Rare Types Of Mesothelioma And Their Characteristics

Introduction

Notoriously known for its difficulties in diagnosis and treatment, mesothelioma has been shrouded in relative obscurity. With a lack of widespread awareness and limited information, we understand how this can be a challenging journey for individuals and their loved ones. This article aims to shed light on this disease's complexities and provide our readers with a comprehensive resource.

Understanding mesothelioma

Mesothelioma describes a cancer of the mesothelium, which essentially is a layer of specialised cells covering the lungs, abdomen, and heart. Since its initial documentation in the 1960s, the number of mesothelioma cases has been steadily increasing. In the UK alone, it is projected that the annual count of cases will rise from the current 1300 to approximately 3000 within the next two decades.¹ The primary cause, asbestos, was once a substance that was widely used in the manufacturing of products such as insulation, roofing materials and fire-proofing agents. Constant exposure to the asbestos fibres within the mesothelium leads to damage and irritation, eventually resulting in cancer.

Diagnosis

When a mesothelioma diagnosis is suspected, a detailed occupational history will be obtained to assess potential asbestos exposure and legal compensation. The standard diagnostic workup includes a chest X-ray, a computed tomography (CT) scan of the chest and upper abdomen, a thoracentesis (examination of fluid surrounding the lungs) and general blood tests.²  

Exploring mesothelioma variations

Mesothelioma encompasses various types, each with distinct features and outcomes. Let's delve into these variations, beginning with well-differentiated papillary mesothelioma and localised malignant mesothelioma, before focusing on the most common variant, diffuse malignant mesothelioma (DMM).

Well-differentiated papillary mesothelioma presents as a tumour with elongated, finger-like growth patterns on the surface. Notably, this type is characterised by only having a singular cell type and with the inability to invade other cells. As a result, it often carries a favourable prognosis. Another rare form is localised malignant mesothelioma, characterised by the presence of a solitary tumour node confined to a specific area. Timely detection and differentiation from other types are crucial. Those diagnosed with this subtype often experience better outcomes than DMM cases, as complete surgical excision is a potentially curative approach, highlighting the importance of accurate identification. However, do keep in mind that treatment options may vary depending on specific tumour characteristics and extent.³

Within diffuse malignant mesothelioma (DMM), further organisation can be achieved based on cell type, including epithelioid, sarcomatoid, and biphasic subtypes. When determining prognosis, the determination of histology, precisely the cell type, becomes the most crucial marker.

Diffuse malignant mesothelioma

Epithelioid mesothelioma

One of the most common cell types of DMM, epithelioid mesothelioma, is described as cells that take on an elongated egg shape. Often clumping together to form clusters, they have a heterogeneous morphology and present with more than two growth patterns.³ Despite presenting with a high rate of division compared to other forms, cancer progression is slower as the clusters take time to metastasise (move to different regions of the body).

Symptoms vary depending on the cancer location. Pleural mesothelioma, which describes the cancer of the mesothelium lining the lungs, presents with symptoms such as chest pain, coughing and fluid build-up around the lungs (pleural effusion). Peritoneal mesothelioma, which describes the cancer of the mesothelium lining the abdomen, manifests with symptoms including abdominal pain and swelling, constipation, loss of appetite and weight loss.

During a biopsy or immunohistochemistry (IHC) testing, specific markers are used to identify certain characteristics in the tissue samples. Here are the markers and their significance:

• Calretinin: This marker is found in almost all epithelioid mesotheliomas. Its presence can help confirm the diagnosis of this subtype
• Cytokeratin: Cytokeratin is present in a majority (70% to 95%) of mesotheliomas. Its detection through IHC testing supports the diagnosis of mesothelioma
• Podoplanin (D2-40): Podoplanin is highly expressed (90% to 100%) in mesotheliomas. Its presence aids in confirming the diagnosis²

Sarcomatoid mesothelioma

Oval-shaped and elongated sarcomatoid mesothelioma is challenging to diagnose and treat. Due to its ability to metastasise to distant cells, it is known as one of the more aggressive types of mesothelioma. The symptoms of sarcomatoid are quite generalised, varying from abdominal or chest pain to decreased appetite and unintended weight loss. Difficulty breathing is a common symptom, often accompanied by shortness of breath and a persistent cough. Excess fluid build-up in the lungs or abdomen can cause discomfort and lead to symptoms such as fatigue and nausea.² 

Sarcomatoid mesothelioma can be classified into various subtypes, each with its own unique features.

Among these subtypes is desmoplastic mesothelioma, characterised by the presence of twisting fibres generated by thick collagen. This subtype can be misleading, often mistaken for conditions like reactive fibrosis or fibrous pleurisy. It is crucial to differentiate between these conditions, as their treatment and prognosis differ significantly. Desmoplastic mesothelioma comprises only a tiny fraction, accounting for less than 2% of cases. Unlike other subtypes, it is typically not accompanied by pleural effusion, which refers to fluid accumulation in the lungs. However, it is associated with a higher incidence of distant metastases, where cancer cells spread to other body parts.

Lymphositiocytoid refers to a tumour of a variety of cells. When examined using microscopic analysis, studies reveal the presence of enlarged, abnormal spindle-shaped cells mixed with white blood cells. In addition, this tumour type is characterised by diffuse thickening of the pleura, the occurrence of small nodules dispersed throughout the lining of the lung, and the development of pleural effusion (the build-up of fluid between the layers of the pleura). These signs collectively contribute to the diagnostic profile of this tumour subtype.

Transitional has a plump spindle shape, and it closely resembles epithelial cells - making diagnosis difficult.

During a biopsy or immunohistochemistry (IHC) testing, specific markers are used to identify certain characteristics in the tissue samples. Here are the markers:²

• Pancytokeratin: Positive stain for sarcomatoid mesothelioma
• WT1 or podoplanin: Positive stain for sarcomatoid mesothelioma
• D2-40: Positive stain for sarcomatoid mesothelioma
• Calretinin: Minority stain positively 

Biphasic mesothelioma

Biphasic mesothelioma is a subtype of mesothelioma that consists of at least 10% of both epithelioid and sarcomatoid components, therefore, prognosis tends to fall between the two subtypes. Research conducted by Vigneswaran et al. demonstrated that patients with less than 50% of the epithelioid component have a survival rate of 6.62 months compared to those with 50% more epithelioid (up to 11.8 months).⁴

Due to the heterogeneous nature of biphasic tumours, accurate diagnosis can be challenging, and misdiagnosis may occur if the biopsy sample does not capture both cell types. Multiple biopsies may be necessary to prevent misdiagnosis, as a single sample may only reveal one tumour component. Various biopsy methods, such as thoracotomy, thoracoscopy, and CT-guided biopsy, have different levels of accuracy in diagnosing biphasic mesothelioma.

Pathologists rely on immunohistochemistry testing to confirm a biphasic mesothelioma diagnosis. This involves examining the biopsy tissue for the presence of proteins produced by both sarcomatoid and epithelioid cells. If proteins from both cell types are detected, it indicates a presence of biphasic mesothelioma.² 

Treatment options for mesothelioma

Surgery has been a treatment option for mesothelioma since the 1950s, although its effectiveness is still debated. Surgery can serve palliative purposes by reducing swelling and pleural fluid or aim to remove visible tumours for enhanced quality of life.

Different Surgical Procedures:

1. Partial pleurectomy (PP): Partial removal of the pleura, either for diagnostic purposes or to provide palliative relief while visible tumours remain
2. Pleurectomy/Decortication (PD): Removal of both the parietal and visceral pleura to eliminate visible tumours without affecting the diaphragm or pericardium
3. Extended Pleurectomy/Decortication (EPD): Removal of both the parietal and visceral pleura, along with the diaphragm and/or pericardium if necessary, to ensure complete tumour removal
4. Extrapleural pneumonectomy (EPP): Comprehensive removal of the parietal pleura, pericardium, diaphragm, lung, and visceral pleura in one procedure⁵

While newer chemotherapy regimens and multimodality treatments have shown some improvements in prognosis, mesothelioma remains a highly symptomatic cancer. Access to palliative interventions is crucial for providing high-quality care.

Other Treatment Options:

• Chemotherapy: The only treatment proven to improve survival in mesothelioma patients
• Radiotherapy: Used to relieve chest wall pain and target chest wall nodules resulting from the tumour spreading
• Chemo-radiotherapy: Sometimes administered as part of a comprehensive treatment plan combining surgery and chemotherapy for patients with limited disease and good health

It's important to note that treatment options may vary depending on specific tumour characteristics and extent.

Summary

In conclusion, mesothelioma is a complex disease with different types and treatment options. Understanding these variations and available treatments can empower patients and their loved ones to make informed decisions and seek appropriate care.

Mesothelioma, a complex and often misunderstood disease affecting the lining of the lungs, abdomen, and heart, presents challenges in diagnosis and treatment. This article has provided insights into the different types of mesothelioma, diagnostic methods, and treatment options, including surgery, chemotherapy, and radiotherapy. By shedding light on these aspects, we aim to equip individuals and their loved ones with valuable knowledge to navigate the journey of mesothelioma with confidence and informed decision-making. Understanding the disease is a crucial step towards effective management and improved outcomes.