Tumor Grading

00:01 Okay. Welcome back.

00:03 We've already talked now about benign versus malignant and including dysplasia and how a pathologist and now you, think about how a cell looks, in terms of deciding whether it's malignant or benign.

00:17 We're going to go now into further pathologic evaluation of tumors and this involves tumor “Grading” and “Staging” and sometimes these terms are confused, so, we'll spend a little bit of time hopefully clarifying it for you.

00:31 Tumor grading general principles.

00:33 This is what we see looking down the microscope, it's a microscopic assessment of various features of the tumor.

00:42 The degree of differentiation, will determine whether something is a well-differentiated, moderately differentiated, poorly differentiated tumor and that will affect the grading.

00:55 We look at the number of mitoses, so, the proliferative index, we look at whether or not the mitosis are normal or abnormal, we evaluate for necrosis and we evaluate histologically, for vascular lymphatic perineural or capsular invasion and all of those things will affect the grade of the tumor, from a high grade tumor which tends to do worse or a low grade tumor which tends to do better and the more abnormalities we have typically the higher the grading.

01:25 Just as an example here, this is showing a differentiation pathway that's used to determine whether a prostate cancer, is well differentiated at the top, versus very poorly differentiated or anaplastic at the bottom and the general features that you see in terms of the organization, whether you have small uniform glands or you have infiltrative margins, whether you have poorly organized glands or whether the cells are just looking totally bizarre, will go from a well-differentiated low-grade tumor at the top, to a poorly differentiated high-grade tumor at the bottom.

02:03 And there are similar sorts of organization and grading schema they're used for every different cancer, this just happens to be the one used for prostate cancer.

02:14 So, what does this mean in terms of looking at a tumor? Well, the tumor on the left, is a low-grade leiomyosarcoma, it's a malignant tumor, most of the cells that are in there, look kind of like smooth muscle cells.

02:33 On the right-hand side is one that's poorly differentiated, looking at that, I don't see any of those spindly cells, that I see on the left-hand side.

02:42 It looks like I just have bizarre things that are all over the place, including wild mutations.

02:48 That cell at the very top, with kind of pentapolar mutation or pentapolar mitosis.

02:54 So, one is well differentiated and will tend to do better, not be as aggressive, versus the poorly differentiated tumors, that tend to do worse.

03:08 So, when we look through the microscope, here's another example of colorectal adenocarcinoma.

03:14 Well differentiated, the glands are nicely formed there are lots of them and it's recognizable as glandular epithelium.

03:25 As it gets a little bit less well differentiated, it gets more hyperplastic, the glands are still there, but they tend to be smaller and not as well formed.

03:34 And finally in poorly differentiated adenocarcinoma colon, oh my goodness, it's almost impossible to see any glandular differentiation, the tumor has acquired so many mutations, that it totally doesn't care that it was supposed to start out life as a colon epithelial cell and now, I just have proliferating cells in nests and bundles throughout the tissue.

04:00 As part of our histologic evaluation, in terms of grading, we will also see whether tumors have other things that they are making.

04:07 So, if they're making lots of mucin, all that kind of clear gray stuff, inside of the cells, or whether they're forming a distinct appearance, so-called signet ring cell, where you have nuclei at the edge of the cell, around a collection of mucus within each individual cell, so, it looks like a signet ring, that you would wear from your fraternity for example.

04:35 Those all will have impact, whether it's well differentiated, poorly differentiated or making mucin, making signet ring cells, all of that will affect the tumor grade and as I said, it's different in terms of the parameters that we look at for every tumor.

04:52 So, in Gleason grading for the prostate, we don't have mucinous or signet ring cells, we just have well differentiated, moderately and poorly.

05:00 So, in colon cancer we do.

05:05 I don't expect you to remember those distinctions, but be aware that, when you become world famous oncologist, pay attention what your pathologist is telling you, in terms of the degree of differentiation other features.