The Role of Surgical Pathology

August 04, 2022

Information

July 31, 2022

Yale Cancer Center

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00:00Funding for Yale Cancer Answers is
00:02provided by Smilow Cancer Hospital.
00:06Welcome to Yale Cancer Answers with
00:09your host Doctor Anees Chagpar.
00:11Yale Cancer Answers features the
00:12latest information on cancer care by
00:15welcoming oncologists and specialists
00:16who are on the forefront of the
00:18battle to fight cancer. This week,
00:20it's a conversation about the role
00:22of surgical pathology in certain
00:24cancers with Doctor Marie Robert.
00:26Doctor Robert is a professor
00:28of pathology and of medicine at
00:29the Yale School of Medicine,
00:31where Doctor Chagpar is a
00:33professor of surgical oncology.
00:36Marie, maybe we can start off by
00:38you telling us a little bit about
00:39yourself and what it is that you do.
00:42Sure, so I am a surgical pathologist
00:45and this is somebody who goes to
00:48medical school and does a residency
00:51in the specialty of pathology.
00:54And that specialty involves looking
00:58at diseases in the tissues in
01:02biopsy samples and and surgical
01:05resection samples from patients.
01:09And we look at that very
01:11deeply under both with our naked
01:13eye and under the microscope,
01:15and then inform the surgeon or the
01:20clinician oncologist
01:22who's taking care of the patient
01:23about what we're seeing and what
01:25their disease process might be?
01:27Yeah, you know I I often tell patients
01:30that there's only two people who
01:32can tell you anything for sure.
01:34God and the pathologist because we
01:36rely so heavily on the diagnosis
01:40that's rendered by pathologists.
01:42So you know, tell us a little bit
01:45more about what got you interested in
01:48pathology and what got you interested
01:50in GI and liver pathology in particular.
01:54So that is an easy question
01:55to answer and no secret.
01:57If you know my family at all,
01:59so I am the daughter of a French Canadian.
02:05Nurse and physician scientist.
02:08My father Andre Robert,
02:11who was a basic scientist studying
02:13gastrointestinal diseases so
02:15he had both the clinical side
02:18MD and the scientific training.
02:20And so I grew up visiting his lab
02:23and seeing and actually, you know,
02:25he would let me do a little help in the
02:28lab in in participating in his experiments.
02:31And so this is when I went to college and.
02:35Medical school, I thought that medicine
02:39was this the study of disease.
02:42And so when I it was,
02:44you know, not a far.
02:47Challenge for me to decide that
02:49pathology was where my heart really lay.
02:51And of course,
02:52the apple doesn't fall far from the tree
02:54and I was immediately drawn towards
02:56all things of the gastrointestinal tract,
02:58liver, and pancreas.
03:00So tell us a little bit more
03:04about kind of what you do.
03:07day-to-day. I mean, because one of
03:09the things that is frustrating.
03:11Anxiety provoking for patients is the wait.
03:16They have the biopsy done and
03:18then we say we need to wait and
03:21I always tell patients you know,
03:23never rush the pathologist because.
03:26You you don't necessarily want a fast answer.
03:30You want the right answer,
03:31because everything that we
03:33do rests on what you say.
03:36So can you give us a little bit more
03:39granularity in terms of what happens in
03:42terms of that black box while we wait?
03:46So delighted to talk about this
03:49because we are believe it or not,
03:51even though we are not meeting
03:53your patient first hand,
03:55we are constantly mindful of the fact
03:57that there is a wonderful human being on
04:00the other end of this specimen and we
04:03are working as fast as we can to provide.
04:06As you say the right answer.
04:08So what does this entail?
04:10So take a biopsy.
04:12It is put in a fluid called.
04:17Formalin, usually that is allowed that
04:19sort of hardens the tissues so that we can
04:22then put them through an overnight process.
04:26And we actually.
04:27This may sound crazy.
04:28We actually take the small samples or large
04:32samples and put them into paraffin wax.
04:36Melted paraffin wax that then
04:38hardens in a small little box.
04:41If you will, we call it a tissue cassette.
04:44And believe it or not,
04:45old fashioned thing like paraffin wax
04:48is what holds the tissue in place.
04:50While we then apply a very sharp knife,
04:54it's called a microtome to the
04:57sample and we're actually taking
04:59small slices of the sample.
05:02We take that put it on a microscope slide.
05:06Remember from science class.
05:07And that microscope slide is then
05:10with the tissue section on it is
05:12stained with some very pretty colors.
05:15Purples and pinks really.
05:16Pathology is like looking at beautiful
05:19art under the microscope and these dyes.
05:22If you will are stains adhere to the
05:25cells and we during our residency
05:28have learned how to recognize cells
05:30with these dyes under the microscope
05:33so that whole process of just
05:35getting to the glass slide takes.
05:38At least one day so you know one day gone.
05:41Now depending on the type of sample it is,
05:46we can then grab it quickly,
05:48begin our process of looking
05:49under the microscope,
05:50and in some situations we are
05:52able to give an immediate answer
05:54doing nothing else to the sample.
05:56Just looking at the microscope for
05:59three or four minutes and we're
06:01able to assess everything and give
06:03a give the the surgeon, oncologist,
06:05whomever gastroenterologist,
06:06and then the.
06:08Patient the answer they need,
06:10but in especially in cancer there
06:13are often other steps we need to
06:16take to get the best possible answer
06:19with the greatest amount of detail.
06:22And nuance that will really help the
06:26person just treating the patient next
06:29to know exactly what therapy to apply.
06:32So these extra steps include things like
06:34we we use these terms called special stains,
06:38so if you think of a stain,
06:39think of like paint or or these
06:42colors I mentioned and there are a
06:45variety of very technical and highly,
06:48you know,
06:49honed technologies that we can
06:51apply to the tissue.
06:53This is getting more and
06:55more finessed every day.
06:56We can now even do molecular and
06:59genetic analysis and and put what we
07:03call biomarker stains and approaches
07:05so we can really get much further
07:09now to helping to guide the even
07:12the exact medication one might use.
07:15But this does take time,
07:17so sometimes there's a first answer.
07:19And then there's another more detailed
07:21answer that comes a day or a week later.
07:23Sometimes we have to hold up the whole
07:25thing for four or five days just to
07:27get the right answer from the start,
07:29so that's sort of a long answer to
07:31your question, but it is complete.
07:33Yeah, yeah, so I mean,
07:35so This is why I think it's good
07:38information for people who are listening
07:40and potential patients to kind of
07:42understand why it can take so long,
07:44because sometimes we expect these days
07:46to to get an answer instantaneously.
07:50And and that's just not
07:52practical or or feasible.
07:54So I want to dig a little bit more into some
07:56of the things that you mentioned, Marie.
07:59So one is that you know in
08:01medical school and in residency,
08:03you, as a pathologist got very
08:07good at recognizing patterns,
08:10understanding what looks benign
08:12under a microscope and what looks
08:16malignant under a microscope.
08:18But can you tell us a little bit more about
08:21the secrets that go into that pattern?
08:23Recognition?
08:24Because that's another piece that
08:27people don't really understand.
08:29I mean,
08:30how can you tell the difference between.
08:33You know a benign polyp,
08:36something that then is perhaps a
08:39carcinoma in situ, a precancer.
08:43And then something that is truly
08:46cancerous that for many people is a
08:49nuance that we don't really understand.
08:52How.
08:52How do you make that distinction?
08:56So thank you for these wonderful
09:00pathology type questions.
09:01The the answer is it all starts
09:05with knowing what is normal,
09:07what is normal tissue appearance?
09:10We use the term Histology,
09:12it doesn't matter,
09:13but it's just what are you expecting to see.
09:16That is normal.
09:17So in anything that you look at and
09:19in looking at, you know anything
09:21around your house or in your workplace.
09:23Your desk is something out of place.
09:25Were first to understand what is normal
09:29tissue, so you want to talk about,
09:30say, a colon polyp.
09:32We first have to learn,
09:34and this is actually, you know,
09:35at least a four year training
09:37process and residency,
09:38and then often today one or two years
09:41of specialty fellowship training,
09:44we learn very quickly what is normal in
09:46our first couple of years of residency,
09:48training and normal means,
09:49how in health are the this
09:52wonderful machine that is?
09:54Our body is organized at the cellular
09:57level so that you know you look at
10:00your skin and you see your skin.
10:02You might.
10:03The freckles or some blood vessels
10:06underneath under the microscope
10:08we learn what all those layers
10:10from the outside of the skin to
10:13underneath the skin down into even
10:15the muscles and the bone look like.
10:19So once we have that template,
10:22sort of that pattern if you will
10:24pattern recognition in our mind.
10:26Then we begin very slowly to build
10:29to learn abnormal and the one of
10:31the first things we start with is.
10:34Inflammation,
10:34you know you get a cut and you
10:37notice that there are bee sting and
10:39you notice swelling right away.
10:41Redness.
10:41Well,
10:42we learn what that looks like
10:44under the microscope with,
10:45you know,
10:46too much fluid and and inflammatory
10:48cells from the immune system
10:49being called to that area.
10:51The same is true when we
10:53start talking about cancer.
10:55There's often a process starting from
10:58an early, let's say, neoplastic,
11:01meaning that the cell is stopped.
11:04Just minding its own business and
11:06staying put where it should be
11:08to maintain the normal but is now
11:11dividing and growing and and we can
11:13see that under the microscope by
11:15changes and actually how the cell looks.
11:19Over overtime that growth.
11:23Can then.
11:25Disrupt the normal to the point
11:28that there is disruption of the
11:30the little little boxes of the the
11:33little alleys and lanes that that
11:35cells need to stay in and they invade.
11:38We talk about invasive cancer.
11:40It's because those cells actually
11:42go into a compartment that they have
11:45no business being like an epithelial
11:47cell which should be on the surface.
11:49So if you look at your skin,
11:50it's lined by a certain kind of cell.
11:52We call it an epithelial cell,
11:54just the lining.
11:55Now if it becomes a tumor,
11:58it can then go down into the soft tissues,
12:01even the muscle and bone,
12:03et cetera.
12:04And we can see this all under the microscope.
12:07So recognizing cancer or recognizing
12:10an abnormal process is recognizing
12:12that the normal has been disrupted.
12:16And so so you know, one of the
12:19questions that people often ask is.
12:22You know how important is it?
12:24Or is it important to get a second
12:27opinion with regards to your pathology?
12:29So very often you may have your
12:32biopsy done at one place if you go
12:35to another place to get treatment,
12:38they'll say, well, we need our
12:40pathologist to look at the slides.
12:42So is it that you know a
12:45pathologist is a pathologist,
12:47is a pathologist and this is a black
12:49and white answer and everybody is going
12:50to say the same thing, in which case.
12:53Why repeat it?
12:55Or is there some nuance there and
12:57and how important or not important
13:00is it to get a second opinion
13:02on your pathology slides?
13:05So another great question.
13:07I am a big fan of second opinions
13:10and I recommend that when folks
13:12are getting impactful diagnosis.
13:15Like a cancer diagnosis,
13:16that's going to change their life and
13:20start a train in motion of serious
13:23therapeutics and operations that a
13:25second opinion should always be obtained.
13:29And I'm not offended if someone would
13:31like to get a second opinion on a
13:35pathology diagnosis that I have made it.
13:37You know it many times as you sort of
13:41allude to probably 90% or more of the time.
13:44There will be no disagreement
13:47in an original diagnosis.
13:49But sometimes there is either a
13:51really a complete disagreement,
13:52very, very rarely,
13:53a complete disagreement between hey,
13:55you know, I actually,
13:56I'm not sure this is cancer.
13:57I know that.
13:58This was thought to be cancer,
14:01but actually I'm doing a little more
14:02extra work on it and I'm finding that
14:04maybe it might be just a precancer,
14:06or it may some nuance about that.
14:09In addition,
14:11in tertiary care centers tend
14:14to have specialized pathologists
14:17that are only doing one thing.
14:20So in my case I'm only doing
14:25gastrointestinal pathology,
14:26whereas in other centers there's
14:28a group of wonderful general.
14:30Pathologists who are looking at all all
14:34all specimens from all parts of the body,
14:36and they are all all outstanding
14:38and and this is a good system.
14:41But if it's a really impactful diagnosis,
14:44it's not a bad idea to have a
14:46very impactful diagnosis reviewed
14:47by someone who is a recognized
14:49specialist and they exist all over
14:51the country and all over the world,
14:54perfect, well, we're going to
14:55pick up the story learning more
14:58about surgical pathology right
14:59after we take a short break.
15:01For a medical minute,
15:02please stay tuned to learn more
15:04with my guest Doctor Marie Robert.
15:06Funding for Yale Cancer answers
15:08comes from Smilow Cancer Hospital,
15:10where you can view videos from their
15:12survivorship team by searching for the
15:15smilo survivorship playlist on YouTube.
15:19The American Cancer Society
15:21estimates that more than 65,000
15:23Americans will be diagnosed with
15:25head and neck cancer this year,
15:27making up about 4% of all cancers
15:30diagnosed when detected early.
15:32However, head and neck cancers are
15:34easily treated and highly curable.
15:37Clinical trials are currently
15:39underway at federally designated
15:41Comprehensive cancer centers such
15:42as Yale Cancer Center and Smilow
15:45Cancer Hospital to test innovative new
15:47treatments for head and neck cancers.
15:49Yale Cancer Center was recently awarded
15:52grants from the National Institutes
15:54of Health to fund the Yale Head and
15:57neck Cancer Specialized program of
15:59Research Excellence or SPORE to
16:02address critical barriers to treatment
16:04of head and neck squamous cell
16:06carcinoma due to resistance to immune
16:08DNA damaging and targeted therapy.
16:11More information is available at
16:14yalecancercenter.org you're listening
16:15to Connecticut Public Radio.
16:18Welcome back to Yale Cancer Answers.
16:20This is doctor Anees Chagpar and I'm joined
16:23tonight by my guest Doctor Marie Robert.
16:25We're talking about the important role
16:27that pathology plays in cancer and
16:29right before the break we were talking
16:32about the role that pathology plays
16:34in actually making the diagnosis.
16:36Like you go for a biopsy and is
16:39this cancer or is this not cancer?
16:41That distinction is actually made by
16:44a pathologist whom you may never meet,
16:48but that your team really relies on.
16:50Now Marie, the other thing that
16:54pathologists often really provide
16:57is some of the genomic information.
17:00Whether that comes in the form
17:02of special stains like you were
17:04telling us about before the break,
17:06or whether it comes in.
17:08Actually you know doing things like
17:11sequencing and telling us about
17:13genetic and genomic mutations,
17:15can you talk a little bit more
17:17about how that's done and and the
17:19importance that that plays in various?
17:21Answers
17:22yes, delighted so I would say so.
17:25I've been practicing for,
17:27you know about 3 decades now and.
17:30Over the course of my career
17:33there has been really in the past.
17:3510 to 15 and I would say even in the past
17:39five an explosion of new technologies
17:43and new information that help,
17:45especially in cancer, help,
17:47oncologists and surgeons fine tune
17:50and find a very specific therapies
17:54for a specific patients tumor.
17:57How is this done?
17:59And it comes under the general
18:01heading of molecular pathology and.
18:06This means that so we talked
18:07about looking at the microscope,
18:09the light microscope and we
18:10can determine a lot from there.
18:12Now we're getting inside the cell
18:15and specifically the cell nucleus.
18:18For the most part.
18:19And so every cell I should say has
18:23a central brain called a nucleus,
18:25and then something called the cytoplasm,
18:27which is where all the working
18:29parts of the cell that do what
18:31they're supposed to do reside.
18:33But the nucleus is where the chromosomes are.
18:36The genetic material that are the,
18:40you know,
18:40the blueprint for what that cell
18:43should do all over the body.
18:45Tumors tend to occur when those
18:47genes or chromas or the chroma,
18:50the genes on the chromosomes.
18:53The chromosome is divided up
18:55into a gazillion genes,
18:56each one doing something and tumors
19:00happen when what we call mutations occur.
19:04Or deletions or other types
19:07of fusions and other damage.
19:10Overall damage to the genes and the
19:14genetic structure on the chromosomes.
19:17When this happens,
19:18when there's an alteration for the bad.
19:22Several things can happen.
19:23One is that a cell just recognizes that.
19:26Oh,
19:26you are no longer functioning normally
19:28and the body's going to sort of
19:30take you right out of Commission
19:31and you're you're off the assembly
19:33line and actually kills the cell.
19:35That's a good thing.
19:37Unfortunately, other times the cell,
19:40the mutations or genetic
19:42alterations give the cell power.
19:45To divide,
19:46make more cells with those same problems
19:50and that is the beginning of a tumor.
19:53We can now detect very smart
19:56scientists have created technologies
19:58that allow us to look even from
20:01the biopsy that you gave us the
20:03same piece of tissue that we made.
20:05The diagnosis of a tumor on.
20:08We can take the rest of that sample
20:11and apply something called next
20:13generation sequencing and other.
20:15Techniques. Why is this important?
20:18This is important because these days
20:21there are more and more specific therapies.
20:25How do you know when you say this doesn't
20:27apply to every patient and to every tumor?
20:29How do you know whether your tumor should
20:32have all of those fancy shmancy tests done,
20:36or whether simply looking at
20:39that pink and purple dyes under
20:42the microscope is sufficient?
20:44So maybe you had your biopsy done.
20:47At a given institution and you were told
20:50that this was a particular kind of cancer.
20:53Should patients know which particular types
20:58of cancer should get advanced kind of
21:02diagnostics done that might help their care.
21:06How do people figure that out?
21:08How do you know which cancers and
21:11which patients need to have more
21:13studies done and which ones don't?
21:15So that is a terrific question.
21:18I think that every patient and I hope every
21:21patient listening who has a some sort of.
21:24Tumor or cancer diagnosis and is
21:27beginning down that path of getting
21:30treated should ask the question.
21:33Does my sample? Will my sample?
21:36Will this tumor benefit from genetic testing,
21:39molecular testing or whatever
21:41phrase you want to use?
21:43And it is the oncologist who knows best,
21:46so if you're not talking to an oncologist,
21:48talk to an oncologist.
21:50The oncologist will know best that,
21:53Oh yes, this tumor,
21:55if it has this mutation,
21:57we have these three drugs that
21:58we might want to try, and this is
22:01certainly true in many tumors of the.
22:03Of the gastrointestinal tract,
22:05liver and pancreas.
22:06And the oncologist will also know well today.
22:10As things stand,
22:11we don't have anything that we're
22:13giving based on genetic analysis,
22:16and so they may say at this
22:18moment in time we know what to do.
22:20This is.
22:21This is exactly what we should do,
22:22and we don't need further information.
22:25I will also share that at many
22:28academic centers there is a philosophy
22:30that really we want to sequence.
22:33Every tumor and we want to start
22:35moving towards a world where every
22:38diagnosis of malignancy, cancer,
22:40type of tumor will automatically
22:43have a gene you know.
22:46Sequencing of the genetics of that tumor,
22:50and this is for two reasons.
22:51One is that.
22:53We want to continue learning about
22:55tumors because we we we are continuing
22:58to develop medicines based on the
23:01information we're finding and the second
23:03reason is that sometimes a tumor of 1 type.
23:07May have a mutation that we
23:09weren't expecting and hey,
23:10you know there's a drug out here.
23:12We usually use this drug to
23:14treat to treat another tumor.
23:16Usually not this tumor,
23:17but now that you tell us this tumor
23:20surprisingly has this mutation.
23:21Well,
23:22you know,
23:22now we've got another thing to
23:23put in the toolkit.
23:26And so one of the questions
23:28that people may be asking as
23:30they're thinking about this is,
23:32you know. Oftentimes,
23:33when patients think about genetics,
23:36they think about their family history
23:38and whether they need to have a
23:41blood test or a saliva test to
23:43look for genetic mutations that may
23:45predispose them to certain cancers.
23:47So, for example, you know the one
23:49that is most often talked about,
23:51at least in my sphere is BRC A1 and two,
23:55which will increase your risk
23:57of breast and ovarian cancer.
23:59How is that different from the
24:02work that you're talking about?
24:05Where you're looking at the
24:07genetics of the cancer itself?
24:10Yeah, that is super and these things
24:14go actually hand in hand so the
24:17the the thing we just discussed
24:20was any particular tumor that one
24:23might have and that is something
24:26that an oncologist and discussion
24:28with their patient may may initiate.
24:32But in addition, the patient their
24:34physician oncologist and sometimes
24:36the pathologist will discover that
24:38there's something about the patient
24:41as they walk in the door with
24:43their first diagnosis of cancer.
24:44That, or even they don't have it yet.
24:47But there's a family history should be
24:50at something in them should be analyzed
24:54for a specific genetic disorder.
24:57Like bracca as you discuss or like in
24:59the GI tract, familial polyposis syndrome,
25:02or something called Lynch syndrome,
25:05which are colon cancer syndromes and
25:08endometrial and other cancer syndromes.
25:11So in these scenarios,
25:13there may or may not be a cancer
25:16diagnosis yet in the patient,
25:19but they may on their annual visit
25:21to their you know physician,
25:22discover that, Oh yeah, well,
25:24you know my mom,
25:25dad and three uncles had colon cancer.
25:28Before the age of 50,
25:29that person that will be a series
25:31of things set in motion like early
25:34screening in the 1st place with
25:36a colonoscopy and possibly some
25:38blood tests in it with a genetic
25:40counselor that might go on where
25:42a pathologist might be.
25:43The first one to initiate something
25:45is that when we get a sample.
25:48From someone of of the right age group,
25:50or maybe a young person,
25:51or that they have for example on colonoscopy,
25:55have you know 10 or more types of
25:58polyps that are all precancerous polyps?
26:01We will raise our hands and say,
26:03hey, here's your diagnosis,
26:04and oh, by the way,
26:06please sign this patient up for
26:08some for genetic screening,
26:09because they they have too many
26:11polyps at age 50 that you know
26:13that's the we want to make sure
26:15it doesn't mean something more.
26:18Right and but, but there's a clear
26:20difference in terms of, you know,
26:23in the one instance when we're
26:25talking about molecular diagnostics,
26:27we're really talking about
26:28doing these tests to look for
26:31mutations in the cancer itself,
26:33whereas when we're looking at
26:36predispositions and genetic screening,
26:39for example, we're really talking about
26:42cells that are baseline that are in
26:45your blood or in your saliva that.
26:48All of your cells carry versus in.
26:50The tumor itself.
26:51Is that right?
26:52That's absolutely right,
26:53and it's such a good, nuanced point.
26:56And and so this again,
26:59it's all good tools that physicians at
27:04all levels of interacting with folks.
27:06So in the in the you know, annual physical
27:10exam at that level by family history,
27:14personal and family history, the physician.
27:18Can can begin the process and say, yeah,
27:20we probably want to check into this.
27:23And at the same time finding finding
27:25early lesions that the pathology level,
27:28in addition to finding a truly already
27:31invasive cancer as they walk in the door.
27:34Someone walks in the door at
27:36age 45 with colon cancer.
27:38They already have it.
27:39We're going to work on that.
27:40They're going to get testing of the
27:42tumor itself to see what might work,
27:44but because they're young,
27:45this will, with all the clinicians,
27:47will say, Oh yes.
27:48And by the way, we want to screen
27:50your family members now too.
27:52We want to just make sure this is.
27:54Not just an isolated thing.
27:56Right,
27:57so Marie, in our last kind of 30
28:00seconds here, where do you think
28:02the field of pathology is going?
28:04Should we be expecting more of these
28:06kinds of genetic and genomic tests?
28:09Yes, I think it's going to go further
28:13and further and deeper in this
28:15direction with hopefully much more
28:17useful information down the line.
28:19I believe we are also poised to enter
28:22the digital era and with artificial
28:24intelligence to apply to samples.
28:27To improve even further,
28:29our ability to glean treatable information.
28:34Doctor Marie Robert is a professor
28:36of pathology and of medicine
28:37at the Yale School of Medicine.
28:39If you have questions,
28:41the address is canceranswers@yale.edu
28:43and past editions of the program
28:46are available in audio and written
28:48form at yalecancercenter.org.
28:49We hope you'll join us next week to
28:52learn more about the fight against
28:54cancer here on Connecticut Public
28:55radio. Funding for Yale Cancer Answers
28:57is provided by Smilow Cancer Hospital.