Mesothelial cells form the mesothelium, a delicate lining covering the body’s major internal cavities, including the pleura (lungs), peritoneum (abdomen), and pericardium (heart). This layer acts as a protective barrier and facilitates movement by secreting a lubricating fluid. Pathologists face a significant challenge distinguishing between reactive mesothelial proliferation, a benign response to injury, and malignant mesothelioma, a life-threatening cancer. The morphological changes in these cells are highly ambiguous, making visual differentiation difficult. Accurately determining the nature of the cells is paramount for directing the correct medical path for the patient.
Defining Mesothelial Cells and Their Environments
Mesothelial cells are simple, flattened cells that constitute the serous membranes (serosa), lining the coelomic cavities and surrounding the visceral organs. The primary function of this lining is to produce a thin, slippery fluid that minimizes friction, allowing organs like the lungs to expand and contract smoothly. These cells also play a role in fluid transport, tissue repair, and immune surveillance.
A “reactive” change is a benign, non-cancerous response to irritation, infection, or injury, such as fluid buildup or a surgical procedure. In this state, the cells multiply and change shape to repair the damaged lining, resulting in reactive mesothelial hyperplasia. This proliferation is the body’s attempt to heal, but the resulting cellular changes can sometimes intensely mimic the appearance of cancer under a microscope. Reactive changes signal an underlying problem that needs treatment, but they do not represent a malignant transformation.
Visual Distinction: Reactive vs. Malignant Morphology
Initial diagnosis relies on the visual assessment of cellular morphology, typically from fluid samples or tissue biopsies. The plasticity of mesothelial cells means that reactive cells can exhibit features associated with malignancy, while some malignant cells can appear benign. For example, highly reactive mesothelial cells may form large, cohesive groups or exhibit multiple nuclei, features that can be suspicious.
Pathologists look for specific attributes that favor a benign diagnosis, such as uniform cell size and shape, smooth nuclear contours, and a low nucleus-to-cytoplasm ratio (abundant cytoplasm). Reactive cells often appear in organized sheets and are seen against a background rich with inflammatory cells, indicating an active healing process.
In contrast, malignant cells typically display significant pleomorphism (variation in size and shape). Malignancy is suggested by a high nucleus-to-cytoplasm ratio, irregular nuclear membranes, and prominent, multiple nucleoli. Malignant mesothelioma cells tend to form disorganized, ball-like aggregates rather than flat sheets, and they may show evidence of necrosis. In tissue biopsies, the most definitive visual feature of malignancy is the invasion of the underlying tissue, which is not seen in benign reactive processes.
Advanced Techniques for Differentiation
When visual features are ambiguous, specialized laboratory tests, primarily Immunohistochemistry (IHC), are employed to definitively distinguish the cell types. IHC uses antibodies to detect specific proteins expressed by the cells, providing a molecular fingerprint of their identity. Testing involves a panel of markers to confirm the mesothelial origin and exclude other types of cancer, such as metastatic adenocarcinoma.
IHC Markers for Mesothelial Lineage
Markers like Calretinin and WT1 are used to confirm mesothelial lineage, as they are strongly expressed in both benign and malignant mesothelial cells.
IHC Markers for Malignancy
To confirm malignancy, pathologists utilize markers that are highly expressed in cancer but absent or weak in reactive cells. For instance, Epithelial Membrane Antigen (EMA) and Glucose Transporter 1 (GLUT-1) show strong, diffuse staining in malignant mesothelioma, while reactive cells are largely negative. Conversely, the protein Desmin is often present in reactive mesothelial cells but is typically absent in malignant mesothelioma.
Molecular testing provides further clarity by focusing on genetic alterations linked to malignancy. Loss of the BAP1 protein, detected by the absence of nuclear staining, is a highly specific indicator of malignant mesothelioma. Normal or reactive mesothelial cells retain BAP1, showing positive nuclear staining. The combined results from these IHC and molecular panels offer the highest level of confidence in the final diagnosis.
The Clinical Impact of Diagnosis
The accurate differentiation between a reactive process and a malignant one carries enormous weight for patient care. If the cells are determined to be reactive, management shifts toward identifying and treating the underlying cause, such as draining excess fluid or administering antibiotics. The condition is monitored, and aggressive cancer treatment is avoided.
A diagnosis of malignant mesothelioma necessitates an aggressive treatment strategy. This cancer typically requires a complex, multi-modal approach, which may include chemotherapy, radiation therapy, and extensive surgery. The definitive diagnosis provided by the pathologist is the direct trigger for either a focused, non-cancerous intervention or an urgent oncological regimen.