Role of Pathology in Cancer
October 11, 2021Information
October 10, 2021
Yale Cancer Center
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- 00:00Funding for Yale Cancer Answers
- 00:03is provided by Smilow Cancer
- 00:05Hospital and AstraZeneca.
- 00:07Welcome to Yale Cancer Answers with
- 00:09your host doctor Anees Chagpar.
- 00:12Yale Cancer Answers features the
- 00:14latest information on cancer care by
- 00:16welcoming oncologists and specialists
- 00:17who are on the forefront of the
- 00:20battle to fight cancer. This week,
- 00:22it's a conversation about the
- 00:23role of pathology and cancer
- 00:25with Doctor Angelique Levi.
- 00:27Dr. Levi is an associate professor of
- 00:29pathology at the Yale School of Medicine,
- 00:31where Doctor Chagpar is a
- 00:33professor of surgical oncology.
- 00:36Angelique, maybe we can start off
- 00:38by you telling us a little bit about
- 00:40yourself and what it is you do.
- 00:42So as a pathologist I am anatomic
- 00:45and clinical pathology trained
- 00:47so a PCP for short and
- 00:50have received fellowship training
- 00:52and in Cytopathology,
- 00:55a subspecialty of the discipline.
- 00:58I have also received some extra
- 01:01training and expertise in GU pathology,
- 01:04all of which I did
- 01:06way back at Hopkins and
- 01:10it's a combined program.
- 01:13If you do both anatomic
- 01:15and clinical pathology
- 01:16it used to be five years and now is
- 01:184 but you can do one of the two
- 01:20disciplines for a little less time now.
- 01:23And the anatomic focuses
- 01:27mostly on the study of tissue
- 01:30and working with a microscope,
- 01:31fluids and cells,
- 01:33whereas the clinical pathology focuses
- 01:36a bit more on laboratory testing,
- 01:39blood tests for example.
- 01:41So let's dive a little bit more into that.
- 01:44I mean, when we think about the role
- 01:47of pathology and cancer automatically,
- 01:49our brain kind of goes to, Oh yeah,
- 01:52it's the pathologists who kind
- 01:53of look at the biopsy and tell
- 01:55me whether or not I have cancer.
- 01:57Can you flesh out a little bit
- 01:59more about what it is you do and
- 02:01how you come up with that answer?
- 02:03I mean everything hinges on what you say,
- 02:07how much pressure is that,
- 02:09and how do you actually come
- 02:10up with the correct diagnosis?
- 02:13It's certainly a team
- 02:15from the very beginning,
- 02:17patients will go to either a hospital
- 02:19or a physician office and will have
- 02:23a procedure done so the procedure
- 02:25could be either a Pap test,
- 02:29screening test for cervical cancer,
- 02:31it could be a fine needle
- 02:33aspiration of a breast mass,
- 02:34or it could be a surgical procedure
- 02:37in the operating room where
- 02:39a tumor or an organ is removed, so
- 02:43all of those tissues come to the lab from
- 02:47those scenarios and in the lab, the
- 02:51histology component is where that
- 02:55tissue is transformed into a medium
- 02:58where it is put onto a glass slide and
- 03:03that process itself is quite intense.
- 03:06We have pathology assistants who help
- 03:09in the gross examination of these
- 03:11tissues when they come to the lab,
- 03:14especially the larger ones where they
- 03:17may note sizes of lesions they may sample.
- 03:21Areas that are critical,
- 03:23close to margins, etc.
- 03:25And those sections are then
- 03:27submitted in cassettes and processed,
- 03:30in an automated lab in a way that
- 03:33they are sliced and stained and put
- 03:37on glass slides for pathologists
- 03:39to then review at the time of a
- 03:43case review and in community practice,
- 03:45often it is just a pathologist,
- 03:47but here at academic centers we
- 03:51have trainees, residents,
- 03:52who are involved in that process.
- 03:54We have many sets of eyes that
- 03:58we call preview slides and then
- 04:00the pathologist sits down at a
- 04:02microscope to sign out.
- 04:03And that's actually transforming as well.
- 04:05Soon we might say we don't sit
- 04:07down at a microscope to sign out,
- 04:09but we may sit at a computer screen
- 04:13if we transform into the digital era,
- 04:16but we're not quite there yet.
- 04:22Then with a microscope is where we
- 04:26really do what we were trained to do,
- 04:28and you use your trained eye to look
- 04:32at the morphology of the tissue and
- 04:35see where it differs from what you
- 04:38have trained yourself to know what's normal.
- 04:41So identifying what's abnormal
- 04:43disease and in that then deciding
- 04:47whether it's cancer or not.
- 04:49So not every disease is cancer,
- 04:51and it's important in some cases
- 04:53where the presumption clinically
- 04:54might be a mass because of cancer,
- 04:56it's a really important piece to
- 04:59be able to say this isn't cancer,
- 05:01and so therefore no treatment is necessary.
- 05:04But at a Cancer Center,
- 05:06many of the referrals that come here often
- 05:10perhaps already with a preliminary
- 05:12diagnosis on a small biopsy of
- 05:15cancer and then our job sometimes,
- 05:17as pathologists, in a larger procedure, or a
- 05:20resection is to then go ahead and stage that,
- 05:24which means assign some more
- 05:27parameters around that diagnosis.
- 05:29So not only is it cancer,
- 05:31but it's a type of cancer that
- 05:34you want to kind of classify.
- 05:37It's given a grade as we call it,
- 05:40well differentiated, poorly differentiated.
- 05:43It might be given certain
- 05:46other parameters regarding size or margin.
- 05:49Different cancers have different
- 05:51parameters that are important,
- 05:52and all of those details are important
- 05:56in prognosis prediction and then
- 05:58treatment and usually
- 06:00associated then with outcome.
- 06:03So I want to pick up on a few
- 06:05things that you said there.
- 06:06So one was this whole process
- 06:09that really goes on that
- 06:12many people who have never stepped into a
- 06:15pathology lab might not know about which is
- 06:17when you have a biopsy done
- 06:20and your surgeon, your radiologist,
- 06:23whoever has done the biopsy,
- 06:25sends that specimen away.
- 06:28Oftentimes, it's the greatest
- 06:29amount of patient anxiety waiting
- 06:31for that result to come back.
- 06:34And sometimes it can take a few days,
- 06:36but there is all of this
- 06:39preprocessing that needs to go on.
- 06:41Can you give us a sense of how long
- 06:45these biopsy results can sometimes take,
- 06:48and why it's important to really be
- 06:51patient and wait for your pathologist
- 06:52to give you the right answer because
- 06:55as you say so much of treatment really
- 06:58rests on what the pathologist says.
- 07:01Absolutely, that pre-analytical phase
- 07:02that you're talking about is a big part
- 07:05of our processing in the lab and
- 07:08that's kind of a traditional laboratory
- 07:10setting where you know pathologists when
- 07:13we talk about where do you work,
- 07:15you work in the lab, well no,
- 07:16we actually work mostly in our offices,
- 07:18but much of what's happening
- 07:19before we even see that glass slide.
- 07:29An Accessioner is the first person in the
- 07:32laboratory that basically does the
- 07:34patient registration that assigns that
- 07:38specimen a unique number.
- 07:40Every specimen in pathology is assigned a
- 07:42unique number and that's how we identify it.
- 07:45The patient information,
- 07:46clinical identifiers are then entered,
- 07:49and that's a really important step in
- 07:52terms of specimens being identified
- 07:54properly and assigned to the right person.
- 07:57That is the first thing that happens and
- 08:00the next step is it goes to the gross
- 08:05Histology bench and so for small biopsies
- 08:09that are cores or maybe liquid,
- 08:11or a pap smear,
- 08:13just single cells,
- 08:14fixation is something that
- 08:16doesn't take as long,
- 08:18so fixation is something that
- 08:20happens in different chemicals,
- 08:23alcohol and or formalin.
- 08:26Now when these tissues are larger,
- 08:29as in the case of a large tumor
- 08:31or resection or a large organ,
- 08:33that fixation process can
- 08:37happen over a 12 hour period.
- 08:39Sometimes overnight,
- 08:40so for example,
- 08:41a prostate that is removed whole
- 08:44or a large breast excision,
- 08:48those are examples of tissues that
- 08:49take a long time to fix in formalin.
- 08:52So before those sections can even be
- 08:54taken to embed in those paraffin blocks,
- 08:57that process has to happen,
- 08:59and it's critically important for
- 09:01that process to happen
- 09:03because these tissues need to be
- 09:06able to be examined in sections
- 09:08in a way where the margins
- 09:10and all of those distinctions
- 09:12between things that are critically
- 09:14important for patient care,
- 09:16whether the person gets radiation
- 09:18or not is the margin positive.
- 09:21Those delineations are critically
- 09:23dependent on that fixation step,
- 09:25and that step is where we really
- 09:28need to wait, and we can't rush it.
- 09:30So we have some technologies,
- 09:33microwave assistance and other things,
- 09:35but in that process there
- 09:39are still very manual
- 09:41pieces that take time and then
- 09:43by the time that slide comes out,
- 09:47if the surgery was on a Monday,
- 09:49that glass slide may not even
- 09:51come to a pathologist's desk until
- 09:54the following afternoon.
- 09:56And if that following afternoon
- 09:58is the first time a pathologist
- 10:00is looking at a cancer,
- 10:02whether it's a complicated case or even
- 10:06a standard morphologic diagnosis of,
- 10:09let's say, breast cancer, there are still
- 10:11additional tests that will have to get done,
- 10:14and so those tests will include
- 10:16immunostains and other markers
- 10:18that are all very important that
- 10:20need to be included in the report.
- 10:25So a lot of those those markers are
- 10:28things that we have to then order,
- 10:30and again it's another day
- 10:33or overnight processing,
- 10:34and so each of these steps
- 10:37requires kind of another decision
- 10:39and potentially another test
- 10:42or stain or molecular marker, for example.
- 10:45So important for people not
- 10:48to rush the pathologist because as
- 10:50I tell my patients,
- 10:53everything rests on what they say.
- 10:56But having said that,
- 10:58many people nowadays are
- 11:01talking about second opinions,
- 11:03either a second opinion
- 11:04from their clinician,
- 11:05but also getting their pathology that
- 11:08may have been reviewed at one institution
- 11:10re-reviewed at another institution.
- 11:12So for example,
- 11:13if they get a second opinion,
- 11:15their outside pathology is often re reviewed.
- 11:19So can you talk about the importance of
- 11:21that and how often do pathologists disagree?
- 11:24I mean, are these diagnoses
- 11:26things that are black and white?
- 11:28That is pretty crystal clear when
- 11:30you see a cancer that it's a cancer.
- 11:32Or are there some nuances that
- 11:34allow for some variability in
- 11:36terms of pathologic opinion?
- 11:38I'll start by saying second opinions within
- 11:42any scenario are always a good thing.
- 11:46I think for another set of eyes to
- 11:48take a look at a cancer case is
- 11:54always good and in the vast majority of
- 11:57cases a confirmation is what you'll find.
- 12:00The confirmation of the original diagnosis.
- 12:04It becomes more important in certain
- 12:07scenarios, so certain cancers
- 12:10have required subspecialty training
- 12:13that not all pathologists have,
- 12:16where you practice,
- 12:18where you've trained,
- 12:20and what you've become an expert
- 12:22in really does matter and standards
- 12:24are different for different places.
- 12:27In the community setting,
- 12:28while there's very high
- 12:30standards of care there,
- 12:32they may not always see all of the unique
- 12:36rare tumors that we might have in a tertiary
- 12:40academic center.
- 12:42Whereas in an academic center like Yale
- 12:45we would be able to kind of explain a bit
- 12:48more if there are nuances to a tumor.
- 12:51So black and white,
- 12:53yes cancer or not,
- 12:54in the vast majority of cases.
- 12:56But for challenging cases,
- 12:58I think second opinions are definitely
- 13:02helpful with expert review and consensus.
- 13:05Daily Conference is something
- 13:07that is part of our routine,
- 13:10not always in all practices.
- 13:12So it's important to kind of
- 13:14understand the nuances of pathology.
- 13:17We're going to pick up this
- 13:19conversation right after we take a
- 13:20short break for a medical minute.
- 13:22Please stay tuned to learn more about
- 13:24the role of pathology in cancer
- 13:26with my guest Dr. Angelique Levi.
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- 14:39More information is available at
- 14:42yalecancercenter.org. You're listening
- 14:44to Connecticut Public Radio.
- 14:47Welcome back to Yale Cancer Answers.
- 14:49This is doctor Anees Chagpar
- 14:50and I'm joined tonight by my
- 14:52guest doctor Angelique Levi.
- 14:54We're talking about the role of
- 14:56pathology in cancer and Angelique,
- 14:58you know one of the things that you
- 15:00mentioned before the break that I
- 15:02was interested in is that you said
- 15:03we are getting close to a
- 15:06time when pathologists might not be
- 15:09looking down the microscope anymore.
- 15:11They might be looking at a computer
- 15:13screen and that brought to mind
- 15:16this whole concept of digital
- 15:18pathology and potentially the role
- 15:20of artificial intelligence in helping
- 15:23pathologists make that diagnosis.
- 15:25You talked a little bit before the
- 15:27break about some of the nuances.
- 15:29Can you talk a little bit about
- 15:32where you see digital pathology and
- 15:35the role of AI kind of playing
- 15:37into pathology as we move forward?
- 15:39Absolutely, the landscape is already
- 15:44changing and the field is rapidly evolving.
- 15:50And pathologists, I think are
- 15:54definitely stepping up and wanting to
- 15:58not just join this era of digital and
- 16:03artificial intelligence as you say,
- 16:05machine learning, but hopefully
- 16:08also take a role in leading that
- 16:11charge and for pathology there are
- 16:14so many potential applications as
- 16:16with everything AI is everywhere.
- 16:19We don't necessarily appreciate
- 16:21it from our phones and our apps,
- 16:23or for many the interfaces we do each day,
- 16:27but it's a tool no different
- 16:30than for pathology,
- 16:32maybe an immunostain and
- 16:34molecular marker or genetic
- 16:35profile and how we use that tool
- 16:39is largely dependent on
- 16:42what help or guidance a particular
- 16:45practice might be looking for.
- 16:48One example of AI and pathology as
- 16:51you mentioned or alluded to would be,
- 16:53helping to make a diagnosis
- 16:56or grading a tumor.
- 16:59So an area of study that I
- 17:03have pursued in GU pathology
- 17:06and in prostate cancer
- 17:07this is a common application now
- 17:11and there are already software
- 17:15companies that are promoting
- 17:19AI programs and software that can
- 17:23reliably help predict grades or
- 17:26Gleason scoring of prostate cancer.
- 17:29But it's not that simple.
- 17:34Depending on the cancers that might be
- 17:38seen in a given institution,
- 17:40whether it's more common,
- 17:43lower grade, or in a tertiary care center,
- 17:46much more complicated,
- 17:48higher grade,
- 17:49algorithms are kind of taught to
- 17:52answer a specific question or grade.
- 17:55So if you're looking for well differentiated
- 17:58prostate cancer 3 + 3 Gleason score,
- 18:01that might be one training set,
- 18:04whereas if you're looking for
- 18:07high grade prostate cancer,
- 18:09that is
- 18:11amenable not to resection,
- 18:13but further treatment,
- 18:14that might be another training
- 18:17software kind of algorithm,
- 18:18so much depends on
- 18:21the question being asked,
- 18:22and it's not just help in grading,
- 18:24but it could also just be help in detection,
- 18:28so different programs can be
- 18:31taught how to do different tasks,
- 18:34and another program might be in
- 18:37a better setting for community
- 18:39practice not to miss cancer
- 18:42as much as
- 18:44focusing on the grade because
- 18:47detection and preventing false
- 18:49negatives would really be the key
- 18:53perhaps in a Community setting
- 18:54with a lower cancer rate,
- 18:56whereas at the tertiary setting something
- 18:59that would be more helpful is perhaps
- 19:03an AI software algorithm that not
- 19:06just helps with detection or grade,
- 19:09but maybe with prognosis.
- 19:10And that's really the key,
- 19:13trying to discern what this AI can help
- 19:16with and how we'd like to apply it,
- 19:21tailoring the solution to the problem.
- 19:22But one of the questions is this.
- 19:26Are these technologies in use now?
- 19:28And is there a way for patients to
- 19:31know whether a particular pathology
- 19:33department is using that or not?
- 19:35For example,
- 19:36if I just had a biopsy at my
- 19:39Community Hospital and I want to make
- 19:42sure that they didn't miss a cancer,
- 19:44should I expect that they have that kind of
- 19:48technology that can help the pathologists?
- 19:51And if I'm not sure,
- 19:52is there a way to find out?
- 19:54There's always a way to find
- 19:56out and certainly just calling that
- 19:58pathologist on the bottom of the
- 20:00report would be the first step.
- 20:05Or wherever those procedures are done would
- 20:07certainly know within the department,
- 20:09I would say we're still on the cusp.
- 20:18I think right now in tertiary care centers,
- 20:22there are many kinds of testing and
- 20:25research scenarios and these
- 20:27are all kind of sprouting
- 20:30up now and it's not to
- 20:33be expected I would say because
- 20:36it requires so much investment and
- 20:39infrastructure.
- 20:47Whether it's cloud based
- 20:51memory or machine or human time,
- 20:55we can't expect that to all be there.
- 20:58Now I would say you know,
- 21:01in the future 5 to 10 years,
- 21:0410 to 15 years, I think
- 21:05then we can start
- 21:07to see where these
- 21:10applications are best suited,
- 21:12and imagine with all of this investment
- 21:17it would probably be helpful as a QC measure.
- 21:21You know there are always reimbursement
- 21:24codes for things that are additive,
- 21:27whether it's a stain or
- 21:29whether it's AI assisted.
- 21:30So I imagine in the future it would also be
- 21:33part of a report and so you know we're not
- 21:37there yet, but it does take a lot of time,
- 21:40infrastructure,
- 21:40and money frankly,
- 21:42and so until those costs come
- 21:45down or those partnerships are
- 21:47established, things
- 21:49may be commercially available
- 21:53at a price that is affordable for you.
- 22:04The other thing that is here now
- 22:08more and more in the cancer world is
- 22:10this whole concept of personalized
- 22:12medicine and so many clinicians are
- 22:15really now trying to unlock and
- 22:18understand the genomics of cancers.
- 22:20And we've certainly had guests on this
- 22:22show who talk about doing stains that
- 22:25look at a number of different
- 22:28genetic and genomic mutations that
- 22:31actually help in figuring out how
- 22:34a particular tumor may be treated.
- 22:37Is that done at the local pathology lab?
- 22:40What's the role of the pathologist in that?
- 22:43How do you decide which of these
- 22:46markers really needs to be done?
- 22:48What's the cost and is that standard
- 22:51of care or is that something that
- 22:54patients need to really individualize?
- 22:57So at the local level I don't
- 23:00think it's necessarily standard of care.
- 23:03Certainly immunostains,
- 23:09certain markers that are common
- 23:12to lay folks would be,
- 23:15we talk about estrogen and progesterone
- 23:17receptors for breast cancer.
- 23:18For example, ER,
- 23:20PR and certain molecular markers.
- 23:22I think in Community practice
- 23:25the idea is
- 23:27to partner often with
- 23:29another lab.
- 23:31Whether it's a tertiary center,
- 23:33a commercial lab that offers those
- 23:36tests because they are not able to
- 23:39have access to all of that in house,
- 23:42and so a lab like
- 23:45ours comes into play,
- 23:47where if we have something to offer,
- 23:50we can partner with other network hospitals,
- 23:54community hospitals,
- 23:55even other labs that might not have
- 23:58the same volume we do in a Cancer
- 24:00Center to provide all of these highly
- 24:03specialized tests that without a certain
- 24:05volume it's not affordable to run.
- 24:08So I think the same thing holds for
- 24:12additional molecular assays.
- 24:15Panel genetic profiling those are highly
- 24:20specialized areas and fields that
- 24:23without partnering with another kind
- 24:26of tertiary care center or larger
- 24:29lab specifically geared towards that,
- 24:32I think it's not
- 24:34expected at the local level.
- 24:36So are the decisions about what
- 24:39additional tests need to be done,
- 24:41so additional molecular
- 24:42tests and so on, EGFR VEGF,
- 24:45various mutational panels
- 24:46and so on are those decisions
- 24:50made by the pathologist, by the
- 24:53treating clinician, by a group?
- 24:56How are those decided?
- 24:58I think in the Community level
- 25:01the oncologist drives a lot of that because
- 25:04the oncologist sees on that leading edge
- 25:06what the potential drugs that are
- 25:10available that are targeted to a
- 25:14particular molecular change, and so in
- 25:17the Community setting,
- 25:19I think the oncologist takes that
- 25:22role more so in asking a pathologist,
- 25:25hey, there's a new drug and it targets
- 25:29this molecular marker.
- 25:30Is that something you do in your lab?
- 25:34Or is it something we can send out for?
- 25:35And then you know,
- 25:37the pathologist facilitates that.
- 25:38And so that I think happens
- 25:40more on the Community side,
- 25:42whereas I think in the tertiary care setting,
- 25:45like here,
- 25:45I think it is a bit more of a
- 25:48collaborative effort because there
- 25:50are there are the pathologists
- 25:54here who are doing those genetic tests
- 25:56and so we also have our tumor boards
- 25:59that while they have been outside
- 26:01at the Community level as well,
- 26:03I think in a Cancer Center,
- 26:05the tumor boards really are
- 26:07putting everyone at the table.
- 26:09Who has that subspecialty expertise?
- 26:12And so I think it's a bit more
- 26:13of a collaborative effort.
- 26:15And if there's something that is
- 26:18clinically warranted or a new drug,
- 26:21I think the pathologists here in a
- 26:25tertiary center are able to create
- 26:28these answers to some of
- 26:30those questions or research them,
- 26:32or they're already a line of research here
- 26:35in the department or collectively.
- 26:41Which segues nicely into you,
- 26:44know, one of my last questions,
- 26:45which is what are the exciting areas of
- 26:48research in pathology and cancer?
- 26:50I mean, it seems like pathology
- 26:53is so central to what we do.
- 26:56Are there some exciting developments
- 26:58that you see coming down the Pike
- 27:00in terms of pathology and cancer?
- 27:03Well, I definitely think the
- 27:06digital pathology component and
- 27:09the artificial intelligence piece
- 27:11is very exciting.
- 27:14It's entirely a new platform
- 27:16and revolution, so to speak.
- 27:18It's something that can be applied
- 27:20to all of the tools that we have
- 27:23and then it's a tool on its own.
- 27:25So what I mean by that is the
- 27:29ability to work with digital images,
- 27:33whether it's radiology or
- 27:36scanned pathology slide and
- 27:39with that scan slide use metrics or
- 27:44segmentation to detect changes
- 27:47that maybe even the human eye can't.
- 27:50And maybe it's not just about morphology,
- 27:53it's just a whole other level
- 27:56of detection
- 27:58in addition to our molecular
- 28:01assays and genetic profiles,
- 28:03is something that can on its own be
- 28:06additive and the exciting pieces when it
- 28:09is also its own prognostic indicator,
- 28:12and so we're always interested in
- 28:15knowing more about the meaning of
- 28:17the cancer and what effect
- 28:19that has on outcome and prognosis,
- 28:22and AI really has the potential
- 28:24to help each of these special
- 28:28techniques that we use and the
- 28:30ability to stand on its own.
- 28:32Doctor Angelique Levi is an
- 28:34associate professor of pathology
- 28:36at the Yale School of Medicine.
- 28:38If you have questions,
- 28:39the address is cancer
- 28:40Answers at yale.edu and past editions of
- 28:43the program are available in audio and
- 28:47written form at yalecancercenter.org.
- 28:48We hope you'll join us next week to
- 28:51learn more about the fight against
- 28:53cancer here on Connecticut Public Radio.
- 28:54Funding for Yale Cancer
- 28:56Answers is provided by Smilow
- 28:57Cancer Hospital and AstraZeneca.