I received an email yesterday that had questions about a post from a couple years ago – and rather than bury the answers way back in 2009, I thought I’d make a new post. The questions provide a good foundation for discussing some of the morphologic differences between squamous cell carcinoma and small cell carcinoma, two common types of lung cancer that can, in some instances, look somewhat similar. Without further ado, here are the questions (in bold):

Hi, i found this website is sooo helpful for me. Thanks for sharing. I have some questions on your photo from “Undifferentiated tumors: solving the mystery” (July 2009). What’s the morphologic difference between squamous cell carcinoma and small cell carcinoma? Small cell carcinoma is said to have a oat-grain shaped cell, but this squamous cell carcinoma also looks like it has oat-shaped cells.

A. If a squamous cell carcinoma is well-differentiated, it’s easy to tell it apart from small cell carcinoma. The squamous cell carcinoma cells are large and somewhat polygonal, with abundant, eosinophilic cytoplasm (often with intracytoplasmic keratinization), intercellular bridging, and scattered keratin pearls. Small cell carcinoma, in contrast, is composed of, well, smallish cells, which have minimal to no apparent cytoplasm and a “salt-and-pepper” chromatin pattern. The cells in small call carcinoma also tend to stick close together, so that their nuclear contours appear “molded” to those of the adjacent tumor cells. Sometimes the cells in small cell carcinoma are more elongated, with tapered ends; cells with this morphology are called “oat cells.” There are other morphologic variants too.

If a squamous cell carcinoma is poorly-differentiated, however, it will lack many of the features described above. Cells may range in size from small to large, and there probably won’t be any keratin formation. In these cases, it could be more difficult to tell a squamous cell carcinoma from small cell carcinoma, particularly if the cells in the squamous cell carcinoma case happen to be smallish. In cases where there isn’t enough morphologic information to make an accurate diagnosis, special stains are used (like cytokeratin, which is positive in most squamous cell carcinomas).

I can see what you mean about the cells in the above photo: some of the nuclei do have sort of an oat shape. However, the cells in this photograph would not be considered classic “oat cells” because their chromatin is not the salt-and-pepper type seen in small-cell (and other neuroendocrine) carcinomas, they are widely distributed, they have abundant amounts of cytoplasm, and they are not “molding” to each other. In addition, the intracellular bridging and keratin pearl formation are giveaways for squamous cell carcinoma. In small cell carcinoma, the cells are tightly grouped, with minimal cytoplasm in between the cells, giving the tumor a dark blue appearance at low power.

Is it true that the nucleolus in squamous cell carcinoma can be seen?
A. Yes: you can see nucleoli in some squamous cell carcinoma cells. I see a number of nucleoli in the image above. By themselves, nucleoli are usually not helpful in distinguishing one type of carcinoma from another; they are more useful in determining the grade of a tumor (a tumor composed of pleomorphic cells with big nucleoli is generally a higher-grade tumor).