Neoplasia can be a tough concept at first. You hear people talk about cancer all the time – but when we use the word “neoplasia” in pathology, it has a very specific definition, and it’s not the same thing as cancer. Here are some great questions I got from a student in this fall’s pathology class.

Q. I don’t understand what is a non-neoplastic epithelial cell and what specifically is a neoplastic cell.

A. A non-neoplastic epithelial cell is just a regular old epithelial cell, sitting there in the skin or in a gland, doing its job and dying off when it’s supposed to.

A neoplastic cell is part of a tumor, and although it may look somewhat like a regular epithelial cell, it is able to grow and divide at a much higher rate than normal. Tumor cells can have lots of different features – but one of their defining features is this ability to continue to grow and divide at a fast rate. They just keep dividing, despite not being told to do so by the body. Pretty soon, there are so many that they actually make a visible or palpable mass. And if you don’t do anything, the mass will get bigger and bigger.

Q. By the definition of neoplasia (new excessive growth) I don’t understand how a non-neoplastic cell can develop into a tumor. If it is non-neoplastic how can there be no new accelerated cell growth and still develop a tumor?

A. In order to become neoplastic, regular old non-neoplastic cells have to undergo a bunch of genetic changes. You’re right: when they are not neoplastic, they don’t have this property of accelerated cell growth. They’re just regular cells that do their job and die off when it’s time.

But if a normal cell acquires certain genetic abnormalities – like the ability to go through the cell cycle without paying attention to checkpoints, or the ability to turn off the normal mechanisms that keep growth under control, or the ability to activate growth receptors when there’s not even any growth hormone attached – then that cell may end up becoming neoplastic.

Sometimes cells that acquire these abnormalities end up getting killed off by normal means (we have proteins that see when our DNA is mutated, and either fix it, or kill off the cell). But if these protective mechanisms don’t work (if a cell acquires a mutation in one of them), then the cell will live on despite all these mutated genes…and it will divide into two cells, and then into 4, and so on.

Usually there are many, many mutations that a cell has to undergo before it officially becomes neoplastic. And every tumor can have its own specific mutations – they’re not the same in every tumor.

Also: sometimes, as the cell acquires these mutations on the way to becoming a tumor cell (a neoplastic cell), it actually looks different too! This seems to be especially true for epithelial cells. As an epithelial cell starts acquiring mutations and goes down the road that leads to neoplasia, it starts showing signs of dysplasia – it grows to an unusually large size, or the chromatin gets darker, or nucleoli show up, or it starts not respecting its neighbors’ space.

These morphologic changes are pretty predictable: cells become mildly dysplastic, then moderately dysplastic, then severely dysplastic. The more dysplastic they become, the more likely it is that they will continue on down the path to carcinoma in situ (and, eventually, invasive carcinoma).

This morphologic progression doesn’t seem to happen the same way in non-epithelial cells. Non-epithelial cells (like muscle cells, or fat cells) may undergo some visible changes as they move towards neoplasia – but those changes are not as predictable or universal as the dysplastic changes that occur in epithelial cells.

Q. And why is it restricted to only epithelial cells?

A. If by “it” you mean neoplasia: neoplasia is not restricted to epithelial cells. Any cell in the body – epithelial, muscle, bone, cartilage, blood, fat, whatever – can become neoplastic.

The restriction we talked about in class was related to the dysplasia (as mentioned above). I don’t know why the same progressive, predictable dysplastic changes don’t seem to occur in non-epithelial cells – but they don’t.

Q. How can non-neoplastic tumors become invasive without accelerated cell growth?

A. Tumors are neoplastic, by definition (tumor is just another word for neoplasia). So all tumors have this propensity to grow autonomously; some are benign (these are not typically invasive), and some are malignant (these typically are invasive).

Q. Also, are all malignant tumors anaplastic?

A. No – malignant tumors can show any level of differentiation they want. They can be well-differentiated (in which they look almost exactly like their cell of origin), moderately-differentiated (in which they sort of look like their cell of origin), poorly-differentiated (in which they really don’t look much like their cell of origin at all), or anaplastic (in which they look absolutely nothing like their cell of origin – they’re just super pleomorphic, with big ugly nuclei, no architecture, and lots of abnormal mitoses).

That being said: malignant tumors are more likely to be anaplastic than benign tumors. Benign tumors are usually well-differentiated (they are rarely, if ever, anaplastic). Malignant tumors can be anywhere on the differentiation spectrum.