Good morning, everybody. It's nice to see some people here on the last day of the conference. We are blessed to have such a great faculty. Before we get started, I just want to make some housekeeping points. Soon, you'll have a barcode on the screen. Please utilize the barcode for two reasons, one, to evaluate the course, tell us what you think of the course, and two, when we get in a little bit to our interactive questions, there'll be one for each case. Make sure that you do the interactive questions, and we'll see if you're thinking as the faculty. We've been doing these puzzlers for 16 years, and I can tell you, it's been such a treat, and to me, the favorite part is right here. The faculty that sits on this dais is really second to none. I want to introduce our faculty. The first one really needs no introduction, Dr. Atul Mehta. If you don't know about him, then you've been under a rock somewhere for the past 25 years, and you really don't know anything about pulmonary and critical care medicine, and in particular, interventional pulmonology, bronchoscopy, but he wears many hats, and actually, Dr. Shah and I were just talking about, we've never seen anyone multitask the way he does. He literally will be editing a paper, doing a bronchoscopy, answering questions, giving transplant evaluations all at once, and know exactly everything that you're saying. And Dr. Mehta, I could really honestly say that you are one of the main reasons I personally got interested in pulmonary critical care. When I was a fellow sitting at these conferences, and I would look up and see him lecture, I would never in my wildest dreams have thought that I would be able to sit here on a dais with him. And Dr. Mehta, we fool around a lot, but I can tell you, you are a true giant in this field, and to share the podium- Let's move on. I'm at the mic, so you could simmer down now. You know, it's almost like he's like a rock star, you know, he's like Elvis. Matter of fact, that's what I call him. So Dr. Mehta, welcome, we're so blessed to have you. Next, our radiologist, Dr. Rakesh Shah, by the way, Dr. Mehta, I know you know, comes from Cleveland Clinic. Dr. Rakesh Shah comes to us from Northwell LIJ in Long Island, New York. And Dr. Shah is really our iron man. There was one year, fairly recently, I think three or four years ago, when Dr. Shah did every session. Now usually, radiologists say, well, you know, whatever little I could do, I'll do. You know, they try to just sort of very easily get through. He had no radiologist, one was from Ireland, and he couldn't make the trip, and another. And Dr. Shah did every session on basically zero notice. And I have, I am a program director, I have nine fellows in my hospital. Every year, our fellows go to ACCP Board Review, which is held, I think it was in Orlando this year, Miami, even better. And when they come back every time, you know, we say, how was the board review? Universally, the one session that they give the highest grades to is Dr. Shah's session. So I think you're all very fortunate. You'll hear him both with an overview and then to dissect the cases. And finally, our MVP, who is our iron man this year. He's pulling a Shah, and he's doing all the sessions. We had one pathologist for all six sessions. So I don't know about you guys, I'm in a big hospital in Brooklyn, New York, as you can tell by my obscene accent. And in our hospital, which is a big hospital, every biopsy specimen we take, we usually have to send out, because we don't have somebody of his ilk and of his expertise to give us the definitive answer. And I'm going to go to my administration when I get back and tell them that we'll save a lot of money on all those specimens going out. Dr. Jones, you're a cosmopolitan guy, you would love New York. So we're going to work on that. So Dr. Jones lectures frequently for ACCP. So this is really a star-studded faculty, and I just wanted to thank all of you for doing so much. And it's really for education, right? These people are so committed to education, and I thank you from the bottom of my heart. I have no disclosures, no financial disclosures. So it is an extraordinary location, Hawaii. But the time difference is unbearable. So I got here Sunday. Monday, I felt hungover all day, like completely drunk, and I didn't have one drink. Yesterday, I felt a little better. Today, I feel great, and my damn flight is tonight, so I'll be miserable again when I get home. So I would be remiss if I didn't thank Lisa Alvarez from ACCP. All of you presenters have submitted your cases to her. All of us on the faculty have submitted our slides, and she's uploaded everything and really done a Herculean job getting everything. So I am a Yankee fan, albeit somewhat tail between my legs as it was a bad year. And I have one additional disclosure. So that additional disclosure is, there is a Cleveland, we can't say Indians anymore, it's Cleveland Guardians fan. And also, Cleveland Browns fan. Now the Guardians, I think last championship was 1947, correct me if I'm wrong. The Browns have never won a Super Bowl, so this original Cleveland Indian, I think one of the reasons he's so good at medicine is he has misery in his sports enthusiasm. So he puts it all in medicine. So here is our bar code. Please make sure you evaluate honestly the session. So the way this works, we're gonna have Dr. Metta come up and give a presentation. I think you'll be most impressed. It's about Ebus bronchoscopy. Then Dr. Shah is gonna talk about radiologic approach to pulmonary malignancies. Dr. Jones will go over pathologic approach, and then we'll get our two cases. So without further ado, Elvis, why don't you come up and Thank you, Tony. That was not, it was not all necessary. He's biased, he's a friend, so just take it with a pinch of salt, what he said. So in next ten minutes, or 15 minutes, I'm gonna talk about- Ten. Ten minutes, Ebus TBNA for the molecular diagnosis of lung cancer. This is a session on pulmonary malignancies. So that's a thing I chose. At my age, at my stage, I'm allowed to have lots of biases, you know? Yes. I do, but none of my biases are financially driven. Okay, so I have no conflict of interest. In all fairness and all defense to the Cleveland and the Cleveland team, our team, Cleveland Guardians, are a homegrown team, we don't steal players from other teams, okay? No greed team, okay, they're reasonably paid, but not billions and billions of dollars, non-pompous group, okay? Down to earth, you know, those type of good sportsman spirit, and giving their all baseball team, so, you know, I was going to call him, it's a big channel, Yankees are playing playoffs this year, and I couldn't find a channel, so I'm so sorry, okay. Anyway, so I'm going to talk about molecular testing for thoracic malignancy, and I'm going to take it in this fashion. Why we need to do molecular testing, what molecular testing you need to do, what you need to do for the molecular testing, how you do it, and Ebus TBNA being the most popular technique these days, can it provide adequate specimen for molecular testing, and that's what I'm going to do. The reason for my talk is very simple, that in year 2023, lung cancer is classified beyond just histology. When I was doing pulmonary fellowship, you know, we just say that it's a non-small cell, or a small cell, and then squamous cell, adenocarcinoma, and a large cell carcinoma. That was the classification, but now, non-small cell cancer is classified based on oncogenic driver alterations. So that is what you need to know today. Targeted therapies, including immunotherapy, towards some of these alterations, they improve the outcome. Tyrosine kinase inhibitors, they're first generation, second generation, and now even third generation tyrosine kinase inhibitors are available. You know, and whenever you have resistance to one and two, first and second generation tyrosine kinase inhibitors, you can use the third generation. And also, combination of these medications plus chemotherapy or anti-angiogenic drugs show improvement, and it's got greater potential. I call this thing as a molecular revolution. That's what is going on when you talk about lung cancer these days. Why? As you see here, so many mutations have been identified. Not only that the mutations have been identified, but the most important thing is in last 13 years, so many medications have come out to deal with all of these mutations. And therefore, identification of all these mutations are extremely important. And therefore, we need to find out, well, does it really, you know, eBus, tBNA, what we are doing is helping in this fashion or not? There was a very nice article published about a couple years ago in CHAST, and it was basically a survey of a number of pulmonologists. And it was quite evident that there was underutilization of the biomarker testing. We don't do enough. There are substantial difference among the pulmonologists, their evaluation of advanced lung cancer knowledge, and available biomarkers, importance of targeted therapy, and institutional coordination. Of course, if you're an international pulmonologist, you may have more knowledge than others. And there was improvement needed in this particular area with acquisition and so on and so forth. So that's where I'm talking, this is the reason just for my talk. Now, what molecular testing you're going to do, very simple. If a patient is from Asian population, you see only 20% would not have any mutation. Western world, 40% do not have any mutations. However, if you look at it, Asian population, almost 50% have some abnormalities related to EGFR. And then you look at it KRAS, MET, ALK, RAS, HERS2, BRF, RET, and NTRK. These are all modifications or mutations are present in both these groups. So if you're dealing with Asian population, you must look at this data, and also for the Western population, okay? This information is exactly the same which I showed you earlier, the outer, this is a pie chart. The outer circle is for the Asian population, the inner circle is for the Western population. And the percentages of abnormalities in the mutations what you have seen. So what molecular testing you must do today, very simple. Testing for EGFR, BRAF, ALK, RAS, it is recommended for every lung cancer diagnosis. Testing for KRAS, MET, NTRK, and RET is recommended that you should do that. What is PDL1, that also you are supposed to test. It is a transmembrane protein which is encoded on the chromosome 9. It forms the basis for immunotherapy in lung cancer. And very important point, 30% of the lung cancers which are EGFR and ALK negative, they have PDL expression representing more than 50% of the cells. And this is what I'm showing you in immunohistochemistry. So how do you do molecular testing? Very simple. Single biomarker assay which is done by immunohistochemistry or FISH testing, PCR, or Sanger sequencing, okay? Multiple assays are this, multiplexed assays are done by next generation sequencing. And this is the artist's rendition of next generation sequencing. PDL1 is done by immunohistochemistry and liquid biopsy, that is even doing the blood analysis to find what kind of mutations your patients have. We know most of all of our lung patients undergo staging with EBUS TBNA. You know the specificity and sensitivity, I'll not go into the details of that for the time sake. When you have the specimen, this is important, what do you do with that specimen? This is the specimen, this is how you did it, this is how you gathered it. First, air dry specimen goes for diff quick, then the pathologist eventually will perform papunicolosmear, as you know. Then this will go into either saline solution, RPMI if you suspect lymphoma, or cytolite that is 95% ethanol, okay? Depending on what your lab prefers for microbiology, for cell block, for flow cytometry, and DNA and RNA analysis. Then we also put the specimen in formalin for PDL testing. And last but not the least, that if you want to do research in the future, you're gonna store it at 80 degree centigrade. So this is what you do when you get the EBUS test specimen. This is what your pathologists do for you, okay? This is diff quick, as we already talked about. This is papunicolosmear, H&E stain, this is immunohistochemistry, this is flow cytometry, this is fish testing. This is your new, what you call next generation sequencing. This is the reverse transcript is PCR, and this is real-time PCR done. And these type of results are available on the specimen you gather. How much do you need? A real-time PCR, you need 40% of the tumor cells. For next generation sequencing, you need about 50%. But nowadays, newer techniques or newer methods, they can detect on 20% cells. For EGFR and KRAS mutation, you need 300 cells. For ALK and RAS, you need about 100 tumor cells. PDL1, you need about 100 viable tumor cells on histology specimen. How do I do it? As long as I see this cell block, this much amount of tissue at the bottom of my test tube, I think this is good enough. About 50 nanograms or something, what they call it. Because of the time, I cannot take you through this slide, but it is an important slide, how you get to this or how you get to the cell block in this particular fashion. This is we do at the Cleveland Clinic. We do next generation sequencing to look at this mutations. We do fish testing for these. And we, of course, do immunohistochemistry for PDL1. Point I would like to make is for PDL1, the specimen must go in formalin. Otherwise, you may have as much as 40% false negative rate. Does specimen you gather give you correct information? Answer to that question is yes. Once again, for the time sake, I will not take you to the entire slide. 774 patients underwent EBUS TBNA, 158 were adenocarcinoma, some large cell carcinoma, some squamous cell carcinoma. EGFR analysis was positive, or possible in 90% of the patients. And this is how they did it in this particular study. That was the first study of its kind in 2012. At the Cleveland Clinic, we are doing for EGFR. We do PCR testing. And again, PCR can reliably detect EGFR gene mutation on EBUS TBNA specimen. We also did it for ALK. For ALK, we actually did the fish testing. And once again, thin prep slides can be used for ALK molecular testing in patients with non-small cell carcinomas. So what I'm trying to tell you, that your EBUS specimen is sufficient enough to give you information on EGFR and for ALK mutations. There is a meta-analysis published, and I'll just take you to the final line on that, EBUS TBNA has a high yield of molecular analysis of both EGFR and ALK mutation. Suitability for TBNA samples for next generation sequence requires further studies. Let me take you to the further studies. And these further studies have also shown that EBUS TBNA reliably provides adequate tissue for next generation sequencing in patients with thoracic malignancy. So answer is yes, you can do all this molecular testing on the specimen you obtain with EBUS TBNA. Cleveland Clinic data, can you do PDL? Yes, 96% success. We take the EBUS TBNA specimen, put it in formalin, and give a false information to the pathologist that it's a histology specimen. They would accept it, and even then, we are 96% positive rate. All right, last couple slides. And now, can this information improve the survival of the patient? So EBUS TBNA specimen is compared with the histology specimen for PDL1. And based on that, when you treat these patients with immunotherapy, with PEMBRO or with Nivolumab, does it give the same result? And answer to that question is yes, that either you obtain specimen with the histology or EBUS, the survival is the same with immunotherapy. The next slide on this one is also that if one patient stop responding, if you switch the immunotherapy, still the survival is as good as EBUS TBNA. All right, and then last but not the least is EBUS TBNA has got great concordance with the endobronchial biopsy specimen, histology specimen. So in summary, there is a molecular revolution in the diagnosis and treatment of non-small cell carcinoma. In year 2023, non-small cell carcinoma is identified based on oncogenic driver alterations. There is underutilization of biomarker testing. EBUS TBNA provides adequate amount of tissue for molecular analysis by immunohistochemistry, by fish analysis, by PCR and next generation sequencing. Formalin-based preservative is recommended for PDL1. 19-gauge provides more tissue than the 21-gauge. I didn't have time to take you through that. Biomarker testing is integral part of advanced diagnostic bronchoscopy. Thank you very much, and I appreciate your attention. Thank you. Good morning, everyone, and thank you for being here. And thank you very much, Dr. Saleh, for having me here. I hope everyone can hear me. So I have nothing to disclose. Lung malignancy, of course, broken that into two components. Lung cancer being the most common, and then there are other types. But I'm gonna focus the talk on lung cancer. As you all know, it's the most common malignancy. The risk factors are smoking is a big one, occupational exposure. Interstitial lung disease is a big one as well, and we're seeing more and more patients living longer with that disease. And so we're beginning to pick up more tumors within them. So I'm gonna show you some examples of that. On imaging, lung cancer can look like a nodule. It can look like a mass. It can be an opacity, a consolidation. Cyst, cystic-like, it can actually look like anything. So how do we go about tackling when we see a finding on an x-ray or a CT whether that's something that we should worry about? So my approach is that your best friend is old films. X-ray, if you see something, try to find an old x-ray. If it's CT, try to find an old CT. Now that doesn't mean that it is just a CT of the chest. It could be a neck CT if the finding is in the upper lungs. It could be an abdominal CT if it's lower lung abnormality. It could be a thoracic spine if something is in the paraspinal region. So look for any prior examination, cuz that's gonna help you tremendously in trying to determine whether the finding that you're observing now, is it benign or malignant? Now as we know, whenever we see that finding, the differential diagnosis is benign malignant. One of the best things I've learned through experience and through lung cancer screening studies is that time is your best friend. If you see a finding, it doesn't hurt to do a short interval follow-up. Two weeks, maybe a month. If it doesn't go away, then I think you have all the right to pursue it and worry about it and consider malignancy to consider. But often time we find that people walk around, especially smokers, they have things that happen in their lungs that come and go. And we observed that in lung cancer screening studies. And so it's important not to get too aggressive too soon, but to do a short interval follow-up. And you'll see, and I'll show you some examples, how that is helpful in your practice. And of course, if it is still there, then you have the guidelines and you have procedures that you can do to help you figure out what that opacity or abnormalities in the lungs. The other thing that I forgot to mention is that whenever you find an observation within the CT scan, look at the studies on both the lung windows and soft tissue windows. It's very obvious that you're gonna look at the lung windows, that's the lungs, the airways, and the pleura there. But very important to look at the soft tissue windows, because that's gonna tell you whether there is something within it, such as calcification, fat, cystic changes, cavitation. And that may help you identify what that abnormality is. So let me just show you a whole bunch of cases. How do I differentiate benign from malignant? Here is an example of a patient who had the CT scan. And obviously, you can see, can you see my pointer? On the left image, you can see this kind of speculated opacity in the right middle lobe. And as I mentioned earlier, you always wanna look at that on the soft tissue windows. If you didn't look at it, you would say, this is pretty ugly, let me pursue it with some procedure, bronch, biopsy, whatever. But on the soft tissue windows, you can see that it has areas of low attenuation. If I can point, there is a low attenuation that look exactly like the low attenuation here in the subcutaneous tissues. So that is fat, this is fat. So visually, you can tell that that looks like fat. You can go back to the PAX machine or the CT scanner, you can measure the Hounsfield units. And if it measures less than minus 30, minus 35, then you can prove, then you can say with certainty that this is fat. So visually, it looks like fat, measurably looks fat, and this is fat. And this is not malignancy, but this is an example of lipoid pneumonia, okay? Lipoid pneumonias can be actually ugly looking, because when patients aspirate mineral oil, it can incite an inflammatory reaction. And they can look kind of speculated. And here's another one in the left lung, kind of ugly looking, but on the soft tissue windows, you can see it looks like fat, just like the subcutaneous tissues. And I've had patients who have been referred to me for a biopsy because people have forgotten to look at the soft tissue windows. Sometimes they'll just see the lung windows, they'll get a PET scan. These things are quite inflammatory. There could be a significant amount of uptake and say, OK, can you do the biopsy? And then if you look at the soft tissue windows, you can answer the question. You don't need to do a mega workup. So always look at both the windows. Here is another case, a patient with this nodule in the left lower lobe. Fairly smooth, but on the soft tissue windows, you can see with visually fat, just like the subcutaneous tissues. If it's well-rounded, this is an example of a hematoma. Here's another example of a hematoma. Well-circumscribed lesion, contains fat within its benign. Next patient here, who has got this sort of lobulated or spiculated lesion in the right lower lobe. And as I mentioned, your best friend is all studies and time. Without getting too aggressive, the patient was referred to me for a biopsy. I said, why don't we wait two weeks? And what I do is, if the clinician disagrees, then I just say, we're super booked. That's his book that came out two weeks later. And you can see that two weeks later, the nodule is much smaller. And you can see it's gradually going away. It doesn't hurt to do a short interval follow-up, in some cases, not all the cases. Here's another patient who had this sort of part solid-looking lesion, a little grand glass in the periphery, a lot more solid in the center. And where I live, if a patient had some finding like this, the next day they're getting a PET scan, which is really a terrible way to practice medicine. But unfortunately, that's how it is in the world. And you can see there is significant uptake. Patient was, again, referred to me because of this for biopsy. And I said, why don't we wait? There's nothing about it that says that this has to be cancer. It could be. And you can see that after two, three weeks, it is getting smaller. And it eventually resolved. So I'm just showing you some examples of nodules that can be cancer. But if you wait, sometimes some of them will go away. And it will prevent you from doing unnecessary PET scan intervention. And it won't delay the diagnosis in any significant way. So infection. Now, many faces of lung cancer. Lung cancer, as I mentioned, can look like a lot of things. And you're all familiar with this grand glass nodule here in the right upper lobe. We follow them. After two years, you can begin to see that sort of density or solid component growing within it. This is slowly growing lung cancer. Couple of things about lesions like this. It's important to review them on thin section CTs to look for the solid component. Don't look at them on the larger, thick slices. The second is it's also very important to be careful not to misconstrue the vessels as solid components. So what you want to do is scroll images up and down and make sure it's not the blood vessel that's a solid, but truly a solid component within it. Here's a different patient. Grand glass lesion in the left lung. And over three years, it became pretty solid. For sure, this is malignancy. Couple of other examples of lung cancer. These are all part solid nodules. They probably started as grand glass. They have solid components growing within them. And again, whenever I encounter this the very first time, I always get a very short interval follow-up. If it doesn't go away, then I rewrite to continue to pursue and consider them as tumors. We're all familiar with this. Typical adenocarcinoma in the lung in the background of central lobular emphysema. This is pretty classic for small cell cancer. They tend to be central. They often tend to obscure and compress the airways in the background of emphysema. One other thing that I wanted to sort of teach you is, when I look at a chest X-ray, I look at the eye of the radiograph. This is one of the things that I learned from my friend, Dr. Paul Molina at University of North Carolina. So, as we all know, lung cancers occur more so in the upper lungs. We humans are kind of lazy. We don't like to look at things that are crowded. It's very easy to identify things in the middle of the lung. Anyone can see that, where eyes kind of go there. But the upper lungs are, as we know typically, where lung cancers occur more often. The ribs are there. The clavicles are there. But you have to force yourself to look there. So the eye kind of reminds you that I got to look at the apices much more carefully. So one of the things that I do is I count the first three ribs and I mentally subtract them. And once you do that, you know, and if you keep doing it, you should be able to see the apices very clearly. And of course, the other areas where lung cancers can hide are things in the paraspinal area. You have a lot of nodal, a lot of blood vessels in the parahilic region. Again, our eyes don't go there. But you have to be very careful and look in those places. And again, the bottom horizontal bar of the eye is things behind the liver and spleen. So this example is showing this large opacity in the right apex. The lung or the air should be touching the inner portion of the cortex all around the hemithorax. And here it's not touching it. So you know you're dealing with this large mass in the apex. And this is a pancreas tumor. And of course, you want to identify this before patient has involvement to this sympathetic ganglia or brachial plexus. A couple of more examples. Here's an example of a patchy opacity in the right middle lobe. They thought this was pneumonia. Patient never got a scan back. A year later, it has grown. They thought, oh, probably the patient had another pneumonia in the same region, didn't bother to do anything. But it has continued to grow. And finally, we did the biopsy. And of course, this is a pretty typical example of adenocarcinoma. It can look just like a consolidation. And if it doesn't go away after a month or two after treatment, you should pursue it for sure and not ignore it. Here's a different patient who has this sort of patchy opacities, sort of ground glass. And you can see some interlobular lines within it. And that has been termed a crazy paving pattern. Of course, we all know crazy paving was characterized initially for alveolar prognosis. In our everyday practice, though, CHF, pneumocystic pneumonia are some good examples that we would see that pattern with. But adenocarcinoma is one of them as well. So this is a patient who has multifocal adenocarcinoma. Here's a different patient, multifocal areas of consolidation in both lungs. And some people have described this in the right lower lobe as hepatization of the lung parenchyma. Again, an example of adenocarcinoma. So when you see this sort of opacities and they don't resolve, then don't just think of it that this is just pneumonia that's not going away. It could absolutely be lung cancer in some patients. This patient actually had a very classic presentation of bronchorrhea. They tend to be mucin producing and sort of bring up a lot of secretions. Now, the last five, ten years, we've been seeing a lot more patients with interstitial lung disease. And when patients have interstitial lung disease, they have all these reticular changes, opacities in the lung. And nodules can hide within those areas, so we have to be very careful about looking for those findings. So you can see in the upper, this patient in 2018 had reticular opacities consistent with pulmonary fibrosis. In 2021, we noticed a small nodule. It can be very hard to tell whether is that part of their fibrosis or is that a true nodule. And of course, a year later, it's grown. So they have increased incidence of tumor and we have to be more careful about looking and trying to pick them up. And then finally, the last five, ten years, we're seeing a lot more of this. And now, even the lung cancer screening guidelines talk about this, which are lung cancers that look like cysts or cystic-like or cystic changes within them. And you can see this patient on the left image has this small cyst with a little irregular thick wall in the right lower lobe. A couple of years later, it has grown. This was resected, this was squamous cell carcinoma. Oops, sorry. Here's a different patient, cyst with some areas of internal septation, thickening, nodularity. So whenever you see one of these things that is a cyst that is kind of complex-looking, it has septations, thickening of its wall which is asymmetric, nodularity, you should always consider that you may be dealing with tumor here. And this is our example of another lung cancer. Here's a different patient. Again, a very complex, irregular-looking cyst. Mark thickening very asymmetrically, there are septations, another lung cancer. Here's another one. Multiple, did I go backwards? No. Complex-looking cysts, septations, and over the period of year, it has grown and become pretty ugly. So my teaching points, whenever you see an abnormality, all scans are your best friends. Look at the findings on both soft tissues and lung windows. Time is your best friend. Short interval will not hurt you, I don't think so. And lung cancer can look like anything. So, but I did show you some of the more common types of lung cancers. So with that, I'll end. Thank you very much. Thank you. Thank you again for the invitation to speak. And I'm happy to share the podium with these three, because I've learned a lot from all of you over the years, including today. So this is going to be a whirlwind tour through histology. I kind of debated whether to do molecular stuff, but I'm glad that Dr. Mehta did it, because then I don't need to. So most of histologic classification is divided up and classified according to the World Health Organization's Blue Book. And we'll just go through these major categories of adenocarcinoma, squamous cell carcinoma, small cell, and briefly touch on some others. So adenocarcinomas, as you know, are recognizable by their gross appearances. And we often talk about the Ps of adenocarcinoma. So it tends to be peripheral. It tends to have plural puckering. It often, as it entraps the native lung, maintains all the carbon and cigarette smoke that's been breathed in over the years, and it looks pigmented. And so here's a case from Dr. Yale Rosen's Flickr page, which I promoted earlier. And you can see this rounded nodule in the sub-plural region with the plural puckering, making it look like a little buttocks there on the bottom. Another case where we've got this peripheral wedge-shaped, almost like, it looks a little bit like a volcano, like Mauna Kea or Mauna Loa. And you can see, again, the plural puckering and the slight hyperpigmentation there from the entrapped carbon. Another case up in the upper right, we can see this nodule. And again, the scarring making it look white, but yet that black pigment from the prior cigarette smoke. And all that stippled cigarette smoke within the meat of the lung, the parenchyma of the lung, that we see in centriacin or emphysema. So the criteria for adenocarcinoma are relatively simple. We're looking for glandular differentiation by formation of glandular spaces or papillary structures or surface alveolar growth, which is known as lipidic growth. Is it producing mucin, which is another form of gland formation? Or do we have immunohistochemical evidence that it's a tumor that has a type two pneumocyte phenotype, so TTF1 expression and Napsin A expression. Here's a typical cancer that has that mixed morphology. The central kind of lighter pink area is the area that we would see as a solid component on the CAT scan, where it's kind of scarring and pulling in. And the peripheral component that we're seeing on the left side of the slide is the lipidic growth, which would look like a ground glass, a pacification on CT. Yeah, I see it here, but my words are as strong as a pointer today. We can see the papillary growth here with these kind of little finger-like projection, just another architectural pattern we see in adenocarcinoma, which is an intermediate grade morphology. And then this, where we're seeing the background of normal lung tissue. You can see the normal alveolar spaces, the alveolar ducts going down into those alveolar spaces. But they're lined by neoplastic epithelium, this hyperchromatic, crowded, lipidic growth, from the word lepidus, meaning scale-like. You can read my paper, Wentz Lipidic, A History of a Canadian Neologism. I wrote it in a fit of anger when someone didn't go out to dinner with me at the American Thoracic Society meeting, dictated into my iPad. So please look it up, it's a fun read. Here's a more solid growing tumor with signet ring cells, which are these little guys that are named after, if you have a class ring, you've got the ring where your finger goes through, and then where the gemstone would be is the nucleus. Another tumor with relatively abundant mucin. A lot of these mucinous tumors correspond molecularly to these fusion mutations. So you might see an ALK mutation in this, or a ROS1 mutation, or a RET mutation in these cases. So it's kind of fun when the histology and the molecular match up. So that's adenocarcinoma. Squamous cell carcinoma is named due to its resemblance to squamous epithelium, similar to skin, right, and it's closely associated with smoking. Because the airway, normally it's delicate ciliated epithelium, with all the irritation from smoking, undergoes squamous metaplasia, then squamous dysplasia, and then squamous cancer. And we can see that characteristic stepwise progression that I've mentioned below there. The gross appearance of squamous cell carcinomas, squamous starts with an S sound, and so it's gonna be central, okay? And so we often will see it arising from a main stem or lobar bronchus, and may have post-obstructive pneumonia. So when it's large, it can be cavitary. Here from Dr. Rosen's Flickr page again, we can see the bronchus coming in with this kind of, the typical kind of linear striations of the bronchial epithelium into this lobulated tumor coming right off of that bronchus. Another case, with the hilum of the lung here in this large mass with this central necrosis, it'd be all cheesy, let's move on. So the histologic criteria of squamous cell carcinoma, are that you're going to see this evidence of keratinization. So we're gonna see keratin pearl formations, we're gonna see intercellular bridging, where the desmosomes are connecting the two cells. And you can, again, stain these with P63 or P40, which are nice markers that we can use immunistochemically to show squamous differentiation. So here's a tumor, we can see these classical squamous pearls. It's almost like when we're at the Rainbow Village here at the Hilton, and you can pay to get an oyster and pop it open and get a pearl out of it. That's the pearl you want, not this one. If you're trying to make a diagnosis, it's nice to have. You can see the intercellular bridging here, but it's relatively subtle. It's kind of up in this, it's not too bad here. It's up in this corner, we can see the little train tracks. And these are just other ways of seeing keratinization, this is called single cell keratinization. So squamous cell carcinoma derived from squamous dysplastic epithelium, centrally located and associated with smoking, squamous central smoking. Small cell carcinoma has the same sounds that we can use, so it's small cell, it's central, and it's very closely related to smoking. It's named after the shrunken appearance that was often observed in sputum samples, so early pathologists that get these sputum samples, then they'd have these degenerated pycnotic apoptotic cells. And that was kind of the harbinger of badness, because these patients did very poorly, particularly at the time. And still to this day, do tend to do poorly. Derived from bronchial epithelial basal cells, with a partial neuroendocrine differentiation. And I already mentioned those other two points. Perihilar tumors are most common. The primary tumor can often be quite small, so sometimes you'll actually see it at the periphery as a smaller nodule, but then this bulky mediastinal disease. So here is a CAT scan showing that bulky hilar mediastinal lymphadenopathy. And here, again, from Dr. Rosen's Flickr page, we can see where there used to be lymph nodes. We can see the pigment, and just replaced by this bulky white tumor. And the white often corresponds to either high cellularity or to sclerosis with scarring. Under the microscope, we see, why is it advancing? There we go, densely packed ovoid cells. And the WHA criteria is twofold, scant cytoplasm in an indistinct or absent nucleolus, okay? So here we have on one side a large cell neuroendocrine carcinoma, abundant cytoplasm, prominent nucleolus. And then small cell carcinoma, scant cytoplasm with indistinct nucleoli. Both of them gonna be very mitotically active, small cell often more so. Small cell carcinoma often will have this zonal necrosis, and it will occasionally coat the blood vessels nearby by the chromatin from the dying cells, a phenomenon known as the azaparty phenomenon, named after Dr. Azaparty, and again, small cell cancer. So many peroneoplastic syndromes that you can see in these patients, which can sometimes be what the patient presents with, and I just listed them here. So small cell cancer, highly aggressive, undifferentiated tumor, central location, almost exclusively in smokers, to the point that if it's a non-smoker, I'll do additional stains, for example, for NUT, for NUT midline, high-grade carcinomas. And occasionally, NUT's the most important one to think about in these cases, if it's a non-smoker. Other malignancies that we can see, that I just wanna briefly mention, so bronchial salivary gland, analog tumors. So in the tracheobronchial tree, right, the subepithelial glands have that seromucinous appearance, that if you took a little bit of it, would be indistinguishable from the submandibular gland. And it does the same thing. It's secreting various mucins and protective enzymes. Sarcomas are relatively unusual in the lung that can occur, particularly in the pleura, and then lymphomas. So here is a mucopidurboid carcinoma of the bronchus. We can see it hanging out there, wiggling. You'd probably be able to see this on bronchoscopy and snare it. But if we did a lavage, we would not use wall suction. That's the first thing I learned from Dr. Mato in 2008, I believe. So next slide, sorry, is a mucopidurboid carcinoma on higher power, showing the colloid-like mucus. This is an unusual pleural biopsy from a young woman with multiple spontaneous pneumothoraces. You can see the darkly staining cells here. This is a synovial sarcoma, which is an uncommon but described cause of multiple or recurrent spontaneous pneumothoraces in young patients. And then finally, this mass in the lung growing out along the interlobular septum to the subpleural region, this lymphangitic spread from the mass is a lymphoma. So with that, I'll stop. There's so many different things in lung malignancies, and I just wanted to give you guys a quick image-based tour. So thank you for your attention. Thank you so much, Kirk, phenomenal. Okay, so you've gotten everything. You've gotten the clinical approach. You've gotten the radiologic approach, pathology approach. Now we're gonna delve into two really great cases. I wanna introduce Dr. Jane. Come up and present your case. Welcome. Hi everyone, my name is Kavisha. I'm a resident at Danbury IM program in Connecticut. So we had a 72-year-old male with a history of smoking about, thank you. So we had a 72-year-old male with history of smoking. He quit about 30 years ago, but he did have like a 60-pack year history of smoking. On and off steroid courses for presumed COPD exacerbations, like several months prior to his presentation. And when he presented, he presented with fever, chills, malaise, chest discomfort, shortness of breath, and it's been going on, like again, on and off for several months, worse than a few days prior to his presentation. He had been treated with several courses of against steroids, and most recently for presumed bacterial pneumonia, COPD exacerbation, so with antibiotics and steroids. He had no environmental or occupational exposures. And on physical exam, coming in, he was well-built, tachycardic, tachypneic, hypoxic. On auscultation, he had decreased breath sounds bilaterally and diffused crackles, no wheezing, cyanosis, clubbing, regular heart rhythm, no murmurs or JVD, and no lower extremity edema. On labs, he was found to have leukocytosis. Later, he was noted to have lymphocytosis and atypical lymphocytes. Initially, in the diff, he did not. No is in Ophelia. He did have an elevated CRP, fungitilla of 266. His RVP, aspergillus antigen, cryptococcal antigen, anti-GBM antibody, ANCA, Lyme antibody, CMV, HIV. The viral workup was unremarkable. Also, in case of coccidioides and strongyloides, it was unremarkable. It was just like an IgG. Okay. Hi, so we have one CT image of lung windows. And there are several findings, actually, on the image. So even though it's a lung window, it would be nice to have soft tissue windows, but you can still see that there is a fairly large subchorional lymph node. And probably, there is higher adenopathy bilaterally as well. Now, the airways are here, so the pulmonary arteries should be next to them, and they should be about equal. So once you see such large lobulations, and even on a non-contrast CT, you can often tell that there is adenopathy or not. So clearly, bilateral, higher, and subchorional adenopathy. The second thing is, the patient has a very small pleural effusion on the left side. They have multiple nodules in both lungs. And the nodules are somewhat ill-defined. That's the third finding. And the fourth finding is, there are even smaller nodules that are scattered within both lungs. And when you look at them a little bit more carefully, you can see that they're kind of aligned in a very longitudinal manner. Connect, kind of sitting on a line. On some of the images, some of the images, they're kind of sitting next to the peribronchovascular bundle. So when you see nodules that are sitting in a straight line along the vessel, this sort of beaded look, then you know those nodules are in the lymphatic distribution. That's where the lymphs are. So they're sitting on the interlobular septa in the peribronchovascular interstitium. So that interstitium contains lymphatics, and they're infiltrated with something. Granulomas from sarcoid is a classic example. If the finding was in the upper lobes, symmetric, then I would have said maybe sarcoid. But it's unusual for sarcoid to have pleural effusion and look like this. But it's still a possibility. You can have tumor infiltration, malignancy, and we would call that lymphatic spread of cancer. So this patient could have malignancy from somewhere else that is shattering the lymphatics and giving you a medicellar and hyaluronopathy. So that's a possibility. And the third thing is, Dr. Jones just described also, you also have lymphatics there. So you can have lymphoma infiltrating that region as well. And it's possible that lymphoma within the lung can look like this and can have hyaluronodes. So malignancy, that would be the consideration, you know, either metastatic disease or lymphoma. Infection, the fungital was positive. Invasive aspergillosis is unusual to have a nodal disease and unusual that it would have pleural effusion. And you would not see nodules and lymphatic distributions. So despite having that as a positive test, I don't think this is invasive aspergillosis and I wouldn't consider infection here. Vasculitis is also not going to have this look. So I think when putting all of this together, I would favor some sort of tumor here. Thank you, Dr. Shawn. So let's get to our first interactive question. Please use your device to scan the barcode. So what do you want to do next? Do you want to do a surgical lung biopsy? Do you want to do a bronchoscopy with BAL and transbronchial biopsy? Do you want to repeat a CT chest in three months, or do you want to do none of the above? Let's get a few more votes, and then we'll get to our master clinician. Okay, so we got 15 votes. Let's stop. So the vast majority, that's one great thing. In pulmonary critical care conferences, most people opt for bronchoscopy. I was scared to say anything else with him sitting next to me. So let's get to what Dr. Meadow will do. I believe you have your own little presentation, and we will get to it right now. So I agree, I think a bronch was reasonable there. I'm sure Dr. Meadow will have something to add. Kavisha, I'm going to be as nice to you as I am to my fellows, okay? So. So, I mean, you pay attention to every word which is given in this history. Elderly, male, COPD, lower the FEV1, more chances of malignancy, okay? So that's what you want to, but now he has got fevers and chills. Does he have obstructive, post-obstructive pneumonia? That's, I would keep it in mind. The guy is too sick. Tachycardia, tachypnea, I'm sorry, next slide. Is tachycardia, tachypnea, his hypoxic bilateral breath sounds slightly decreased and crackles, but there is no wheezing, meaning that there is no endobronchial lesion, so that fever and chills doesn't go along with that post-obstructive pneumonia. Lymphocytosis has been mentioned, atypical lymphocytes have been mentioned, so I would keep that thing in mind. If this is a board question, this is what you want to keep it in mind. Now, we are also given fungital, which is 266, which I presume is elevated according to your lab. However, all other serologies for fungus are negative. That is what I would keep it in mind. So the first point I would like to make here is, what is fungital? It is a test, okay, it measures 1,3-beta-D-glucan in the serum or the BAL that is present in the fungus wall, all right? But it has got very low sensitivity and specificity, 80% sensitivity and 63% specificity, okay? So there are lots of false positives and false negatives. So if this is crypto or mucor, it's not gonna pick up in most instances. So don't rely on that information all the time. If it really matches, as you saw the chest x-rays or CT scans, where you think it is invasive aspergillosis matches, then only it will have value. So it supports the diagnosis, it does not make the diagnosis. Now, indeed, I must be listening to Dr. Shah for all these years, 17 years. So you won't believe his and my interpretation of this CAT scan is exactly the same, exactly the same. And I'm glad that I wrote it down. That is micro and macronodular infiltrates. You mentioned this is perilymphatic, I said it is lymphatic involvement. I mentioned bilateral hyaluroniferinopathy. I didn't have upper or lower cuts, but there is a sub-canine lymphadenopathy. And I went one step further, large masses and the small masses, and I say it is a galaxy sign. His first differential diagnosis was sarcoidosis. I put it on my first differential diagnosis was sarcoidosis as well. However, when you see the lymphatics involvement, in my mind there are very few differential diagnosis, okay? That your lymphatics are involved, congestive heart failure, this is not congestive heart failure, okay? This is not, we know, occlusive disease. Very likely this is a perilymphatic malignancy, that is what I would keep it in mind. So I put the lymphogenic spread as my next differential diagnosis, and lymphoma as my third differential diagnosis. I don't think it is fungimia, I should count only top three diagnoses. So for what I just put it for my defenses, it could be fungimia. But I think this could be a galaxy sign of sarcoidosis, that is what my differential diagnosis was. And yes, I would do bronchoscopy with BAL and a transbronchial biopsy. Do you want me to continue? She'll, she'll- She'll, okay, all right. So now that he told you what to do, what would you do? Right, okay. So he did undergo the bronchoscopy, and it revealed normal bronchial mucosa. No endobronchial lesions or secretions in the examined portion of the tracheobronchial tree. He did have lymph node sampling from various stations, including 4R, 7, 10R, multiple others, and cytology from all of the samples was negative. So can I just stop you there? Mm-hm. I want to address this to you. Okay. Looking at those nodes, they're juicy, they're huge. Looking at those nodules, I'm shocked that a transbronchial biopsy and an EBUS-TBNA did not give a diagnosis. Well, that's what I want to talk about. That's the reason I put the question marks. So I, I think- Are those question marks over there? He's voicing his dad. We're in his slides now, not yours. Yeah, so- It's not my slides, so- So one of the issue is maybe you needed Dr. Jones. That's, that's what I was talking about. Yeah, well, the thing, we'll talk about it. Before we go to Dr. Jones, I want to make a point. May I? You may, yes. All right. So, I think Dr. Saleh gave you a correct test to be done. And the test was bronchoscopy with a transbronchial biopsy. But Kavisha decided not to do transbronchial biopsy, because it is not fashionable to do transbronchial biopsy. Correct? They just did EBUS, EBNA, because it is so glamorous. And that is what, that is what the point is. Now, you see that lymphoma is in differential diagnosis, and you have rapid onsite psychological examination. And you are not getting the diagnosis. And what is, what is the story about that? And it is very simple. Look at this. Lymphoma is Achilles heel for trans, EBUS TBNA. If you want to make a diagnosis of lymphoma, it may not be the best thing to do EBUS TBNA, unless you are doing. Nowadays, you know, they do all the fancy things. They put a hole in the lymph node, and then they put a cryoprobe in the lymph node, and then they get the tissue. That is not EBUS TBNA, that is biopsy, cryobiopsy of the lymph node. It was Dr. Bandopadhyay, he wrote a very nice editorial in Annals of American Thoracic Society. That EBUS TBN lymphoma is Achilles heel, because you need to show Reed-Stanberg giant cell to make the diagnosis of Hodgkin's disease, and you need to show other proper things to make the diagnosis. So I think that they should, now, another thing which I would like to mention, as a bronchoscopist, and as an old bronchoscopist. When you have lymphangetic spread on the CT scan of the chest, the value of transbronchial biopsy is almost 100%. So you would have done an EBUS TBNA and a transbronchial biopsy? Yes, I would have done EBUS TBNA, and the minute my pathologist says there doesn't seem to be bronchogenic carcinoma, this patient would, I would then at least six to eight transbronchial biopsies. And the problem is this, this is what, again, I'm not, the thing is, we are not taught how to do a transbronchial biopsy, because we have EBUS TBNA, because we have cryobiopsy, but in this situation, I would have taken a large alligator fenestrated forceps to do transbronchial biopsy. Very few bronchoscopists even can tell what forceps to use for this. Let me repeat, large crocodile fenestrated forceps to do transbronchial biopsy, and I would have made the diagnosis of this, okay? But we are so much into EBUS TBNA. So let me just prove my point, this last slide here, just because it could be done, that does not mean it should be done. Simple things perform well, they could be equally good or better than the expensive, time-consuming, complicated alternatives. Be a champion for your patient, not for the procedure, okay? That is what the teaching point would be, okay? Great, thank you. Dr. Jones, do you want to go over these slides, which look very nice? Yeah, so on this, was this the autopsy? Yeah, this is the autopsy, because you can see how much tissue is. I know it was confusing you, because this looks like a typical one of your transbronchial biopsies, so abundant. So we have this solid growth, though, of these small round blue cells. We zoom in, and there's some variation in the nuclear size, which you see in some lymphomas. In particular, T-cell lymphomas often will have this pleomorphism. We don't see Reed-Sternberg cells of Hodgkin lymphoma. It's not kind of the sheet-like growth of a monomorphic of a B-cell lymphoma. T-cell lymphomas will stain with various T-cell markers, but have T-cell antigen loss. So it might be CD2 will be lost, but CD4 might be expressed, or CD3 might be expressed. But here we have CD30, which is, KEY1 was the old name for this, I believe. So it's a CD30 positive lymphoma that's ALK negative. That puts it into a category of anaplastic large cell lymphoma, ALK negative, it's a high-grade T-cell lymphoma. Thank you, Dr. Jones. In the sake of time, let's get moving. Thank you so much for that great case. So, Dr. Mehta, I agree of transbronchial biopsy. Many of my fellows barely know how to go through the nose. Whenever we do a bronch with them, so many of them are done with the LMA and EBIS. Whenever we do a bronch through the nose, I almost always have to do, it's really. That's the simple things, basics of bronchoscopies are extremely important. And unfortunately, as I say, basics are left for the boot camps. The only day you will learn about the basics of bronchoscopy is in a half a day boot camp, and then they would not talk about basics of bronchology. That's what the problem is, nevertheless. Great, all right, I'm sorry we're running a little late. We're gonna get to our next case. Dr. Nally, if you will, please, I'm sorry, this was presented under Dr. Nally. What's your name, doctor? Dr. Zaidy, come on up. So sorry about that. Thank you. This is another good case. Thank you, I'm sorry about that. Hi guys, thanks for having me. It's an honor to be here. My name is Veliz Zaidy. I'm one of the medicine residents at Creighton University in Phoenix, Arizona. I'm in PGY-2. So we have a case of basically a patient who was in an advanced pulmonary disease clinic, a 72 year old male, previously healthy. Known known mass spasms, hypertension, and hyperlipidemia. Who presented with a five week history of fever with chills, productive cough, shortness of breath, and recent onset weight loss, about four pounds or so. He'd been treated with a course of antibiotics and a steroid taper. Prior imaging, outpatient had basically shown a right lower lobe consolidation. On physical exam, the patient was found to be tachypneic tachycardic, was appearing to be short of breath, oxygen saturation was at 86%. An auscultation revealed bilateral basilar crackles. There was no peripheral edema. Laboratory data done in the ED was completely unremarkable for any infectious parameters. There was no leukocytosis. The differential count was also completely normal. Repeat chest x-ray in the ED also showed a right lower lobe consolidation. And any infectious parameters checked in the ED, which include HIV, hypoxia, varicella, strep pneumo, and legionella antigen studies were also subsequently negative. Hi, so we have one axial CT image. Actually, it's kind of a hybrid image of soft tissue and lung. We don't have a great look at either one. But in any case, on this image, you can see the heart is normal. We don't see any pleural effusions. We are seeing this fairly large consolidation in the right lower lobe, right here. And maybe there are some other small areas of patchy opacity in the left as well. So consolidation, alveolar filling process with whatever. So when we see this, we think about infection organizing pneumonia. I showed you examples of adenocarcinoma that can look like this. Lymphoma can look like this. It's focal, so less likely to be sarcoid. But if you've seen multiple, then people may call that alveolar sarcoid. Sarcoid couldn't look like this. So just on this one axial image, all we can do is provide a differential diagnosis. Pneumonia, organizing pneumonia, or some tumor. Thank you, Rakesh. Okay, in the sake of time, we'll get to our question. What would you wanna do next? There's the bar code. Who wants to do a surgical biopsy? Who wants to do a bronchoscopy with BAL and transbronchial biopsy? Who wants to do a repeat CT chest, or none of the above? And then we'll get to Dr. Sputum for AFB negative, yes. TB testing was done. Although with the lower lobe location, unless it was HIV positive, that would be a little less. Okay, do we have another few votes? No, that's it. That's it? Yep. So again, the vast majority wanna do a bronchoscopy. Let's get to our master clinician and see what he would do. I have a feeling I know what he would do, but let's get to him. Okay, Dr. Mehta. Good, okay, thank you. Go. Wally, I'll be as nice to you as I was with Kavisha, okay? So again, pay attention to every word which is given here. Non-smoker, yellow tinge productive cough is given to us. And the next thing on physical examination, there are bi-basilar crackles. This time, I went a little bit further than what Dr. Shah mentioned. We do agree that this is an alveolar process. There is alveolar filling process. And there are five, only five things would do that, right? It is fluid, that is congestive heart failure. It is pus, that is pneumonia. It is protein, that is alveolar proteinosis, right? And then last but not the least, it is cells. That is what we used to call it as broncho-alveolar cell carcinoma, which is now called as mucinous adenocarcinoma or something like that. But when I was looking at only one film which is provided to me, I concentrated on this and I almost felt that this is almost like a crazy paving pattern, okay? What is a crazy paving pattern is thickened interlobular septa on the background of diffused ground glass opacity. The GGOs, the alveolar process represent, this is a concomitant alveolar process. What is crazy paving? In the CT scan, you see this is a real crazy paving on the floor or the ground, okay? Now, another thing I forgot to mention that there is a process going on also on the left side. Do you know why it is called as crazy paving? If you ever go to Barcelona, you go to Gaudi's Park. It is the architect Antonio Gaudi who never believed in straight lines. So everything he designed, he built. And this is Gaudi's Park in Barcelona, Spain. And this is where the term crazy paving comes about. And that is what you are seeing on this chest x-ray. And as Dr. Shah mentioned, that first time it was described in patients with alveolar proteinosis. But now, very many conditions, PJP pneumonia, bronchoalveolar carcinoma, we talked about, alveolar proteinosis, sarcoid, nonspecific interstitial pneumonia, organizing pneumonia, lipoid pneumonia, even ARDS and pulmonary hemorrhage would cause crazy paving. And this is what I'm trying to show you here, which you've already seen. This is PJP pneumonia causing that. This is papillary adenocarcinomas or mucinous adenocarcinoma causing crazy paving pattern, alveolar hemorrhage, and ARDS can do it as well. This is a beautiful case of lipoid pneumonia can also give you crazy paving. And in this patient, Kirk, if you just do the lavage, proper lavage, you can see the fat floating on the fluid and that gives you the diagnosis of lipoid pneumonia. Here you don't even need to do transbronchial biopsy, but one of my interventional pulmonologists not only did a transbronchial biopsy, they did a cryobiopsy. Just because it could be done, they did the cryobiopsy. There's a beautiful history. This lady was using Wix Vapora for last five years every night before she went to sleep. And this was a lipoid pneumonia clinically and just by BAL. But there is no need to do transbronchial biopsy anyway. Even COVID-19 pneumonia can cause crazy paving. In a very nice article published from Dr. Shah's institution showed beautiful x-rays of crazy paving. A COVID-19 pneumonia can also produce reverse halo or atoll sign as well, which I call it emperor has got no clothes. It can present in any different fashion. Nevertheless, I would have done bronchoscopy, transbronchial biopsy. As I mentioned to you, in a situation like this, in good hands, the diagnostic yield is almost 100%. And one other thing which I want to show you and which you touched upon, Kirk, is bronchorrhea. This patient has got significant amount of yellow sputum production. With that particular finding, I think once again, papillary carcinoma or mucinus adenocarcinoma, that would be my first differential diagnosis. Once again, same point I would like to make. Be a champion for the patient, not for the procedure. In my opinion, this patient also underwent EBUS-T-BNA. Now, if a bronchoalveolar cell carcinoma is bilateral, it's already staging. I rest my case. Thank you very much, okay? Dr. Mehta, let me ask you something because I think that we run into this all the time. I think some people do EBUS because you can get anesthesia more readily available with an EBUS. Many times with the transbronchial biopsy, you do conscious sedation. What if you can get general anesthesia alone for the transbronchial? You would prefer just conscious sedation? Yes, I prefer conscious sedation. However, the COVID epidemic has changed the practice of many institutions. That at the Cleveland Clinic, and I feel it, unfortunately, for me and for my fellows, that we are losing the skills of doing bronchoscopy under conscious sedation. Okay, it increases the cost of care. You don't have anesthesiologists to do bigger and better things than they are just sitting there and doing bronchoscopies. But that is the way it is. And there are several other, we need another meeting to talk about this. Devil's advocate would say as an interventionalist or as a pulmonologist, I don't have to worry about anything but the procedure. Yes, exactly. The thing is, I strongly feel that what is best for the patient, that is what we should do. That's all that counts. Doing EBUS TBNA all the time in every patient is being a champion for the procedure, it is not being champion for your patient. That's what my philosophy is. Thank you. Kurt. So it looks like I have a couple slides. And I'm glad I have a couple because the first one is completely normal. So this is normal lung. I don't know if they're from two different sides or not. And then the second one shows a pulmonary adenocarcinoma papillary subtype. And I think that they wrote the right lower lobe, papillary features, TTF1 and napsinate positives, so that type 2 pneumocyte morphology. So different than mucinous adenocarcinomas, which would be negative for those two markers in general. And I don't know if they did it the opposite side or not, but I'll leave it at that. So pulmonary adenocarcinoma papillary type, if we were going to subtype it. Yeah, so we had to see the entire CT scan. And if he has got similar infiltrates on the other side, that is multi-centric papillary adenocarcinoma. And that is seen in patients. These are the patients who have got bronchorrhea, okay? Patients who have got bronchorrhea, they usually have bilateral disease and automatically. Now this tumor could be nodular in nature, and if it is nodular, it is resectable, and yes, doing staging is important on those patients. But when you have this disease where you have similar infiltrates on both the sides, this patient has got unresectable disease because it is bilateral. We are not going to do surgery on these patients. Another thing is molecular testing is extremely important in these patients. Because invariably, they would have EGFR mutation, and they respond very nicely to your tyrosine kinase inhibitors therapy, okay? So I apologize, we've gone a little over, I really apologize. But to listen to Dr. Mehta's pearls sometimes supersedes any time constraints. One last question. Kirk, you mentioned the one never, as far as I'm concerned, is never, ever, ever do bilateral transbronchial biopsies, ever. Yes, short answer to that is yes. I would never do bilateral transbronchial biopsy at the same sitting for 24 hours. I would never do it. There is no need to, okay? Only rare circumstance is that patient is bilateral chest tubes already. Patient has a lung transplant, and whatever. So then you can do that, but I do not, for all practical purposes, just once, and then there is no pneumothorax next day. You may decide if it is, but in all my entire career, never had to do biopsies on both the sides. Well, Dr. Mehta gave us all the information we need to know on papillary adenocarcinoma, so thank you all for your attention. We do have one more session at 1 o'clock, and enjoy your time in Hawaii, and safe travels. Thank you, and thanks to the two presenters, and to the amazing faculty. Thank you.

lung pathology

patient's history

diagnosis

adenocarcinoma

smoking history

tumors

non-smoker

fever

cough

differential diagnosis

bronchoscopy