promising areas of study include:

Molecular Profiling: Identifying genetic mutations and biomarkers that can guide targeted therapies.
Immunotherapy: Exploring combinations of immune checkpoint inhibitors and other immunomodulatory agents.
Gene Therapy: Investigating the use of gene-editing technologies to target mesothelioma cells.
Early Detection: Developing blood-based biomarkers, such as mesothelin and fibulin-3, for earlier diagnosis.
Conclusion
Epithelioid mesothelioma, while the most treatable subtype of mesothelioma, remains a challenging disease due to its aggressive nature and late-stage diagnosis in most cases. Advances in diagnostic techniques, multimodal treatment strategies, and emerging therapies offer hope for improved outcomes. Continued research is essential to further refine these approaches and provide better care for patients with this devastating disease.

For more detailed information on epithelioid mesothelioma, consult the latest guidelines from the International Mesothelioma Interest Group (IMIG) or recent studies published in peer-reviewed journals.