Malignant mesothelioma is an aggressive cancer that develops from the thin layer of protective tissue lining many internal organs. Spindle Cell Mesothelioma (SCM) is a rare subtype, classified under sarcomatoid mesothelioma. This variant is defined by the unique, elongated morphology of its cancerous cells, which results in a distinct growth pattern and biological behavior compared to more common forms. Understanding SCM’s cellular structure is important, as it significantly influences both the diagnostic process and the effectiveness of available treatment options.
Defining Spindle Cell Mesothelioma
Spindle Cell Mesothelioma is histologically identified by its “sarcomatoid” morphology, meaning the malignant cells are noticeably oblong and spindle-shaped under a microscope. This differs from the epithelioid subtype, which features cube-shaped cells that stick together in sheets. SCM cells grow in a less cohesive, more haphazard pattern, often forming disorganized fibrous nodes or lesions.
This lack of cellular cohesion contributes to the disease’s aggressive nature. Since the cells do not clump together, they are more prone to breaking off and spreading quickly to distant organs, a process known as metastasis. SCM is the rarest of the three main mesothelioma cell types, accounting for 10 to 20% of all diagnoses, and is associated with a poorer prognosis and greater resistance to traditional therapies.
While SCM can arise in the lining of the abdomen (peritoneum) or the heart (pericardium), it is most commonly found in the lining of the lungs (pleura). Tumors containing both epithelioid and sarcomatoid cells are classified as biphasic mesothelioma. If the sarcomatoid component dominates, the tumor is often treated similarly to pure SCM due to its aggressive behavior.
Primary Environmental Causes
The cause of Spindle Cell Mesothelioma, like all forms of malignant mesothelioma, is exposure to asbestos fibers. Asbestos is a group of naturally occurring mineral fibers that, when inhaled, can penetrate deep into the lungs and travel to the pleural or peritoneal linings. The disease has a long latency period, often spanning 20 to 40 years between initial exposure and development.
Once the asbestos fibers reach the mesothelial lining, they initiate cellular damage through chemical and mechanical means. Chemically, the fibers generate reactive oxygen species that cause direct damage and breaks in cellular DNA. Mechanically, the physical presence of the fibers interferes with the cell’s internal machinery, tangling with mitotic spindles during cell division.
This mechanical interference leads to chromosomal structural abnormalities and aneuploidy, resulting in an incorrect number of chromosomes within the cell. These accumulated genetic defects drive the malignant transformation of the mesothelial cells. While all types of asbestos are dangerous, amphibole fibers, such as crocidolite and amosite, are considered more carcinogenic than the serpentine fiber chrysotile.
Beyond asbestos, certain inherited genetic alterations can increase susceptibility to mesothelioma. For example, mutations in the BAP1 tumor suppressor gene are known to predispose individuals to the disease. Asbestos remains the primary etiology, though other potential risk factors, such as radiation exposure or infection with Simian Virus 40 (SV40), are also being studied.
In the United States, the use of asbestos is regulated under the Toxic Substances Control Act (TSCA). The Environmental Protection Agency (EPA) uses this authority to restrict the substance, recently finalizing a rule in March 2024 to prohibit the ongoing uses of chrysotile asbestos.
Confirming the Diagnosis
Confirming a diagnosis of Spindle Cell Mesothelioma is challenging because the tumor tends to mimic other cancers, particularly soft-tissue sarcomas. The initial step involves medical imaging, typically using computed tomography (CT) or positron emission tomography (PET) scans, to visualize the tumor’s location and extent of spread. However, imaging alone cannot determine the specific cell type.
A definitive diagnosis requires obtaining a tissue sample through a biopsy, which is then examined by a pathologist. Specialized techniques are necessary to distinguish SCM from other spindle cell neoplasms or sarcomatoid carcinomas of the lung. This differentiation is important because treatment strategies vary significantly between these tumor types.
The most reliable method for confirming SCM is immunohistochemistry (IHC), a process that uses specific antibodies to identify proteins expressed by the cancerous cells. Pathologists use a panel of markers to determine the tumor’s origin. SCM cells must stain positive for mesothelial markers, confirming their lineage:
- Calretinin
- WT-1
- D2-40
- Cytokeratin 5/6
Concurrently, the cells must be negative for epithelial markers, such as MOC-31, which are typically found in carcinomas. Pathologists also look for the loss of expression of tumor suppressor proteins, such as BAP1, which indicates the spindled cells are malignant.
Current Treatment Approaches
The management of Spindle Cell Mesothelioma is a multimodal strategy combining therapies to control the disease. Because of the aggressive nature of sarcomatoid cells and their limited response to localized treatments, systemic therapies that circulate throughout the body are often prioritized. The distinct cell type significantly determines the most effective course of action.
Surgical intervention, such as pleurectomy/decortication (removal of the lung lining) or extrapleural pneumonectomy (removal of the lung and its lining), is generally less effective for SCM than for the epithelioid subtype. Poor cellular cohesion and rapid spread make it difficult to remove all microscopic disease with surgery alone. Therefore, surgery is often reserved for patients with localized disease or for palliative purposes to relieve symptoms like pain or fluid buildup.
Chemotherapy remains a standard systemic treatment option for SCM, often using platinum-based drugs like cisplatin in combination with pemetrexed. This regimen works by directly attacking and killing rapidly dividing cancer cells. However, the sarcomatoid subtype is known to be less responsive to these agents than other forms of mesothelioma.
Immunotherapy has emerged as a promising approach for SCM, often offering superior results to traditional chemotherapy. This therapy uses checkpoint inhibitors, such as the combination of nivolumab and ipilimumab, to “unblock” the body’s immune system. This allows immune cells to recognize and attack the cancer cells more effectively.
Clinical trials have shown that this immunotherapy combination offers a survival benefit over chemotherapy, especially for patients with the sarcomatoid or biphasic cell types. Other emerging treatments include targeted therapies, which focus on specific molecular pathways to limit cancer cell growth, and the use of electric fields, such as Tumor Treating Fields (TTFields), which disrupt the cell division process.