Squamous cell carcinoma, well-differentiated

Well-differentiated squamous cell carcinoma

Squamous cell carcinoma, moderately-differentiated

Moderately-differentiated squamous cell carcinoma

Squamous cell carcinoma, poorly-differentiated

Poorly-differentiated squamous cell carcinoma

“Differentiation” is a term used to describe the appearance of malignant tumors. It refers to the extent to which a tumor resembles its tissue of origin. Well-differentiated tumors resemble closely their tissue of origin, whereas poorly-differentiated tumors barely resemble their tissue of origin.

Check out the images above. The well-differentiated squamous cell carcinoma cells (top image, right side)  look a lot like the adjacent benign squamous epithelium. They are large, eosinophilic, and polygonal, and they are layered in an architectural pattern that looks like squamous cell epithelium. Sometimes, well-differentiated squamous cell carcinomas will even produce keratin, which usually it appears in the center of a group of epithelial cells with a whorled appearance (there are a couple such groups on the far right side of this image, but without keratin). This type of keratin is called a “keratin pearl” because it looks like a little pink pearl surrounded by a nice group of epithelial cells.

The moderately-differenatiated squamous cell carcinoma looks less like normal squamous epithelium. The tumor cells are still in nests, and there are some larger, eosinophilic, polygonal cells that are trying to layer themselves in a squamousy way, but the overal resemblence to normal squamous epithelium is less striking. The poorly-differentiated squamous cell carcinoma has lost most of its squamous epithelial characteristics and architecture, although if you were able to look closely, you might still be able to see some intercellular bridging like you do between normal squamous cells.

The concept of differentiation is not just some arcane exercise in morphologic skills. There is a clinical correlation between the degree of differentiation of a tumor and its clinical behavior; well-differentiated tumors tend to act nicer and be less aggressive than poorly-differentiated ones.