शैडोइंग अभ्यास: Accurately Diagnosing the Soft Tissue Sarcoma - YouTube के साथ अंग्रेजी बोलना सीखें

You know, as our lead surgeon and one of the lead surgeons in the world,

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You know, as our lead surgeon and one of the lead surgeons in the world,

I think it's always, you know,

very important that our surgical colleagues are dramatically involved in the treatment of sarcoma

because usually you're the gatekeeper in the entrance of a lot of this.

And so, you know, I think it would be good to ask you what your typical workup is for a patient

is suspected of having a sarcoma.

Sure, thanks, Brian.

You know, it's generally a patient will present to a primary care doctor

or an orthopedic surgeon or a general surgeon with a mass that is growing,

something that is changing, or maybe abdominal distension and discomfort.

But like we all learn in medical school,

a good history in physical is the first thing we do.

If this mass has been there for a long time,

it's less likely to be a malignant process or an aggressive malignant process.

If it's rapidly changing, the acuity is obviously there and something needs to be done about it.

But it's very important to stress the history and physical.

I always joke with my trainees that the most important test we order is the history and physical.

With that being said, we generally do recommend plain film imaging,

radiographs, orthogonal views in the extremity particularly,

because that can shed a lot of information in the area of cost containment.

If it's completely radiolucent in an extremity film,

it is very likely to be lipomatous,

well-differentiated liposarcoma at the worst,

versus if it has some calcifications on it,

the acuity is probably there and that it's a synovial sarcoma or potentially a higher grade liposarcoma,

things of that sort.

So radiographs are important and they're inexpensive.

Beyond that, we do think that advanced imaging is important before any biopsy is done.

We generally recommend an MRI in the extremity,

sometimes in the pelvis, but often a CT is adequate.

And if we really suspect that it's a sarcoma,

we prefer getting a chest CT first before any intervention is done.

But if you're seeing the patient in the clinic

and you're going to do a biopsy in the clinic because it's amenable to that,

you can hold off on some of that advanced imaging.

But we certainly recommend getting advanced imaging of the primary before any intervention is done.

As we all will talk about,

the most common site for these metastases is the chest,

and so we do think chest imaging is of paramount importance.

No, I agree, and I think it's always important to remember that,

you know, we hear lots of interesting things and you know,

car doors do not cause hematomas unless you're on blood thinners.

And so, you know, it's very important to always do that history and physical,

because these masses sometimes just get found by car doors.

Otherwise, you know, surgeons go and explore in the middle of a sarcoma,

and if you don't do these right,

I mean, you can get inferior outcomes.

And so, I mean, as we're moving through from the history and physical to imaging,

I think the next most important thing is really an understanding of diagnosis

and grading of these tumors and really what that means.

And I think maybe Dr. Jones can give us a little insight about how they approach that.

Thank you.

So as Dr. Patel mentioned,

these are heterogeneous and a complex group of diseases.

So it's very important to obtain a clear and accurate histological diagnosis prior to starting treatment.

Each histological subtype can have different clinical behavior due to different underlying biology and can also have a different treatment approach.

So it's important to have an experienced pathologist make the diagnosis prior to starting treatment.

The World Health Organization classification system is generally regarded as the standardized publication for classifying these tumors.

and it's very important that newer techniques such as molecular techniques are incorporated into the diagnosis as well.

In terms of grading, the most common grading system that's used is the French,

so-called French grading system, incorporating three grades,

high, intermediate and low, based on tumor differentiation, necrosis and mitotic count.

and the grading system has implications in terms of prognosis.

I think that's really, really important.

And, you know, in the year 2015 with our ability to sequence everybody

and our ability to look at all sorts of molecular markers,

you know, I think we're into a very complex world and a very rare group of tumors.

And so, you know, Jonathan,

what is your goals of molecular testing and how do you incorporate that into your practice?

Good question.

And thank you for the invitation to participate in the panel.

And I agree with, certainly with Shreyas and Robin,

regarding the complexity of sarcomas.

In fact, there's over 200 different types,

if you look at the pathology textbooks.

And I think that molecular testing is underutilized in the world of sarcoma and that it can help in diagnosis.

For instance, there are a number of histologies

that have specific genetic abnormalities such as gene amplification and MDM2 and some of the liposarcomas,

de-differentiated and well-differentiated.

And this testing can not only help make the diagnosis,

but there could also be therapeutic relevance.

For instance, in the era of targeted therapies,

we are now able to pair specific molecular events such as

a mutation in a gene called KIT in GI stromal tumor with a therapy such as imatinib

or sunitinib or regorafenib and be able to really precisely treat patients based on the molecular rearrangements or abnormalities.

And this is particularly pertinent to sarcoma since we have

so many histologic subtypes that have a very high frequency of these molecular abnormalities.

So, Brian, if I could add a few comments with this too.

I think has been well stated.

It's a huge number of different tumors.

And just like you would never classify carcinomas as one disease,

you wouldn't lump breast carcinoma and prostate carcinoma into the same thing.

We do that in sarcomas where we have these different diseases.

We lump together sarcomas because they're so rare and they can have similar presentations but markedly different genetics and different behavior.

And one of the key parts is to make sure,

as Robin was saying, that an expert in sarcoma pathologies reviewing the material,

especially

when it's obtained at a community hospital where pathologists may only

see a few cases of these in the course of their career.

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The hierarchical testing that they do is based not just on the specimen they have,

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but also based on the presentation of the patient.

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So it's also very important that the medical

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and surgical teams are in communication with the pathologist about the location of the tumor,

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the behavior of the tumor, and those other aspects.

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So a multidisciplinary approach is really important.

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And their testing often looks at the shape of the cells first and where it is located,

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and then that helps drive other testing like immunistic chemistry and other molecular testing.

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I think we're still very early in the question of the wide-scale genomic testing that's performed either for research

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or for clinical commercial purposes right now.

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In our experience, and I think a lot of the other centers are doing this as well,

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where we've sequenced large panels of genes,

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we've seen a disappointingly few number of mutations that we didn't already expect in sarcomas.

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I think it's still a very important area for research,

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but personally I'm not yet ready to order huge screening panels for genetic mutations,

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but instead stay focused, as John was just talking about based on the appearance of the tumor,

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suspected appearance of the tumor,

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and the possible mutation types.

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Dr. Yeah, I'd like to,

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if I may, an illustrative example is in the pediatric realm of a very practical fusion product,

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you know, the fusion-associated tumors,

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rhabdomyosarcoma, where historically it's been either in pediatric realm, conventionally alveolar versus embrinal.

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And now it's actually fusion-driven,

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and that's the gold standard.

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And if there's some Pax-Foxo associated tumor that may have some embryonal features,

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they're still going to call it alveolar.

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And it's really that and the clinical trials moving forward through the Children's Inchology Group,

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et cetera, are all doing this.

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And I think Synovial and Ewings are following suit with that.

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So it's really boots on the ground.

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This is happening today, not just some academic ivory tower concept.

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And I'd like to just highlight the importance of a multidisciplinary team in making the diagnosis.

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Andy said, very often it's important to have the clinical features

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and the radiological features together with the pathology to make the diagnosis.

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And that's really, really important to highlight.

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I think it's important to highlight the fact that the one thing that these are all mistaken for are melanomas,

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and melanomas are, you know, they're mistaken for sarcomas.

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And if you really make that error,

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you've altered radically a treatment path for a patient.

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And this is why having a highly experienced sarcoma pathologist confirming what they're seeing is really that important.

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And what's very interesting is it's very hard,

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I believe, to have the discussion we're having today

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because we're talking about at least 80 different diseases that probably break up in six different categories of each one.

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And we go from probably one of the best understood tumors on the planet,

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which is the GI stromal tumor,

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where we understand what mutations go with what drug,

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to the undifferentiated pleomorphic sarcoma,

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where we're still doing lots of clinical trials,

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which we'll get into later.

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