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Podcast Transcript: Pathology 101: Solid Advice for Percutaneous Biopsies

with Dr. Andrew Sholl

In this episode of the BackTable Podcast, host Dr. Chris Beck interviews guest Dr. Andrew Sholl, who demystifies the ins and outs of percutaneous biopsies and their impact on diagnoses. Dr. Sholl is a pathologist at LCMC Health in New Orleans, Louisiana. You can read the full transcript below and listen to this episode here on BackTable.com.

(1) The Path to Pathology: Fellowships & Specialization

(2) A Pathologist's Perspective: The Highs & Lows of the Job

(3) Thyroid Biopsy Techniques: Gauges, Cores & FNAs

(4) Essential Biopsy Practices for Reliable Results

(5) Determining Sample Allocation: Next-Gen Sequencing & Molecular Analysis

(6) Evaluating Biopsy Devices for Accurate Sampling

(7) Navigating Diagnostic Uncertainty in Pathology

(8) Clinical History as the First Step to Accurate Pathologic Diagnosis

(9) Importance of Cultures & Biopsies in Diagnosing Infections & Tumors

(10) Challenges in Diagnosing Kidney and Liver Tumors via Pathology

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Pathology 101: Solid Advice for Percutaneous Biopsies with Dr. Andrew Sholl on the BackTable VI Podcast

Ep 422 Pathology 101: Solid Advice for Percutaneous Biopsies with Dr. Andrew Sholl

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[Dr. Chris Beck]
Hey guys, and welcome to The Backtable Podcast. Today we're going to be-- I think the title of this episode is going to be Pathology 101. To help us with this discussion, I've asked a friend and colleague who works at my hospital in New Orleans, Dr. Andrew Sholl, who is a pathologist and is going to talk about their process and talking about their process, hopefully, uncover some tips that interventional radiologists can do to improve what we do. All right, Andrew, welcome to the show. Thanks for coming on, man.

[Dr. Andrew Sholl]
Thanks, Chris. Thanks for having me, man. Appreciate being on.

(1) The Path to Pathology: Fellowships & Specialization

[Dr. Chris Beck]
Can you just give us a background of first, your practice, how you got to pathology and then also what the pathology training looks like now? Because we-- not that I want to siphon off med students are interested in IR, but just a quick plug for pathology. What's cool about it?

[Dr. Andrew Sholl]
Sure. Pathology is great. It's something you're not really exposed to in med school. Very often you just are thrown into the path course and they throw some slides on a microscope, which are poorly prepared, and then they expect you to get the answers right on the test. That leaves a sour taste in a lot of med students' mouth but it's really neat on the back end.

After med school, you do four years of residency and then you go do a fellowship. My subspecialty fellowship was in cytopathology at MD Anderson Hospital. Basically what that means is that you're looking at individual cells on the slide. That's FNAs and small biopsies like you guys do in IR.

[Dr. Chris Beck]
Got it. Is everyone in pathology doing, or a majority of people, fellowship train these days?

[Dr. Andrew Sholl]
Yes. A majority is at least one year of fellowship training, sometimes two, depending on the job market and stuff.

[Dr. Chris Beck]
What are some of the other fellowships out there? Just curious.

[Dr. Andrew Sholl]
Oh, there's a bunch. You split it into two. There's the AP, which is Anatomic Pathology, and then there's the CP, which is Clinical Pathology. The AP is your cells, your biopsies, your slides, your tumors, diagnosing things. Then on the back end, which is where all the lab work is done, which is, CBCs, the blood bank, chemistry, all those tests are overseen by a pathologist on the back end.

There's this big smorgasbord of things that you can do. Within the CP, you have a blood bank fellowship, you have a chemistry fellowship, molecular pathology is becoming very popular. Then in the AP, you can subspecialize. Cytopathology, GU, breast, kidney, all these things. You do your four years of general residency, and then you decide, okay, I want to be a subspecialty GU pathologist or longer or whatever.

[Dr. Chris Beck]
For the general pathologist coming out, is the-- and I'm sure the job market's all over the place, but is it more that pathologists have to know how to do just about everything? Is it better to be well-equipped at a lot of different things and then have your specialty or-- Now, when you're coming out, are you almost doing exclusively cytopath, like percentage--

[Dr. Andrew Sholl]
No. Right now, you really want to be a general pathologist.

[Dr. Chris Beck]
Really? Okay.

[Dr. Andrew Sholl]
For the job market, that's the best place to be, a general AP. You can do a general surgical pathology fellowship, and that gives you exposure to a whole bunch of different organ systems. Then you can subspecialize within that. Depending on your practice, makeup, who's doing what thing, I've found myself pigeonholed into GU and breast and then cytopathology as well.

That's how I've subspecialized after practice outside of the fellowship. Your practice needs, hey, we do a bunch of GU at this institution, so you're going to have to learn how to do it. Then you do a fellowship after fellowship.

[Dr. Chris Beck]
Yes, the after fellowship fellowship.

[Dr. Andrew Sholl]
Yes, exactly.

(2) A Pathologist's Perspective: The Highs & Lows of the Job

[Dr. Chris Beck]
Out of curiosity, I'd like to ask this of other specialties. What's the coolest part of the job? Then also on the converse, what's the-- what everyone avoids doing, it's like the leftover at the end of the week?

[Dr. Andrew Sholl]
To be honest, my favorite part of the job is this puzzle, right? You get-- and you're the first piece of that puzzle. Someone comes in, they have a cough, they get a CT scan, and then there's a lung nodule. The question is it a MET? Is it a primary? What tumor is it? You get your needle in there and then I get on the back end. My job is to figure out, okay, this is an adeno versus a squame. What is the molecular profile? What is this?

I'm putting all these pieces together so that the heme-onc doctors can actually come together with a plan to treat that patient. I apply immunohistochemistry stains and figure out exactly what that answer is for these guys to treat them appropriately. That's the fun part for me is that it's a mystery until it gets on my microscope slide.

[Dr. Chris Beck]
That's cool. All right. On the converse, what's the part that everyone hates to do?

[Dr. Andrew Sholl]
To be honest--

[Dr. Chris Beck]
Maybe there's nothing. Maybe that's the sell. Everything in pathology is great.

[Dr. Andrew Sholl]
It's a good life, Chris. It really is.

[Dr. Chris Beck]
Okay. All right. The grass is actually greener over in the pathology?

[Dr. Andrew Sholl]
Yes. I thought I wanted to be a surgeon for the longest time. You had this ideal, oh, I'm going to go to med school and be a surgeon. Then you come to realize, oh, pathology, it's the ultimate answer for these people. You got a problem to solve and it's really neat but-- just like you, I think it's the pre-analytical stuff that's problematic where you got a team of people who got to put together the slides and do it correctly and label everything.

You got to trust a bunch of people and make sure that what you're seeing under the microscope is actually coming from the right patient, coming from the right laterality.

[Dr. Chris Beck]
Yes. That's true. That's something I think that has got to be a bigger problem in the pathology than it is radiology. I talk about it all the time with ultrasound for diagnostic or for people doing diagnostic ultrasounds over there, if you're reading something, you don't know if the sonographer is taking a picture of their liver or the patient's liver. There's a lot of trust involved but assuming pathology, you're really relying that, like you said, it's coming from the nodule that they're saying at the location from the--

[Dr. Andrew Sholl]
Oh, yes. Left nodule, right nodule. Because a lot of these people, they got bilateral stuff.

(3) Thyroid Biopsy Techniques: Gauges, Cores & FNAs

[Dr. Chris Beck]
Sure. That's pretty funny. Okay, let's get into it. I just want to set the groundwork for my biopsy practice or just the biopsy side of things and that way lay some groundwork. At our institution, interventional radiology does a large majority of the biopsies, like of course, exclusional biopsies. For the percutaneous biopsies, it's mostly interventional radiology, the breast radiologists.

Then we have a smattering like that come from Neil Lynan [phonetic], his interventional pull. Where else do some of the small tissue biopsies coming from at Turo?

[Dr. Andrew Sholl]
You guys do most of the thyroid FNA. Sometimes we see those come from the endocrinologist across the street. Neil's doing EBUS, Joshi, and a few of those. The GI guys will do an endoscopy and do FNAs and cores of pancreatic head masses and that sort of stuff.

[Dr. Chris Beck]
I'll just say that at our practice, and it can vary from provider to provider, we do 18-gauge cores of just about everything with the exception of lung, where it's either going to be a 20 or an 18-gauge. That can vary depending on operator experience, comfort, and what we're biopsying. If we think architecture is needed, if we think it's adenocarcinoma in situ, then we try and push for bigger biopsies.

All our thyroids-- I want to say all of our thyroids that we do coming from IR, FNAs, but I think some of my partners are core, maybe a combination of cores and FNAs. I just mean to say that in general, we're coring most of what we do, and FNAs are reserved for thyroids. Can you speak anything to what you're--

[Dr. Andrew Sholl]
What size needles are you typically using for your thyroids?

[Dr. Chris Beck]
25 gauge as recommended by you.

[Dr. Andrew Sholl]
Yes, excellent.

[Dr. Chris Beck]
You want to comment on that at all? Because my partners, I don't know if they've really bought into--

[Dr. Andrew Sholl]
Yes, I think some of them are just using that core needle and then just scraping it on a slide and calling it an FNA.

[Dr. Chris Beck]
Yes, exactly.

[Dr. Andrew Sholl]
I don't know what size they're using.

[Dr. Chris Beck]
20 gauge.

[Dr. Andrew Sholl]
20, okay. Yes, that can make it bloody. To be honest, the cores of the thyroids are not really helpful because things fall apart. You're not getting the architecture and within a subspecialty side of pathology, you have these parameters that you use to put it into these Bethesda categories. When you have chunks of core on a slide, that just totally mucks up the Bethesda category and so it's blood and tissue fragments. Really you want that nice fine 25 gauge smear on those slides to apply the Bethesda.

[Dr. Chris Beck]
Let me ask you this because this actually comes up and I don't know if it's all that common knowledge, but if you have like a 20 gauge or let's say even an 18 gauge core of a thyroid nodule, is there any way to get-- say we take it and then I know that some people will smear it around a slide and they call it an FNA, but is there any way to extract like smaller cells from a bigger core or you have what you have?

[Dr. Andrew Sholl]
Yes, you have what you have, but smearing it on a slide, it does it. The thing with the papillary thyroid carcinoma is that you're using nuclear features and architectural features. Those are best coming out on a slide from an FNA and not so much from a core that's just full of blood.

[Dr. Chris Beck]
Any advantage at all to taking a core of a thyroid biopsy?

[Dr. Andrew Sholl]
I find none because the way that you're categorizing these is utilizing years and years of categorization via Bethesda on a cytology smear. The cores, yes, they might have some papillary architecture. Yes, they might have that, but you're going to get that from the FNA anyway. When you're looking at follicular lesions, adenoma versus carcinoma, it's the capsule that you're really worried about, but you're not getting a capsule on a core.
Again, that doesn't help you further categorize any of these lesions. The PTC that you were going to see on the cytology is not going to be enhanced by the core in any way. I actually discourage cores as much as possible.

[Dr. Chris Beck]
Hold on, how about this? Why 25 gauge? Why not 23, 21, or 27? 25 is just that [crosstalk].

[Dr. Andrew Sholl]
Yes, 25, 27, 23 is fine. Sometimes those nodules are a little bit more fibrous and to get through that fibrosis, you need a 23 to push through it, and that's fine. I don't discourage that, but, 20, 18, that's too big.

[Dr. Chris Beck]
I'll tell you, I think a lot of interventional radiologists, so like the way we train, it's like you're left with the general sense that bigger is better. Then also you may go through a training program for interventional radiology, and you may not actually do a lot of thyroid FNAs just because that complexity is low. You may spend your time training, doing these other different procedures, and then you have to do a lot of thyroid FNAs in actual private practice. Actually, would you actually--

[Dr. Andrew Sholl]
Is it just ingrained in your head that a core, just-- I core this.

[Dr. Chris Beck]
Yes, core equals better is really-- and so that's what I wanted to get at today is that, hey man, that's not always the case.

[Dr. Andrew Sholl]
No, it's not.

[Dr. Chris Beck]
Yes, but I will say, just so everyone knows, it's not like I was-- I knew this inherently, my practice changed whenever you came and gave us a pathology crash course about like, "Hey, just do the smaller gauge needles. You're going to get better core or you're going to get better FNAs and better--"

[Dr. Andrew Sholl]
Yes, you get better stuff. Oh, they look fantastic at Turo now. They really do.

[Dr. Chris Beck]
Oh yes?

[Dr. Andrew Sholl]
Yes. They talk about getting blood in the hub too and that drives me insane because the first piece of the specimen that's coming up is going to come through that needle. It's going to get up into the hub and then everything in front of it is just blood. The blood in the hub is actually the sample. Then when you put it down on the slide, you're just pushing the blood that was in the tip of the needle onto the slide.

[Dr. Chris Beck]
Yes, so you don't need any of the blood, you just want--

[Dr. Andrew Sholl]
No, you don't want the blood, you want the sample. The sample-- so I always advocate that don't stay in a lesion longer than 10 seconds. I don't care if blood in the hub or not because the sample is going to be in that needle.

[Dr. Chris Beck]
When you're saying blood in the hub, just for people who may not have a perfect visual on this, you have a 25 gauge needle. I usually hook it up to the back of a syringe, like a 3 or 5 CC syringe, but just stay in the nodule long enough. You don't have to see blood return into the hub of the needle. You just stay in it for five, 10 seconds and then whatever else, put that onto the slide.

[Dr. Andrew Sholl]
Yes, exactly. That's the best way to do it.

(4) Essential Biopsy Practices for Reliable Results

[Dr. Chris Beck]
Okay, that's a good tip. See, we're already getting into it. All right, so let's get a little bit out of thyroid FNAs and get in a little bit to core biopsies. Once a biopsy is taken, whether it's interventional pull, GI, or more likely IR, the pros, can you talk a little bit about what happens when we put it in to-- or actually talk about the different ways you can send out a sample because you don't just have to put in formal, you have options. When does it change? It may not be formal, which is the default, I would say.

[Dr. Andrew Sholl]
Yes, formal is typically the default. Usually, you need some clinical history in order to triage things. If you're going into a lymph node in a patient who's got lymphadenopathy and you're thinking lymphoma, you got to go not put some in formalin so you can get some flow cytometry out of that sample.

[Dr. Chris Beck]
Why can't you get flow cytometry out of a formalin sample? I know that you can't, I just never really knew why.

[Dr. Andrew Sholl]
Formalin fixation cross-links proteins. Once those proteins are cross-linked, they stick together. Flow is a procedure in which each individual cell has to flow in a laminar fashion through an aperture. You attach different signals to those cells. Then a laser reads, okay, this is signal X and this is signal Y. This is a B cell, this is a T cell, this is a macrophage. If you have cross-linked those proteins, they're not going to flow through that aperture.

That's why you need a fresh sample where you can have individual cells that are still alive and healthy in the flow cytometer.

[Dr. Chris Beck]
Whatever you're putting it, getting a sample, and you think you have a lymphoma, you have a high pre-test probability, what's the preferred-- because I've done different things with them, RPMI, just having fresh sample on a wet Telpha pad. What's the preferred--

[Dr. Andrew Sholl]
Immediately into RPMI is preferred.

[Dr. Chris Beck]
Immediately into RPMI?

[Dr. Andrew Sholl]
Yes. You're going to want to fix some too. You're going to want formalin fix and RPMI but yes, immediately in RPMI, which is basically a cell culture medium that just keeps the cells alive.

[Dr. Chris Beck]
Got it. Why do we put everything in formalin? Why is that the default? What's so great about formalin? Why aren't we just putting everything in saline?

[Dr. Andrew Sholl]
Tissue after being exposed to air and saline--

[Dr. Chris Beck]
I feel like you're thinking about like a way that you can actually dumb this down for interventional radiologists that are listening. For people who don't see the audio, Andrew looked up to the sky and was like, how can I explain this to this guy?

[Dr. Andrew Sholl]
How can I explain this? Right. Basically, tissue dies when it's left away from its blood supply. In order to preserve architecture and the integrity of that tissue, you need to cross-link the proteins, cross-link the DNA, the RNA in that specimen. Formalin is a substance that basically cross-links proteins and DNA, RNA in the cells, in the individual cells. That preserves the architecture.

In that process, basically a water molecule is produced. You're kicking out water and cross-linking proteins. That's what's going to preserve that specimen for a long period of time so it can be processed and put under a microscope. Lung, for example, so lung has alveolar spaces, it's got the interstitium, it's got the blood vessels in there. If you let that sit on a Telpha pad, it's all going to disintegrate. The alveolar spaces are going to collapse. The tissue is going to degrade.

Then the architecture that, we as a pathologist require to see, okay, this is an alveolar space, this is a tumor cell, this is a pneumocyte, this is a blood vessel, that just melts into itself. The formalin is what allows that architecture and that integrity to be there.

[Dr. Chris Beck]
In terms of samples, and I know it's hard to paint everything with a broad brush, but I just want to see where this takes us. The way I think about it is bigger samples are better. That means not only by gauge but on length. I want to get your thoughts on that outside of thyroids.

[Dr. Andrew Sholl]
Yes, I agree with that.

[Dr. Chris Beck]
Okay, bigger is better. All right.

[Dr. Andrew Sholl]
Yes, bigger is absolutely better when you're talking about cores of tissue. Your trade-off is, am I going to give this person a pneumo? Am I going to, give this person a hemothorax? Yes, bigger is always better.

[Dr. Chris Beck]
All things being equal, bigger is better.

[Dr. Andrew Sholl]
Yes, if you can get a bigger sample safely, then you absolutely have to do that.

[Dr. Chris Beck]
More samples, always better?

[Dr. Andrew Sholl]
Yes, absolutely.

[Dr. Chris Beck]
How about if you're getting though-- sometimes I'll take 10 or 12 cores. The reason I'm doing this is sometimes I'm in a big lung lesion, and I feel like the needle, I'll be a little bit too central and so I'm getting what appears to me, on--

[Dr. Chris Beck]
Necrotic stuff.

[Dr. Andrew Sholl]
Yes, necrotic or I just feel like I'm not getting a good sample, but I'm putting it all into the same formula. I end up with 12 passes, but maybe only three or four of those are really good tan white tissue. Sometimes I think would it be better if you separate it out the "good passes" for the "bad passes" in two different containers.

[Dr. Andrew Sholl]
Yes.

[Dr. Chris Beck]
All right. Talk about that a little bit in that.

[Dr. Andrew Sholl]
If you're getting 12 course and say, seven of them are bad.

[Dr. Chris Beck]
Yes. Little shitty mushy fragment.

[Dr. Andrew Sholl]
In that sense, if you put that into one single formula and container, the processing of that sample has to go through a fixation process. We basically embed it with paraffin and then it has to be put in a flat plane into a mold where then we cut sections on it. Those tiny little cores, they're not 2D, they're 3D. They flow up and down a little bit and getting 12 pieces on the same plane is much harder than getting four good ones.

If you feel that your first couple of passes are bad, put those in one container formula and then the good ones that are separate. If you separate them out, then you can get the good stuff in a single plane much easier than trying to combine good and bad cores into a single cassette.

[Dr. Chris Beck]
How about if you have a big lesion and so all things being equal, you can get into any component of it safely? Is it at all helpful to have-- let's say we're in liver, a little bit of what looks like by imaging, normal liver on the periphery. If you're getting into a lesion and I don't think it's necrotic, so I can either bullseye and what you get is all core, all tumor, or I can get a little bit to the side and give you 90% core, a little bit on the periphery or, maybe 20% healthy liver and then 80% tumor. Does any of that make a difference?

[Dr. Andrew Sholl]
Yes, I think it would. I didn't know that you really could be that precise with it.

[Dr. Chris Beck]
Yes, we're like snipers. Not always and sometimes you can't be, but then sometimes you have total control of the situation and that is totally possible.

[Dr. Andrew Sholl]
The way that our brain works is that, the first thing that I look at when I get a slide is what's the specimen? Is it lung? Is it liver? My brain can turn on, what is the background supposed to look like. When my brain can turn on like what the background is supposed to look like, then it's much easier for me to pick out stuff that's not appropriate or not supposed to be there. Same thing with you when you're looking at a lung, you know from top to bottom what it looks like and okay, there's a lesion there. It comes up and it disappears.

That's not a vessel. It's not part of the normal background lung process. You can see it. The same thought process works for the pathologist as well in that if I know you're supposed to be in liver, okay, that is not a bile duct. That is not a hepatocyte. It helps me. In that sense, if you are as good as you claim you can be, then having a little bit of background liver in there would be helpful because then when I want to categorize that type of tumor, so is it HCC? Is it a metastatic colon? Is it something?

We have stains that we can put on it and I know that a hepatocyte doesn't stain with this, whereas a tumor would. If I have that background benign liver there that picks up the stain in the expected manner, then A, I know it worked. B, I know that the tumor is in fact real staining for this colon cancer marker. Yes, having normal stuff back there is super duper helpful. We call it an internal control. TTF is an immunostain that we use, for example, that's a marker of lung.

If you have a metastatic lung and it goes to the liver, the TTF will stay in the nuclei of the lung tumor-positive. What's interesting about hepatocytes is that the cytoplasm of the hepatocytes takes up that TTF1. I can see in the background that that TTF1 is staining the hepatocytes in a granular cytoplasmic way appropriately and the tumor in the nucleus appropriately, so I know that my stain worked, it covered the tumor, and it's a real positive stain.

[Dr. Chris Beck]
Got it. Right. Rather than a false positive. It's like an internal control there.

[Dr. Andrew Sholl]
Yes. The internal control is super helpful if you guys were that good.

[Dr. Chris Beck]
Like I said, depends on the day, depends on the doc. All right. We said bigger is better. How about-- and I know it's hard to say, but if you're getting good high-quality samples, how many samples would you say-- what's the bare minimum? What's like, all right, you got it. That's fantastic. Then what's like, all right, man, if you're taking 20 great cores, I just don't need that many. You know what I mean?

[Dr. Andrew Sholl]
Yes.

[Dr. Chris Beck]
I bet if I had to guess, it's probably on a spectrum. Too few is too bad. Too many it's--

[Dr. Andrew Sholl]
How long are your cores? They're 1 centimeter long, basically.

[Dr. Chris Beck]
Let's say, let's say 2-centimeter cores, 2-centimeter 18 gauge cores.

[Dr. Andrew Sholl]
2-centimeter cores, yes, you need 3.

[Dr. Chris Beck]
Three?

[Dr. Andrew Sholl]
You need three to four to do what you need to do, like in a lung tumor.

[Dr. Chris Beck]
That includes next-gen sequencing?

[Dr. Andrew Sholl]
Yes, exactly. Two of those I'll need for, the diagnosis. Then the two can go for PL1, next-gen sequencing, all the adenocarcinoma, BRAF, whatever you need. Let's say four.

[Dr. Chris Beck]’
Okay. Let's say four. All right. There's IRs across the country that are listening to this and they're going to take it to their pathologist at different hospitals like, "Andrew Scholl said four."

[Dr. Andrew Sholl]
Oh, no. Andrew Sholl said this. Four good ones.

(5) Determining Sample Allocation: Next-Gen Sequencing & Molecular Analysis

[Dr. Chris Beck]
Yes, four good ones. I think that's the caveat. That's helpful to know. I think it just puts people in the ballpark. Can you talk a little bit about-- because I feel like next-gen sequencing now is-- how about this? Let me frame the question in-- Is next-gen sequencing always getting sent out? Is it like a reflex send out or do you always have to save some-- are some cores getting saved for potentially sending out for molecular markers?

[Dr. Andrew Sholl]
The way that we've been doing it, I think you've been doing it now too, is that you've been putting a few cores in one container and then a few cores in another.

[Dr. Chris Beck]
Right, we've been separating it in two different--

[Dr. Andrew Sholl]
That is helpful because the first two cores we're using to get to the name. The name is adenocarcinoma or the name is metastatic renal cell carcinoma. Then that second block can be saved for the next-gen sequencing. Those for the most part are PCR-based tests where they're amplifying the DNA in that specimen and then using it to find all of these different mutations, whether it's HER2, BRAF, KRAS, NRAS, all of these things that potentially have therapeutic direct, meanings going forward.

What I wanted to say is that it's important to have that specimen available for you. The way we're going now is that all these patients are getting it. It's not reflex as of right now because there's so many mutation possibilities. There's a next-gen for breast, there's a next-gen for kidney, there's a next-gen for whatever. You have to have a name before you can send it out at this point in time.

[Dr. Chris Beck]
Got it. My thought on that, just to back up the audience because there's some things that me and Andrew know that I just want to update you on. Originally, we were doing some biopsies and everything went in one formal container and we were coming back with some-- it wasn't non-diagnostic, we were getting a name, but then we didn't have enough tissue for next-gen sequencing.

Then we changed our processes. I think it was y'all's suggestion that we put them in two separate formalin containers and that way you could use one for the diagnosis and then two for the send-out. Whenever we say send out, where do y'all send it? Where do these things go?

[Dr. Andrew Sholl]
There are these big labs that have these large PCR machines that can run at volume.

[Dr. Chris Beck]
It's not like any place has these in-house, like if you're at MD Anderson or something.

[Dr. Andrew Sholl]
No, a place like that would have this in-house.

[Dr. Chris Beck]
All right. Anderson does.

[Dr. Andrew Sholl]
Yes. Where we're at or a rural hospital, whatever, they're going to have to send it to a big lab to get these tests done.

[Dr. Chris Beck]
Anywhere in Louisiana? Are there any hospitals that actually do their own? I know you don't know all the hospitals, but you have to have the scale of a big center?

[Dr. Andrew Sholl]
Yes. What's happened is that it requires these big expensive machines that need to be running basically 24/7 in order to make it profitable based on reimbursement.

[Dr. Chris Beck]
You have to have the volume.

[Dr. Andrew Sholl]
You got to have a volume. Yes. These big labs have just bought five machines and are running them 24/7 from around the state.

(6) Evaluating Biopsy Devices for Accurate Sampling

[Dr. Chris Beck]
I want to talk to you a little bit about biopsy devices. I'm just curious from a pathologist perspective, can you ever tell-- surely you can tell the difference between whether we're using an FNA or a core, but can you tell the difference between when we give you an 18 gauge versus a 20 gauge core?

[Dr. Andrew Sholl]
Yes, I can tell the difference, yes.

[Dr. Chris Beck]
In theory, if you had a side-cutting needle, for some reason, if we thought-- because in IR, there's-- it's not a big debate, because a lot of times your biopsy device is dictated by where you're biopsying, operator preference, critical structures nearby but sometimes in some situations, you'd prefer to use a side-cutting needle or a notched needle. From your perspective, that looks like, if it's an 18-gauge is pretty close because in theory, the full core would actually get a fuller core.

[Dr. Andrew Sholl]
It's the same size. It's really more about what your preference is and what you feel you can get in there and get a good specimen right.

[Dr. Chris Beck]
Whatever device gives you the most comfort to get a good sample, that's which device.

[Dr. Andrew Sholl]
Yes. As long as it's there. We always laugh at you guys because you're like, "Well, my needle was in the lesion." I was like, well, the lesion's not in the needle.

[Dr. Chris Beck]
[laughs] We're like fighter pilots. We always think we hit, it's always like, hey, but look, it's in there. It's got to be.

[Dr. Andrew Sholl]
That's how I always joke. I was like, I understand that the needle is in the lesion, but the lesion is not in the needle and there's nothing I can do.

[Dr. Chris Beck]
That's a really good line. How about the difference between what GI and interventional pulm is giving? Are their samples any different? Because I think they'll use a 20 gauge sometimes, but I think they do different advanced techniques, like a cryo freeze then to pull it out or something.

[Dr. Andrew Sholl]
Given that they are accessing lesions that are deep via an endoscope and an ultrasound probe, the cores have to be small. To be honest, what I found, and I'm probably biased because I am trained as a cytopathologist, I would prefer they just effinate them. I really would. Particularly the pancreas.

[Dr. Chris Beck]
That probably draws an important point here to drill down on. That's what you would definitely prefer, but it's good to open up a lot of communication with your pathologist and say, what's going to help you get the best answer.

[Dr. Andrew Sholl]
That's absolutely true because-- and some of these lesions, particularly the fibrotic ones in the pancreas to get cells out of there, it's just better to use a 22, 23 gauge endoscopy needle and effinate it. Because a lot of the times too, you got chronic pancreatitis in the background and you just got fibrosis on the cores and it's not very helpful.

(7) Navigating Diagnostic Uncertainty in Pathology

[Dr. Chris Beck]
This gets to a point. When is it the-- how certain do you have to be to then put out a pathology report that says this is the answer? Because sometimes it says non-diagnostic, maybe we need-- it'll make a different recommendation and maybe that varies from practitioner to practitioner. Even in straightforward cases, it's probably hard to be 100% certain but when I think about radiology, in diagnostic radiology, there's always that out that some radiologists will say like, "Oh, correlate clinically."

Or maybe if we had a super secret MRI or something, but you guys don't really have much of an out other than saying, "Hey, we need more tissue." But you have to have some degree of certainty to then say like, "This is the diagnosis. Treatment recommendations are based on like what you guys say, so how certain--

[Dr. Andrew Sholl]
That harkens back to how good is the biopsy. When I hedge and when I hedge, that typically falls into one or two categories. You basically have benign, atypical, suspicious, and malignant. That's the big four that we're falling into. When I fall into the atypical and suspicious categories, it's usually because I don't have enough tissue. That's usually what it comes down to.

I'll have a lung cancer, there's tiny stuff on the edge. I can't do any immunostains on it because it will disappear. If I do do immunostains, then the cells are not there anymore. My hedge is that I know this is non-small cell cancer, but I can't call it squam, I can't call it adeno, I can't call it a met. It falls into the, I know it's cancer, but I can't tell you anything more than that. That makes it sometimes difficult for the hematologist, oncologist to treat.

[Dr. Chris Beck]
Sometimes I feel like samples can get sent out and not necessarily for next-gen sequencing, but you can send them out for a second opinion. Is everyone's threshold different for that?

[Dr. Andrew Sholl]
Everyone's threshold is different, but I can speak to my threshold. My threshold is this looks like tumor X, but the immunostains stain like tumor Y and I don't have a name for it. There's plenty of tissue there, but the name that I want to put on it doesn't have enough supporting evidence, whether it's immunostains or flow or whatever to put that name-- rubber stamp that name on it.

That's when I will step back and say, okay, the tumor looks like an adeno, but it stains like a squamous. It looks like this, but it stains like a kidney, but the guy's got a history of colon. When the clinical picture doesn't fit with what's on the slide, that's another reason for me to step back and say, I'm not sure what I'm doing here. Let me send this out somewhere where they can do more advanced testing whether that's next-gen sequencing or more immunostains that I don't have access to.

[Dr. Chris Beck]
Is that sometimes the case? It's not necessarily-- I'm framing it like this, like a caricature, but it's not like, "Oh, Dr. Sholl's brain is too small, so he has to have someone else think about it." People have access to different tools that you just-- if were to-- okay, that you just don't have access to.

[Dr. Andrew Sholl]
No, that's absolutely correct. As an example, they will do brain tumor biopsies, excisions at our institution. The way that these brain tumors are now categorized is whether they're IDH1 mutant or not. Then, so the glial neoplasms, they need these tests in order to categorize them that I just don't have access to. I know it's a glial neoplasm. I know it's a high-grade glial neoplasm, but in terms of categorizing it, I don't have the tools at hand to do that.

It's cheaper for me to send it out to a higher-end neuropathology institution that has an IDH1 immunostain or-- yes.

[Dr. Chris Beck]
Just sitting there on the counter, I guess. I don't know.

[Dr. Andrew Sholl]
Yes.

(8) Clinical History as the First Step to Accurate Pathologic Diagnosis

[Dr. Chris Beck]
The other question I wanted to get at was how much history-- I think each place can vary. Do you work at some different sites other than Turo?

[Dr. Andrew Sholl]
Yes. We sign out stuff all over the state.

[Dr. Chris Beck]
Great. This is good. I would imagine the amount of information that you have about a sample can vary widely.

[Dr. Andrew Sholl]
Yes.

[Dr. Chris Beck]
Can you talk about that and how that makes a difference? And if that makes a big difference where you're like, "Look, just give me the sample." You know what? Whether I have dog shit or whether I have filet mignon, I can tell you what it's going to be.

[Dr. Andrew Sholl]
As much clinical history as you can possibly give me is absolutely important. For example, you always hear this, "Oh, I don't want to bias my pathologist." Are you not going to bias me by just not telling me where the sample came from? I got to figure it out on my own? That just wasted 10 minutes of my time to figure out that Dr. Beck sent me a liver core and not a lung core.

It makes a huge difference for my brain to figure out what I need to be looking for and what the differential diagnosis in my head is. If you're doing a kidney mass, I have a catalog of kidney tumors in my head and so I need as much information as possible. You're doing a core of a lung but the guy's got a history of colon cancer, he's got a history of renal cell cancer. That can help me immensely get to the right answer.

Whereas if my differential is everything, inflammatory, neoplastic, possibly the guy traveled to Kenya--

[Dr. Chris Beck]
Sure, wherever.

[Dr. Andrew Sholl]
Pneumoconiosis. If that's the differential, I can't possibly get to a meaningful answer in a reasonable amount of time with the material that you're providing me. Four cores. If I have four cores to figure out, neoplasm of unknown origin, inflammatory lesion of unknown origin, bacteria/fungus of unknown origin, I'm lost. I'm not going to be able to give you a good answer but if I know as much clinical history as possible, I can narrow down what I need to figure out quickly and accurately.

[Dr. Chris Beck]
Got it. Okay. That's what I suspected but--

[Dr. Andrew Sholl]
Yes, I love clinical history because-- and the other thing too is that when you're asked to do a biopsy, you want to know pretest probabilities of it. Is this going to be malignant? Is this going to be lymphoma? Does the guy have lymphadenopathy elsewhere, does he have a history of Hodgkin when he was 15 years old? There are all these things that help you triage that specimen that you're going to get.

Then on the back end, it's the same way that we're dealing with it too because if the guy's got a history of Hodgkin, I don't want you to waste stuff on flow because Hodgkin doesn't flow. These are all things where I just wasted four cores flowing on a guy with a history of Hodgkin. That's not a meaningful test in that clinical scenario. The better information we have before, the better the diagnosis is going to be at the back end.

(9) Importance of Cultures & Biopsies in Diagnosing Infections & Tumors

[Dr. Chris Beck]
One of the things that interventional radiologists will say, or one of the things I was taught is you biopsy your infections and you culture your tumors. Meaning that almost in all scenarios, whether you think it's a tumor or infection, you're going to get a culture. The same thing with if you think it's an infection, you biopsy it. Do you see the cultures? Do you find that helpful? Are there ever situations where like, interventional radiology thinks like it's a primary lung tumor and then you get all these cores back and you're like, "Man, they didn't send any of this for culture?"

[Dr. Andrew Sholl]
Oh yes. It drives me crazy.

[Dr. Chris Beck]
[laughs] Okay.

[Dr. Andrew Sholl]
For example, last week we had an orbital tumor that was biopsied and he thought it was a tumor. He thought it could be, whatever. Then I put it on the microscope and it's granulomatous inflammation. I better go check the EMR and see if there's cultures in there. You look and you're like, well, there could be an acid-fast bacillus in there but the sensitivity of a tissue and a stain is so much smaller than a culture.

Yes, that saying is absolutely-- I will go to the EMR and look and see if a culture has been done all the time. The other thing too is that it's particularly in lung, you get those obstructive lesions and you'll get a pneumonia behind it. The needle might be in the pneumonia, but you're going to treat the tumor and you're also going to treat the pneumonia. In that instance, it's important to get both. Yes, absolutely.

[Dr. Chris Beck]
Okay, because sometimes you see on the pathology report where you guys do actually make a lot of comments about an infectious etiology, like if cultures aren't said, it's always-- I read those, I'm like, oh, well, it looks like they got it. They figured it out. It's not infectious. What you're saying is you're doing the best with what you have, but having a culture would've been very nice.

[Dr. Andrew Sholl]
Yes. I mean, could put a gram stain on a core, but it's going to tell you gram-positive cocci. Then your ID doc is going to call you and be like, "Anything else?" Because they need to know sensitivities and all that stuff on the bug that's there. All I can tell them is that it's a gram-positive cocci.

(10) Challenges in Diagnosing Kidney and Liver Tumors via Pathology

[Dr. Chris Beck]
Fair statement. Going back to primary liver tumor, primary kidney tumor, I guess it was always my understanding that HCC or renal cell can be difficult to diagnose from a pathology side, but maybe that's incorrect or maybe that's old thinking?

[Dr. Andrew Sholl]
Hepatocellulose are a little bit more difficult, particularly the well-differentiated ones. That's again where the pre-analytical clinical history is going to be absolutely immense. This guy's got cirrhosis, he's got HCV for 20 years, my pretest probability for hepatocellular carcinoma is going to be much higher and therefore I can work harder to get to that diagnosis because HCC, it doesn't stain differently from benign hepatocytes in that I don't have as many tools at my disposal to categorize HCC versus a MET, for example.

I have to work a little bit harder on the backend to get to that diagnosis. Having that pretest probability is super helpful for me to get to, well-diff HCC on my diagnostic line.

[Dr. Chris Beck]
What about for kidney tumors? Because what we talk about on the biopsy side is that you may have a renal cell with oncocytic features or for us, we just talk about sampling error but I was curious if it-- as long as you have a good sample on the right part of the tumor, you think it's straightforward or?

[Dr. Andrew Sholl]
For the most part, yes. I think the tricky part about renal tumors though, is that there is so much overlap. Clear cell with oncocytic features, chromophobe, oncocytoma. Those things require a little bit more background architecture to better differentiate. There's immunostains that can help you in that setting, but the architecture is helpful. Then as you know, the tricky thing with renal tumors is they're highly vascular.

You'll stick that core in there and then you'll just, it'll just turn into a mush of blood. From an interventional perspective, coring of kidney tumors is just technically difficult. Then on the back end, it's pretty hard to categorize them unless you have a very good sample.

[Dr. Chris Beck]
Just thinking about specialty situations is sometimes we're doing biopsies of native kidneys or native livers. I've never run into any problems with native livers, but sometimes native kidneys seem to be difficult to get diagnostic samples. Can you speak a little bit about that? What you see on your end? People talk about it ad nauseum, like interventional radiologists about glomerulide, or are you seeing the right number of glomerulide, how many gloms did you get?

Maybe the gloms change based on the disease process. I wouldn't pretend to know enough about it, but I was curious, what's your thoughts on native kidneys?

[Dr. Andrew Sholl]
When you all do the native kidneys, we'll look at the cores under a dissecting microscope and we have a very good one at our institution. It's helpful to have a good dissecting microscope.

[Dr. Chris Beck]
That's not always the case?

[Dr. Andrew Sholl]
That's not always the case. There were places where people would just take the eyepiece from their microscope and just try to look at the kidney. Having the right tools to see the glomerulide is actually super duper important. We're lucky enough in our group to have a medical renal pathologist who-- and you do not see that very often, outside places. That's difficult to come by and so because we're lucky enough to have that, she can make cake out of ingredients that aren't necessarily--

[Dr. Chris Beck]
Vinegar. [laughs]

[Dr. Andrew Sholl]
Yes. That being said, if you can see the glomeruli, you, A, can make sure that it's adequate before you guys take the needle out, number one. And then number two, the tricky part with medical kidney is that there are these diseases that require electron microscopy, immunofluorescence, as well as just formalin fixation. I'm taking those cores and I'm splitting them up into these three special processes that will give you the best diagnosis.

As someone who has dealt with this before and has a medical renal pathologist on staff, we know, okay, I need this many gloms to put into EM, I need this many for IF, and then the rest goes into light microscopy. That triage up front is super duper helpful for her into getting that good final diagnosis, but you just don't have that in a lot of institutions where you have a good dissecting microscope, you have someone who knows what a glomerulus looks like, and then can, divvy it up appropriately.

They might miss some glomeruli and put that in EM and then you can't diagnose minimal change disease. That's the tricky part about it is that medical kidney has a minimal number of glomeruli and three very specific essential tests on the back end that are required to make that final diagnosis.

[Dr. Chris Beck]
Is there anything that an IR doc can do to make sure that they're getting-- I know there's plenty of things that I can advise another interventional radiologist to do, but is there anything that you can see on your end that would translate into us getting a better core for you?

[Dr. Andrew Sholl]
It's more of are you guys getting the needle through the cortex and getting nice glomeruli in the cortex and maybe a little bit of medulla. It's really the angle of the needle going into the kidney to make sure that you maximize the compartments, the anatomic locations to get the glomeruli out of as many or in as few cores as you possibly can.

[Dr. Chris Beck]
Got you. Is there a number of glomeruli that is a minimum threshold? Because you'll hear people say different things that-- and what I suspect is the answer is it just depends. Sometimes you need fewer glomeruli to get to the answer and then sometimes you need more glomeruli.

[Dr. Andrew Sholl]
More is better. Always.

[Dr. Chris Beck]
More is better? [laughs]

[Dr. Andrew Sholl]
No, it's true. Because again, when you're--

[Dr. Chris Beck]
That could be the name of the podcast. More is better.

[Dr. Andrew Sholl]
When you're divvying things up, you have to triage it but if you have a ton of glomeruli, then divvying it up is easy. Then you don't have to worry about, oh, should I put a little bit extra into the immunofluorescent fixative or should I put a little bit more into the EM. I don't have enough. I'm going to skip the EM and hope that it's not minimal-change disease.

[Dr. Chris Beck]
Got it.

[Dr. Andrew Sholl]
The more you get, the easier it is.

[Dr. Chris Beck]
How do you guys prefer to receive those samples? Is there any different process?

[Dr. Andrew Sholl]
Just on a Telfa pad.

[Dr. Chris Beck]
Telfa pad?

[Dr. Andrew Sholl]
Yes. A saline, wet Telfa pad.

[Dr. Chris Beck]
Yes, saline-soaked Telfa pad. Got it. All right. What I wanted to leave you with, Andrew, is open-ended. Is there anything that you have wanted to tell interventional radiologists, interventional pulmonologists, or whatever about, hey, this would just be general advice for procedure lists, people who are taking biopsies, getting biopsies, to have a conversation with their pathologist and these are the things that you should talk about or any, just open-ended advice that would be helpful?

[Dr. Andrew Sholl]
I think the advice is I would like more history. I know that you guys don't always have that, but it would be helpful to, on the requisition, just say, history of colon-- if you're FNA-ing or coring along and the guy's got a history of renal cell cancer, just tell me something. Just anything.

[Dr. Chris Beck]
No, you've already said too much, Andrew.

[Dr. Andrew Sholl]
Just tell me something.

[Dr. Chris Beck]
We're going to cut this.

[Dr. Andrew Sholl]
Then the more you can get as safely as you can get is always better. More is better and like I said, of the four categories, the benign, the atypical, the suspicious, and the malignant, the reason I'm in the atypical and suspicious categories is not typically a pathologist problem, it's a specimen problem. That's where, you fall into, just needed a little bit more to get to get to that category that you guys are looking for.

[Dr. Chris Beck]
All right. Well said. The one thing I'll leave the audience with is that I wanted to have this conversation with Andrew because I thought it would be immensely helpful to have a pathology perspective. Just on the other end of things, I'll just say that the times I've actually talked with you and some of the pathology colleagues, it's always been very eye-opening. A lot of times it's led to practice changes and to the positive for our patients.

If you're an interventional radiologist, you've never reached out to your pathology department, what's the worst that can happen? Give it a go. You may at the very least learn that you have a very cool colleague on the other end of the line but more likely, you'll end up with a different set of procedures or processes that are going to lead to better patient outcomes or [crosstalk] diagnosis.

[Dr. Andrew Sholl]
I think it's good to go back to the-- different pathologists have different subspecialties and are comfortable with different things. Myself, I'd prefer that my colleagues FNA the pancreatic head, whereas some people are just not comfortable with that and they prefer a different specimen. I think to get your patients the best answer that they can possibly get, it would be worthwhile for you to go and just chat with your pathologist and say, hey, what's your subspecialty? What are you comfortable with? What is best for you to get out of the atypical categories and into more definitive places?

[Dr. Chris Beck]
Nice. Well said. All right. Guys, I think that's going to wrap things up for this podcast. Andrew, thanks for coming on.

[Dr. Andrew Sholl]
Thanks, Chris. I appreciate it.

Podcast Contributors

Dr. Andrew Sholl

Dr. Andrew Sholl is a pathoogist at Delta Pathology Group in New Orleans, Louisiana.

Dr. Christopher Beck

Dr. Chris Beck is a practicing interventional radiologist with Regional Radiology Group in New Orleans.

Cite This Podcast

BackTable, LLC (Producer). (2024, March 5). Ep. 422 – Pathology 101: Solid Advice for Percutaneous Biopsies [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.