Lung Pathology

Transcript

00:00 --> 00:02Funding for Yale Cancer Answers is
00:02 --> 00:04provided by Smilow Cancer Hospital.
00:06 --> 00:08Welcome to Yale Cancer Answers with
00:08 --> 00:11your host doctor Anees Chagpar.
00:11 --> 00:12Yale Cancer Answers features the
00:12 --> 00:15latest information on cancer care by
00:15 --> 00:16welcoming oncologists and specialists
00:16 --> 00:19who are on the forefront of the
00:19 --> 00:20battle to fight cancer. This week,
00:20 --> 00:23it's a conversation about lung cancer
00:23 --> 00:25pathology with Doctor Robert Homer.
00:25 --> 00:27Doctor Homer is a professor of pathology
00:27 --> 00:29and director of thoracic pathology
00:29 --> 00:31at the Yale School of Medicine,
00:31 --> 00:33where Doctor Chagpar is a
00:33 --> 00:34professor of surgical oncology.
00:35 --> 00:37Doctor Homer, maybe we can start
00:37 --> 00:39off by you telling us a little bit
00:39 --> 00:40about yourself and what exactly you do.
00:41 --> 00:44So I've come to New Haven in 1979 to
00:44 --> 00:47be part of the Yale MD PhD program.
00:47 --> 00:49I did a PhD in Immunology,
00:49 --> 00:52did a residency in anatomic pathology,
00:52 --> 00:54and then subsequently I sort of
00:54 --> 00:55risen to the ranks eventually
00:55 --> 00:57become a professor in 2009,
00:57 --> 00:59so anatomic pathology is an area
00:59 --> 01:03that I not sure a lot of people in
01:03 --> 01:05the community are familiar with.
01:05 --> 01:06It is a branch of medicine.
01:06 --> 01:08So pathologists are those people
01:08 --> 01:10who've gone to medical school.
01:10 --> 01:12We have medical training,
01:12 --> 01:15but we've then specialized really
01:15 --> 01:17in looking more on the diagnostic
01:17 --> 01:20end rather than on, you know,
01:20 --> 01:23the the immediate clinical care of patients.
01:23 --> 01:2411 way to say it is that we
01:24 --> 01:25care so much about our patients.
01:25 --> 01:28We want to make sure everybody
01:28 --> 01:30has the right diagnosis.
01:30 --> 01:31In my particular case,
01:31 --> 01:33the area of pathology that I'm in,
01:33 --> 01:34which is which is pathology,
01:34 --> 01:36is a very broad field,
01:36 --> 01:39but the area which I specialize in
01:39 --> 01:41predominantly involves looking at
01:41 --> 01:44histologic sections of lung tissue.
01:44 --> 01:46In order to understand what's
01:46 --> 01:47going on with the patient.
01:47 --> 01:49We do review radiographs.
01:49 --> 01:52I look at X rays,
01:52 --> 01:55CT scans and PET scans and other
01:55 --> 01:57radiologic imaging routinely.
01:57 --> 01:59I look at other clinical information
01:59 --> 02:01that's available in patients,
02:01 --> 02:02but at the end of the day,
02:02 --> 02:07the particular skills that I bring is
02:07 --> 02:09understanding the histopathology of
02:09 --> 02:11variety of diseases involving the lung,
02:11 --> 02:12in particular lung cancer,
02:12 --> 02:13but not only lung cancer.
02:14 --> 02:17So you know, we've talked on
02:17 --> 02:19this show previously about.
02:19 --> 02:20About lung cancer and the
02:20 --> 02:23fact that almost universally,
02:23 --> 02:25for most cancers.
02:25 --> 02:27Nearly everything starts with the
02:27 --> 02:29pathologist everything starts with
02:29 --> 02:32the biopsy so can you tell us a
02:32 --> 02:33little bit about the different
02:34 --> 02:36kinds of biopsy there are the The
02:36 --> 02:38Advantages and disadvantages and how
02:38 --> 02:40that impacts you as a pathologist.
02:42 --> 02:43I think that's a great question,
02:43 --> 02:46so it is certainly true that for
02:46 --> 02:48some tumors there are variety
02:48 --> 02:50of ways of getting a diagnosis,
02:50 --> 02:51but for lung cancer,
02:51 --> 02:53particular, as you say,
02:53 --> 02:54histopathology really is.
02:54 --> 02:58Still is a central element of
02:58 --> 02:59the diagnostic process.
02:59 --> 03:02The kinds of biopsies when could
03:02 --> 03:04obtain range from getting a what's
03:04 --> 03:08called a cytology or a smear of cells,
03:08 --> 03:10and those cells can be obtained
03:10 --> 03:11in a number of different ways.
03:11 --> 03:15If a patient happens to have a what's thought
03:15 --> 03:18to be a possible metastasis in another site,
03:18 --> 03:20you could put a needle in,
03:20 --> 03:22maybe even through the skin,
03:22 --> 03:24like into a lymph node around the
03:24 --> 03:26neck or or under the arms and
03:26 --> 03:29just obtain a smear and aspirate.
03:29 --> 03:30Just put a needle in.
03:30 --> 03:32With a syringe on it,
03:32 --> 03:34put a little suction on it at
03:34 --> 03:36get a few cells into the Chamber
03:36 --> 03:39and then smooth them onto a slide
03:39 --> 03:40and stained and looked at it.
03:40 --> 03:41Historically,
03:41 --> 03:43that was really the major way in
03:43 --> 03:45which a lot of lung cancer diagnosis
03:45 --> 03:47were made and there was a very
03:47 --> 03:49simple classification that that we
03:49 --> 03:51used what's called non small cell
03:51 --> 03:55and small cell carcinoma and by and
03:55 --> 03:57large that very simple technique
03:57 --> 03:59of just putting smear cells on
03:59 --> 04:01the slide was adequate for that.
04:01 --> 04:04And we still use things along those lines.
04:04 --> 04:06It might involve, as I said,
04:06 --> 04:09putting a needle into the skin into
04:09 --> 04:11some very superficial part of the body.
04:11 --> 04:11Like I said,
04:11 --> 04:13a lymph node or a lymph node
04:13 --> 04:15under the armor around the neck.
04:15 --> 04:19But it might also involve a medical
04:19 --> 04:21procedure where they put a bronchoscope
04:21 --> 04:23down the patient into the lungs and
04:23 --> 04:26just do a washing where you put in fluid,
04:26 --> 04:28and then you aspirate the fluid
04:28 --> 04:30out and then again he is take that
04:30 --> 04:31fluid and you smear it on his slide.
04:31 --> 04:33Or if you have fluid around the lungs
04:33 --> 04:34that might take some of that fluid,
04:34 --> 04:36and again smeared on a slide,
04:36 --> 04:38those are all ways in which, again,
04:38 --> 04:40you can use the vast majority
04:40 --> 04:42of cases can make a diagnosis,
04:42 --> 04:44as one might imagine,
04:44 --> 04:46the sensitivity of that is going
04:47 --> 04:49to depend on a lot of factors,
04:49 --> 04:51the amount of tissue obtained,
04:51 --> 04:52the kind of tumor it is,
04:52 --> 04:53if it is in fact the tumor,
04:53 --> 04:56what else is going on with the patient,
04:56 --> 04:59and so those are all you know historically,
04:59 --> 05:01that sort of the classic ways
05:01 --> 05:02which we did it.
05:02 --> 05:03More recently,
05:03 --> 05:06I have to say that the we're much more.
05:06 --> 05:09We get more information out of what's
05:09 --> 05:11called the histopathology of tumors,
05:11 --> 05:14whereas if you take that same smell,
05:14 --> 05:17cell smear and then you can
05:17 --> 05:18prepare it such that you could
05:18 --> 05:20make a pallet of cells you make,
05:20 --> 05:22take those cells, use pin them down,
05:22 --> 05:24you make a collection of cells.
05:24 --> 05:27You then actually can take a fix.
05:27 --> 05:30Those cells in a fixative in process
05:30 --> 05:32them as if they were regular.
05:32 --> 05:35Tissue biopsy and then two sections of it.
05:35 --> 05:36And then you'll have cells that
05:36 --> 05:38you can actually look at in a
05:38 --> 05:39diff slightly different way.
05:39 --> 05:41The advantage of that method
05:41 --> 05:42is a couple of things.
05:42 --> 05:45One is you can start looking
05:45 --> 05:46at so-called immunostains.
05:46 --> 05:49That is, we take antibodies
05:49 --> 05:51against cellular components.
05:51 --> 05:52We apply them to the tissue,
05:52 --> 05:55stain to the tissue section,
05:55 --> 05:57and then we sort of see which
05:57 --> 05:59elements of the cells are present
05:59 --> 06:00and different cells will be
06:00 --> 06:02able to stay in a different.
06:02 --> 06:03The different patterns in a large
06:03 --> 06:06part of my job has to do with
06:06 --> 06:07understanding the exact patterns
06:07 --> 06:09from different kinds of stains.
06:09 --> 06:10They're used again,
06:10 --> 06:12they have different degrees of sensitivity.
06:12 --> 06:13That is, you know,
06:13 --> 06:16are they true positive if it stains,
06:16 --> 06:17or if it's negative,
06:17 --> 06:18is that really a negative?
06:18 --> 06:19And how you know?
06:19 --> 06:21And that's a large part of my job,
06:21 --> 06:24has to understanding just how good
06:24 --> 06:26that processes and understanding it.
06:26 --> 06:28In addition to staining again,
06:28 --> 06:30these kind of small samples where you
06:30 --> 06:33take a smear and you can make a cell
06:33 --> 06:35so called cell block out of them.
06:35 --> 06:38You can also do biopsies of various types.
06:38 --> 06:43One biopsy technique is to again to take a.
06:43 --> 06:43Bronchoscope,
06:43 --> 06:45which goes into the patient's lungs,
06:45 --> 06:47and the bronchoscopies would then
06:47 --> 06:49maneuver it down into the lungs,
06:49 --> 06:52where he then takes a small piece of tissue.
06:52 --> 06:54Using a biopsy forceps and there's
06:54 --> 06:56a variety of tissues they can get.
06:56 --> 06:58This way they can get some
06:58 --> 06:59lung tissue itself,
06:59 --> 07:01but they also they're extremely good
07:01 --> 07:03at getting using that technique to
07:03 --> 07:05get lymph nodes within the chest,
07:05 --> 07:07which gives you a sense of whether
07:07 --> 07:09the tumor has spread or not
07:09 --> 07:10spread to adjacent lymph nodes.
07:10 --> 07:13And this is critical for understanding
07:13 --> 07:15a therapeutic approaches.
07:15 --> 07:15Alternatively,
07:15 --> 07:18sometimes the tumor or this deletion
07:18 --> 07:22of the suspicious lesion is in the very
07:22 --> 07:24periphery of the lung near the chest wall,
07:24 --> 07:26and sometimes you'll then have a
07:26 --> 07:29go to CT scan and then you can have
07:29 --> 07:31someone who can put a needle through
07:31 --> 07:33the skin into the lung that way,
07:33 --> 07:35so and then of course,
07:35 --> 07:37people who have unfortunately more
07:37 --> 07:39advanced disease where they might have
07:39 --> 07:42a lesion somewhere in the liver or in bones,
07:42 --> 07:45those can be biopsied again by.
07:45 --> 07:47Usually by CT scan or by under ultrasound
07:47 --> 07:49guidance and obtain piece of tissue,
07:49 --> 07:51which then again is submitted
07:51 --> 07:53for routine Histology.
07:53 --> 07:53Finally,
07:53 --> 07:55not very commonly,
07:55 --> 07:57but occasionally we'll have cases
07:57 --> 08:00where there might be a surgical
08:00 --> 08:02intervention where you're really
08:02 --> 08:04not sure what the lesion is.
08:04 --> 08:06And it might be small.
08:06 --> 08:08It might be difficult to obtain
08:08 --> 08:10and the one way you're absolutely
08:10 --> 08:12certain to obtain the tissue that's
08:12 --> 08:14diagnostic is to surgically resect it
08:14 --> 08:16even without a specific diagnosis,
08:16 --> 08:18because if you go through the
08:18 --> 08:19appropriate work up from there,
08:19 --> 08:20clinicians who really think,
08:20 --> 08:21look,
08:21 --> 08:23we really think this is probably a cancer,
08:23 --> 08:25and the only way we can know for sure,
08:25 --> 08:27it's really take it out
08:27 --> 08:28and really show the entire
08:28 --> 08:30thing to a pathologist.
08:30 --> 08:32Problem one of the problems
08:32 --> 08:34in lung pathology is that.
08:34 --> 08:36Lung cancers or lung tumors commonly
08:36 --> 08:38have areas where there's lot of
08:38 --> 08:40scarring and a lot of inflammation,
08:40 --> 08:41and if you get a biopsy,
08:41 --> 08:43which only shows that you're
08:43 --> 08:45never completely sure that you
08:45 --> 08:47haven't missed an actual cancer.
08:47 --> 08:49And so again, with the appropriate work
08:49 --> 08:51up and with really careful thinking
08:51 --> 08:54and with discussion with the patient,
08:54 --> 08:56you might go ahead and actually
08:56 --> 08:59surgically remove a nodule entirely
08:59 --> 09:01and then send it to a pathology.
09:01 --> 09:02At that point,
09:02 --> 09:04there's really two choices.
09:04 --> 09:06You can either send it to what's
09:06 --> 09:08called the frozen section area,
09:08 --> 09:10where we have people who are stand by,
09:10 --> 09:12you know all the time and we'll
09:12 --> 09:14take those and get make a rapid
09:14 --> 09:17section out of that and you can
09:17 --> 09:19do that by literally freezing the
09:19 --> 09:21tissue and then cutting sections
09:21 --> 09:23on specially equipped machines
09:23 --> 09:25called cry items which can make
09:25 --> 09:27sections which the pathologist can
09:27 --> 09:29look at within a few minutes of the
09:29 --> 09:31specimen arriving in pathology.
09:31 --> 09:33Pathologist looks at that and
09:33 --> 09:35very quickly makes a decision.
09:35 --> 09:38Is this look like a cancer or does
09:38 --> 09:40this look like something else?
09:40 --> 09:42And those are you know those though.
09:42 --> 09:44That kind of analysis is extremely accurate.
09:44 --> 09:47I just recently looked at our jails,
09:47 --> 09:50institutions experience and,
09:50 --> 09:50you know,
09:50 --> 09:52in almost all cases it's not perfect.
09:52 --> 09:54There are certainly examples where
09:54 --> 09:55it's not completely accurate,
09:55 --> 09:57but by and large it's a very,
09:57 --> 10:00very accurate technique and you can tell
10:00 --> 10:03immediately whether it is in fact a cancer.
10:03 --> 10:03Alternatively,
10:03 --> 10:05sometimes people will simply
10:05 --> 10:07take that tissue and submit it
10:07 --> 10:08for so-called permanent section,
10:08 --> 10:09whereas.
10:09 --> 10:13Where we process it as we would any other
10:13 --> 10:15specimen where we fix it in fixative,
10:15 --> 10:16we then section it.
10:16 --> 10:19We then submit it for routine astrology
10:19 --> 10:21and that usually takes overnight
10:21 --> 10:22if the tissue is small enough,
10:22 --> 10:24we might be able to do it the same day,
10:24 --> 10:25but usually we do it overnight.
10:25 --> 10:28And again we look at it the next day.
10:28 --> 10:29And in all these cases again,
10:29 --> 10:32we're very commonly would be using.
10:32 --> 10:32As I said,
10:32 --> 10:34these stains that we can use to
10:34 --> 10:35highlight specific molecular
10:35 --> 10:37features of the tumor or to
10:37 --> 10:38understand exactly what it is and
10:38 --> 10:40characterize it a little bit.
10:40 --> 10:40Better.
10:41 --> 10:44So there are a whole variety,
10:44 --> 10:45as you alluded to,
10:45 --> 10:48of types of biopsies and types of
10:48 --> 10:50techniques of looking at the these
10:50 --> 10:53tissues to come to a diagnosis.
10:53 --> 10:55I think a few questions come to mind.
10:55 --> 10:58The first is when you're
10:58 --> 11:00looking at these tiny cells.
11:00 --> 11:02You know when you talked about
11:02 --> 11:04putting a needle into something
11:04 --> 11:06and aspirating a few cells.
11:06 --> 11:08I'm sure that people wonder how
11:08 --> 11:11easy is it for you to tell that.
11:11 --> 11:14Is a cancer cell versus not a cancer
11:14 --> 11:17cell or a non small cell cancer cell
11:17 --> 11:20versus a small cell cancer cell?
11:20 --> 11:20How?
11:20 --> 11:23How sure are you when you make that
11:23 --> 11:26diagnosis of the diagnosis that you make,
11:26 --> 11:29especially when it's just a few cells.
11:30 --> 11:32I think I agree that this is
11:32 --> 11:33really part of the training.
11:33 --> 11:35I think we've all you know,
11:35 --> 11:37one of the things that pathology
11:37 --> 11:39involves is really a lot of
11:39 --> 11:41a lot of hands-on experience.
11:41 --> 11:43That's number one number two.
11:43 --> 11:44We are very sensitive to the notion
11:44 --> 11:46that we don't want to, you know,
11:46 --> 11:48call something a cancer that's not cancer,
11:48 --> 11:50and so again, as part of the training,
11:50 --> 11:53we learn very carefully that there's a
11:53 --> 11:55minimum number of cells you really need
11:55 --> 11:57in order to make a specific diagnosis.
11:57 --> 11:58And there's no, you know,
11:58 --> 12:00magic number in terms of
12:00 --> 12:01exactly how many cells that is.
12:01 --> 12:03But I you know one cell is
12:03 --> 12:05certainly not going to be enough.
12:05 --> 12:08And you know, is 100 cells necessary?
12:08 --> 12:10We certainly get down into,
12:10 --> 12:11maybe, you know, 100 cells,
12:11 --> 12:13or maybe in some cases fewer.
12:13 --> 12:15But largely we're very sensitive for
12:15 --> 12:18the notion we really want to see a
12:18 --> 12:20population of cells that are really
12:20 --> 12:22clearly represent a malignancy.
12:22 --> 12:24And the other thing we do is particularly
12:24 --> 12:27on the smaller samples we commonly, you know,
12:27 --> 12:29pathologists will commonly show things we,
12:29 --> 12:30each other.
12:30 --> 12:31We're totally, you know,
12:31 --> 12:34there's no sense of you know, ego involved.
12:34 --> 12:35We show each other things.
12:35 --> 12:36What do you think?
12:36 --> 12:36What do you think?
12:36 --> 12:39Is this enough and we generally anything
12:39 --> 12:41where there's even a marginal call.
12:41 --> 12:43We show things to each other and
12:43 --> 12:45we document that we've shown it to
12:45 --> 12:47somebody else who agrees with us.
12:47 --> 12:49So that's really sort of
12:49 --> 12:51intrinsically baked into our process,
12:51 --> 12:52and I think that the you know,
12:52 --> 12:53if you actually were to go
12:53 --> 12:55and look at the literature.
12:55 --> 12:58You'd say that the based on you
12:58 --> 13:00know if summaries people have done
13:00 --> 13:01this in pathology extensively,
13:01 --> 13:03whereas you ask and you go back and
13:03 --> 13:05you look at other peoples diagnosis.
13:05 --> 13:07How often are you correct and you know,
13:07 --> 13:09I can't say everything is perfect.
13:09 --> 13:10There's nothing in life which
13:10 --> 13:11is completely perfect.
13:11 --> 13:15But by and large it's extremely good.
13:15 --> 13:16And so I think that you know if
13:16 --> 13:18there is really any doubt you know
13:18 --> 13:19patients can always ask for to
13:19 --> 13:21send it to another institution.
13:21 --> 13:22I don't recall a case at Yale
13:22 --> 13:24where you know we've had a change
13:24 --> 13:26diagnosis along this line, certainly.
13:26 --> 13:29People can have other opinions
13:29 --> 13:31exactly how to classify a tumor,
13:31 --> 13:33but by and large we are very
13:33 --> 13:36careful to try to prevent anything
13:36 --> 13:38where that's really an issue.
13:38 --> 13:39Terrific,
13:39 --> 13:41well we're going to learn a lot
13:41 --> 13:43more about lung cancer pathology
13:43 --> 13:44right after we take a short
13:44 --> 13:46break for a medical minute.
13:46 --> 13:48Please stay tuned to learn more about
13:48 --> 13:50lung cancer pathology with my guest
13:50 --> 13:51Doctor Robert Homer.
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15:06 --> 15:09Welcome back to Yale Cancer Answers.
15:09 --> 15:10This is doctor Anees Chagpar
15:10 --> 15:12and I'm joined tonight
15:12 --> 15:14by my guest doctor Robert Homer.
15:14 --> 15:15We're learning more about lung
15:15 --> 15:17cancer pathology and Doctor Homer,
15:17 --> 15:19right before the break you were
15:19 --> 15:21talking about the fact that
15:21 --> 15:22there's a lot of training that
15:22 --> 15:24goes into being a pathologist,
15:24 --> 15:26and that's really important because.
15:26 --> 15:29You know you really need to be able
15:29 --> 15:30to recognize the difference between
15:30 --> 15:33a cancer cell and a non cancer cell
15:33 --> 15:36when making that diagnosis and when
15:36 --> 15:39you have questions or concerns,
15:39 --> 15:42do you have enough of a sample or
15:42 --> 15:44it's kind of a borderline call?
15:44 --> 15:47There's really no issue in terms
15:47 --> 15:49of seeking another opinion and
15:49 --> 15:52you as pathologists do that a lot.
15:52 --> 15:55You'll show that to other pathologists.
15:55 --> 15:57So one question that people who
15:57 --> 15:58are listening might.
15:58 --> 16:03Ask is you know, should patients,
16:03 --> 16:06when given a lung cancer diagnosis,
16:06 --> 16:07seek a second opinion with
16:07 --> 16:09regards to their pathology?
16:11 --> 16:13At another institution,
16:13 --> 16:16if they're not sure, and because,
16:16 --> 16:18how can a patient really be sure,
16:18 --> 16:20aside from the fact that most of
16:20 --> 16:22us have a lot of confidence in the
16:22 --> 16:23institutions that we frequent?
16:25 --> 16:27I, I think that anytime if there
16:27 --> 16:29is a patient really unsure,
16:29 --> 16:31you know I'm you know.
16:31 --> 16:33I sort of think about this in medicine.
16:33 --> 16:34I think this is sort of a general
16:34 --> 16:36question about any medical advice.
16:36 --> 16:39So pathology report is is medical advice.
16:39 --> 16:41I think that if you see an oncologist and
16:41 --> 16:43aren't sure about their advice you give,
16:43 --> 16:45you should be free to seek another opinion.
16:45 --> 16:47If you seek a surgeon and get different
16:47 --> 16:49advice you want and you're not happy
16:49 --> 16:50with it or you're concerned and you
16:50 --> 16:52want to make sure that you've seen it,
16:52 --> 16:53you can get a second opinion.
16:53 --> 16:54I don't think that.
16:54 --> 16:56Salty diagnosis or any different?
16:56 --> 16:58I think you would put it in the same
16:58 --> 17:00category as any other medical opinion,
17:00 --> 17:02and you know if there's really
17:02 --> 17:03any any concern.
17:03 --> 17:05I think that that's a fine thing to do.
17:06 --> 17:09And so you know, I think one of the big
17:09 --> 17:12distinctions is cancer versus no cancer,
17:12 --> 17:15and one of the things that you
17:15 --> 17:17mentioned before the break was that
17:17 --> 17:20you're really very careful about
17:20 --> 17:22calling cancer versus not cancer.
17:22 --> 17:25And so tell us a little bit more about
17:25 --> 17:28the nuances you mentioned that you
17:28 --> 17:30know there's classifications in terms
17:30 --> 17:32of small cell and non small cell.
17:32 --> 17:35How do you make that distinction
17:35 --> 17:37and why is it important?
17:37 --> 17:39Or is it important to patients treatment?
17:40 --> 17:43So the historical distinction between
17:43 --> 17:46so-called small cell and non small
17:46 --> 17:48cell carcinoma really goes back
17:48 --> 17:51to the 1960s and 70s where it was
17:51 --> 17:54understood that the vast majority of
17:54 --> 17:56people with what's so called small
17:56 --> 17:59cell carcinoma were most likely had
17:59 --> 18:02a systemic disease on presentation,
18:02 --> 18:05and they responded to certain types of
18:05 --> 18:07chemotherapy that patients with so-called
18:07 --> 18:09non small cell carcinoma did not.
18:09 --> 18:11And that's really sort of become.
18:11 --> 18:13Sort of a founding principle of the field
18:13 --> 18:15of thoracic oncology for a long time.
18:18 --> 18:20We certainly at the you know,
18:20 --> 18:22back in the 60s to 70s we didn't
18:22 --> 18:24have really any ancillary so called
18:24 --> 18:26ancillary techniques like immunostains
18:26 --> 18:28for molecular diagnostics and so
18:28 --> 18:30that was really just based on the
18:30 --> 18:31morphologic appearance of the cell.
18:31 --> 18:33With a few relatively by
18:33 --> 18:34our current standards,
18:34 --> 18:36crude stains these days,
18:36 --> 18:38it's really pretty clear that you
18:39 --> 18:41can improve the reproducibility of
18:41 --> 18:44the diagnosis by getting some stains.
18:44 --> 18:47There is a one particular paper
18:47 --> 18:48that I use routinely.
18:48 --> 18:50But that's an international that
18:50 --> 18:52show that international consensus of
18:52 --> 18:54difficult cases cases that people
18:54 --> 18:56agreed were not straightforward could
18:56 --> 18:58be improved by using immunostains.
18:58 --> 19:00And I also think that these days,
19:00 --> 19:02with molecular diagnostics being
19:02 --> 19:04as advanced as it is,
19:04 --> 19:06there are very rare cases where
19:06 --> 19:07that can be helped.
19:07 --> 19:08It's clear that, again,
19:08 --> 19:10so called small cell carcinoma has
19:10 --> 19:12a very distinct molecular signature,
19:12 --> 19:15whereas tumors of so called non
19:15 --> 19:17small cell have a range of other
19:17 --> 19:19signatures which really would not
19:19 --> 19:20be expected to be seen in that.
19:20 --> 19:23So I think that there is,
19:23 --> 19:24you know,
19:24 --> 19:26the basic diagnosis is certainly
19:26 --> 19:28suggested by just routine Histology,
19:28 --> 19:29and there's clearly cell,
19:29 --> 19:32clearly tumors which are just not small cell.
19:32 --> 19:33If you just look at it and say there's yeah,
19:33 --> 19:35that's just not what it is,
19:35 --> 19:36you know I don't really care about
19:36 --> 19:38any of the other markers that are
19:38 --> 19:40present and there's other tumors
19:40 --> 19:42where you say you know I'm just
19:42 --> 19:44not sure those are relatively.
19:44 --> 19:45You know,
19:45 --> 19:46maybe 5% of cases where people
19:46 --> 19:48sort of have that thing.
19:48 --> 19:49But of course you know at
19:49 --> 19:50any larger Cancer Center.
19:50 --> 19:51You know,
19:51 --> 19:53like Yale or other large cancer centers,
19:53 --> 19:55we see enough cancers that they they show up.
19:55 --> 19:57You know, all the time.
19:57 --> 20:00So we do have a sort of a,
20:00 --> 20:01you know,
20:01 --> 20:05a standard protocol for a for resolving that.
20:05 --> 20:07In terms of non small cell carcinomas,
20:07 --> 20:10we know that there is really two
20:10 --> 20:12major subtypes within that admin,
20:12 --> 20:15so called adenocarcinoma and
20:15 --> 20:17squamous cell carcinoma.
20:17 --> 20:19And there's excellent markers that
20:19 --> 20:22distinguish those two things from each other.
20:22 --> 20:24We know that there's a large
20:24 --> 20:25percentage of those cases which
20:25 --> 20:27might be surgically resectable.
20:27 --> 20:29We also know that all of the you know,
20:29 --> 20:30oncology protocols for patients
20:30 --> 20:34who do not have resectable tumors.
20:34 --> 20:36That's like the first thing,
20:36 --> 20:38pretty much in all the protocols is to
20:38 --> 20:40understand which of those two pathways it is.
20:40 --> 20:42It's in pretty much all the
20:42 --> 20:44molecular work up after that depends
20:44 --> 20:46on that fundamental distinction,
20:46 --> 20:47and a lot of the therapeutic.
20:47 --> 20:49Decisions are based on that as well.
20:49 --> 20:49Not entirely,
20:49 --> 20:50but largely.
20:50 --> 20:52We have excellent markers that
20:52 --> 20:54distinguish those two things these days,
20:54 --> 20:58and all lung tumors that have
20:58 --> 21:00enough tissue to evaluate would
21:00 --> 21:02most likely get one of those,
21:02 --> 21:03unless it's, again, histologically.
21:03 --> 21:05You know, quite straightforward.
21:06 --> 21:09And so that's really important because
21:09 --> 21:11it it influences the type of treatment
21:11 --> 21:14that that patients get. Is that right?
21:14 --> 21:16It is it distinguished influences
21:16 --> 21:17the treatment they get,
21:17 --> 21:20but also to a certain extent the work up.
21:20 --> 21:23If you have somebody with which seems
21:23 --> 21:25to be a like a localized, there rarely.
21:25 --> 21:27Again you have cases which are
21:27 --> 21:29look like a localized small cell.
21:29 --> 21:31The oncologist might try much harder to
21:31 --> 21:34really convince himself or herself that
21:34 --> 21:36that's really a truly localized tumor.
21:36 --> 21:38Because the likelihood that
21:38 --> 21:39they're probably missing something,
21:39 --> 21:41so they might do a more extensive
21:41 --> 21:42work up than they might otherwise.
21:44 --> 21:46And it's also true that a lot of our
21:46 --> 21:48patients have more than one tumor,
21:48 --> 21:51unfortunately, and so a lot of lot
21:51 --> 21:53of much of what I do, you know,
21:53 --> 21:55is direct with fast conchology is a
21:55 --> 21:57pathology or other is to really look at
21:57 --> 21:58patients who have more than one tumor
21:58 --> 22:00and really connect yourself that what
22:00 --> 22:02you're seeing is which of those you know.
22:02 --> 22:04Is this really a primary lung tumor,
22:04 --> 22:07or is this really coming from somewhere else?
22:07 --> 22:08And so understanding that distinction
22:08 --> 22:10is important in order to help with
22:10 --> 22:12that decision making process as well.
22:13 --> 22:16You know you mentioned molecular
22:16 --> 22:18diagnostics a few times and I want
22:18 --> 22:20to dive a little bit more into that.
22:20 --> 22:22It on this show.
22:22 --> 22:23We've talked about personalized
22:23 --> 22:26medicine and targeted therapies.
22:26 --> 22:30The idea that these days pathologists,
22:30 --> 22:33can you know, look at these tumors in
22:33 --> 22:36a variety of ways to kind of unlock
22:36 --> 22:38the genomic signatures of them,
22:38 --> 22:40identify whether they express
22:40 --> 22:42certain receptors or certain
22:42 --> 22:44proteins that then are targetable.
22:45 --> 22:49With certain drugs, how common is that done?
22:49 --> 22:51It should, should patients be
22:51 --> 22:53going to their medical oncologists,
22:53 --> 22:55asking about you know whether they have
22:55 --> 22:59a a BRAF mutation or a veg F mutation,
22:59 --> 23:00or that kind of thing?
23:01 --> 23:03Well, the good news is that there
23:03 --> 23:05are quite a number of consensus
23:05 --> 23:07statements on which tumors are
23:07 --> 23:09really the appropriate ones to do.
23:09 --> 23:11The mock their testing on their
23:11 --> 23:13variety of professional societies,
23:13 --> 23:15which include both pathology and oncology,
23:15 --> 23:17which is really very, you know,
23:17 --> 23:20very explicitly stated who should
23:20 --> 23:23get this kind of profiling.
23:23 --> 23:25So for example, as I mentioned,
23:25 --> 23:26the distinction adenocarcinoma
23:26 --> 23:28and squamous cell carcinoma is
23:28 --> 23:30really critical and it's really
23:30 --> 23:32quite clear that the guidelines.
23:32 --> 23:34Or recommend that anyone with a
23:34 --> 23:36nano carcinoma should absolutely
23:36 --> 23:38have unlocked the profiling.
23:38 --> 23:40That's really and at Yale.
23:40 --> 23:43Let's say that 100% anyone with
23:43 --> 23:45adequate tissue will have that done.
23:45 --> 23:47I should also point out the fact
23:47 --> 23:48that even though we like to think
23:48 --> 23:50of this as a tissue based process,
23:50 --> 23:53there's now also the options
23:53 --> 23:55to get some of that molecular
23:55 --> 23:57profiling done just by a blood test.
23:57 --> 24:00It is not as sensitive as getting
24:00 --> 24:02adequate piece of tissue, but if it's,
24:02 --> 24:03you know if it detects it,
24:03 --> 24:05appropriate genetic abnormality,
24:05 --> 24:07then it can be.
24:07 --> 24:09I think we're all pretty comfortable
24:09 --> 24:11that we can rely on it.
24:11 --> 24:13On the other hand, as I said,
24:13 --> 24:15having an adequate piece of tissue to do
24:15 --> 24:17that is still considered the gold standard.
24:17 --> 24:20Patients with squamous cell carcinoma,
24:20 --> 24:23unless with with relatively few exceptions,
24:23 --> 24:26are not thought to benefit from sequencing.
24:26 --> 24:27Again,
24:27 --> 24:27there are few.
24:27 --> 24:29There are a few exceptions and
24:29 --> 24:31because there are a few exceptions,
24:31 --> 24:33some oncologists do would like
24:33 --> 24:35to see their lung cancers from
24:35 --> 24:37these patients sequence as well.
24:37 --> 24:38But that's a much,
24:38 --> 24:41it's more of a very specific decision.
24:41 --> 24:43That needs to be done individually,
24:43 --> 24:46I think now and I should also point
24:46 --> 24:48out the fact that from my perspective,
24:48 --> 24:50even though we like to talk about
24:50 --> 24:53Gnostics as being particularly important
24:53 --> 24:54for specific therapeutic decisions,
24:54 --> 24:57so do I have a mutation in a gene
24:57 --> 24:59where there's a specific drug that
24:59 --> 25:01targets that specific mutation,
25:01 --> 25:04which is great when when we have have it.
25:04 --> 25:06It's also true that from my perspective,
25:06 --> 25:07sometimes that but profiling
25:07 --> 25:09could be very useful to decide
25:09 --> 25:11whether something is in fact a lung
25:11 --> 25:13cancer or from somewhere else,
25:13 --> 25:16or it's actually fairly common to have
25:16 --> 25:18patients who have had a lung cancer
25:18 --> 25:20to then have a second lung cancer.
25:20 --> 25:21And sometimes we use it to
25:21 --> 25:23distinguish whether is this really
25:23 --> 25:24the same tumor which is record?
25:24 --> 25:26Or is this really a new tumor?
25:26 --> 25:28And at the again there may be
25:28 --> 25:29therapeutic implications from that,
25:29 --> 25:31depending on the specific
25:31 --> 25:32patient circumstance.
25:33 --> 25:36So it sounds like you know these decisions
25:36 --> 25:41are are really critical and or can be.
25:41 --> 25:44Now you mentioned that with Frozen section
25:44 --> 25:47you can make a diagnosis in minutes,
25:47 --> 25:50but in terms of getting all of the
25:50 --> 25:53information you know small cell versus
25:53 --> 25:56non small cell adeno versus squamous,
25:56 --> 25:57the molecular profiling.
25:57 --> 26:00How long does that take?
26:01 --> 26:06So the add new versus squamous distinction
26:06 --> 26:08so frequently that you know that
26:08 --> 26:11depends on the specifics of the tumor.
26:11 --> 26:14It's pretty common in a tumor which is so
26:14 --> 26:16called well or moderately differentiated.
26:16 --> 26:18That is still has histologic
26:18 --> 26:20evidence that is producing these
26:20 --> 26:22particular histologic features.
26:22 --> 26:23You can tell it just at the
26:23 --> 26:25time of frozen section would be
26:25 --> 26:26pretty comfortable with that.
26:26 --> 26:28There are other tumors where it's
26:28 --> 26:29a very undifferentiated tumor.
26:29 --> 26:31It really does not the Histology
26:31 --> 26:33of the just looking at it doesn't
26:33 --> 26:34really tell you very much.
26:34 --> 26:36They needed a stains.
26:36 --> 26:38No, it depends on you know
26:38 --> 26:40that could be a day or two.
26:40 --> 26:41Might be your students
26:41 --> 26:42aren't terribly helpful.
26:42 --> 26:44You might do a second round,
26:44 --> 26:47so that might be a few days
26:47 --> 26:50and then the molecular work,
26:50 --> 26:53which includes one marker which helps
26:53 --> 26:56determine how available you are or how
26:56 --> 26:59effective immunotherapy is likely to be.
26:59 --> 27:00With civil PDL.
27:00 --> 27:02One stain that should be done
27:02 --> 27:04within another few days or a week,
27:04 --> 27:05and then they'll look up profiling.
27:05 --> 27:06Again, should be done.
27:06 --> 27:08There's again national standards
27:08 --> 27:10that should be done within two weeks.
27:11 --> 27:14So it can take up to two weeks to get,
27:14 --> 27:16you know, kind of a thorough
27:16 --> 27:17pathologic work up of your cancer
27:17 --> 27:19is that is that about accurate?
27:20 --> 27:21I think that for lung cancer,
27:21 --> 27:23I think that's where we are the
27:23 --> 27:24the peripheral blood testing.
27:24 --> 27:26If it shows something,
27:26 --> 27:27might be a few days before that,
27:27 --> 27:29but it's not going to be.
27:29 --> 27:30You know, it's not going
27:30 --> 27:31to be just a few days,
27:31 --> 27:33it might be 10 days instead of two weeks,
27:33 --> 27:34but that seems to be where
27:34 --> 27:36we are at the moment.
27:37 --> 27:39The reason I bring it up is because you
27:39 --> 27:41know when patients and people hear that.
27:41 --> 27:43You can make a diagnosis in
27:43 --> 27:44minutes with frozen section.
27:44 --> 27:47They often will then go to their
27:47 --> 27:49clinician saying why is it taking
27:49 --> 27:51so long to get the pathology back.
27:51 --> 27:54On my lung cancer can we
27:54 --> 27:56get started with treatment?
27:56 --> 27:58So I think that you've kind of
27:58 --> 28:00elucidated why it takes so long
28:00 --> 28:02and I personally have a maxim that
28:02 --> 28:04says never rush the pathologist.
28:04 --> 28:06Their opinion is too important.
28:07 --> 28:10I appreciate that we all you know
28:10 --> 28:12we want to get it right. We all.
28:12 --> 28:13I think in pathology we're all
28:13 --> 28:15really very aware that somebody
28:15 --> 28:17is waiting for these diagnosis.
28:17 --> 28:19You know we're not, you know, I,
28:19 --> 28:21I always personally have a feeling that
28:21 --> 28:23you know should you know should do it.
28:23 --> 28:24You should be accurate,
28:24 --> 28:26but you should also be fast and I think
28:26 --> 28:28that that they're they're both important.
28:28 --> 28:30You know nobody is going to cut corners.
28:30 --> 28:30On the other hand,
28:30 --> 28:34nobody wants to, just, you know.
28:34 --> 28:36Slow walk this the diagnosis out the door
28:36 --> 28:40yeah so in in our last minute or
28:40 --> 28:42two maybe you can tell us what's on
28:42 --> 28:44the horizon in thoracic pathology?
28:44 --> 28:46What do we have to look forward to?
28:47 --> 28:48That's a great question.
28:48 --> 28:51I think one of the things going forward
28:51 --> 28:54is really a better understanding of
28:54 --> 28:55exactly how the immune system works.

Information

Lung Pathology with guest Dr. Robert Homer February 6, 2022 Yale Cancer Center visit: http://www.yalecancercenter.org email: canceranswers@yale.edu call: 203-785-4095