Pathology of Mesothelioma

Incidence of Mesothelioma

• Increase in Cases: The incidence of mesothelioma in Japan has been rising, with the number of deaths increasing from 500 in 1995 to 953 in 2004. This rise correlates with the high importation of asbestos between 1960 and 1975, reflecting the long latency period of the disease.
• Demographics and Location: The majority of mesothelioma cases occur in men, with a male-to-female ratio of 3:1. The disease predominantly affects individuals aged 60 and above in men and 70 and above in women. Mesothelioma mainly occurs in the pleura (84% of cases), with smaller percentages found in the peritoneum (12%) and pericardium (1%).

General Findings on Mesothelioma

• Types: Mesothelioma is classified into localized and diffuse types, with the diffuse form being much more common. The localized type, once more frequently diagnosed, is now often identified as a solitary fibrous tumor, distinct from mesothelioma and unrelated to asbestos exposure.
• Disease Progression: In pleural mesothelioma, the disease begins with small nodules in the parietal pleura that spread to cover the entire lung parenchyma. Peritoneal mesothelioma often presents as a large tumor in the omentum or mesentery. Early-stage pathology is less understood, particularly for peritoneal mesothelioma.
• Diagnosis Challenges: Identifying the tumor’s location and characteristics is crucial before histological examination. Differentiating between pleural mesothelioma and lung cancer, or between ovarian cancer and peritoneal mesothelioma, is challenging and requires detailed histological analysis.

Histology of Mesothelioma

• Classification: Mesothelioma is histologically classified into four major types:
  1. Epithelioid Mesothelioma: Accounts for approximately 60% of cases.
  2. Sarcomatoid Mesothelioma: Makes up about 20% of cases.
  3. Biphasic Mesothelioma: Comprises roughly 20% of cases, featuring both epithelioid and sarcomatoid characteristics.
  4. Desmoplastic Mesothelioma: Rare, representing about 1-2% of cases, with features of fibrous pleuritis.
• Variants: Other rare variants include lymphohistiocytoid, deciduoid, anaplastic, and well-differentiated papillary mesotheliomas.

Differential Diagnosis

• Complexity: Differentiating mesothelioma from other diseases is complex and varies based on histological type. For example, epithelioid mesothelioma must be distinguished from lung adenocarcinoma, while sarcomatoid types must be differentiated from sarcomas originating in various body parts.
• Sarcomatoid Challenges: Sarcomatoid mesothelioma is particularly difficult to differentiate from sarcomatoid carcinoma (spindle cell carcinoma) of the lung, often requiring gross clinical findings or imaging for accurate diagnosis.

Usefulness of Immunohistochemistry

• Role in Diagnosis: Immunohistochemical staining is essential for differentiating mesothelioma from other tumors, although no single antibody is specific to mesothelioma. Therefore, a combination of positive and negative markers is used for a comprehensive diagnosis.
• Markers for Types:
  • Epithelioid Mesothelioma: Positive markers include calretinin, WT1, thrombomodulin, mesothelin, and D2-40. Negative markers include CEA, TTF-1, Napsin A, and surfactant apoprotein.
  • Sarcomatoid Mesothelioma: Cytokeratin (AE1/AE3 or CAM5.2) is highly specific. Other antibodies help differentiate from true sarcomas, like MyoD1 and desmin for rhabdomyosarcoma.
• Distinguishing Features: Immunohistochemistry aids in distinguishing between fibrous pleuritis and desmoplastic mesothelioma and between reactive mesothelial hyperplasia and early-stage epithelioid mesothelioma.

Compensation or Relief of Patients

• Importance of Accurate Diagnosis: Accurate diagnosis is crucial for patients to receive compensation or relief under Japan’s compensation system for asbestos exposure. Misdiagnosis affects 10-15% of mesothelioma cases, highlighting the need for improved accuracy.
• Role of Pathologists: Pathologists play a critical role in ensuring accurate diagnosis through appropriate immunohistochemical staining, which is vital for patients’ eligibility for compensation.

Conclusion

The article emphasizes the growing incidence of mesothelioma in Japan, largely due to historical asbestos exposure. It underscores the complexity of diagnosing mesothelioma, the importance of histological and immunohistochemical analyses, and the critical role accurate diagnosis plays in patient compensation. Both clinicians and pathologists are urged to improve diagnostic accuracy to better serve patients and support compensation claims.