0:01

Good morning everybody, and thank you for joining us today, wherever you are,

0:05

if it's morning, afternoon, or evening. Um, thank you for attending today.

0:10

Uh, today, we'll, Dr. Ssim will be,

0:13

we're having presenting our first lecture of the course. Uh,

0:17

the topic is E V V and H p v, head and Neck Cancer. Um,

0:22

just reminders, uh,

0:24

we always encourage you to turn on your cameras and ask questions. Um,

0:29

you can ask a question by raising your hand in the Zoom chat. Um, you can also,

0:34

uh, pose a question in the chat or pose a question directly. Dr. Ssim,

0:38

please wait until he's, um, completed speaking,

0:41

or if you can hold your questions till later in the lecture,

0:43

that would be appreciated. Um, Dr. Em, whenever you're ready.

0:49

Okay, great to see you guys. I'm sure it's, uh, different time zones,

0:53

which is always, uh,

0:55

challenging for us to decide when to present our material. Uh,

1:00

it's currently 6:00 AM where I am, which is in the mountains. I'm, uh,

1:05

out of the mountain time zone just outside of Colorado, uh,

1:09

just outside of Denver in Colorado. I'm in a town called Evergreen,

1:13

and it really is, uh, green all year round with evergreen trees,

1:18

but I'm at about 8,000, uh, feet high, which,

1:23

uh, metric system, I guess that would be around maybe 2300,

1:28

uh, meters high. Um, and it's really beautiful here.

1:33

Um, and I'm very close to,

1:36

some of you may know the resorts like Vail and Aspen.

1:40

That's where I go skiing in the winter time. So I'm looking,

1:43

actually looking forward to the,

1:45

the colder weather and a little bit of snow on the ground.

1:48

Although Colorado's great all year round. Uh,

1:51

it's got great hiking and biking and, uh,

1:54

a lot of stuff you could do in the Colorado River with, uh,

1:57

rafting and kayaking, et cetera. So, uh, a neat location.

2:01

Strange as it may seem, I still work for Johns Hopkins Hospital in Baltimore.

2:06

So I'm one of these remote tele radiologists who reads the cases

2:11

from afar every month.

2:14

I travel from Denver to Baltimore to do weekends on call.

2:18

So that way, um, if there's any procedures that need to be done,

2:22

I I do them in Baltimore and don't have someone have to cover me. So, um,

2:27

good friend of Siresh Mukerji, who, as you know,

2:31

is one of the preeminent head and neck radiologists in the world,

2:35

and he's asked me to help out with the course.

2:38

So I will be doing a little bit of grading and a little bit of talking to you

2:42

about, um, you, the cases in office hours.

2:46

And he's also asked me to talk about a topic that I really enjoy,

2:50

which is the role of H P V and E B V

2:55

in head and neck cancer. So this actually, um,

2:58

some of you who are in the, uh,

3:02

Pacific region are probably more familiar with the role of E B V

3:07

than, than I am as far as it, its role with, uh,

3:10

head and neck cancer and nasal pharyngeal cancer. So, uh,

3:13

jump right in if I'm saying anything wrong and let me know.

3:17

So I'm gonna share my screen at, at this juncture.

3:20

Any quick questions before I go to the PowerPoint?

3:27

All right,

3:27

so I'm gonna pick up my microphone so you'll hear me a little bit better. So,

3:32

how H B V and E B V positive cancers have changed staging and thinking

3:37

about pharyngeal neoplasms?

3:42

So the two viruses that I'm gonna be talking about,

3:45

human papilloma virus and Epstein-Barr virus are

3:50

depicted here in these, uh, graphic descriptions.

3:54

And H P V is a

3:59

virus that has been classically shown to

4:04

cause quite a bit of oropharyngeal cancers,

4:07

particularly around the tonsils and base of tongue.

4:10

And E B V is seen associated with

4:15

nasopharyngeal carcinoma. You see that this is, uh,

4:18

near the eustachian tube and a tumor in the, in the nasal vault.

4:26

We're gonna start with H P V. Um, you know,

4:30

it's been known for a very long time, uh,

4:33

about the impact of H P V for Lary Laryngotracheal

4:38

Papillomatosis in that it caused this benign condition.

4:43

And similarly with E B V,

4:44

people have known about its relationship with Burke's Lymphoma, for example,

4:50

for over six decades. Um,

4:53

H P V has been described

4:58

to cause or be associated with a lot of

5:03

cervical cancers, not cervical with regard to the neck,

5:06

but cervical with regard to the female reproductive system, uh, and the vagina.

5:12

So this is a virus that encodes for six proteins for virus

5:17

replication and two for virus structure.

5:19

It's amazing that something as small as this and as compact

5:24

as this is able to wreak such havoc on the oropharynx and the

5:28

cervical region. So, uh,

5:30

it causes or associated with about 70% of cervical cancer,

5:35

and it may also call cause genital warts.

5:39

So as you look here at the cancer site

5:44

and you look at the percentage probably caused by H P V type,

5:47

you see cervix 91% vulva, 69%.

5:51

So it's been known for a very long time about its impact with regard to the

5:55

cervix. However, over the last three or four decades,

6:01

it's also been shown to

6:05

lead to oropharyngeal cancer. And we'll talk about why that is.

6:08

Here is a little diagram of the genome of the H

6:13

P V virus, and again, very efficient. You know,

6:18

basically just these two capsid pro, pro protein

6:24

genome, pro portions, and then all this for the virus replication.

6:31

If you look at the incidences of,

6:34

or the prevalence of head and neck squamous cell carcinoma,

6:38

you note that oropharyngeal cancer has, if anything,

6:41

been slightly on the rise at the same time that the larynx

6:47

and the floor and gum and other mouth areas have been

6:52

declining the tongue because of the impact of H P V at the base of the tongue

6:57

has actually been increasing. So why are things decreasing?

7:01

They're decreasing as we know more about that risk factor of smoking

7:06

and chewing tobacco such that our youth are engaging in

7:11

it less frequently. They still do, but less frequency. I don't know,

7:15

I don't know the impact of vaping, but, well, we should probably learn that. Um,

7:21

when you look at the impact however of H P V on oropharyngeal

7:25

cancers,

7:27

you see that 70.1% are attributable to any

7:32

type of H P V in the most common one that we're usually doing with is H P V 16,

7:36

second most common, 18 at 60%.

7:42

So it now, as you can see,

7:45

the average annual numbers exceeds that for, uh,

7:49

women's cervical cancer.

7:53

And you see that now, it, it's more,

7:56

it's more men here used to be women.

8:03

And again, here's oropharyngeal cancers, you notice it's number one,

8:07

and the percentage probably caused by any H P V is about 70%.

8:11

Now you still have oropharyngeal cancers caused by alcohol, chewing tobacco,

8:16

beetle nut chewing, squib, and, um, smoking,

8:20

but higher percentage now with H P V.

8:25

So overall worldwide, not just talking about America,

8:30

400,000 cases of oropharyngeal cancer,

8:33

of which 46,000 occur in the us and 60 to 75%, as you saw,

8:38

are H P V related.

8:40

The good news is that those patients who have H P V positive oropharyngeal

8:44

cancer have a better prognosis than those who do not have the

8:49

virus associated with the cancer.

8:51

Those people that have cancers associated with tobacco smoking

8:56

have a worse prognosis than those associated with H P V. Now,

9:01

the demographics and the risk factors of H P V are very interesting,

9:06

and they were largely described by a woman named Carol Fery

9:11

at Johns Hopkins Hospital.

9:14

And in looking at the H P V virus, um,

9:18

she understood that it was very prevalent in the

9:23

cervical and vagina regions of women and obviously caused

9:28

the cancers there.

9:30

And so she looked at the habits of patients who have H P

9:35

V positive oropharyngeal cancer,

9:38

and what she showed was there was a 20 fold increase in the risk

9:43

if that individual was engaging with multiple partners in

9:48

oral sex.

9:49

So her premise was that there was some transmission

9:54

via the vagina and cervical region of the woman to the

9:59

person who was engaging in the oral sex with that person

10:04

leading to the exposure in the oropharynx, um,

10:09

of the patients who develop oropharyngeal cancer.

10:12

And she also looked at, uh, women who were lesbian,

10:17

who engaged in oral,

10:18

in oral sex and also showed that it was a higher risk factor.

10:22

So somehow that activity that one does in sexual,

10:28

uh,

10:28

relations with a partner was leading to the increased risk.

10:34

And, um, and in part that's why you see it more commonly in the men.

10:40

If you look at the prevalence of H P V positive

10:45

cancers versus H P V negative of those who have oropharyngeal cancer,

10:50

you could see that the H P V positives are on the rise at the same time that

10:55

the H P V negatives are declining. Why is it declining?

10:58

Because less people are smoking, at least in America.

11:05

So, uh,

11:05

here you see those numbers again for the oropharynx versus the cervix and those

11:10

associated with H P V 1618.

11:13

This is the H P V 1618 is what we test for.

11:16

So there are some oropharyngeal cancers that are by the other viral types that

11:20

we don't specifically test for. We're usually testing for the 1618 variant.

11:27

What about risks of other location

11:33

cancers associated with H P V exposure?

11:37

Why is it specific to the oropharynx?

11:41

And some people say it has to do with the lymphoid tissue associated with the

11:45

palatine tonsil that it collects there. However,

11:49

we are seeing ever increasing, um,

11:55

exposures and associations of other areas of the head and neck

12:00

with H P V positivity. So oral cavity,

12:05

squamous cell carcinomas, you know,

12:06

the oral cavity includes the oral tongue and the retromolar trigone

12:11

and the areas around the teeth and the alveolis, for example.

12:15

Those areas of the oral cavity are associated with 23.5%

12:20

H P V positive laryngeal cancers, 24% hypopharynx,

12:24

much less so in all,

12:28

they all show a better prognosis when it's H P V positive

12:33

associated cancer than with H P V negative.

12:40

So, um, this is just showing, um,

12:42

the laryngeal cancer rates, uh, uh, associated with H P V,

12:47

uh, D N A positive versus negative.

12:51

And you could see that things do change over the course of time

12:55

towards a greater risk factor,

12:58

increasing rate from 16.5% to 28.1% in

13:03

this five year period. This is a while ago, and this has continued to increase.

13:09

So I mentioned that the H P V positive cancers have a much better prognosis than

13:14

those, which with the H P V negative,

13:17

that led to a revision to the American Joint Commission

13:22

on Cancer, the A J C C staging manual for

13:27

oropharyngeal cancer.

13:29

They separated those that were H P V positive from those that were H

13:34

P V negative oropharyngeal cancer.

13:36

So a separate table if it's H P V positive versus H P V negative.

13:41

What they found was even those that were T four cancers did

13:46

well if they were H P V positive.

13:53

So I mentioned that H P V positive is not exactly the same as

13:57

what we test for, which is that P 16 and P 18 variants.

14:01

But suffice it to say it is a good marker for H P V

14:06

positivity.

14:07

Remember that there are other subtypes of H P V positive and

14:13

also remember that this is not specifically testing for the

14:17

virus, it's testing for a particle a P 16 particle.

14:22

So here is the T staging of oropharyngeal cancer.

14:27

That used to be what was listed

14:33

under oropharyngeal cancer globally.

14:36

Now this only relates to those that are H P V negative and it

14:41

lists the T staging by the size less than two centimeters,

14:45

two to four centimeters greater than four centimeters, T four,

14:48

a invasion of larynx or the deep muscles of the tongue, oid, et cetera.

14:53

T four B advanced cancer goes into the masticator space musculature,

14:59

OID plate, skull base carotid artery.

15:01

The T staging of H B V associated P 16 positive oropharyngeal cancer

15:07

you note does not separate T four A and T four B.

15:10

It used to be that T four B was basically unresectable incurable disease.

15:15

Now it is no longer separated as such

15:20

and they're all lumped under T four because with chemotherapy and radiation you

15:24

can eradicate this cancer.

15:29

So let's look at this. This patient is H P V negative.

15:33

There is a cancer at the tongue base, which is extending into the ula.

15:38

This is the edge of the epiglottis. So a decent sized cancer.

15:42

We would measure this, see whether it's two, two to four sore.

15:46

As far as the T staging,

15:47

unfortunately there is a necrotic lymph node here. This,

15:52

the lymph node is in an H P V negative cancer. However,

15:56

it has been shown that cystic lymphadenopathy is a

16:01

characteristic of H P V positive cancers.

16:05

It can happen in H P V negative,

16:07

but more commonly when you have a cystic or necrotic lymph node like this,

16:12

it's gonna be H P V positive. Here's another cancer,

16:16

again, base of tongue cancer. It's sort of triangular shape.

16:20

It's less than two centimeters, it's a T one cancer. However,

16:24

you notice that the patient does have a,

16:26

an enlarged lymph node on the right side as well.

16:30

Another cancer, this one in the palatine tonsil on the right side.

16:34

This is a T two weighted MR scan. Um,

16:39

MR is very good for identifying oropharyngeal cancers as high in single

16:43

intensity, generally on the T two A sequences.

16:47

And usually it does show contrast enhancement.

16:50

Here's a patient with a tonsor cancer.

16:53

It was growing into the base of the tongue via the gloss tonsor sulcus.

16:58

So glosso tongue tonsil palatine tonsil

17:03

sulcus, that sulcus that joins the two.

17:06

And you can see here that at the base of the tongue,

17:09

this actually crossed the midline from the, uh,

17:14

palatine tonsil.

17:15

You also note that the patient has on this PET scan positive lymphadenopathy

17:20

on the left side. So

17:26

we use, um, PET scan quite frequently,

17:29

both for the initial evaluation as well as follow-up after treatment

17:34

of oropharyngeal cancer because it does light up very nicely,

17:37

whether it be H P V negative or positive.

17:45

We at Johns Hopkins do employ diffusion weighted imaging as part of our

17:49

protocol for M R I of head and neck cancer.

17:52

I can tell you that sometimes it's helpful.

17:55

Sometimes you just get so much artifact that it,

17:58

it is blows away. Um, can you please, uh,

18:02

everyone please kind of mute themselves 'cause we're getting a little background

18:04

noise. Thank you. Um, so here for example,

18:08

is a patient who has enlargement of the left palatine tonsil.

18:12

It does look like it's entering the, uh, base of the tongue.

18:16

This is an A D C map from the diffusion weight scan.

18:20

You can see it's dark in signal intensity.

18:22

And that would argue that this is not just lymphoid hyperplasia,

18:26

which can occur in the tonsor region,

18:30

but is indeed a cancer.

18:32

So here's another example of a patient with a, um,

18:37

molecular cancer. This is the epiglottis.

18:40

This is the area of the epi of the Mula.

18:42

This is the D W I image showing the high signal intensity in D w.

18:47

I remember that when you do the A D C maps,

18:49

you expect this to be dark in signal intensity.

18:54

And as I mentioned, after treatment,

18:55

we are using the PET scan with a combined contrast enhanced

19:00

CT scan to better assess the results of the treatment usually in the

19:05

oropharynx, particularly with H P V positive, that's radiation and chemotherapy.

19:14

So, um,

19:14

with regard to H P V positive versus H P V negative head and neck squamous cell

19:18

ca cancers,

19:19

there are no imaging features that will consistently predict H P V status.

19:24

I just completed a radio radios, um,

19:30

review of the literature to look at the features

19:35

of

19:37

H P V positive versus H P V negative oropharyngeal cancer.

19:41

And the radios accuracy was about 74%

19:46

at predicting H P V positive cancers as opposed to H P V

19:51

negative cancer. And, um, in general,

19:54

they were smaller cancers and more homogeneous cancers.

20:00

So smaller primaries, cystic nodal metastases,

20:03

that will get you about 74% accuracy. Uh,

20:07

I expect that with time and artificial intelligence improvements,

20:12

this accuracy will increase.

20:14

Right now we have immunohistochemistry to pretty easily identify that P 16

20:20

P 18 virus particle,

20:22

but it may be a time where we will do the M R I or a

20:27

CT scan and be able to predict the H P V status as

20:32

AI methodology and machine learning improves.

20:40

What about T four cancer? So again, T four a,

20:43

T four B for the H B V negative, if you have involvement as you do here,

20:48

this is an a palatine tonsil cancer on the right side.

20:52

And you see that you've lost the border between the cancer and the

20:57

OID muscle, and it's showing some enhancement right along those fibers of the

21:02

OID muscle compared to the contralateral side where it's nice sharp border.

21:07

This involvement of the medial OID muscle is

21:12

a T four A characteristic. If it goes into the, uh,

21:16

lateral OID or the OID plates, it's uh,

21:20

it's considered T four B

21:24

extrinsic tongue muscle involvement is another feature of oropharyngeal cancer

21:29

that may lead to a T four cancer. Now remember,

21:32

this is H P V positive base of tongue cancer.

21:36

Remember with the H P V positive, we don't separate T four A from T four B. Um,

21:41

the extrinsic tongue muscles are the geno gloss muscle,

21:46

the hi glossy stylos muscle and the pallo

21:51

muscle. So if you have the geno gloss muscle,

21:55

this is the right geno gloss muscle. This is the left geno gloss muscle.

21:59

You see, this cancer is infiltrating this muscle and widening it.

22:03

That is considered extrinsic tongue muscle involvement and therefore T four

22:08

cancer. Here we have the involvement of the

22:13

hi gloss muscle.

22:14

So the stylo gloss muscle comes from the styloid process and then

22:19

inserts on the tongue.

22:21

The hi gloss muscle is that extension of that same muscle from the tongue to the

22:26

hyoid bone. So at this level,

22:28

we're at hilos and the infiltrating enhancing

22:33

tumor that you see here has entered the, uh,

22:38

hi gloss muscle. This is the contralateral hilos muscle.

22:42

This is the mylohyoid muscle over here.

22:45

And in between right through here is your sublingual space

22:50

or your floor of the mouth. So this muscle, again,

22:55

mylohyoid muscle stylo, uh, hilos muscle,

23:01

genio gloss muscle, intrinsic muscle of the tongue, uh, seen here,

23:06

here on the other side, mylohyoid muscle hilos,

23:10

muscle genio, gloss muscle

23:16

hilos mylohyoid.

23:24

So depending upon whether it's H P V positive or H P V negative, this may be,

23:30

um, characterized as T four or T four a,

23:35

T four B. I mentioned about the cystic nodal metastases, as I, as I said,

23:39

that is a characteristic of H P V positive or oropharyngeal cancer,

23:44

but may also occur in H P V negative. Here's one that was cystic nodal mass.

23:49

This one ended up being a bronchial cleft cyst.

23:55

This one, a malignant cystic necrotic lymph node.

24:00

So that's our differential diagnosis.

24:03

We had a neck radiologist now are very wary about calling things

24:08

brachial cuff cyst, um,

24:12

because of the prevalence of cystic nodal metastases associated with

24:17

H P V positive cancer.

24:19

So if I see something that looks like a pure cyst in the neck in this location,

24:24

I pay a lot of attention to the palatine tonsil in the base of the tongue and

24:29

the molecular region to see whether there's anything that could possibly be a

24:33

primary tumor. And then if there's any nodularity to this rim,

24:38

like you see here,

24:41

I would say most likely a broncho cuff cyst cannot exclude a cystic nodal

24:45

metastasis from an H V V positive cancer recommend aspiration cytology.

24:51

That's fair. Okay,

24:55

so as I mentioned, the good news is that H P V positive cancers,

24:58

although they're much more common now and are increasing in frequency,

25:02

they have a much better prognosis.

25:04

Even if there's positive margins after surgery,

25:07

radiation therapy and chemotherapy seems to wipe this cancer out pretty readily.

25:12

And even if you have positive lymphadenopathy, you can still effect a,

25:17

a cure. So here is the good news.

25:21

This is the disease-free survival and overall survival.

25:25

And you see that with H P V positive cancer. This is 0.8,

25:30

this is 0.6, this is 0.4, you're at above 0.8.

25:35

With H P V negative cancer,

25:36

you're somewhere between 0.4 and 0.6 over the course of 60 months.

25:41

So this is a five year survival.

25:43

This is five year overall survival here at 0.4

25:47

for H P V negative,

25:49

but still above the 0.8 for H P V positive.

25:54

And if you look at the treatment that's been going on over the course of time,

26:00

oh, excuse me,

26:06

um, what you see is the green arrow, which is chemoradiation therapy.

26:10

Now is the predominant way that we treat

26:15

H P V positive oropharyngeal cancers.

26:19

Another table showing that benefit of H P V

26:23

positivity.

26:26

Another area where we have seen an

26:31

impact of H P V positivity is in the cases of

26:36

carcinoma of unknown primary.

26:38

These are patients that have discovered a lymph node in their neck

26:43

and the E n T doc does an a full endoscopy and finds

26:48

nothing.

26:48

We do a CT or an M R I scan and don't find anything except for the big lymph

26:53

node. So they aspirate the lymph node and they find H P V positive,

26:58

uh, cells.

26:59

So that will lead to a bilateral or ipsilateral,

27:05

uh, tonsillectomy with the assumption that it's a microscopic primary tumor.

27:11

So quite often now,

27:12

the unknown primaries are H P V positive and there's an assumption that it's

27:16

from the head and neck region and consular region or base of tongue.

27:20

And those patients will, uh,

27:22

either get the tonsillectomy for removal of the cancer or the chemoradiation

27:27

protocol.

27:29

Some unknown primaries are E B V positive and we'll talk about that because the

27:33

nasopharynx is another area where you can have occult primary tumors.

27:41

The nodal staging is also different depending upon whether it's

27:46

H P V positive or negative.

27:48

The nodal staging in the eighth edition of the A J C C incorporated

27:53

extra nodal extension, that's what e n E is.

27:55

And once you have extra nodal extension,

27:58

it bumps up the t staging into the N three category.

28:04

Um, or if it's a single lymph node that's e and e positive,

28:09

sometimes that will bump it into the N two category. So,

28:14

um,

28:18

any lymph uh, lymph node, a single lymph node, um,

28:22

less than three centimeters will uh,

28:24

get bumped up to e N E negative E E n E positive and, uh,

28:28

will increase the, uh, end staging.

28:32

Now on the, uh, the extra nodal extension,

28:37

this is specified to be pathologic e n e,

28:41

not radiologic, e n e.

28:43

And the reason for that is because we actually are relatively insensitive

28:48

to the presence of extra nodal extension, although, um,

28:53

we are good at when it's grossly like this,

28:57

when it's microscopic disease, which is the majority of cases,

29:04

it's pathologically positive, but imaging negative.

29:08

So as you can see, uh, CT evaluation for this, uh,

29:12

for sensitivity was only 43.7% for all comers.

29:20

If you look at grade four,

29:21

where clearly the lymph node has been exploded with cancer,

29:25

then we get up to a sensitivity of 74%.

29:28

But even that is relatively low.

29:35

So, you know, when we look at our cancers,

29:37

if we see this fuzzy margin around this necrotic lymph node or, or you know,

29:41

extension into the sternal cardio mastoid muscle,

29:44

we're gonna call extra nodal extension on our imaging,

29:47

even though the staging requires it to be by pathology. Of course,

29:51

what happens a lot of times is that the patients don't get that lymph node

29:55

dissection or, or uh, um,

29:58

resection and therefore they never know that it's e n E positive,

30:01

but they go with the radiologic impression.

30:06

So here's one that's clearly infiltrating into the skin surface and around the

30:10

carotid artery.

30:11

The end staging of H P V positive oropharyngeal cancer just looks at

30:17

one or more ipsilateral nodes less than six centimeters.

30:20

It doesn't even separate them into the less than three, three to six.

30:24

It just separates them based on six centimeters in size because even a five

30:29

centimeter lymph node will melt under the impact of radiation

30:34

therapy and chemotherapy with H P V positive cancer.

30:38

So a different nodal staging based on six centimeters or

30:43

less or greater than six centimeters at M three

30:47

doesn't even list the extra nodal extension.

30:51

Why even extra nodal extension can be sweeped swept clean with

30:56

treatment for H P V positive cancer. Okay,

31:00

so we've exhausted H P V positive cancer in our first half hour.

31:04

We're now ready to move to the Epstein Bar virus.

31:07

So maybe I should stop and see whether there are any questions about H P V

31:12

positive cancers and oropharyngeal cancer

31:17

questions out there. All right, hearing none,

31:20

I will shift gears and go to the nasopharynx and EP Epstein bar virus.

31:25

So Epstein Bar virus, uh, also is a relatively simple virus,

31:29

and yet it has huge impact in the head and neck.

31:33

You can see you have your late latent membrane proteins and your nuclear ones

31:37

that are going to enter the cell and lead to the replication of

31:42

the virus. And here's some depiction of that virus.

31:48

So we start our story about Epstein Barr virus in 1964

31:53

with Tony Epstein and Yvonne Barr,

31:57

who were the first to grow lymph human lymphocytes in culture.

32:01

And this was from a Burkitt lymphoma.

32:04

So remember that E B V is associated not just with nasal pharyngeal carcinoma,

32:08

but with many types of lymphoma.

32:10

And burki lymphoma was the first one that was described in 1964.

32:15

So we are now 60 years later. Wow.

32:20

If you look at E B V positivity, this is not in cancer,

32:25

but just routine, you know, exposure in your life.

32:29

You notice that in many situ

32:35

countries and locations,

32:37

the positive E B V titers are very high.

32:41

This E B V is the,

32:45

is the virus that's associated with mononucleosis,

32:47

which is a viral illness that is associated with lymphadenopathy and fatigue,

32:52

et cetera. Um, many,

32:54

many of our college age kids get this once they're exposed in

32:58

college and they have mono mononucleosis. So this is Pennsylvania.

33:03

You could see the number here by age, you know,

33:08

16 or 18 when they enter college, they're already exposed at 80%.

33:13

Look at it here. This is Greenland.

33:17

And if you of Greenland, you'll see a lot of E B V.

33:22

And here we have Uganda and Denmark. Wow.

33:25

So high rates of basic exposure from the very beginning, early in life.

33:31

So the E B V lifecycle, you know, as as they typically do, they enter the virus,

33:35

they start to replicate, they deal,

33:38

they interfere with the T cells and therefore shed additional

33:43

viruses late, um,

33:45

in the B cells and then out it comes in either infection

33:50

or if it infiltrates into the genome of the nasopharyngeal cells.

33:55

Cancer

33:57

E B V has been associated with so many illnesses. Oh my god,

34:02

we talked about, you know, mono,

34:05

but look at all the lymphomas that have higher rates of E B V exposure,

34:11

pt, post-transplant, lymphoproliferative disorder, P T L D,

34:16

all these other cancers of which we're gonna be talking about nasopharyngeal

34:19

carcinoma, but thyroid as well, salivary gland, et cetera.

34:27

When we look at the W H O characterization of nasal

34:32

pharyngeal carcinoma,

34:33

it's described as keratinizing squamous cell type, which is type one.

34:39

And then the non keratinizing squamous cell carcinomas are separated into those

34:44

that are differentiated Type two and undifferentiated type three

34:49

types two and three are the ones that are predominantly E B V positive type

34:54

one, not as much,

34:56

but the risk factors for nasopharyngeal carcinoma, um,

35:02

include Southeast Asian ancestry as well

35:07

as alcohol, less so the smoking exposure.

35:16

Now we said that H P V positive cancers had a better prognosis.

35:21

Is it the same with regard to E B V

35:27

positive cancer?

35:28

And what you see here is that those that are E B V positive have

35:33

a higher rate of distant metastases and a

35:38

lower rate of disease-free survival and a lower rate of overall survival.

35:43

So as opposed to H P V,

35:46

which in imparts a beneficial effect,

35:49

those cancers that are E B V positive do worse. And they,

35:54

as you saw, were usually those un uh, different, uh,

35:58

non keratinized undifferentiated cancer type. Um, lemme go back

36:05

the non keratinizing ones,

36:06

which include the differentiated and undifferentiated ones.

36:09

So type two and type three, and they generally have a worse prognosis.

36:16

The t staging of pharyngeal carcinoma requires you to understand the

36:21

adjacent tissue. So T one is confined to the nasal pharynx,

36:26

no para pharyngeal space extension T two extension

36:31

to the para pharyngeal space.

36:32

I will tell you that almost all nasal pharyngeal cancers when by the time we

36:36

detect them, have gotten into the paranal space.

36:40

Medial or lateral OID involvement, prevertebral muscular involvement.

36:45

So that's T two T three into the bone

36:50

spread to the sinuses.

36:52

And then T four intracranial extensional on the cranial nerves.

36:55

Remember that nasopharyngeal carcinoma has a quick exit out the nasal pharynx

37:00

into all the areas of the tego palatine fossa and the second

37:05

division of fifth cranial nerve foramina,

37:09

including frame and rotundo, the Vian canal and et cetera,

37:12

tega maxillary fissure. And once it gets into the cranial nerves,

37:16

it's considered T four cancer.

37:18

Now you notice that there is not T four A and T four B here. Why is that?

37:22

Once again,

37:23

this is a cancer that can be cured with chemo and radiation treatment,

37:27

even though it is spread far afield, even intracranial.

37:34

So here's a T one nasopharyngeal cancer.

37:37

You look here and you see that there is asymmetric

37:42

appearance to the FOSS of romule where it's showing contrast enhancement.

37:48

You see that normally we have these little fat planes between the muscles here.

37:52

These are the tens and levator valley palatini muscles. You notice that those,

37:58

that that bright signal between the musculature is missing here and then it

38:03

shows enhancement. This is a T one cancer.

38:06

It may also involve the fingal bas fascia over here.

38:14

Then that, um,

38:15

also is a means of spread to the base of the skull.

38:22

Here's another one. This is T two cancer. Why is it T two? Well,

38:26

here's the left sided cancer,

38:28

but you see that you have asymmetric enhancement here of the longest

38:33

coline musculature complex.

38:36

So this is the normal appearance post contrast.

38:39

Here you have this muscle that's infiltrated the prevertebral muscular

38:43

involvement imparts a T two cancer. Um,

38:47

right here this is still muscle, if it was skull base,

38:52

it would shift it to T three cancer. Oh,

38:57

I'm sorry. So this one is a different cancer.

39:00

And you see that it's infiltrating the paranal space

39:06

and extending, um,

39:12

here at the skull base. Here's another one.

39:16

This is a cancer over here in the romule.

39:21

Or you note that the patient has a retro pharyngeal lymph node associated with

39:26

the primary tumor.

39:28

So sometimes these are pretty subtle and they are even harder to detect via

39:32

endoscopy because the up here at the nasal vault and nasal pharyngeal vault,

39:38

it's, it's,

39:38

there's a lot of lymphoid tissue and the cancers are sometimes obscured by the

39:42

lymphoid tissue. So that endoscopy, it's negative. And this is again,

39:46

one of the sources of carcinoma of unknown primary,

39:50

maybe in the nasal pharynx. Most of them occur in the palatine tonsil skull, uh,

39:54

tongue-based region.

39:56

But the nasopharynx is the next most common of the sites for a primary tumor.

40:01

Sometimes we have a carcinoma of unknown primary and we never know where the

40:05

primary tumor came from. It's just too microscopic.

40:11

Let's look at this case. So this is a nice case.

40:12

You notice that there is blunting of the phospho romule.

40:16

You have infiltration of the para pharyngeal fat on the right side.

40:20

You notice that there is tissue here that is going along the retro antral

40:24

region, nice and clean on the normal side.

40:28

And you see that this turid musculature looks a little

40:32

funky. The OID plate here is involved. Here's the OID plate.

40:37

It looks like it's kind of eroded as opposed to this normal OID plate.

40:42

So we are now, um,

40:44

dealing with something that is into the OID musculature.

40:49

And if we, uh, look for cranial nerve involvement,

40:52

well we're kind of very concerned about it since the OID plate is

40:58

involved. And the tego palatine fossa is right here,

41:00

should be fat containing. And here we have soft tissue.

41:05

So if we look at the next, um, slide,

41:08

we see the infiltration here of the tego palatine fossa.

41:11

There's likely seno palatine foramen involvement right here.

41:15

This is the normal seno palatine foramen.

41:18

We know that we've got tissue going on the retro antral region.

41:21

We've got the involvement of the, uh, medial tego muscle.

41:25

We probably are going to have involvement of the lateral oid muscle,

41:29

which we'll see in just a moment.

41:31

And we have extension into the nasal cavity.

41:35

This is the same patient post gadd coronal and higher.

41:39

Up here we have involvement of the inferior orbital fissure.

41:44

Here's the normal inferior orbital fissure with fat.

41:47

Here we have involvement of the foramen rotund. We follow this.

41:52

This is mecca's cave. Is there too much tissue here?

41:56

Here is the coronal scan. It's showing involvement of

42:03

the medial terra goin muscle, which is here.

42:06

The lateral terra goin muscle shows involvement right here

42:11

compared to here. And where's it coming from? It's coming from frame. And val.

42:16

So this tumor from the nasopharynx has gained access to the

42:21

intracranial compartment through frame and val remember frame.

42:24

And val is the egress of the third division of the fifth cranial nerve.

42:27

Here's meccas cave.

42:29

It looks different than the caval in the contralateral side with contrast

42:34

enhancing tissue. So by virtue of this,

42:39

we've got lateral OID involvement. We have involvement of the cranial nerves.

42:43

We have intracranial extension. This is T four nasopharyngeal carcinoma.

42:47

Curable, still curable.

42:51

Oh my goodness, look at this one.

42:54

So here we have lateral OID mediater,

42:58

both of which are infiltrated here.

43:00

We have the world's largest frame in val compared to the normal frame in

43:05

val, clearly intracranial extension to the cavernous sinus.

43:11

And this is your T four cancer.

43:15

If it gets into the orbit via that inferior orbital fissure that I showed

43:20

previously, this inferior orbital fissure getting into the orbit,

43:24

that's another reason to call it T four cancer. So

43:30

E B V and squamous cell carcinoma.

43:32

So we talked about its impact in nasopharynx and we also saw that there were

43:36

some hypo parental cancers and gastric cancers. Um,

43:40

it is increased in oral cavity. Can cancer, um,

43:43

particularly those individuals who have the risk factors of beetle quid chewing.

43:48

So there's a higher proportion,

43:50

proportion of oral cavity cancer in those patients who have beetle quid chewing

43:55

that is associated with E B V.

44:02

Um, nodal staging for nasal pharyngeal carcinoma is listed here. Uh,

44:07

n one retropharyngeal lymph nodes and unilateral ones or six centimeters or less

44:13

above the cricoid. And two bilateral lymph nodes,

44:15

less than six centimeters above the cricoid. And three,

44:18

if they're greater than six centimeters or below the cricoid.

44:21

And remember that nasopharyngeal carcinoma is a little bit, um,

44:27

perplexing in that it is a cancer that seems to have a

44:31

high rate of supraclavicular lower neck lymph nodes.

44:35

There's some spread in that it seems to jump sometimes.

44:40

Some of the jugular lymph nodes, you know, level three and level four.

44:43

And yet you have these supraclavicular lower level four, uh, lymph nodes.

44:51

Here's a nice, um, medial, um,

44:55

retro pharyngeal lymph node, um,

44:59

nodes of ruber and um, this case unilateral.

45:04

So N one,

45:06

here's one that had multiple lymph nodes in the cerv vicular fossa here

45:12

that was associated with nasopharyngeal carcinoma. A curiosity,

45:20

we do follow nasopharyngeal carcinoma with PET scanning

45:25

with the treatment.

45:26

So many of these patients who receive chemoradiation therapy,

45:32

um,

45:33

they are followed with PET ct or in some cases PET mr.

45:38

And you can see the tumor shrink over time.

45:43

And in this case, combined with the ct,

45:45

you can see where the localization of that is and also evaluate the

45:50

nodal metastases. And, uh, this is a, this is again,

45:55

pretty routine in America at least.

46:00

Now I mentioned that E B V is also associated with lymphoma.

46:04

So sometimes when you have oropharyngeal masses because of

46:09

the lymphoid tissue at the base of the tongue,

46:12

the lingo tonsor tissue as well as the palatine tonsor tissue,

46:17

you may have lymphomas in these locations that simulate squamous cell carcinoma.

46:23

Far and away squamous cell carcinoma is much more common than lymphomas,

46:27

but lymphomas do occur in the nasal pharynx and they

46:32

are difficult to distinguish from the presence of squamous cell carcinoma.

46:37

And they may also be infiltrative. Here you see my fino valley once again,

46:42

Fino Valley,

46:42

bilateral involvement of Fov Valley as well as infiltration of the

46:47

Kern sinus bilaterally. This tumor may be E B V positive as well.

46:56

Look, if you had a bacterial infection, I could prescribe something,

47:00

but that's clearly a virus.

47:03

I just can't help you virus retrovirus.

47:07

So I hope that this, um, let me, uh, stop sharing.

47:13

I hope that this, uh, discussion about these two sites of cancer,

47:19

oropharyngeal cancer and nasopharyngeal cancer has been elucidating

47:24

for you with regard to the staging and,

47:27

and also the impact of two viruses,

47:31

H P V for oropharyngeal cancer and E B V for nasal pharyngeal cancer.

47:36

And those, the impact that it has on the cancer itself.

47:41

Remember, H P V generally a good thing to have.

47:44

E B V unfortunately is associated with a worse prognosis.

47:50

Both of them are prevalent in society

47:55

across the world and have led to increases in

48:00

these specific types of cancers.

48:03

Questions from the audience?

48:09

Let me see whether there's any chat questions.

48:12

I'm seeing nothing and, uh,

48:16

q and a I don't see any questions to answer with that. Oops, what'd I do?

48:20

Let me get my, uh, zoom back up here. Alright,

48:23

so not having heard anything,

48:25

we'll take a quick opportunity to hear where you are from

48:30

and a little bit about, um, how it is that you're taking the course.

48:35

So, Philippe, are you still on? Is it Phillip or Philippe?

48:41

Uh, I can't hear you. Uh, I think you have to. Everyone unmute.

48:43

And if you have your cameras available and you're not, uh, in bed closed, go,

48:48

go ahead and open the camera. Philippe, uh, you, uh, where are you from? And,

48:54

Uh, how are you? Uh, I, I, I am from the Philippines. Uh, I already, yeah,

48:59

I already took the neuro case. Yes, I

49:02

Remember you. Yeah. Yeah.

49:04

And then I'm now taking this, uh, also I also took the stroke.

49:09

Oh, good, good.

49:11

Uh, online voice.

49:12

All right, so you're a regular.

49:14

Great.

49:15

Thank you. Thank you for your money. Okay, Andrea, you're next.

49:21

Uh, hello. Hi, uh, I'm from Hungary and I'm radiology resident.

49:26

Actually, I'm on call right now, but we call during the lecture,

49:31

so it was nice. Uh, so I would like to improve a little bit in head and neck.

49:36

I never really reported head and neck before. Uh,

49:38

and as an attending I would like to prepare for attending life and just

49:43

In case. Yeah,

49:43

head and neck is the area that even is imposing for neuroradiologist.

49:48

Everyone's worried about the head and neck, so hopefully, uh,

49:51

you're gonna learn a lot of anatomy and pathology and feel really comfortable

49:54

after the course. Good luck with, thank you, Andrea. Nice to meet you.

49:58

Nice to you. I'm gonna pronounce it Ganga. Chowdry, where are you from?

50:03

Hi. Um, I'm basically from Pakistan, but I'm based in Ireland.

50:08

Okay. And, um, this is my first time taking the course and um,

50:12

I'm just preparing to get back to work.

50:14

I've been on a career big for several years.

50:17

Okay, good to have you back. Mark Holland.

50:22

Are you with us, mark?

50:24

Yeah. Hi there. Um, so I'm in Australia at the moment in Perth,

50:29

start getting ready for bed. Um, I love head and neck.

50:33

I've done it for a long time.

50:34

I love seeing all the fun cases and watch how the, um,

50:40

these goes along the nerves.

50:43

Very good. Very good.

50:44

I do a lot of general radiology, so it's nice just to keep in touch with e t.

50:50

Right, right. Very good. Well,

50:51

I think you're going to enjoy the course and eSSH is a wonderful teacher,

50:55

so Great, great. Sudir, Sudir,

50:59

PA pa are you with us? If you are on mute.

51:07

All right. Sudir might be virtually with us. Gory bock.

51:15

Gory, where are you from? Hello. Yes, I hear you. Uh,

51:18

Uh, hi sir. I'm from, I'm from Mumbai,

51:21

India and I'm a senior resident at Tata Memorial Hospital. Uh,

51:26

I really like Radi and being from a tertiary onpro

51:31

center, we have come across lot of cancer cases in my period of residency.

51:36

So I'm hoping that from this course I would be able to gain confidence in

51:41

other radiology that we usually did not get to see during a residency.

51:45

And yeah, hoping to pursue any radiology future as well. Thank you.

51:50

Thank you. Well, good to, good to meet you. Um, I've, uh,

51:54

been to India five times, including Mumbai, and enjoyed that very much.

51:59

Thank you for your attendance. And, uh, finally Han

52:04

Um, hi David. Um, I'm also from Australia, um, the East Coast, Sydney.

52:08

Um, I'm not a neuroradiologist. I'm a, I'm more of a body radiologist,

52:12

but I do find head and neck cases interesting. And I do them from time to time.

52:16

Yeah, I enjoyed this course. Thank you. Yeah,

52:18

Very good. Well, I think, uh, everyone's gonna be much,

52:21

much more comfortable with head and neck radiology by the end of the course,

52:24

and I think you're going enjoy it quite a bit. So good luck and, uh, you'll be,

52:29

uh, hearing Dr. Yes,

52:30

Dr.

52:31

I'm, I'm so sorry to inter, inter reflect, um,

52:34

we do have one question in the chat.

52:36

Oh, okay. Right. Gory. Thank you.

52:39

Is there any difference in management in cases of carcinoma of unknown primary,

52:43

which present with nodal metastases and are H P V negative? So,

52:48

um, in general, what happens,

52:52

at least in at Hopkins is they will get an a ipsilateral nodal

52:57

dissection and an ipsilateral tonsillectomy at the same

53:02

time with a presumption that it's a tons primary

53:07

tumor. Um, fortunately, um,

53:12

these patients often will get PET scans and sometimes we will identify the

53:16

primary tumor on a PET scan that might redirect them

53:21

to, for example, the nasopharynx or another location.

53:25

The PET scan may also include the chest, and sometimes we do find that the,

53:30

uh, the primary tumors are in the lungs, the upper lung fields,

53:34

or even in the esophagus.

53:36

So that's generally how it's approached here at Hopkins.

53:41

And, um, if it's H P V positive, they're less likely to,

53:46

uh, pursue the things in the chest or the, uh, esophagus. If it's, you know,

53:51

like a, uh, a, a a non-active lung nodule,

53:56

they may just follow that nodule, assuming that's a benign granulomatous thing.

54:00

So, uh, H P V positive, they're,

54:02

they're going to assume it's a head and neck primary. Hope that's,

54:07

that's helpful. All right, y'all,

54:11

well have a good evening as the, oh, Sader, you have a question?

54:14

Y Yes. Hi. Sorry, I was trying to figure out the mic earlier. Oh, okay.

54:17

I wanted to introduce, uh, Sadir from Chicago, uh, the, uh,

54:21

advantage of taking your, uh, brain and spine course previously. Excellent. And,

54:25

uh, taking the head and neck to see if I can start reading those as well.

54:29

Excellent. Well, I'm sure you'll thank you. Alright, very good. Alright,

54:33

well with that, I'll uh, sign off to Courtney unless you have, uh,

54:38

any comments Courtney for, or instructions for them for the coming up week?

54:43

Uh, no, not at this time. Thank you. Just a reminder that, um,

54:46

cases are going to be due, um, on Tuesday,

54:50

September 20th by 11:59 PM Eastern Time.

54:53

And thank you for everyone that did attend.

54:55

This recording will be made available on demand and will be posted to the course

55:00

website and emailed directly to you. So if you have any additional questions,

55:04

you know how to contact me. Um, and thank you again for attending. Thank you,

55:07

Dr. Sso and everyone. Have a good day.