Role of the Pathologist in Diagnosing Malignancy

by Richard Mitchell, MD, PhD

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    00:01 Welcome back.

    00:02 You've made it all the way through our complete discussion of malignancy.

    00:07 The final thing, is I want to just share what with you, what I do on a day-to-day basis, in terms of tumor diagnosis.

    00:14 One, I think it's intrinsically really cool, but number two, you need to understand when you are discussing with your pathologist, about the diagnosis, what he or she is telling you.

    00:25 So, that's we're going to go into now and hopefully some of you will go, “Hey that's an interesting field, that's a good career that I could go into.” All right, let's see.

    00:36 So, the role of surgical pathology and cytopathology, is to basically accurately diagnose pathology within a specimen.

    00:45 This is a hunk of lung, a partial pneumonectomy, that was taken out and we have clearly within it at the top a white tan, lobulated, focally necrotic, focally hemorrhagic lesion, but that's not enough.

    01:01 I need to actually now sample this.

    01:04 One, to see if it really is a malignancy, as opposed to some sort of funny benign tumor or perhaps some sort of odd infection and also, whether the surgeon has got it all, okay.

    01:17 So that's just the simple questions that we need to ask.

    01:21 I also need to be able to talk, convey the diagnosis and other associated relevant information to the treating clinicians.

    01:30 So, for those of you who may think that, pathologists just sit all day at a microscope and never interact with the outside world or we're down in the morgue, doing autopsies, nothing is further from the truth.

    01:42 I spend the best part of my day, talking with fellow clinicians and saying, “Take a look at this. This is what this is. This is what you need to do.” I really have a very important role in the treatment of patients, so, hopefully again you'll say, “Hmm that's sounding better and better.” So, the sorts of questions that I need to answer, so, that I can tell the treating clinicians, the treating surgeons, the treating oncologists etc.

    02:08 What is this mass? That's number one.

    02:11 Is it malignant, what type of malignancy is it? Because it makes a difference whether this is a sarcoma, a metastatic tumor, a primary lung cancer or something else.

    02:23 Can we predict its behavior.

    02:25 Yes. So, I need to look at this and look at the features of this and based on a huge volume of information, I can in many ways say, “This tumor tends to be fairly aggressive and that patients who go untreated will die within two years,” or “This tumor surprisingly enough has a rather indolent, but not semi-benign course and patients can live for years without doing anything.” So, I looking down the microscope and looking at the gross, can often make some of those statements.

    03:00 Are there potential treatment options and I’ll show you examples, where what we do in pathology, will tell the oncologist what drug to choose.

    03:09 Did they get it all? Obviously, I mean that's a very important thing, because if they haven't gotten it all, we need to either go back in and have a second surgery or we need to radiate the field, so that we can kill any residual tumor cells that may be in the vicinity.

    03:23 And what are the implications for the family. on Does this have a genetic basis? Is it possible there's a germline mutation, that's shared by sisters, brothers, parents, children.

    03:35 Those are all sorts of things that I as a pathologist, do in my day-to-day life.

    03:42 Okay. Some painful truths, I painted the rosiest picture I can possibly paint, but now, I'm going to tell you some painful truths and for those of you who may think that the pathologist knows all, well, sometimes we think we do, but we really don't.

    03:57 So, among the painful truths with human tumors and in pathologic diagnosis, one, we don't have any universal molecular definition of what a neoplasm is, we've talked about things that grow on in an uncontrolled fashion, that have genetic instability, but there are exceptions to all of that, so, we don't have one universal molecular definition.

    04:22 In most cases, I can say, I don't know exactly what it is, but that's cancer, other cases it gets a little bit fuzzy.

    04:30 We have some states where it's not clear that it's a borderline neoplasm, so that's number one.

    04:37 Number two, there's absolutely no reliable marker of malignancy, we can't just do a stain or do a molecular signature or do a particular test and say, “That's cancer, that's not cancer.” It does require a bit of thinking, it requires a lot of kind of knowledge and experience and there are always inconsistencies, in how we do this.

    05:05 So, I wish that there was a way that we could do, a test, and say, “It's cancer and not cancer,” unfortunately, we can't.

    05:12 There are absolutely no reliable predictors of outcome, in any individual case.

    05:16 So, every time I see a particular malignancy and say, “The treatment for this is X,” I also know that, at very best 90% of the patients are going to have a successful response.

    05:29 But there's going to be 10% of the patients out there that don't do well.

    05:34 So we have no perfect way to say, “You're going to live and you're not” in any individual case, there are a lot of other factors, that come into play.

    05:47 Again, there's almost no truly specific immunohistochemical markers, in the same way there's no reliable marker malignancy, there's no antibody, that I can dump onto a tissue, that will come up with, a yes or no, it's not quite like a pregnancy test that you do at home, wish that there were but there isn't.

    06:08 Currently, we can actually find out much more information and stratify tumors into many more little cubicles or little boxes, than we have therapeutic options for.

    06:20 So, I can now say this tumor has a particular KRAS mutation and I know that that is a likely driver mutation, but I may not have or the oncologist may not have, the appropriate therapeutic option to take advantage of that.

    06:36 So, pathologists are a little bit further ahead of the game, than are the pharmaceutical companies that are making the drugs, but that's changing.

    06:45 And then, there are some tumors that I don't care how hard we try, with all of our magical tricks, everything from electron microscopy, flow cytometry, cytogenetics, molecular signatures we cannot classify them.

    07:01 There are some tumors that are so poorly differentiated, that we have no idea what they are, we can say, “I think that's a cancer, but we don't know what kind of cancer.” Okay. But many of these are exceptions rather than the rule.

    07:16 In general, I know a cancer when I see one and I can say, in many cases, how they're going to behave, but I’m never ever going to be perfect at it.

    About the Lecture

    The lecture Role of the Pathologist in Diagnosing Malignancy by Richard Mitchell, MD, PhD is from the course Surgical Pathology of Tumors.

    Included Quiz Questions

    1. There is no absolutely reliable marker of malignancy.
    2. Therapy is easily determined just by the diagnostic tumor classification.
    3. There are reliable predictors of outcome in any individual case.
    4. There are specific immunohistochemical markers for malignancy.
    5. All tumors are classifiable.
    1. To make an accurate diagnosis and interact with the treating clinician
    2. To determine the precise therapy needed
    3. To accurately stage the tumor
    4. To find the best single predictor of outcome
    5. To work with the clinician at the microscope to help arrive at the diagnosis

    Author of lecture Role of the Pathologist in Diagnosing Malignancy

     Richard Mitchell, MD, PhD

    Richard Mitchell, MD, PhD

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