Epithelioid cells are a specific cell type frequently referenced in medical reports and pathology findings, primarily associated with chronic inflammation and certain diseases. The term “epithelioid” literally means “like epithelium,” indicating that these cells possess a shape resembling the true epithelial cells that line organs and body surfaces. This morphology is encountered in two distinct contexts: as a specialized form of immune cell and as a descriptive feature used in classifying various tumors. Understanding the difference between these two contexts is fundamental to interpreting their medical significance.
Defining Epithelioid Cells
The defining feature of epithelioid cells is their distinctive morphology. These cells are typically polygonal or somewhat flattened with abundant cytoplasm that stains a pale pink color (eosinophilic) using standard laboratory techniques. The nucleus is often oval or elongated and appears less dense than the nuclei found in surrounding immune cells, such as lymphocytes.
Adjacent epithelioid cells often display indistinct boundaries, appearing to merge into one another within a tissue cluster. This tight interdigitation mimics the close organization of true epithelial tissue. However, epithelioid cells are not derived from the epithelial lineage and lack the structural polarity or keratin markers characteristic of true epithelial tissue. This clarifies that “epithelioid” refers only to shape, not to developmental origin or function.
Immune System Origin and Function
Epithelioid cells are specialized derivatives of the monocyte and macrophage lineage, which are types of white blood cells. Monocytes enter tissues and transform into macrophages, the immune system’s primary phagocytic cells responsible for engulfing foreign material. When a pathogen or foreign substance is difficult for a macrophage to destroy, the macrophage undergoes further transformation and activation to become an epithelioid cell.
This transformation is often triggered by persistent irritants, such as certain bacterial or fungal components. Once activated, epithelioid cells exhibit a reduction in their typical phagocytic activity compared to their macrophage predecessors. Instead, these modified cells adopt a secretory role and organize themselves to form a physical barrier, effectively walling off the offending agent from the surrounding healthy tissue.
The Role in Granuloma Formation
The primary functional outcome of epithelioid cell activation is the formation of a granuloma, which is a highly organized, localized cluster of immune cells. Epithelioid cells form the central structural scaffold of this aggregate, tightly interdigitating to create a compact barrier around the source of inflammation. This process serves to contain pathogens or foreign bodies that the immune system cannot immediately clear, preventing their spread throughout the body.
As part of this containment mechanism, multiple epithelioid cells often fuse together to create a much larger structure known as a multinucleated giant cell. The most common type is the Langhans giant cell, characterized by multiple nuclei arranged in a horseshoe or peripheral pattern within the cell’s abundant cytoplasm. These giant cells contribute to the walling-off process and can surround and degrade large, non-digestible particles.
Granulomas containing epithelioid cells are the hallmark feature of several chronic inflammatory conditions, including infectious and non-infectious diseases. Tuberculosis is the classic example, where the epithelioid granuloma often develops a central necrotic area known as caseation. Other significant conditions characterized by epithelioid granulomas include sarcoidosis, Crohn’s disease, and certain fungal infections like histoplasmosis.
Epithelioid Appearance in Malignant Tumors
The term “epithelioid” is also used descriptively in oncology when cancer cells adopt this specific shape, regardless of their origin tissue. In this context, the term indicates that the tumor cells are polygonal, possess abundant cytoplasm, and have a clear, distinct appearance, similar to true epithelial cancers. These malignant epithelioid cells are not immune cells and do not perform the barrier function associated with granuloma formation.
This morphology can create diagnostic challenges because a non-epithelial cancer that looks epithelioid must be distinguished from a true carcinoma. Examples of non-epithelial malignancies that frequently display this morphology include epithelioid sarcoma, epithelioid melanoma, and epithelioid variants of soft tissue tumors like epithelioid leiomyosarcoma. Pathologists rely on specialized techniques, such as immunohistochemistry, to determine the true lineage of the cancer cells and differentiate them from both immune-derived epithelioid cells and true epithelial tumors.