Professional Documents
Culture Documents
42: Neoplasia
42: Neoplasia
leukemias, for lymphomas, for multiple myelomathose are the tumors that are
related to bone marrow.
Lymphomas start where do you think a lymphoma would develop? In lymph
nodes, okay? Well its multiple lymph nodes so surgery is not the mechanism so
lymphomas are usually treated either by chemotherapy or radiation therapy and the
radiation therapy for lymphoma might be a more localized radiation therapy than
full body radiation thats done for leukemias. And leukemia and sometimes its
done if the lymphoma has escaped from the lymph nodes and is traveling around
the body.
In a primary tumor that has a thats a solid tumor, for those tumors, surgery
and if they are radiosensitive, surgery plus radiation treatment is usually the first
line of treatment for those tumors. And if the tumor is sensitive to chemotherapy
and thats been figured over time and research thats looking at how tumors
responds to treatment then the surgery would be followed with chemotherapy
even if the entire tumor is thought to be removed because there is the possibility
that there are cells that have escaped and now are moving onto metastasis and
theres no way you could find them. And so chemotherapy is done as a way to trying
to eliminate anything that might have escaped from the main tumor.
Malignant tumors, for the most partand there is no completely clear word on this-but most of them are most susceptible early in their development. The longer a
tumor is around, the harder it is to treat. The more times it has recurred, the harder
it is to treat. And so one of the things that happens is tumors become resistant to the
chemotherapy and so if you can get the thing out with surgery and you can get
chemotherapy to wipe out any straggling cells that have decided to escape the
treatment--even of nasty tumors that are very hard to treat--can still be successful.
So sometimes you see youll meet people that have tumors that are malignant
tumors that really think this is not going to go well and patients do well. And the
chemotherapy works well and patients are free of tumor for many, many years. So
its really hard to predict exactly how an individual is going to respond to treatment.
[Slide #29] [Metastasis]
[Dr. Phelan] We know what the literature says and what the statistics are but
individuals are never statistics.
Okay, metastasis we talked about and if you define it, it is the tumor that has is not
connected to the primary tumor and it is an implanted tumor somewhere else.
Benign tumorsand Ill say it over and over againdo not metastasize. Only
malignant tumors metastasize. And all malignant tumors, by definition, could
metastasize. That doesnt say they do but they could.
[Slide #30] [Pathways of Spread]
[Dr. Phelan] There are a couple of different ways that tumors can spread. One
possibilityand this happens for tumors in the abdomen and also lung tumors
2
where theres body cavities surrounding those tumorsthe tumor can actually
break off from the main mass and travel through the body cavity fluid and then take
up residence in another part of that cavity. So, for example, with ovarian tumors you
can have seeding of the tumor, throughout the peritoneal cavity. You can have
tumors that seed throughout the chest cavity because they are loose in the fluid in
that cavity.
Lymphatic spread is very important way and its usually carcinomas that spread
through the lymphatics. And you can imagine what happens, okay? We have those
sewers that are present in the tissue. The tumor cells break off and get themselves
into the lymphatic drainage and then get themselves into the lymph nodes. Usually
the first place that these tumors are going to develop a new tumor is in the lymph
nodes. And if you have any experience in the hospitals when you are there either as
a resident or sometimes even when youre there now on a rotation, when squamous
cell carcinoma of the oral region is treatedit kind of depends on where it isbut
very often what we've done is that in addition to removing the primary tumor, there
will be a removal of either the lymph nodes in the upper neck or of the entire lymph
node chain that drains that area in the neck to make sure that any lymph nodes that
picked up the metastatic tumor are removed so that it doesnt go any further.
So the lymph node drainage and the lymph nodes in the neck is the protection from
the intraoral squamous cell carcinoma getting from the oral cavity to the rest of the
body. So carcinomas tend to follow that lymphatic drainage. Sarcomas dont do that
real well. Okay? They really dont use the lymphatic drainage. They usually use the
blood route and their cells break off from the main tumor and they get into the
bloodstream and they go where they're going. Carcinomas can do the same thing
and when we're looking at a carcinoma under the microscope, when you see that
carcinoma wrapping itself around all the blood vessels in the are, you know that that
carcinoma has the ability to get from the main mass into the vascular supply and
then go anywhere it wants to go in the rest of the body. So both carcinomas and
sarcomas can follow the hematogenous route but usually its carcinomas that go by
lymphatics.
And some of them really dont metastasize much. Okay? And one of them is basal cell
carcinoma. Basal cell carcinoma, I think
[Slide #31] [Eye and nose picture]
[Dr. Phelan] yeah, heres one. Basal cell carcinoma is a skin tumor. They can get
huge and still not metastasize. It doesnt mean they never and they cant but they
usually dont. So usually basal cell carcinomas can very nicely be treated by wide
excision of the area. And I know when I worked for the VA we, every once in a while,
would find somebody who had been, I dont know, out in the without medical care
for a long time and would come in with a huge, huge basal cell carcinoma. And again,
you would think how could this carcinoma not metastasize and get this big? But
basal cell carcinomas, as a rule, you can remove them and theres very, very, very
little chance of them metastasizing.
3
Squamous cell carcinomas of skin, also, very slow to metastasis. And if you look at
the difference in the prognosis of a squamous cell carcinoma when it occurs on the
vermillion of the lip, it behaves like a skin tumor. The ones intraorally behave
different. So the prognosis of a squamous cell carcinoma on the lip is much better
than a squamous cell carcinoma intraoral. Yes?
Heres another very small carcinoma. And you guys will pick these up when you do
your skin exams. Dental students are very good at picking up basal cell carcinomas
and most of my pictures of basal cell carcinomas are from the ones that dental
students have very nicely picked up in their very thorough skin exams.
[Slide #32] [Tongue picture]
[Dr. Phelan] Okay, here is a squamous cell carcinoma. Intraorally, its going to
behave differently.
[Slide #33] [Cheek pictures]
[Dr. Phelan] These are both patients who have metastatic lymph nodes or
carcinoma to metastatic lymph nodes in the neck. They both had intraoral
carcinomas and they metastasized through the lymphatic channels into lymph
nodes in the neck.
[Slide #34] [Radiograph]
[Dr. Phelan] This one I believe is a ... you know I dont have which one it is because I
looked it up trying to figure out which one this is. Its either prostate or breast.
Because both of those can do bone metastasis and they will stimulate the formation
of bone. And even though this doesnt look like much more than a dense bone island,
this turned out to be a metastatic lesion that was either from prostate or breast.
[Slide #35] [Liver picture]
[Dr. Phelan] This is an autopsy specimen, obviously because this patient no longer
has his liver. But each one of these is a metastatic carcinoma that has gotten itself to
the liver and has taken and each one of them is an individual squamous cell
carcinoma that has now become a tumor separate from where it came from and its
now in the liver. These carcinomas this carcinoma started out in the lung. This is
not an oral this was a lung carcinoma. Somebody had a question? No? Okay. Yes?
[Student]Is there a good way to be able to distinguish between the cancer and
bony islands on the x-ray?
[Dr. Phelan]Yeah, there is. Well get there when you go to clinic. Yeah, there
probably is. Okay, usually the dense bone island is much better circumscribed and
the not necessarily cancer but the ones we worry about are the ones that are very
diffuse in their appearance rather than just the density.
4
would. But youre getting a multiplication of the cells. Now, [C] were beginning to
get dysplasia, okay? And its moving on continued exposure to the mitogen or the
components of tobacco smoke that is continuing to change the epithelium. Now, [D]
look at how much change we have in the epithelium. This would be from the same
area, okay? Here, [E] we have some, again, very severe dysplasia. Both of these [D
and E] would probably fit the characteristics that were going to call carcinoma in
situ, carcinoma in placeit hasnt gone through the basement membrane yet. When
we get here, [F], you probably cant see what its doing but heres the surfacethese
are the basal cells. And this is actually nasty epithelium that is actually infiltrating
into the underlying connective tissue but it started with the hyperplasia. And this
hyperplasia [A] is of concern if a biopsy of this tissue is taken and the pathologist
sees this hyperplasia, there is a concern about the possible progression of this type
of hyperplasia to squamous cell carcinoma. So here, [still A] this kind of hyperplasia
is of concern as pre-malignant. Where hyperplasia in the oral cavity is usually in
response to an irritant and not at that point considered premalignant.
[Slide #42] [Metaplasia]
[Dr. Phelan] You know the definition of metaplasia, okay? Conversion of
differentiated cell type to another and it can be fully reversible. If you can reverse
the injuryand weve done this beforeand the usual replacement is glandular or
columnar epithelium by squamous. Usually its the more specialized glandular or
columnar epithelium that then reverses to squamous. And this happens with you
can see it here
[Slide #41] [the more tissue cross-sections slide]
[Dr. Phelan] the columnar is switching to squamous here [B]. Thats the most
common metaplasia
[Slide #42] [Metaplasia]
[Dr. Phelan] at least in this area. Okay. Tobacco smoke can do it. In esophageal
epithelium in GERD something different happens, okay? Its not this squamous
epithelium, so its different. Endocervix responds to chronic infection. There we
would also get a switch to squamous. And the cells in the tissue have the ability to
reprogram.
[Slide #43] [Tissue cross-section and diagram]
[Dr. Phelan] This is the one thats different. You will remember this from Dr.
Kinnally from the beginning of the year. What happens is there is a change in the
esophagus. The esophagus is normally lined by squamous epithelium. Here, in a
person with gastric esophageal reflux disease, where stomach acid is refluxing into
the esophagus, the esophagus takes on the type of epithelium thats lining the
stomach. And over time, what we know is that change puts the patient in increased
risk of developing squamous cell carcinoma in this area. But the metaplasia here just
happens not to be squamous I mean metaplasia to squamousits from
squamous to columnar.
severe, then were more, if you want to make it comfortable, but were more sure
that those are going on to become squamous cell carcinomas. And so at this point, all
epithelial dysplasia is considered a premalignant lesion but we dont know where
that line is in the mild dysplasias. And in the oral cavity its associated with smoking.
In the cervical, the vaginal cervix, its associated with inflammation but its
associated with the human papilloma virus. Sunlight can make a difference and is
seen to be related to dysplasias of epithelium that is exposed to sunlight and then
human papilloma virus.
[Slide #49] [Vermillion border]
[Dr. Phelan] Here is a patient that has sun damaged lips ... did we talk about actinic
cheilitis? Okay? Well, hes got it, okay? And actually, hes young. Hes in his early
thirties and if you can see the line between the vermillion and the skin is blurred.
The vermillion, instead of being a nice pink color is a mottled gray color. And you
see more linear configuration of cracks at the border of the skin and the mucosa.
Here is a lesion, right here, that when biopsied was epithelial dysplasia. This is a
condition that is very worrisome for the development of carcinoma of the lip but he
doesnt have it yet, okay? Right here was the dysplastic lesion.
[Slide #50] [Tongue]
[Dr. Phelan] This one looks much nastier. And this one is a more severe dysplasia
and at this point we would expect that if we left that there its going to move onto a
squamous cell carcinoma. But we have to biopsy it to see exactly what is going on
and figure out what the Ill tell you what the dysplasia was but you could only find
it with a microscope.
[Slide #51] [Cheek]
[Dr. Phelan] Heres another. Patient also has an amalgam tattoo on his buccal
mucosa over here. He had teeth once, okay? And heres the dysplasia.
[Slide #52] [Epithelial Dysplasia]
[Dr. Phelan] Okay. So. Oral mucosa dysplasia is divided, as we talked about earlier,
into mild, moderate, and severe. And on both of these, I think you can see the
epithelium doesnt look the way its supposed to, okay? Normal epithelium has one
basal cell layer and then it moves to the spinous layers and then up to keratin and
then if its parakeratin, theres no granular layer. If its orthokeratin, we find a
granular layer. And this has a lot of dysplasia and a lot of inflammation. These are all
inflammatory cells. This one has dysplasia here with a lot of inflammatory cells.
[Slide #53] [Descriptors of epithelial dysplasia: Tissue architecture]
[Dr. Phelan] So the way, in 2014, the way we divide oral epithelial dysplasia is into
mild, moderate, and severe. And it goes on the amount or the component or the
percentage, if you will, of the epithelium that is involved going from the basal layer.
So anything up to a third of the thickness from the basal layer to the keratin layer is
considered mild. So sometimes, its just the basal layer and maybe one cell layer
above that, okay? But sometimes it covers the entire third and that whole up to a
8
third we would call it mild. If it goes up to halfway into the middle of the epithelium,
we call it moderate. And if its two thirds or so or almost the whole well call it
severe, okay? If the entire epithelium is involved from the basal layer all the way up
through the keratin, thats called carcinoma in situ and it means theres carcinoma in
the epithelium but theres no evidence of anything breaking through the basement
membrane. And sometimes when we find a biopsy of a case of carcinoma in situ
well have the technician just cut that piece of tissue with many, many more slices
than we usually do just to make sure that theres no place that we can see the
epithelial cells breaking out of the in situ into the underlying connective tissue.
And so there are some characteristics, whether its mild, moderate, or severe that
are the characteristics of epithelial dysplasia. There is more basal cells than there
are supposed to be. So normal is one layer one and a half layer we still probably
ignore. But anything over two layers is a hyperplastic basal layer. And you can have
epithelium that is either hyperplastic as epithelium or atrophic as epithelium and
still have hyperplastic basal layer. So you can have very thin epithelium with more
basal cells than theyre supposed to. So, you can have thicker epithelium or thinner
epithelium and still be dysplasia. Okay? But the one of the hallmarks of dysplasia
is theres more than one layer of basal cells. Okay? And so theres two ways of
looking at the hyperplasiathickness of the epithelium or the number of rows of
basal cells.
And then because the basal cells are proliferating, instead of having a flat or even
nice wavy rete ridges, the basal cells proliferate and the epithelial rete ridges get
very bulbous. Its like youre packing more basal cells into the rete ridge and its
making a bulbous rete ridge. We call those teardrop shaped. So when youre looking
at it under the microscope from low power you get to see these rete ridges that are
rounded at their bottoms. Yeah?
[Student]So you classify dysplasia that involves thickness of the basal layeryou
cant do the mild, moderate, severe classification thats just for
[Dr. Phelan]Yeah, you can. No matter how atrophic it is, we can. And if its really
thin, and it goes all the way up to the top, thats severe.
[Student]On the top of the epithelium?
[Dr. Phelan]All the way up to the keratin. Okay? So even if its thin it goes all the
way up to the top. Sometimes its thin and its only maybe two layers of the basal
layerthat we will still call mild. So it depends on no matter whether its thick or
thinit depends on the percentage of the epithelium thats involved.
[Student]No, Im talking about as you said theres two ways to
[Dr. Phelan]Right. Actually what I was saying you misunderstood me. What I
was saying is you know already that hyperplastic epithelium is thicker, atrophic
9
epithelium is thinner, right? Has nothing to do with dysplasia. It has to do with how
thick or how thin, okay? And the tissue in dysplasia can be either. But the
hyperplasia refers only to the basal cells. Did that get clear? Okay. That may be a
confusing way of putting it in here.
Okay, then if you look at whats supposed to happen in the epithelium, its supposed
to mature normally. So youre supposed to have basal cells, merkel cells, keratin.
What sometimes happens is you begin to get basal cells in the middle of the
epithelium, keratin down near the basal cells so you have individually keratinized
cells near the base of the epithelium where they dont belong. So there is just the
progressive maturation just doesnt work right in a dysplastic lesion. And again, the
keratin pearls, I showed you one in a carcinoma before, but you can even get those
in the epithelium where the keratin keratin is supposed to be on the top. Its not
supposed to be in the middle of the epithelium. So anytime theres keratin where it
doesnt belong, something has gone wrong with the epithelium.
Okay. Here we were looking at architecture. Okay? So, architecturesometimes, if
youre looking at cases under the microscope, Ill say were looking at the satellite
view and its the satellite view from which you can see the architecture. Because you
can see that epithelium even without looking carefully on high power, you can see
that the epithelium is messed up. Okay? Thats architecture. And its looking from
afar to see, and you should be able to see where the keratin is, how the rete ridges
are arranged, where the connective tissue is, you can see if theres inflammatory
cells and you can actually see if the epithelium looks like youve got basal cells,
spinous layer, keratin, everything where it belongs, okay? Thats architecture and
its really important.
Have you all heard about the test thats called the brush test or the brush biopsy?
Okay? The problem with the brush biopsy is that you have no idea of the
architecture. And what it does and it does a good job of taking the brush and going
down right through the epithelium from the keratin down to the connective tissue
and it will pick up cells all the way through those layers. And the cytologist who
reads the brush biopsy or the brush test will be able to tell you that you got all the
cells. They can tell you if you got deep enough and they can tell you if you got basal
cells. But they cant tell you as how this whole thing was organized because they just
have cells from all through that. So they can tell you if you have cells that are
atypical but they have no architecture, okay? So what we talked about first here is
the architecture.
[Slide #54] [Epithelial Dysplasia: Cellular Characteristics]
[Dr. Phelan] Then this is what the cytologist does when the cytologist is doing the
brush test. But its also what were doing when we take the microscope and we go
down into higher power and look at individual cells. And in epithelial dysplasia,
again, depends still on where were looking at and how much is involved.
10
We look for nuclei that are too large, okay? And cells that are too large. We look for
nucleoli in the cells that are very prominent. And we talked about this increased
nuclear to cytoplasm ratiowhen the nuclei get larger, almost by definition, they
pick up more of the cell. So we get this change in nuclear to cytoplasm ratio.
Because theres more chromatin in the nucleus, because its dividing I mean the
chromatin is dividing, the cells become hyperchromatic. They take up more
hemotoxalin and they get very dark blue because theres more chromatin in the
nuclei.
The nuclei take on and the cells can be pleomorphic but usually the nuceli are the
ones that you can see. The nuclei are all sizes and shapes like I showed you earlier
when we were looking at the squamous cell carcinoma. Dyskeratosis means that
keratin is anywhere except where it belongs, okay? Normal keratin is on the surface.
You dont expect to have keratin deeper in the tissue.
And sometimes we see increased mitotic activity. We can have dysplasia and not
find any mitotic figures but usually if you look long enough youre going to find
some. But even if we have no dysplasia and we have increased thickness of the
epithelium how did the epithelium get thicker? Well the only way the epithelium is
going to get thicker is for those basal cells to divide. So just having some mitotic
figures in the basal layer of the epithelium, especially if its thicker doesnt mean we
have dysplasiait just means the epithelium is doing what its supposed to do and
its dividing to do the protection.
And anytime that we find a abnormal mitotic figures then thats very worrisome.
[Slide #55] [More histology pics]
[Dr. Phelan] Okay. So here we have [A] what looks like epithelial hyperplasia.
Everythings going pretty normally. The cells are a little clearer than normal but
thats all. Heres the basement membrane and it looks like one layer. And can you
see when Im looking at what I would call the satellite view there, that epithelium
really looks pretty good, okay? If I start looking at those cells on high power before
Ive seen the architecture, then its very hard to determine whether or not things are
maturing carefully. So the pathologist usually spends a long time on low power on
the satellite view before starting to look at individual cells. Because individual cells
can look atypical if you get them big enough if you havent really looked at the whole
architecture.
Here, [B] now weve got basal hyperplasia. Okay? Those dark cells are basal cells
and hyperchromaticitytheyre darker. And I think in this one, you probably want
to call this all the way up to moderate because it looks like its atypical in here
someplace.
Over here, [C] I think it looks like its going if its maybe up to here, Im not sure
what Id do with this I probably would spend some time this is at least severe.
11
And this [D] is through and through dysplasia. So that is carcinoma in situ. Okay?
And thats the way so if you get a pathology report that says mild dysplasia, it
means that the dysplasia is only in the basal third. If you get a report that says its
moderate dysplasia it means its halfway and if you get the carcinoma in situ its all
the way through.
Were finished. You can have the microphone.
12