Lung Pathology

Transcript

• 00:00Funding for Yale Cancer Answers is
• 00:02provided by Smilow Cancer Hospital.
• 00:07Welcome to Yale Cancer Answers with
• 00:09your host doctor Anees Chagpar.
• 00:11Yale Cancer Answers features the
• 00:13latest information on cancer care by
• 00:15welcoming oncologists and specialists
• 00:17who are on the forefront of the
• 00:19battle to fight cancer. This week,
• 00:21it's a conversation about lung cancer
• 00:23pathology with Doctor Robert Homer.
• 00:25Doctor Homer is a professor of pathology
• 00:27and director of thoracic pathology
• 00:29at the Yale School of Medicine,
• 00:31where Doctor Chagpar is a
• 00:33professor of surgical oncology.
• 00:36Doctor Homer, maybe we can start
• 00:37off by you telling us a little bit
• 00:39about yourself and what exactly you do.
• 00:41So I've come to New Haven in 1979 to
• 00:45be part of the Yale MD PhD program.
• 00:47I did a PhD in Immunology,
• 00:50did a residency in anatomic pathology,
• 00:52and then subsequently I sort of
• 00:54risen to the ranks eventually
• 00:56become a professor in 2009,
• 00:58so anatomic pathology is an area
• 01:00that I not sure a lot of people in
• 01:03the community are familiar with.
• 01:05It is a branch of medicine.
• 01:07So pathologists are those people
• 01:09who've gone to medical school.
• 01:11We have medical training,
• 01:13but we've then specialized really
• 01:15in looking more on the diagnostic
• 01:18end rather than on, you know,
• 01:20the the immediate clinical care of patients.
• 01:2311 way to say it is that we
• 01:24care so much about our patients.
• 01:26We want to make sure everybody
• 01:28has the right diagnosis.
• 01:30In my particular case,
• 01:31the area of pathology that I'm in,
• 01:33which is which is pathology,
• 01:35is a very broad field,
• 01:36but the area which I specialize in
• 01:39predominantly involves looking at
• 01:41histologic sections of lung tissue.
• 01:44In order to understand what's
• 01:46going on with the patient.
• 01:48We do review radiographs.
• 01:50I look at X rays,
• 01:52CT scans and PET scans and other
• 01:56radiologic imaging routinely.
• 01:57I look at other clinical information
• 02:00that's available in patients,
• 02:01but at the end of the day,
• 02:03the particular skills that I bring is
• 02:07understanding the histopathology of
• 02:09variety of diseases involving the lung,
• 02:11in particular lung cancer,
• 02:12but not only lung cancer.
• 02:15So you know, we've talked on
• 02:17this show previously about.
• 02:19About lung cancer and the
• 02:21fact that almost universally,
• 02:23for most cancers.
• 02:26Nearly everything starts with the
• 02:28pathologist everything starts with
• 02:29the biopsy so can you tell us a
• 02:32little bit about the different
• 02:34kinds of biopsy there are the The
• 02:37Advantages and disadvantages and how
• 02:39that impacts you as a pathologist.
• 02:42I think that's a great question,
• 02:44so it is certainly true that for
• 02:46some tumors there are variety
• 02:48of ways of getting a diagnosis,
• 02:50but for lung cancer,
• 02:52particular, as you say,
• 02:53histopathology really is.
• 02:55Still is a central element of
• 02:58the diagnostic process.
• 03:00The kinds of biopsies when could
• 03:02obtain range from getting a what's
• 03:05called a cytology or a smear of cells,
• 03:09and those cells can be obtained
• 03:10in a number of different ways.
• 03:12If a patient happens to have a what's thought
• 03:15to be a possible metastasis in another site,
• 03:18you could put a needle in,
• 03:21maybe even through the skin,
• 03:22like into a lymph node around the
• 03:24neck or or under the arms and
• 03:27just obtain a smear and aspirate.
• 03:29Just put a needle in.
• 03:31With a syringe on it,
• 03:32put a little suction on it at
• 03:34get a few cells into the Chamber
• 03:37and then smooth them onto a slide
• 03:39and stained and looked at it.
• 03:41Historically,
• 03:41that was really the major way in
• 03:43which a lot of lung cancer diagnosis
• 03:46were made and there was a very
• 03:48simple classification that that we
• 03:50used what's called non small cell
• 03:52and small cell carcinoma and by and
• 03:55large that very simple technique
• 03:57of just putting smear cells on
• 03:59the slide was adequate for that.
• 04:01And we still use things along those lines.
• 04:04It might involve, as I said,
• 04:07putting a needle into the skin into
• 04:09some very superficial part of the body.
• 04:11Like I said,
• 04:12a lymph node or a lymph node
• 04:14under the armor around the neck.
• 04:16But it might also involve a medical
• 04:19procedure where they put a bronchoscope
• 04:22down the patient into the lungs and
• 04:24just do a washing where you put in fluid,
• 04:26and then you aspirate the fluid
• 04:28out and then again he is take that
• 04:30fluid and you smear it on his slide.
• 04:32Or if you have fluid around the lungs
• 04:33that might take some of that fluid,
• 04:35and again smeared on a slide,
• 04:37those are all ways in which, again,
• 04:39you can use the vast majority
• 04:41of cases can make a diagnosis,
• 04:43as one might imagine,
• 04:44the sensitivity of that is going
• 04:47to depend on a lot of factors,
• 04:49the amount of tissue obtained,
• 04:51the kind of tumor it is,
• 04:52if it is in fact the tumor,
• 04:54what else is going on with the patient,
• 04:57and so those are all you know historically,
• 04:59that sort of the classic ways
• 05:01which we did it.
• 05:02More recently,
• 05:03I have to say that the we're much more.
• 05:07We get more information out of what's
• 05:10called the histopathology of tumors,
• 05:12whereas if you take that same smell,
• 05:14cell smear and then you can
• 05:17prepare it such that you could
• 05:19make a pallet of cells you make,
• 05:20take those cells, use pin them down,
• 05:23you make a collection of cells.
• 05:25You then actually can take a fix.
• 05:28Those cells in a fixative in process
• 05:30them as if they were regular.
• 05:32Tissue biopsy and then two sections of it.
• 05:35And then you'll have cells that
• 05:37you can actually look at in a
• 05:39diff slightly different way.
• 05:40The advantage of that method
• 05:41is a couple of things.
• 05:43One is you can start looking
• 05:45at so-called immunostains.
• 05:47That is, we take antibodies
• 05:50against cellular components.
• 05:52We apply them to the tissue,
• 05:53stain to the tissue section,
• 05:55and then we sort of see which
• 05:57elements of the cells are present
• 06:00and different cells will be
• 06:01able to stay in a different.
• 06:02The different patterns in a large
• 06:04part of my job has to do with
• 06:06understanding the exact patterns
• 06:08from different kinds of stains.
• 06:09They're used again,
• 06:10they have different degrees of sensitivity.
• 06:13That is, you know,
• 06:14are they true positive if it stains,
• 06:16or if it's negative,
• 06:17is that really a negative?
• 06:18And how you know?
• 06:19And that's a large part of my job,
• 06:21has to understanding just how good
• 06:24that processes and understanding it.
• 06:26In addition to staining again,
• 06:29these kind of small samples where you
• 06:31take a smear and you can make a cell
• 06:33so called cell block out of them.
• 06:35You can also do biopsies of various types.
• 06:38One biopsy technique is to again to take a.
• 06:43Bronchoscope,
• 06:43which goes into the patient's lungs,
• 06:46and the bronchoscopies would then
• 06:47maneuver it down into the lungs,
• 06:49where he then takes a small piece of tissue.
• 06:52Using a biopsy forceps and there's
• 06:54a variety of tissues they can get.
• 06:56This way they can get some
• 06:58lung tissue itself,
• 06:59but they also they're extremely good
• 07:02at getting using that technique to
• 07:04get lymph nodes within the chest,
• 07:06which gives you a sense of whether
• 07:08the tumor has spread or not
• 07:09spread to adjacent lymph nodes.
• 07:11And this is critical for understanding
• 07:14a therapeutic approaches.
• 07:15Alternatively,
• 07:16sometimes the tumor or this deletion
• 07:19of the suspicious lesion is in the very
• 07:22periphery of the lung near the chest wall,
• 07:25and sometimes you'll then have a
• 07:27go to CT scan and then you can have
• 07:30someone who can put a needle through
• 07:32the skin into the lung that way,
• 07:34so and then of course,
• 07:35people who have unfortunately more
• 07:37advanced disease where they might have
• 07:40a lesion somewhere in the liver or in bones,
• 07:43those can be biopsied again by.
• 07:45Usually by CT scan or by under ultrasound
• 07:48guidance and obtain piece of tissue,
• 07:50which then again is submitted
• 07:52for routine Histology.
• 07:53Finally,
• 07:54not very commonly,
• 07:55but occasionally we'll have cases
• 07:58where there might be a surgical
• 08:00intervention where you're really
• 08:02not sure what the lesion is.
• 08:05And it might be small.
• 08:06It might be difficult to obtain
• 08:08and the one way you're absolutely
• 08:10certain to obtain the tissue that's
• 08:12diagnostic is to surgically resect it
• 08:15even without a specific diagnosis,
• 08:17because if you go through the
• 08:18appropriate work up from there,
• 08:19clinicians who really think,
• 08:21look,
• 08:21we really think this is probably a cancer,
• 08:23and the only way we can know for sure,
• 08:25it's really take it out
• 08:27and really show the entire
• 08:29thing to a pathologist.
• 08:30Problem one of the problems
• 08:33in lung pathology is that.
• 08:35Lung cancers or lung tumors commonly
• 08:37have areas where there's lot of
• 08:39scarring and a lot of inflammation,
• 08:40and if you get a biopsy,
• 08:41which only shows that you're
• 08:43never completely sure that you
• 08:45haven't missed an actual cancer.
• 08:48And so again, with the appropriate work
• 08:50up and with really careful thinking
• 08:52and with discussion with the patient,
• 08:54you might go ahead and actually
• 08:56surgically remove a nodule entirely
• 08:59and then send it to a pathology.
• 09:02At that point,
• 09:03there's really two choices.
• 09:04You can either send it to what's
• 09:07called the frozen section area,
• 09:08where we have people who are stand by,
• 09:11you know all the time and we'll
• 09:13take those and get make a rapid
• 09:15section out of that and you can
• 09:17do that by literally freezing the
• 09:19tissue and then cutting sections
• 09:21on specially equipped machines
• 09:23called cry items which can make
• 09:25sections which the pathologist can
• 09:27look at within a few minutes of the
• 09:30specimen arriving in pathology.
• 09:31Pathologist looks at that and
• 09:33very quickly makes a decision.
• 09:35Is this look like a cancer or does
• 09:38this look like something else?
• 09:40And those are you know those though.
• 09:42That kind of analysis is extremely accurate.
• 09:45I just recently looked at our jails,
• 09:48institutions experience and,
• 09:50you know,
• 09:51in almost all cases it's not perfect.
• 09:52There are certainly examples where
• 09:54it's not completely accurate,
• 09:56but by and large it's a very,
• 09:58very accurate technique and you can tell
• 10:01immediately whether it is in fact a cancer.
• 10:03Alternatively,
• 10:04sometimes people will simply
• 10:05take that tissue and submit it
• 10:07for so-called permanent section,
• 10:09whereas.
• 10:09Where we process it as we would any other
• 10:13specimen where we fix it in fixative,
• 10:16we then section it.
• 10:17We then submit it for routine astrology
• 10:19and that usually takes overnight
• 10:21if the tissue is small enough,
• 10:22we might be able to do it the same day,
• 10:24but usually we do it overnight.
• 10:26And again we look at it the next day.
• 10:28And in all these cases again,
• 10:30we're very commonly would be using.
• 10:32As I said,
• 10:33these stains that we can use to
• 10:34highlight specific molecular
• 10:35features of the tumor or to
• 10:37understand exactly what it is and
• 10:39characterize it a little bit.
• 10:40Better.
• 10:42So there are a whole variety,
• 10:44as you alluded to,
• 10:46of types of biopsies and types of
• 10:48techniques of looking at the these
• 10:51tissues to come to a diagnosis.
• 10:53I think a few questions come to mind.
• 10:56The first is when you're
• 10:58looking at these tiny cells.
• 11:01You know when you talked about
• 11:03putting a needle into something
• 11:04and aspirating a few cells.
• 11:06I'm sure that people wonder how
• 11:08easy is it for you to tell that.
• 11:11Is a cancer cell versus not a cancer
• 11:14cell or a non small cell cancer cell
• 11:17versus a small cell cancer cell?
• 11:20How?
• 11:20How sure are you when you make that
• 11:23diagnosis of the diagnosis that you make,
• 11:26especially when it's just a few cells.
• 11:31I think I agree that this is
• 11:32really part of the training.
• 11:34I think we've all you know,
• 11:35one of the things that pathology
• 11:37involves is really a lot of
• 11:40a lot of hands-on experience.
• 11:41That's number one number two.
• 11:43We are very sensitive to the notion
• 11:45that we don't want to, you know,
• 11:47call something a cancer that's not cancer,
• 11:49and so again, as part of the training,
• 11:51we learn very carefully that there's a
• 11:53minimum number of cells you really need
• 11:55in order to make a specific diagnosis.
• 11:57And there's no, you know,
• 11:59magic number in terms of
• 12:00exactly how many cells that is.
• 12:02But I you know one cell is
• 12:04certainly not going to be enough.
• 12:06And you know, is 100 cells necessary?
• 12:08We certainly get down into,
• 12:10maybe, you know, 100 cells,
• 12:12or maybe in some cases fewer.
• 12:14But largely we're very sensitive for
• 12:16the notion we really want to see a
• 12:18population of cells that are really
• 12:20clearly represent a malignancy.
• 12:22And the other thing we do is particularly
• 12:25on the smaller samples we commonly, you know,
• 12:28pathologists will commonly show things we,
• 12:29each other.
• 12:30We're totally, you know,
• 12:32there's no sense of you know, ego involved.
• 12:34We show each other things.
• 12:36What do you think?
• 12:36What do you think?
• 12:37Is this enough and we generally anything
• 12:39where there's even a marginal call.
• 12:42We show things to each other and
• 12:44we document that we've shown it to
• 12:46somebody else who agrees with us.
• 12:48So that's really sort of
• 12:49intrinsically baked into our process,
• 12:51and I think that the you know,
• 12:52if you actually were to go
• 12:54and look at the literature.
• 12:55You'd say that the based on you
• 12:59know if summaries people have done
• 13:00this in pathology extensively,
• 13:02whereas you ask and you go back and
• 13:03you look at other peoples diagnosis.
• 13:05How often are you correct and you know,
• 13:08I can't say everything is perfect.
• 13:10There's nothing in life which
• 13:11is completely perfect.
• 13:12But by and large it's extremely good.
• 13:15And so I think that you know if
• 13:17there is really any doubt you know
• 13:18patients can always ask for to
• 13:20send it to another institution.
• 13:21I don't recall a case at Yale
• 13:23where you know we've had a change
• 13:25diagnosis along this line, certainly.
• 13:27People can have other opinions
• 13:30exactly how to classify a tumor,
• 13:32but by and large we are very
• 13:34careful to try to prevent anything
• 13:36where that's really an issue.
• 13:39Terrific,
• 13:40well we're going to learn a lot
• 13:41more about lung cancer pathology
• 13:43right after we take a short
• 13:45break for a medical minute.
• 13:47Please stay tuned to learn more about
• 13:49lung cancer pathology with my guest
• 13:51Doctor Robert Homer.
• 13:53Funding for Yale Cancer Answers
• 13:54comes from Smilow Cancer Hospital,
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• 14:05To learn more, visit
• 14:08yalecancercenter.org/genetics.
• 14:11The American Cancer Society estimates that
• 14:13over 200,000 cases of Melanoma will be
• 14:16diagnosed in the United States this year,
• 14:18with over 1000 patients in Connecticut alone.
• 14:21While Melanoma accounts for only
• 14:24about 1% of skin cancer cases,
• 14:26it causes the most skin cancer deaths,
• 14:29but when detected early,
• 14:31it is easily treated and highly curable.
• 14:33Clinical trials are currently underway
• 14:36at federally designated Comprehensive
• 14:38cancer centers such as Yale Cancer
• 14:40Center and at Smilow Cancer Hospital.
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• 15:02yalecancercenter.org you're listening
• 15:03to Connecticut Public Radio.
• 15:07Welcome back to Yale Cancer Answers.
• 15:09This is doctor Anees Chagpar
• 15:10and I'm joined tonight
• 15:12by my guest doctor Robert Homer.
• 15:14We're learning more about lung
• 15:16cancer pathology and Doctor Homer,
• 15:18right before the break you were
• 15:20talking about the fact that
• 15:21there's a lot of training that
• 15:23goes into being a pathologist,
• 15:24and that's really important because.
• 15:27You know you really need to be able
• 15:29to recognize the difference between
• 15:31a cancer cell and a non cancer cell
• 15:33when making that diagnosis and when
• 15:37you have questions or concerns,
• 15:40do you have enough of a sample or
• 15:42it's kind of a borderline call?
• 15:45There's really no issue in terms
• 15:47of seeking another opinion and
• 15:50you as pathologists do that a lot.
• 15:53You'll show that to other pathologists.
• 15:55So one question that people who
• 15:57are listening might.
• 15:58Ask is you know, should patients,
• 16:03when given a lung cancer diagnosis,
• 16:06seek a second opinion with
• 16:08regards to their pathology?
• 16:12At another institution,
• 16:13if they're not sure, and because,
• 16:16how can a patient really be sure,
• 16:19aside from the fact that most of
• 16:20us have a lot of confidence in the
• 16:22institutions that we frequent?
• 16:25I, I think that anytime if there
• 16:28is a patient really unsure,
• 16:30you know I'm you know.
• 16:31I sort of think about this in medicine.
• 16:33I think this is sort of a general
• 16:35question about any medical advice.
• 16:37So pathology report is is medical advice.
• 16:40I think that if you see an oncologist and
• 16:42aren't sure about their advice you give,
• 16:44you should be free to seek another opinion.
• 16:46If you seek a surgeon and get different
• 16:48advice you want and you're not happy
• 16:49with it or you're concerned and you
• 16:51want to make sure that you've seen it,
• 16:53you can get a second opinion.
• 16:54I don't think that.
• 16:55Salty diagnosis or any different?
• 16:56I think you would put it in the same
• 16:58category as any other medical opinion,
• 17:00and you know if there's really
• 17:02any any concern.
• 17:04I think that that's a fine thing to do.
• 17:07And so you know, I think one of the big
• 17:10distinctions is cancer versus no cancer,
• 17:13and one of the things that you
• 17:15mentioned before the break was that
• 17:18you're really very careful about
• 17:20calling cancer versus not cancer.
• 17:23And so tell us a little bit more about
• 17:25the nuances you mentioned that you
• 17:28know there's classifications in terms
• 17:30of small cell and non small cell.
• 17:33How do you make that distinction
• 17:36and why is it important?
• 17:37Or is it important to patients treatment?
• 17:41So the historical distinction between
• 17:43so-called small cell and non small
• 17:47cell carcinoma really goes back
• 17:49to the 1960s and 70s where it was
• 17:52understood that the vast majority of
• 17:54people with what's so called small
• 17:57cell carcinoma were most likely had
• 18:00a systemic disease on presentation,
• 18:02and they responded to certain types of
• 18:05chemotherapy that patients with so-called
• 18:07non small cell carcinoma did not.
• 18:09And that's really sort of become.
• 18:11Sort of a founding principle of the field
• 18:14of thoracic oncology for a long time.
• 18:18We certainly at the you know,
• 18:20back in the 60s to 70s we didn't
• 18:23have really any ancillary so called
• 18:25ancillary techniques like immunostains
• 18:27for molecular diagnostics and so
• 18:28that was really just based on the
• 18:30morphologic appearance of the cell.
• 18:32With a few relatively by
• 18:33our current standards,
• 18:34crude stains these days,
• 18:36it's really pretty clear that you
• 18:39can improve the reproducibility of
• 18:42the diagnosis by getting some stains.
• 18:45There is a one particular paper
• 18:47that I use routinely.
• 18:49But that's an international that
• 18:51show that international consensus of
• 18:52difficult cases cases that people
• 18:54agreed were not straightforward could
• 18:57be improved by using immunostains.
• 18:59And I also think that these days,
• 19:01with molecular diagnostics being
• 19:02as advanced as it is,
• 19:04there are very rare cases where
• 19:06that can be helped.
• 19:07It's clear that, again,
• 19:09so called small cell carcinoma has
• 19:11a very distinct molecular signature,
• 19:13whereas tumors of so called non
• 19:15small cell have a range of other
• 19:18signatures which really would not
• 19:19be expected to be seen in that.
• 19:21So I think that there is,
• 19:23you know,
• 19:24the basic diagnosis is certainly
• 19:26suggested by just routine Histology,
• 19:28and there's clearly cell,
• 19:30clearly tumors which are just not small cell.
• 19:32If you just look at it and say there's yeah,
• 19:34that's just not what it is,
• 19:36you know I don't really care about
• 19:37any of the other markers that are
• 19:39present and there's other tumors
• 19:40where you say you know I'm just
• 19:42not sure those are relatively.
• 19:44You know,
• 19:45maybe 5% of cases where people
• 19:47sort of have that thing.
• 19:48But of course you know at
• 19:50any larger Cancer Center.
• 19:51You know,
• 19:51like Yale or other large cancer centers,
• 19:53we see enough cancers that they they show up.
• 19:55You know, all the time.
• 19:58So we do have a sort of a,
• 20:00you know,
• 20:01a standard protocol for a for resolving that.
• 20:05In terms of non small cell carcinomas,
• 20:08we know that there is really two
• 20:11major subtypes within that admin,
• 20:13so called adenocarcinoma and
• 20:16squamous cell carcinoma.
• 20:18And there's excellent markers that
• 20:20distinguish those two things from each other.
• 20:22We know that there's a large
• 20:24percentage of those cases which
• 20:26might be surgically resectable.
• 20:27We also know that all of the you know,
• 20:29oncology protocols for patients
• 20:31who do not have resectable tumors.
• 20:35That's like the first thing,
• 20:36pretty much in all the protocols is to
• 20:39understand which of those two pathways it is.
• 20:41It's in pretty much all the
• 20:43molecular work up after that depends
• 20:45on that fundamental distinction,
• 20:46and a lot of the therapeutic.
• 20:48Decisions are based on that as well.
• 20:49Not entirely,
• 20:50but largely.
• 20:51We have excellent markers that
• 20:53distinguish those two things these days,
• 20:55and all lung tumors that have
• 20:58enough tissue to evaluate would
• 21:01most likely get one of those,
• 21:02unless it's, again, histologically.
• 21:04You know, quite straightforward.
• 21:07And so that's really important because
• 21:09it it influences the type of treatment
• 21:12that that patients get. Is that right?
• 21:14It is it distinguished influences
• 21:16the treatment they get,
• 21:17but also to a certain extent the work up.
• 21:20If you have somebody with which seems
• 21:23to be a like a localized, there rarely.
• 21:25Again you have cases which are
• 21:27look like a localized small cell.
• 21:29The oncologist might try much harder to
• 21:32really convince himself or herself that
• 21:34that's really a truly localized tumor.
• 21:37Because the likelihood that
• 21:38they're probably missing something,
• 21:40so they might do a more extensive
• 21:41work up than they might otherwise.
• 21:44And it's also true that a lot of our
• 21:47patients have more than one tumor,
• 21:48unfortunately, and so a lot of lot
• 21:51of much of what I do, you know,
• 21:53is direct with fast conchology is a
• 21:55pathology or other is to really look at
• 21:57patients who have more than one tumor
• 21:59and really connect yourself that what
• 22:00you're seeing is which of those you know.
• 22:02Is this really a primary lung tumor,
• 22:04or is this really coming from somewhere else?
• 22:07And so understanding that distinction
• 22:09is important in order to help with
• 22:11that decision making process as well.
• 22:14You know you mentioned molecular
• 22:16diagnostics a few times and I want
• 22:18to dive a little bit more into that.
• 22:20It on this show.
• 22:22We've talked about personalized
• 22:24medicine and targeted therapies.
• 22:26The idea that these days pathologists,
• 22:30can you know, look at these tumors in
• 22:33a variety of ways to kind of unlock
• 22:36the genomic signatures of them,
• 22:38identify whether they express
• 22:40certain receptors or certain
• 22:42proteins that then are targetable.
• 22:45With certain drugs, how common is that done?
• 22:49It should, should patients be
• 22:51going to their medical oncologists,
• 22:53asking about you know whether they have
• 22:56a a BRAF mutation or a veg F mutation,
• 23:00or that kind of thing?
• 23:02Well, the good news is that there
• 23:04are quite a number of consensus
• 23:06statements on which tumors are
• 23:08really the appropriate ones to do.
• 23:10The mock their testing on their
• 23:12variety of professional societies,
• 23:13which include both pathology and oncology,
• 23:16which is really very, you know,
• 23:17very explicitly stated who should
• 23:20get this kind of profiling.
• 23:23So for example, as I mentioned,
• 23:25the distinction adenocarcinoma
• 23:26and squamous cell carcinoma is
• 23:29really critical and it's really
• 23:31quite clear that the guidelines.
• 23:32Or recommend that anyone with a
• 23:35nano carcinoma should absolutely
• 23:37have unlocked the profiling.
• 23:39That's really and at Yale.
• 23:40Let's say that 100% anyone with
• 23:43adequate tissue will have that done.
• 23:46I should also point out the fact
• 23:47that even though we like to think
• 23:49of this as a tissue based process,
• 23:51there's now also the options
• 23:54to get some of that molecular
• 23:56profiling done just by a blood test.
• 23:58It is not as sensitive as getting
• 24:00adequate piece of tissue, but if it's,
• 24:02you know if it detects it,
• 24:04appropriate genetic abnormality,
• 24:05then it can be.
• 24:08I think we're all pretty comfortable
• 24:10that we can rely on it.
• 24:11On the other hand, as I said,
• 24:13having an adequate piece of tissue to do
• 24:15that is still considered the gold standard.
• 24:18Patients with squamous cell carcinoma,
• 24:20unless with with relatively few exceptions,
• 24:24are not thought to benefit from sequencing.
• 24:27Again,
• 24:27there are few.
• 24:28There are a few exceptions and
• 24:30because there are a few exceptions,
• 24:31some oncologists do would like
• 24:33to see their lung cancers from
• 24:35these patients sequence as well.
• 24:37But that's a much,
• 24:39it's more of a very specific decision.
• 24:42That needs to be done individually,
• 24:44I think now and I should also point
• 24:46out the fact that from my perspective,
• 24:49even though we like to talk about
• 24:51Gnostics as being particularly important
• 24:53for specific therapeutic decisions,
• 24:55so do I have a mutation in a gene
• 24:58where there's a specific drug that
• 25:00targets that specific mutation,
• 25:01which is great when when we have have it.
• 25:05It's also true that from my perspective,
• 25:06sometimes that but profiling
• 25:08could be very useful to decide
• 25:10whether something is in fact a lung
• 25:12cancer or from somewhere else,
• 25:14or it's actually fairly common to have
• 25:16patients who have had a lung cancer
• 25:18to then have a second lung cancer.
• 25:20And sometimes we use it to
• 25:22distinguish whether is this really
• 25:23the same tumor which is record?
• 25:25Or is this really a new tumor?
• 25:27And at the again there may be
• 25:28therapeutic implications from that,
• 25:29depending on the specific
• 25:31patient circumstance.
• 25:34So it sounds like you know these decisions
• 25:36are are really critical and or can be.
• 25:41Now you mentioned that with Frozen section
• 25:44you can make a diagnosis in minutes,
• 25:48but in terms of getting all of the
• 25:51information you know small cell versus
• 25:54non small cell adeno versus squamous,
• 25:56the molecular profiling.
• 25:58How long does that take?
• 26:02So the add new versus squamous distinction
• 26:06so frequently that you know that
• 26:09depends on the specifics of the tumor.
• 26:11It's pretty common in a tumor which is so
• 26:14called well or moderately differentiated.
• 26:17That is still has histologic
• 26:19evidence that is producing these
• 26:21particular histologic features.
• 26:23You can tell it just at the
• 26:24time of frozen section would be
• 26:25pretty comfortable with that.
• 26:26There are other tumors where it's
• 26:29a very undifferentiated tumor.
• 26:30It really does not the Histology
• 26:31of the just looking at it doesn't
• 26:33really tell you very much.
• 26:34They needed a stains.
• 26:37No, it depends on you know
• 26:39that could be a day or two.
• 26:41Might be your students
• 26:42aren't terribly helpful.
• 26:43You might do a second round,
• 26:45so that might be a few days
• 26:48and then the molecular work,
• 26:50which includes one marker which helps
• 26:53determine how available you are or how
• 26:57effective immunotherapy is likely to be.
• 26:59With civil PDL.
• 27:00One stain that should be done
• 27:02within another few days or a week,
• 27:04and then they'll look up profiling.
• 27:05Again, should be done.
• 27:07There's again national standards
• 27:08that should be done within two weeks.
• 27:11So it can take up to two weeks to get,
• 27:14you know, kind of a thorough
• 27:16pathologic work up of your cancer
• 27:18is that is that about accurate?
• 27:20I think that for lung cancer,
• 27:21I think that's where we are the
• 27:23the peripheral blood testing.
• 27:25If it shows something,
• 27:26might be a few days before that,
• 27:28but it's not going to be.
• 27:29You know, it's not going
• 27:30to be just a few days,
• 27:31it might be 10 days instead of two weeks,
• 27:34but that seems to be where
• 27:35we are at the moment.
• 27:37The reason I bring it up is because you
• 27:39know when patients and people hear that.
• 27:42You can make a diagnosis in
• 27:44minutes with frozen section.
• 27:45They often will then go to their
• 27:47clinician saying why is it taking
• 27:50so long to get the pathology back.
• 27:52On my lung cancer can we
• 27:55get started with treatment?
• 27:57So I think that you've kind of
• 27:59elucidated why it takes so long
• 28:01and I personally have a maxim that
• 28:03says never rush the pathologist.
• 28:05Their opinion is too important.
• 28:08I appreciate that we all you know
• 28:11we want to get it right. We all.
• 28:12I think in pathology we're all
• 28:14really very aware that somebody
• 28:15is waiting for these diagnosis.
• 28:17You know we're not, you know, I,
• 28:20I always personally have a feeling that
• 28:22you know should you know should do it.
• 28:24You should be accurate,
• 28:25but you should also be fast and I think
• 28:27that that they're they're both important.
• 28:28You know nobody is going to cut corners.
• 28:30On the other hand,
• 28:31nobody wants to, just, you know.
• 28:34Slow walk this the diagnosis out the door
• 28:37yeah so in in our last minute or
• 28:40two maybe you can tell us what's on
• 28:43the horizon in thoracic pathology?
• 28:45What do we have to look forward to?
• 28:47That's a great question.
• 28:49I think one of the things going forward
• 28:52is really a better understanding of
• 28:54exactly how the immune system works.