Q. How can basal cell carcinoma be considered both malignant and invasive if it never metastasizes? I thought we learned that one of the characteristics that defines the term “malignant” is metastasis. And if a tumor is invasive, how can it not metastasize?
A. Your question is a great one. First of all, you are correct in saying that basal cell carcinoma is considered malignant, and it is definitely invasive…but it (virtually) never metastasizes. That sure seems incongruous.
When you’re trying to tell whether a tumor is benign or malignant, there are four features that you can use: differentiation/anaplasia, rate of growth, local invasion and metastasis.
Let’s just review those features quickly:
Differentiation refers to how much the tumor cells resemble their cell of origin (so if it’s breast carcinoma, how much do the tumor cells resemble normal breast tissue?). Tumors can be well-differentiated (closely resembling their tissue of origin), moderately-differentiated (sort of resembling their tissue of origin), or poorly-differentiated (hardly resemble their tissue of origin at all). The word anaplasia means a state of complete un-differentiation (the tumor cells are so poorly-differentiated that you really can’t tell what the heck kind of tissue it is). Benign tumors tend to be more well-differentiated; malignant tumors tend to be less well-differentiated. Anaplasia almost always indicates malignancy.
Note the words “tend to” and “almost always” in the last sentence. This particular characteristic, and most of the others that we will discuss, have nice generalizations like that (but they are just that: generalizations…which means that there are exceptions). The one characteristic that has an “always/never” in it is metastasis (see later).
2. Rate of growth
Here’s another generalization: malignant tumors tend to grow faster than benign ones.
3. Local invasion
Benign tumors are often encapsulated, and as they grow, they “push” other tissues away – but they don’t truly invade. Malignant tumors generally are not encapsulated. As they grow, they tend to infiltrate, invade, and destroy surrounding tissue.
Metastasis means that there is a secondary implant of a tumor in a distant tissue. Here’s the big “always/never” statement we alluded to earlier: benign tumors never metastasize. They always remain where they are. Malignant tumors, on the other hand, usually do metastasize. So if you see a metastasis of a particular tumor, you can safely say that the original tumor is a malignant one.
Note that we said malignant tumors usually (but not always) metastasize. Not all malignant tumors metastasize! Basal cell carcinoma is a great example. It is definitely malignant (it grows fast and invades surrounding tissue), but it very very rarely metastasizes. So: metastasis does define the term “malignant” as you mentioned – but only if metastasis is present. If something metastasizes, it’s definitely malignant.
The last part of your question brings up an interesting point: if a tumor is invasive, how can it not metastasize?
The genetic damage in cancer cells can impart any or all of the following “powers” to the cancer cells:
1. Autonomous growth (cells grow on their own without any growth signals from the outside)
2. Insensitivity to growth-inhibitory signals (cells don’t respond to the normal signals that curtail growth)
3. Evasion of apoptosis (cells don’t undergo normal apoptosis…they basically just live forever)
4. Limitless replication (normal cells have only a limited number of possible divisions, then they die; cancer cells sometimes are able to outwit this constraint and just keep on replicating)
5. Sustained angiogenesis (cells are able to stimulate and maintain angiogenesis – so they get a nice supply of blood)
6. Invasion and metastasis (cells are able to invade surrounding tissue and have the potential to metastasize.) These are similar, but distinctly different qualities. Invasion requires that the cell know how to dissolve the surrounding stroma and reach out into the normal tissue; metastasis requires that the cell know how to invade a vessel, exit the vessel at some point, and implant itself in a distant tissue.
These characteristics are not present in every kind of cancer; and even within one particular tumor, they are not present in all of the tumor cells! While malignant tumors are “clonal” (meaning that all the cells in the tumor descended from one crappy genetically damaged cell), they also have “subclones” (parts of the tumor with their own particular characteristics – e.g., ability to grow autonomously, or ability to invade, or ability to metastasize). These subclones evolve over time; new ones can appear and old ones can die off. Some malignancies have all of these “powers” and other have only a few.
So, to answer your last question, a malignant tumor may be great at invading – but may not readily metastasize. Just like it may evade apoptosis but not stimulate angiogenesis very well. The underlying genetic abnormalities in the cell determine what particular characteristics the tumor will have…but that’s for another post!
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