Welcome to RSNA Session T1-CCH01, HRCT of Interstitial Lung Disease Interactive Read with Experts. I'm Jeff Galvin. I'm a professor at the University of Maryland in Baltimore, Maryland, and I also work at the Joint Pathology Center in Silver Spring, Maryland. And in the next hour and a half, we're going to look at a diffuse lung disease and the interpretation and diagnosis of that disease, period. A number of you have read a number of the consensus classifications over the years, and you can see the typical descriptions, which we will talk about later in this session. But one of the most useful parts of this was a sentence that said that some patients with the idiopathic interstitial pneumonias are difficult to classify. You and I know this in our day-to-day practice, a substantial group of patients that we see don't fit cleanly into these classifications. And what we hoped is with a panel of experts, people with substantial experience from around the world, to begin to explore those differences and maybe help all of us better understand how to move forward with diagnosing these patients. Now, I could spend the entire hour and a half talking about the accomplishments of the people who are going to look at these images, but that probably won't serve any of us. And so I'm just going to introduce them. First is David Lynch, who's the Professor of Radiology and Medicine at National Jewish in Denver, Colorado. Marie-Pierre Ravel, Professor of Radiology and Head of Cardiothoracic Imaging Unit in Koshan Hospital in Paris Descartes University in Paris. Cornelia Schaefer Prokof, also Professor of Radiology, Medical Center of Amersfoort and University of Hospital in Nijmegen in the Netherlands. Santiago Rossi, who is the Chairman of Centro Rossi and Section Head of Hospital Centrogo and Centorio Finocchetto in Buenos Aires, Argentina. And Terry Franks, who's a Senior Pulmonary and Mediastinal Pathologist at the Department of Defense Joint Pathology Center, formerly the Armed Forces Institute of Pathology in Sinclair Spring, Maryland. These are the cases. We're going to try to get through eight of them. I've also provided you with the DICOM images. If you have a QR code reader on your phone, every time we show a case, we will show the QR code associated with them. First, we're going to have Dr. Lynch talk about the categorization of IPF based on the Fleischer criteria, and then I will provide a short approach to diffuse lung disease. With that, let's get started with David Lynch. Thank you very much. Thank you, Jeff. This is the segment of the session that talks about the diagnostic criteria for idiopathic pulmonary fibrosis. When we think about fibrosing interstitial pneumonias, this is the most important category of interstitial disease. The first thing we think about, because it's the most common, is usual interstitial pneumonia. It's important to remember that that may be primary or it may be secondary. If it's primary, it's called idiopathic pulmonary fibrosis. If it's secondary, it can be secondary to those diseases I've listed here. Similarly, for NSIP, it may be idiopathic, but much more commonly, it's secondary to an underlying connective tissue disease, hypersensitivity pneumonitis, or drugs. The third entity we think about every time we look at one of these cases is chronic hypersensitivity pneumonitis, now called fibrotic hypersensitivity pneumonitis. And then there's this rare entity, which we may discuss later, called idiopathic chloropulmonary fibroelastosis. And this is why this is important. This is an old slide, but it shows that the prognosis of UIP, the mortality rate from UIP is substantially worse than NSIP or other interstitial lung diseases. Now the good news is that's changed a little bit with the availability of treatment, but UIP remains the most poor prognostic group of the fibrosi interstitial pneumonia. So that's why it's important for us as radiologists to distinguish among these people, because your diagnosis of UIP will tell the patient a pretty adverse prognosis and also assign them to pretty aggressive and expensive treatment. We really have to be cautious about making this diagnosis. We published these criteria about three years ago now for making this diagnosis of idiopathic pulmonary fibrosis, and these are the criteria that are in that paper. We divide these appearances into four, a UIP or confident UIP or IPF-CT pattern, probable UIP slash IPF, indeterminate, and consistent with an alternative diagnosis. And we go through each of these in turn. The most important and useful category is this definite UIP pattern, which I think is probably still the most common and where we make a difference. It's characterized by this basal and subplural predominant distribution, occasionally diffuse, and often quite patchy, as you can see in these images. Additionally, there is honeycombing, reticular pattern, traction bronchiectasis, and bronchiolectasis, and absence of non-UIP features, which we'll talk about later. And this coronal image really, to me, sums up the features. It's lower lung predominance, peripheral predominant, subplural predominant, and you can see the honeycombing and the traction bronchiectasis more on the right than on the left. The probable UIP pattern is similar to the definite UIP pattern, with the important exception that we do not see honeycombing. And so here we have a reticular pattern without honeycombing. And again, the coronal images help very much in evaluating this because we see the reticular pattern, we see that it's very tightly subplural, and there's a gradient as you go up into the upper lungs, the abnormality gets less, but notice that the upper lungs are involved, and that's an important contrast that I'll talk to about later. So, this is a fibrosing interstitial pneumonia, subplural predominant, ground glass and reticular meets criteria for probable UIP. The next category, I think, is important because we as radiologists are not good at saying when we don't know, and this pattern means we don't know. And as I'll show you in a little bit, if we see this pattern, it's 50-50 call. 50% of this kind of people have UIP, 50% do not. So, and it can be indeterminate for a number of reasons. It can be because of the more variable distribution. In this case, you can see a bit more peribronchovascular extension than we're used to. We see evidence of fibrosis, but we may also see features suggestive of a non-UIP pattern. In this case, we're seeing a bit more ground glass abnormality than we typically see. So, and again, this probably is a better example of that. So, just a bit more ground glass abnormality, a bit more peribronchovascular extension than we are comfortable with for typical UIP. And on the coronal images here, we're also seeing a little bit of mosaic attenuation. So, this kind of case is an indeterminate pattern, and these cases actually still often will go for surgical biopsy. And then the final category is this pattern that is most consistent with a non-IPF diagnosis. So, you do that if you have upper or mid-lung predominance, if you have peribronchovascular predominance with subplural sparing, and if you have predominant consolidation, ground glass, mosaic, or diffuse nodules or cysts. You can see this patient here has upper lung predominant fibrosis. Now, I think what's important about this category is we used to call this inconsistent with UIP, but we've learned that, in fact, some of these patients with this atypical appearance turn out to have UIP. This patient did not. This patient had hypersensitivity pneumonitis. Here's another upper lung predominant fibrotic abnormality, which again turned out to be hypersensitivity pneumonitis. Now, it's important to know that the American Thoracic Society, just a little after our paper, came out with this classification, which fortunately is very similar to what we've just talked about. The same categories, slightly different definitions for indeterminate and alternative diagnosis, but for practical purposes, they're very similar. This, I think, is the most important thing to remember. What we do when we describe a pattern like this is we're ascribing a probability of disease, right? So, if you see the typical UIP pattern, you are describing your probability of histologic UIP is about 90%, not 100%, but about 90%. If you see that probable UIP pattern, we're about 80%, and if it's indeterminate or if it's an alternative diagnosis, both of these are about a 50-50 call. So, these people do need further investigation, probably biopsy, but don't be surprised if they turn out to have UIP or IPF. And that's from two large cohorts from Jonathan Chung. This was from National Jewish in Denver, and this was University of Chicago, showing roughly the same figure. So, I think this is useful information for your clinicians. We're going to briefly discuss the other patterns, nonspecific interstitial pneumonia. In contrast to UIP, it tends to be much more homogeneous and much more confined to the upper lung, to the lower lung. Notice that the upper lungs, in this case, are almost completely spared. And additionally, the subplural lung is often spared. And we see a pattern of ground glass abnormality and reticular abnormality, often with traction bronchiectasis, which of course looks like UIP. Honeycombing is uncommon. So, your diagnosis of NSIP is really based on the homogeneity of the issue and the lower lung predominance with subplural sparing. Here's another example, lower lung predominant, slight subplural sparing, peribronchovascular extension. And here's, again, showing the sparing of the upper lungs. And finally, fibrotic HP is the difficult one, because it may be upper, mid, or lower lung predominant. It often has peribronchovascular extension. You have the features of fibrosis, but the clue to the diagnosis is the ground glass and mosaic attenuation. And on expert tree imaging, which I'll show you, you can see air trapping. Honeycombing may or may not be present, but this is the big mimic that may sometimes look exactly like UIP. And here's an example, inspiration, expiration, showing the lobular mosaic air traffic. I think we need to be aware of limitations of the Fleischner criteria, and we've learned every time you write something down, you realize what's wrong with it. So, there's a lot of, there's a moderate amount of subjectivity. How do we distinguish lower lung predominance versus the diffuse distribution? I think people have difficulty with that. How much peribronchovascular extension is acceptable? How much ground glass attenuation is too much? And whether, you know, some people have different degrees of honeycombing. So, that's, you know, there's still some subjectivity in this diagnosis that we need to work to get rid of. And we've, this is some data from our institution, presented in abstract form, showing that looking at two radiologists who read the same images, this was a total of about 177, we're up to 2000 now, but notice that even among experienced thoracic radiologists, you know, we're pretty good, but there is substantial overlap among the categories. Our kappa value was 0.54, increased to 0.60 when we grouped together the indeterminate and the alternate diagnosis. So, in summary, when we're assessing the fibrosing interstitial pneumonias, these diagnostic categories of UIP that we've just gone through reflect the probability of histologic UIP, and those need to be integrated with the clinical probabilities that the clinician has. The axial and cranial caudal distribution of abnormality remain the most important. Honeycombing clearly adds to diagnostic specificity, and associated features such as mosaic attenuation and air trapping may suggest alternative diagnosis such as hypersensitivity pneumonitis. Thank you very much for your attention. So, before we get to our cases and review by our panel of experts, I'd like to provide you with a general approach to fibrotic lung diseases and the so-called idiopathic interstitial pneumonias. The first thing I'd like to dispose of is this concept of alveolar versus interstitial. I don't find it very helpful. This is a case that you see of desquamative interstitial pneumonia. These are heavy smokers with lots of macrophages in their lungs and ground glass opacity, usually in the mid and lower lung zones. And if we look at the histology associated with these patients, the first thing to recognize is that their alveolar walls are quite abnormal. You can see the alveolar wall on the right here, normal size. In contrast, this alveolar wall is strikingly fibrotic and widened, and the alveolar spaces are filled with smokers' macrophages. So, it is both alveolar and interstitials. And I find that most of these cases of diffuse lung disease have involvement of both the alveolar walls and the alveolar spaces, and as a consequence, it doesn't separate out very much for me. The second thing to recognize is that the lung has a limited number of ways that it can respond to injury. Most commonly, if the lung is injured, it responds with organization and some degree of inflammation. Sometimes you get alveolar collapse, and when all of these are involved, you may get some deposition of collagen directly in the lung. But as a consequence, diagnosis in the lung is difficult. The opacities tend to be all quite similar. So, what's important here is going to be location, and we're going to key on location for all of these diseases with diffuse injury. So, let's not look at smoking, and we'll deal with that right at the end. What I'd like to deal with right now are the common diffuse diseases outside of cigarette smoking-related fibrosis. And the most important of which is going to be organizing pneumonia. I've placed organizing pneumonia and nonspecific interstitial pneumonia together because I think that NSIP is just a follow-on to organizing pneumonia. We'll talk about acute interstitial pneumonia and IPF. So, organizing pneumonia is the most common response in the lung when the lung is injured. And if the lung is severely injured or recurrently injured, you can get incorporation of this material into the alveolar walls and forms a pattern that you and I would recognize as nonspecific interstitial pneumonia. Both of these are nonspecific injuries. They are not diseases. If the lung is injured, and this is a study, a very good study from the NIH in the 80s, and what they showed here and they're trying to illustrate is what is happening at the respiratory bronchiolar level in the alveolus. This is an alveolar wall. The black line that is open is a damaged basement membrane. When the lung is damaged, fibroblasts come out into the alveolar spaces. It fills that alveolar space and is involved in the process of repair. Type II cells will cover it. If the lung is severely injured, as indicated by this dashed line, then the lung will get covered by this organizing material and get incorporated, and this turns into permanent fibrosis. This is a beautiful image of organizing pneumonia, and I show it to you because even though it's in the idiopathic interstitial pneumonias, these green blobs of organizing fibroblastic tissue are in the alveolar spaces, not in the alveolar walls. In diffuse organization, the abnormality tends to be along the bronchovascular bundles, and there is clearing wherever there is the most respiratory motion. In patients who have organizing pneumonia, you tend to clear whatever the toxic injury is from where there's most respiratory motion. In this case, the diaphragms, the anterior chest wall, and whatever the inciting agent tends to cluster around the small airways, and there's most response in that area. The secondary lobule clears itself of toxic materials and gases, both centrally and peripherally, and it tends to leave an abnormality along the interlobular septum, and it forms these arcades, which you see down at the right base here, and the greatest density is again going to be along where the small airways are. This pattern of a concentric band of density near the chest wall with peripheral clearing and arcade formation is proof positive of organization. Over time, this organization will continue to contract, and you'll be left with a line that is still a couple of millimeters distant from the chest wall. If organization goes on, either because of recurrent injury or a severe injury that leaves the lung with a fragmented basement membrane, then you begin to incorporate the material, and you get an NSIP pattern. So again, both of these are just different points of time in a diffuse lung injury. You'll notice here that in the area of ground glass, where there was consolidation before, is now traction bronchiectasis. But also, you can still note that where there was sparing, there is still sparing in the periphery of the lung. This is just the late phase of organizing pneumonia. The histology from this case shows that the organized material is now being incorporated into the walls. As it gets incorporated into the walls, this becomes a permanent area of fibrosis. So what I want to leave you with, with organizing pneumonia, is that this is the beginning of the workup. So someone says organizing pneumonia to you, you don't walk away thinking about, oh, this is just an idiopathic or cryptogenic disease. This is in fact, the lung's most common response to a variety of injuries, most of which are infectious. You and I have seen now, unfortunately, hundreds of COVID patients who have enough severe injury to have organization, and then an NSIP type of fibrosis, which keeps them on the venom inhaler and on ECMO. Acute interstitial pneumonia, or ARDS, is a diffuse lung injury, all five lobes, more severe usually than patients with just regular organizing pneumonia. They start with edema of the alveolar walls, damage to the type one cells, formation of hyaline membranes over the first four to five days. And then over a period of a week or more, you begin to get organization. So organizing pneumonia is involved here. And then as that organization begins to contract, you have diffuse fibrosis in a patient with ARDS. All five lobes are involved. Patients usually intubated when you and I as radiologists see them. If we look at the histology in a patient with ARDS slash acute interstitial pneumonia, these are the alveolar walls. This is the type one cell that has been damaged and is floating freely in the alveolar space. Over time, this free floating type one cell will autolyze and become a hyaline membrane. And this hyaline membrane is proof positive of an acute injury within the lung. This acute injury and damage to the alveolar wall leads to widespread collapse. And obviously the patients are treated with intubation, high pressures, and are maintained on ventilators in an attempt to keep those airway and alveoli open. For us as imagers, the most important thing is that we see an abnormality in all five lobes. Usually 90% of the more of the lung is involved. But what helps me make the diagnosis is that these patients tend to have focal areas of sparing. And the focal areas of sparing are related to intravascular thrombosis. When a pathologist reads the histology and calls this diffuse alveolar damage, what they mean is that all layers of the alveolar wall are involved from the epithelium to the endothelium of the capillary. And within the endothelium of the capillary, the damage to that wall leads to platelets, which are attached in thrombus formation and reduction in blood flow in individual lobules and sometimes within segments. In this severely abnormal lung, there will be organization and attempt to repair. This organization is persistent because of the severity of the injury. Over time, the organized material gets incorporated into the wall. And as it contracts, you start to get fibrosis and retraction in the lung. When we see traction bronchiectasis in a patient with acute interstitial pneumonia slash ARDS, we know that they're in the organizing phase and that their prognosis is poor. You can see day one on the right-hand side, ground glass opacity, normal looking airway, hyaline membranes. 10 days later, now you have a coarse pattern. You can see what's happened to this airway, significant traction bronchiectasis. And if we look at the patient 10 days later on the coronal, we see how much volume they have lost in 10 days. A patient with IPF loses this volume in years. A patient with diffuse alveolar damage loses it within weeks. That leaves us to talk about idiopathic pulmonary fibrosis. So the first thing is nothing is idiopathic. And this is a disease with a multitude of injuries. And it's some combination. We know these are older people and older people tend to get small airway injury and closure. Cigarette smokers, lots of inflammation in the lung, either current or prior smokers. And the inflammation often is persistent in these smokers, even if they stop. 100% of the people with idiopathic pulmonary fibrosis have evidence of gastroesophageal reflex. In some of them, it is the dominant cause. And in some of them, they will have abnormal genetics and have abnormal mucin or may have shortened telomeres and have rapid aging of the lung. In any case, there's some combination of these factors that lead to so-called idiopathic pulmonary fibrosis. You and I generally look for the disease to be most severe in the lung bases, but recognize that all five lobes are involved. If we look at this minimum intensity projection in which the vessels have been removed by the computer, you'll see what looks like normal lung to us on this left-hand image is in fact, markedly abnormal lung as marked by these abnormal airways. In explants, and this has been true for all studies in explants of idiopathic pulmonary fibrosis. If you look at the area of the lung, that's relatively normal here in two, and it also looks normal to us in the upper lung zones here, you will see that histology at that point shows organization again, as we showed in just typical organizing pneumonia, implying that the alveolar walls under here are diffusely injured. The other thing to recognize that in patients with IPF, there's a substantial amount of volume loss. There's a lack of air, and it is collapse of the secondary lobule around a respiratory bronchiole, which is dilated, which in fact, it relates to the cause of this volume loss. The histology shows us this nicely. In this biopsy of a patient with IPF, you can see that this abnormal lobule is still of relatively normal size. The pink material is predominantly collapse of millions of alveoli in the periphery of the lobule, and you can see the lobule next to it is less than 10% of the size of that lobule. This is where this lobule is heading. So it is honeycombing, is nothing more than a collapsed lobule with a respiratory bronchiole in the middle. And that respiratory bronchiole with the collapsed lobule is what causes honeycombing. And this honeycombing are these cysts, which are in the periphery of the lung. Now you and I have often been asked by other people, either in the room or the clinicians and say, well, is this traction bronchiectasis, which would mean it's not honeycombing, or is it true honeycombing, which are cysts in the periphery? And if we look at the images just this way, they do look different. But what I want to point out to you is that honeycombing is nothing more than the dilatation of the most distal airway, the respiratory bronchiole. You can see that in this image, in the standard coronal image, this hole looks like it's a separate cyst. And yet, if you take this image, excuse me, and you do a minimum intensity projection, you can see that the holes really are nothing more than a continuation of abnormal dilated and distorted airways. So honeycombing is nothing more than a respiratory bronchiole with a collapsed lobule around it. You can see that this is an airway with airway mucosa. So then the question is, why is the dependent portion of the lung so prone to collapse and to create honeycombing in a patient with IPF? Well, it has to do with the alveolar gradient, and that has to do with gravity and the size of alveoli. Alveoli at the top of the lung are very large because of the pull of gravity. Alveoli at the bottom tend to collapse easily. In a patient with a diffusely abnormal lung that is likely to collapse and stay collapsed, those dependent alveoli are the ones that are going to collapse first. And that's also true anteriorly and posteriorly. When you're lying on the back, the distending forces that hold the lung open are very low. There's very little negative intrapleural pressure. So if you're an older person laying on their back will get atelectasis, and in this markedly damaged inflamed lung, those areas of atelectasis may not open. If they're laying on their abdomen, the same process occurs, but to a lesser extent because the gravitational gradient is not as steep. So the last thing we're going to talk about here is separating what I would call cigarette smoking related fibrosis without honeycombing to patients with IPF. Notice first that the holes in the patients with cigarette smoking related fibrosis are going to be in the upper lung zone. These are pre-existing areas of emphysema in which collagen has been laid down around them. These are not collapsed alveolus. The patients with idiopathic pulmonary fibrosis, these are collapsed alveolus. The typical emphysema and fibrosis, and these patients are often very short of breath, has diffuse ground glass opacity, emphysematous spaces that are very well circumscribed. And if you were to just look at individual cystic spaces, you would be hard pressed to separate them from honeycombing. But what separates them from honeycombing is their distribution. The fact that they're in the upper lung zone and the biopsy of this patient shows that in fact, these are alveolar walls. These are alveolar walls. These are not honeycomb cysts with an airway in the middle. These are smokers macrophages within the middle. So let's finish this up by looking at how these holes are formed in emphysema and fibrosis on your left versus UIP on the right. So in patients who are cigarette smokers, in fact, both are, but in emphysema and fibrosis, you get destruction of alveoli around a damaged small airway. In patients with UIP in the lung bases, there's collapse of alveoli in the periphery of the lobule, and the central airway begins to enlarge. Over time, there's continued collapse in the patient with UIP. In the patient with emphysema and fibrosis, there's continued destruction of the alveolar spaces. And finally, there's true deposition of fibrosis in the emphysema and fibrosis patient, where in the patient with UIP, it is now an entirely collapsed lobule with an airway which is dilated. I think this screen helps me the most understand the difference. Emphysema and fibrosis, pre-existing emphysema with fibrosis around it. The secondary lobule is relatively normal in size. In the patient with UIP, these holes are collapsed lobules with respiratory bronchioles in the most gravity-dependent portion of the lung. So that leaves us with a general approach to pulmonary fibrosis. And for me, it is location of all of these that helps me the most. So with this, let's go on and take a look at the cases with our expert panel. Thank you very much. Well, this is the final part of the HRCT of interstitial lung disease with multiple experts. They've already been introduced. And we're gonna, each one of the people that I'm gonna show cases to will see two cases and we'll do them in rotation. And the first case that we're gonna show is to David Lynch. And so David, I'm gonna show you this first case. This is a 70-year-old male with a 50-pack year history of smoking. He did stop a number of years ago, but has had progressive dyspnea. And I'm gonna stop for one minute. To the people in the audience, there is a QR code to the left here. And if you have a QR code reader, it would bring up the DICOM files that you can look at as we're going along. So David, I'm gonna step through, but stop me at any point. And here we go. Well, thanks, Jeff. We can stop here because I think most of the facts are on these two images. Okay. This is a 70-year-old man. And as you can see, he has a fibrosing interstitial pneumonia characterized by some reticular abnormality and some honeycombing. And the striking thing is the distribution of the abnormality. It's really tightly subplural predominant, and it is also lower lung predominant. And I think those are the salient features. Next, please. So this gives us the axial images, which gives us a better resolution of the pattern of abnormality. You can see better the reticular abnormality and particularly the subplural honeycombing. Next. I have for you both the mid-lung zone and the lower lung zone, and you're welcome if you want to see one or the other more, let me know. That's fine. Yeah, we can just look at this one. Again, just very clearly subplural predominant and lower lung predominant and multifocal reticular abnormality and a lot of honeycombing. And you can also see, it's important to observe the traction bronchiectasis, which I see in that left lower lung here and there in the region of honeycombing. And this highlights some of Jeff's teachings that the honeycombing and the traction bronchiectasis are probably part of the same phenomenon. Very good. How would you, let's see, we've got two more for this. I don't know that this adds anything particularly much, whether the sagittal, do you use these much? Does this help you beyond there? I've learned from you to use sagittals actually, and I do use them particularly for looking at the axial or at the anterior distribution here. But yeah, in this particular case, I think the answer was on the coronal and the axial images. Okay. And so, yeah, and this is an interesting thing though, on this sagittal image, you can see that there is this striking involvement of the anterior upper lung. And some people may get thrown off by that because we think, I think this is a confident UIP, but yet there's this patch of abnormality in the upper lungs, which is often confusing. And I think it has been previously described in IPF that sometimes the anterior upper lobes are involved. So I have a confident diagnosis here of UIP. It's also supported by his age and his sex, 70-year-old man, history of smoking, really supports my level of confidence as well. Yeah, and I agreed with you when I saw this. And part of the reason I use the sagittal is to look for areas that aren't involved. The more I see anything in the apex, the more it starts to worry me in other directions. So Terry, what did you think about this? Histologically, this is typical UIP. There, I have no other differential for this histologic appearance. The salient features here are number one, collapse of the secondary lobule. There are multiple secondary lobules here. Here's another one, one over here. And you can see this hole here has airway epithelium lining it. So as the secondary lobule collapses, it pulls the airway open, creating what is called honeycomb spaces. And then on this slide, this highlights an area of organization. We also call it organizing pneumonia. I like to see this in the walls of the honeycomb spaces because then I know it's part of the injury pattern in the periphery of the lung. Otherwise, and we would call them fibroblast foci then. Otherwise, this is just organizing pneumonia. Okay. And I thought that this was, David was integrally involved in the paper for the Fleishner Society here. And I thought it looked very much like the case, David, that you had in your paper for a typical case of IPF slash UIP. Did you think? Yeah, I agree, yeah. So, and this was the assessment, Terry showed me this case. Again, we see three to five cases every day. I see the imaging. I try very hard to look at, I don't try very hard, I only look at the imaging without any history and histology and she looks at the histology without anything. So the question is, what would you call this if you didn't know anything else? And I thought this was typical UIP. She did, the histology was typical. And honestly, you would, I mean, it's nice that we got to see this, but I think the reality is here, this person underwent a biopsy that was unnecessary and has substantial risk associated with it, especially people in UIP. So this case I think was pretty clear and I was glad, David, that you were able to describe it since no one would be better at doing it than that. So case number two, Marie-Pierre, this is 71 year old male, also a history of smoking. They did stop 10 years ago and I'll step through and then feel free to stop me at any point or we have a number of the axial sections. You wanna start with this? So in this first axial transverse image, the main feature is the presence of so-called reticulations. So it's certainly an ILD, an infibrative Lyme disease. And then I need to check if there are sign of fibrotic changes and for sure there are some traction bronchiectasis. So I would say this is a fibrotic ILD. And then the next step would be, are there features consistent with or inconsistent with UIP because UIP means most of the time IPF, which has a bad prognosis. So this would be in that order. My reasoning would be in that order. And so in my opinion, there is no evidence of Honeck-Combing, which in itself does not rule out the possibility of UIP, but there are some features inconsistent with UIP. If you can go back to the axial image showing some very bronchovascular extension like in this patient. I thought that maybe this patient was treated by steroid because he has a really lipomatous infiltration in the midostinum, but it's just a detail. So what would be for me, a little inconsistent with UIP is this very bronchovascular extension, but also the presence of some low density lobules on the right-hand side here on the minimum intensity projection, there are more than three low density lobules. So as differential, we should also discuss chronic HP. So my level of confidence is going back to the clinic, which is important. The patient is a male, is 70 years old. So, and he has a smoking history, so it works well for UIP slash IPF. But due to this very bronchovascular extension and due to the presence of these several low density lobules, I was asked if there are some exposures to birth or other. And so I would hesitate between atypical UIP or chronic HP, but I would favor the first one. Okay. Yeah, I had the same problem you did. When I looked at this, I thought this was fibrotic and that it was predominantly peripheral. I never know quite how to handle how much airways disease or evidence of airways disease before I begin to worry about something else. I think like you, I think the concerns for HP that was not otherwise understood is the more that I see of it. But I think UIP, IPF has a fair amount of airways disease within it. And then what was interesting was that Terry showed me this case and I said what you did, which was, I'm not exactly sure. I think it's possible or indeterminate for UIP and other concerns. And she said to me, what, you can't call this UIP? And so she asked me to show it to somebody else. Anyway, so what did you find Terry? So histologically, this is UIP there. I have no other differential for the histologic findings. Again, you see the collapse of several secondary lobules here. You have the large spaces that are due to the lobules collapsing, pulling the airways apart. In this case, these spaces are filled with mucin. And I felt that that might have attenuated the appearance radiographically to the extent that those holes were not as well defined. So this is histologically typical UIP. So we thought this was interesting is that the holes themselves make it filled with mucin, at which point, even if we could see the small holes, Marie-Pierre, I didn't call it. And I think there's clearly times when it's either the holes are so small that we can't make the diagnosis, or in this case, where the holes are not necessarily all that small, but in fact, cause some opacity. And again, I think it looked like one of the nice figures from David's paper where you've got striking peripheral reticulation, it's fibrotic, but it's not gonna be enough to make the diagnosis. Would anybody here have made the diagnosis? Would they be certain? Or would you be, I mean, that's what I said, I was uncertain. Cornelia, David? Yeah, no, I would also not be certain. I'm a little bit surprised that you say here probable, just based on the CT, I would not have said probable because I didn't know- No, we said indeterminate. Yeah, indeterminate. Based on the CT, indeterminate, I would agree because I missed the core gradient. And I would like to have, maybe to ask also David, how much air trapping do you accept? Not taking into account chronic exogenic alveolitis or HP, because that is indeed a tough question. Yeah, this is a, and I showed this in my talk just a little earlier, that's one of the huge areas of uncertainty, this borderline between probable and indeterminate. These are not clear-cut things. There is a spectrum, as Jeff said, of air trapping in patients with UIP. In fact, we published a paper on that, that some patients with UIP and IPF have substantial mosaic attenuation. So I think it's a difficult area, and we try to use, as Marie-Pierre did, that criterion of more than three lobules and more than three lobes, and that's written in some of the guidelines. But the truth is that it's a spectrum. I personally probably would have fallen on the side of probable UIP here, because everything else is so typical. But yeah, this is the issue that we have had. We've just reviewed, actually, a thousand pulmonary fibrosis cases for the Pulmonary Fibrosis Foundation, and we had two readers, and this was part of the issue that we had. People found it very hard to agree on whether this type of case will fall in probable or indeterminate. And that's why I put this in. Santiago, you get 10 seconds. What would you have said? Oh, I would have called it probable. Okay, very good. So that's where we're stuck, and I was stuck there, and that's why Terry was surprised. But it was, and I think we have really gone over what are the issues here, and I think this is very helpful. Thank you very much, Marie-Pierre. So case number three, Cornelia. So a 50-year-old male, short of breath. PFTs are restrictive. That helps us very much. Progressive shortness of breath does help you that the person has a positive ANA. And then how would you describe this? Okay, that is a coronal slide, and we do see the first impression is it's a strikingly lower-lobed, predominantly, disease. We do see some brown glass in a bronchovascular distribution on both sides. Actually, you see that the brown glass is surrounding the dilated bronchi. The brown glass is relatively sharply defined. Now you move to the next one. We have another coronal NPR on the left and minimum intensity projection on the right side. The slide on the right shows you that there is distortion of the bronchi. There is dilatation of the bronchi. They go too far into the periphery and there is no caliber reduction. And if we go to the slide on the left and just to the right lower lobe, we see something which we could describe as a reversed hollow sign. It's a sharply defined brown glass with a little bit consolidations around. There's something also like a lobular sparing. And then there is something like a perilobular pattern. We do see the intensity or the density around the periphery of the secondary lobule. There's also a lobular pattern on the right side. Can you go back to one slide? Because I missed one important aspect. Do you see the interlobular fissure on the right side? There's displacement of the interlobular fissure on the right side, indicating that there's volume loss of the lower lobes. So now we go further. And again, the next one, please. Okay, is that where you have anything else here? So now we have an upper lobe slide and a slide in the lower lobe. So we do see, it's not exclusively in the lower lobes. We also see some brown glass again around the bronchovascular structures in the upper lobes, but to a much lower extent than as compared to the lower lobes. We see the widening of the bronchi. We see the lobular sparing. We see the perilobular pattern. There is a sparing of the peripheral areas. I don't see reticulation. I haven't seen honeycombing in any of the slides thus far. So if we just summarize, we have a restrictive pulmonary function test. We have a volume loss of the lower lobe. We have a bronchovascular distribution, not a peripheral distribution. The dominant density is brown glass, sharply defined. And we have some aspects which would remind us of an organising pneumonia, reverse thalassine, lobular pattern. But let's say there is something to say about a fibrotic component, the lower lobe volume loss, the restrictive pattern. So it is somewhere between organisation and maybe already going to a fibrosic component, fibrosing organising pneumonia. What would I do in an MDO? Because I do think that at least part of it is really maybe even reversible organising pneumonia. I would, of course, I mean, this particular patient got an open lung biopsy, but I think I would recommend to treat that patient to see further on how much of that disease is reversible. I do expect some reversibility. I don't expect a complete reversibility. Very good. Yeah, so let's take a look, Terry. So what did you see in this open lung biopsy? So this is organising pneumonia. And this pale blue-gray tissue here is the fibroblastic material that comprises that. This is kind of a boat-shaped shape here. Oftentimes these are quite round when they fill out the other spaces. The interesting thing I find here, we don't see interlobular septa unless they are abnormal. In this case, this is edematous with focal areas of fibrosis. You can see that the edges of it are quite jagged and ratty as it goes out into fibrosis, organising pneumonia, and some chronic inflammation in the parenchyma itself. And this correlates with what you see over here. And the line is quite different than what we see, that smooth line that we associate with edema or the lumpy, bumpy line that you often see with infiltration by carcinoma. I'm gonna interrupt you just for a moment, is that I've learned a lot from doing this and that these peripheral areas of quote-unquote reticulation are nine out of 10 times turn out to be septal lines of various kinds, which I had never known before. And they can be quite distorted, not surprising, because of all the material which is around them. And they often start out as edematous and then can become fibrotic. And even in UIP, a lot of these really are the interlobular septa. So that was a beautiful thing that Terry was able to show us that correlates with this. And then showing this peripheral sparing that Cornelia so nicely described is that how the lung begins to clear itself. It could be that it's predominantly an airway-associated process, but we often see diffuse densities in organising pneumonia that are periphery and we watch it clear. So let's keep going here, sorry. Well, I'm gonna show you, this is another case from Maryland. I'm gonna just step through. This is another person who started out with, who turned out to have connective tissue disease, but the lung disease started out first, which is another thing to remember that it can be months to years before the connective tissue disease shows itself. And they had this diffuse consolidation. And Terry, what do we see here histologically? So these are plugs of organising pneumonia that are sitting in air spaces. They are round. Sometimes when they go through the pores of cone, they'll be dumbbell shaped, but the material itself, that pale bluish exterior, and then in the centre of them, if you can just show them there, Jeff, it's transitioning to fibrosis. So I just wanted to show you one of the things that, I mean, this is my belief and you can jump on it either way, but this was when the patient was admitted. This was six months later, and look at how it is cleared and look at what is left. And if I were to ask you, what would you call this? I think this ends up getting called NSIP. You've got traction bronchiectasis. And I think most cases of this form of NSIP are really the late phases of organisation. We've been very lucky over the years to have dozens of cases in which we have either a biopsy early or late and the imaging from both. And so Terry, how does this organisation to NSIP pattern, how does this happen? So some people, this is, so organising pneumonia is the lungs most common response to injury from any etiology. And when you dump things into the alveolar spaces, you begin to organise it. There are fibroblasts and myofibroblasts in here, and then the surface begins covered by macrophages and type two pneumocytes. It butts up against the wall of the alveoli. It begins to get incorporated over time. That gets remodelled, it gets flattened out. And then this transitions to fibrosis. So once it's, this part, Cornelia, you were talking about, you're right, is probably worthwhile having the patient treated because that may be possibly affected. But once you get to the fourth frame and you're transitioning to fibrosis, of course the fibrosis is there for good. So the only point that I want to try to make here is that organising pneumonia is not a disease. I think this whole business with cryptogenic and idiopathic diseases has, a lot of people understand it, but a lot of them walk away saying, oh, this is a disease that has no cause. And that's not true. You know, organising pneumonia occurs in every COVID patient I see. And if you didn't have a COVID test, you would call them cryptogenic organising pneumonia and viruses aren't easy to find. So whenever I see, and if you see organising pneumonia or NSIP, in my opinion, it's the beginning of the day. Now you have to figure out what the injury is. These are not diseases in and of themselves. And if you think about all of the things in which pathologists will see organisation from infection, there's organisation in IPF, drug reaction, hypersensitivity, we see patients who have pulmonary hemorrhage from capillaritis and it gets called organising pneumonia until a pathologist picks up that somebody's bleeding. So it's very, very important for that to be the case. And so my final assessment was like yours. We thought this was organising pneumonia, but I often feel like they need to be very careful about just saying, oh, this is organising pneumonia and figuring out, is this infectious? Is this infections you didn't find? Is this pulmonary hemorrhage? Is it capillaritis? We had a case just last week in somebody who was in congestive heart failure and had organising pneumonia, but they were bleeding from their congestive heart failure. So anyway, so that's for us this. I'm going to keep going so we don't lose. Okay. Can I just make one quick point? Oh, of course. So when we see this pattern, the first thing we do is recommend a very wide spectrum of auto antibody screens. Yes. Because a lot of the time this turns out to be, and that goes beyond, you know, the usual rheumatoid factor and that sort of thing. A lot of these cases turn out to be antisynthesis or myositis. So that's the practical point, because if you make that, if you can make that diagnosis, then the patient does not need a biopsy. They will treat. Very good. Yeah, so that's a very good point. And so again, but just to think that organising pneumonia should start you in thinking about what's the cause, not that they've got organising pneumonia. Exactly. Okay, case number four, I'm going to keep us going so that we don't run out of time here. Because I press it, we could talk about all of these for a while. 77 year old male who's dyspneic and has some severe stroke, has a history of recurrent pneumonias. And so Santiago. Yes, hello. I think that from the clinical history, you have an important clue that's the dyspnea. So in a patient that has this dense plural and sub-plural consolidation with traction bronchiectasis in upper lobe predominant, you have also some volume loss, and it seems to have some reticulation in both sides with those bronchiectasis. So mainly what we have is apical traction changes with fibrosis. And if you can move forward, well, same finding, it's upper lobe predominant. And you have also, there is like, like seems to have some suprasternal deep notch and also some reticulation and traction bronchiectasis in the upper lobe. So it's quite a straightforward diagnosis when you have the clinical history plus the image. You have also some other differential diagnosis, but first what you need to think is a pluroparenchymal fibrillastosis. That is a rare idiopathic interstitial fibrosis. And mainly that's my first diagnosis. If you were with a different scenario clinical setting and in a country like us, perhaps you have to think also in TB, but mainly my first diagnosis is a pluroparenchymal fibrillastosis. And if you have another image, I think there was an axial, I don't remember. I think I just gave you these. Okay, mainly what you need to look in these cases is the distribution, the retraction. Also, some of them have the deep suprasternal notch and also they mainly have some of them tracheal retraction. So those are the main findings. And it's, I think it's a straightforward diagnosis with a clinical history. Great, Terry. So what we see here is a thickened pleura and subpleural alveolated lung. It is elastotic. That is what the black is in this elastic stain. This looks just like an apical cap. So for me on a biopsy, even on a surgical lung biopsy, you can get caught out by calling it apical cap. So it's essential to have the CT because the distribution on the CT is critical to the diagnosis. And people talk about elastic stains, apical caps, invasion of the pleura by tumor all have elastosis. So that stain, although attractive, is not really diagnostic. So this is where I think very often Terry will call and say, you know, is there anything really even wrong? Is this significantly abnormal? Or would you just say that there's a little bit of pleural thickening? And I think Santiago has done a wonderful job of describing, you can see how much volume loss here. Excuse me, there's the minor fissure is pulled up here. Both hilum are pulled up here. This is more than just an apical cap and all those other findings along with the fact that people with just a, you know, adult apical cap are not going to be getting dysmyc and losing volume like this. So it really is a combined diagnosis. And in this case, it turns out the imaging is very important and you really need to be able to help up the pathologist and the clinician to make the diagnosis. And again, I know that again, we call it idiopathic, but things happen for a reason. And so the question is what's driving this? I think we don't know. In some of the reports, there are evidence of recurrent infections. We know in people who have lung transplants, there's a whole series of things. Eventually, I think we'll find it out. But for right now, we don't know. So our final assessment was like yours, which is we were pretty sure that this was PPFE, but it always worries me. We had a case recently this last month, and I think it's important to rule out that the person doesn't have some mycobacterial infection that we're missing or something else that is going on here or a strange case of HP. In this case, the histology still leaves us with the diagnosis of pleural pulmonary fibroelastosis. Okay, any other comments there before we move on? Just a question, no history of pneumothorax in this patient? No. What's that? No history of pneumothorax. No, not that I know of. That's actually an important point because we actually are very cautious about biopsying these people because they often do get postoperative pneumothorax on bronchopular fistula. So we've shied away from biopsying those recently and rely a lot on the imaging. Yeah, and maybe a transbronchial to try to, if they have, just to make sure that we had one person we were concerned about that this was potentially some sort of fungal or mycobacterial infection and they did do a bronch. So I think that's a very good point. Okay, back to you, David. 60-year-old female, history of cough, pulmonary hypertension, patient with severe RA. Yeah, so this is an interesting pair of images, obviously PA and lateral chest x-ray graph. And, you know, it's not that common to be able to identify honeycombing on a chest x-ray. Here we have just classic honeycombing at the lung bases and clearly a lower lung predominant process. Upper lobes, I think, are harder to characterize. So we can go ahead and move to the CT. And then this, you know, really tells, I think, the entire story here. This patient has what's called exuberant honeycombing with, you know, very extensive, relatively large honeycomb cysts occupying a substantial portion of the lung. And in fact, there's very little associated reticular abnormality or other findings of fibrosis. The other feature that's really important here is that there is a really sharp demarcation between the abnormal lower lungs and the fibrotic or the non-fibrotic upper lungs. And those signs, you know, were nicely published in a paper by Jonathan Chung emphasizing that these findings are highly predictive of a collagen vascular disease. And when we see UIP, and this is a UIP pattern, but it's UIP related to underlying connective tissue disease in this case, rheumatoid arthritis. And yeah, as the slide says, this is called a straight edge sign. All right, so I thought this was another one right up your alley. I know David was deeply involved in this. So we're going to both, we have some interesting things to say about this because we agree with some of this. So Terry, what did you find? So you can see on the gross specimen, that straight edge that David just mentioned where you have these large cystic spaces against what is more normal lung parenchyma. And that's of course reproduced here where you have a more normal parenchyma here, but then you have just large holes and they are airways. There are remnants of airway epithelium. You can see these little blue lines segments here. But to my eye, this really lacks the secondary lobular collapse that we saw in the first two cases of UIP. And then there are these infiltrates, these lymphoid aggregates, some of which had not in this section, but in another sections had germinal centers. The lymphoid infiltration isn't specific for a connective tissue disease, but when I see it, it certainly increases the height of my antennae for the diagnosis. But qualitatively, as we've seen these cases come to consultation, these airways that are dilated to me look more proximal. We're not right out at the periphery of the secondary lobule. So I want to show you a case because I think that what David described is, it was beautifully described is that I think I understand this better than I ever have because we've had some histology of cases that were earlier. And one of the things is I wanted to show you, this is a case and I'm going to show you where it goes to, is there's this airway with traction bronchiectasis and this thickening of the airway. And if you look at the histology of that, what do we see here? So this is an airway that's going from proximal to distal, and you can see the airway is quite distorted. There's some segmental obliteration of it, but it is surrounded by just this pipeline of fibrous tissue with some areas of organization in it. And what I wanted to show you is something that I think I look for now, which is the case I showed to David was quite advanced. And there were cysts that went from that straight edge sign all the way to the pleura. What I want you to see is that as the disease actually progresses in a different way from typical UIP. Typical UIP, the first cyst starts right up against the pleura. Here, you'll notice that the holes are not right up against the pleura. They're actually in larger airways that are more proximal and the more distal area of lung has almost none of those cystic spaces. And the difference for me between connective tissue disease early on is that the cysts are more proximal, unlike UIP in which they are strikingly up against the pleura. And if you look at the histology difference between, especially if you catch them fairly early, and that's from this same case. So this slide and the previous slides that we've shown you are from the same case. And here you see this is an airway centered area of fibrosis the periphery of the lobule is not involved. It is not collapsed. And that's in contrast to UIP where the periphery of the lobule is all fibrotic. So it's in many ways different, even though there are great similarities associated with it. It's not a typical, and I think the pathophysiology is different. And I took the slides out, but when we see early cases of this, we see peribronchiolar areas of ground glass. That's how this starts. That's not how UIP. UIP starts with reticulation strikingly in the periphery and works its way in. This literally starts in central airways and works its way out. So I think the pathophysiology is quite different. When it gets to this point, to us, it just looks like a bad case. And for those people who count holes, like they have to have so many cysts, it seems an easier diagnosis to make. But in reality, I think that this is pathophysiologically actually a different thing, even though most pathologists will call it UIP. I don't think that it is. But I think it is the disease associated with connective tissue disease. All right, we're going to go on to case number six. So I think this was for you, Marie-Pierre. Yes. So this is again, a smoker with progressive dyspnea. A heavy smoker. Heavy smoker, indeed. And still smoking, I guess. Yes, absolutely. Okay, so what we have here is the consequence of smoking with this central lobular emphysema and this paraceptal emphysema in the upper lobes. And the second main finding is ground glass that I think we see here and also on the next images on the axial. So axial head, the upper, middle, and lower. Where would you like me to? Just the one before. Okay. Yes, this one. Okay. So in this one, we have ground glass as really the predominant finding. On this, so this case is definitely not a UIP for first of all, because ground glass is really the predominant feature. And then in a heavy smoker, my first question would be, is the patient still smoking? Because in heavy smokers, they can have a lot of macrophage in the alveoli. And this is something which is called DIP, dysplomative interstitial pneumonia. When we can hope that it is hopefully reversible if they stop smoking, which is never really easy for a patient with 65 years smoking history. It's a very, very important addiction. And this, but it is a situation that can really improve on smoking cessation plus steroid. But on the next image, and in DIP, we can have some small cysts. I don't, I read that. I don't know what is the exactly the correspondence on histology. But then on this image on the right lower lobe, there is this hernia with maybe, I'm not sure, traction bronchiectasis because there is no tapering of the bronchial lumen towards the periphery. So I would say as my first diagnosis that I would suspect something not fibrotic, many macrophage filling the alveoli, but possibly with also already some fibrotic changes that I would never call UAP, but due to the smoking history. So I would probably suggest to perform a lavage and try to get the patient on a smoking cessation program and maybe try to start some steroids and then hope that the situation is going to improve. Yeah. So when I first saw this, I had the same thing, which I thought this was, these were all features of cigarette smoke inhalation. I did think that there was some traction, that this was a bronchiectatic airway. And it's when I see ground glass, if I look for them like you did, and I think that there probably is some diffuse fibrosis, I didn't think this was UAP. I also thought that there was some volume loss that the fissures were pulled back a little bit. So that was another sign that moved me towards thinking that there may have been some fibroblasts that were down in there. So Terry, what did you find? So these areas with the holes here are actually enlarged air spaces. This is not honeycombing. These are enlarged air spaces. You don't see the airway epithelium. And then they're all surrounded by rather thick fibrotic alveolar walls. And then the ground glass areas that you see here, there is some air space enlargement, but not like in the upper lobe sections. There is some fibrosis of the alveolar walls, but not as bad as the other slide we just looked at. Then the air spaces are filled with smoker's macrophages. So that combination and its variable of alveolar wall fibrosis and macrophages gives you the ground glass attenuation. Yeah, so we see a lot of, because of a lot of what Terry sees is our people in the military and are often heavy smokers. This is a common presentation for these patients. And I showed you this from, I'm sure I will not do his name right, but Vincent Cotin that is describing this combination. And people have different definitions, whether it's UIP and emphysema, but there are a group of patients that I believe have true fibrosis related to the amount that they smoke. And it's true diffuse alveolar wall fibrosis. And one of his points, and I think this is just for the radiologists in the group here is that it's important to recognize that these people are very short of breath, but have near normal pulmonary functions. And that we in radiology see cases like this where the patient is clearly very abnormal and very short of breath. But from the clinician's point of view, if they're not, and especially depending on their experience, they may have trouble understanding why they're that short of breath, given that their FEV1 and total lung capacity and residual volume are normal, and their diffusing capacity is so abnormal. So that was very nicely described. This is all cigarette smoking related diffuse lung disease, some combination of macrophages in the alveolar space, diffuse alveolar wall fibrosis, and then fibrosis around spaces that I think sometimes people have trouble with and might be worried that they're honeycombing, but these are emphysematous spaces with just fibrosis around them. Any other thoughts from the group here before we move on? All right, let's go ahead to the next case. So case number seven, I think this is Cornelia, right? Yes, I am ready. It's excellent. So it's another smoker. And again, a lot of the cases we see as radiologists and pathologists and clinicians have a history of cigarette smoke. I was showing this, and I don't know if this was a cruel thing to show to you, Cornelia, because I had trouble with it, so I thought I'd show it. Jeff, this is a challenging case. I also had trouble. So this is a maximum intensity projection, and we do see this as a predominant upper lung disease. We see some relatively sharply defined round glass opacifications, which seem to be located around the bronchovascular structures. Some of them have some, I mean, at least in this maximum intensity projection, some solid component. There are some solid nodules. There is a solid nodule, exactly. There is a solid nodule. There are some solid nodules, but not the predominant finding. So if we move to the next one, we see on the left the maximum intensity projection. On the right side, just normal reformation. And we see, again, the sharply defined round glass opacifications. There seem to be around the airways centered around the bronchial structures, some of them. If we really try to look at them very closely on my little laptop here, then there seem to be that there is really the bronchus in the middle of it. I don't see on that particular side the solid components, but let's go back, because let's also look at that airways. So I'm going to make your life easier for a minute. So this was a MNIP on the right-hand side, and it was so that the solid component. Yes, no, that was my fault. So I mean, I knew what I had done. You wouldn't have known what I had done. And I did this to show exactly what you showed, which is the ground glass lesions were really all centered on airways. And I do find that MIPS and MNIPs, if you say you only have chances to look at something, that's all I do, and that it got rid of the solid component, but it did show where the ground glass lesions were strikingly airway associated. So which way do you want me to go? No, I just want to focus here, because there is not much bronchial disease. I didn't really see bronchiectasis. I didn't see a bronchial wall thickening, what you would expect in such a heavy smoker. And that particular MNIP, there is a tiny little subplural cyst on the left side, but actually, I don't see a lot of emphysema. I think in the next one, there was a little bit more emphysema. Yes, I made more of a MNIP here, which I think helped. This is a thicker MNIP. Yes, exactly. So we have a little bit subplural emphysema. We have some central lobular emphysema. But we do see that there's not much distortion of the airways. So that's it. We are dealing with a heavy smoker and upper lung disease. I think both is very suggestive for an inhalational disease. But it doesn't really fit what I have learned so far. I mean, I have now the respiratory bronchiolitis. Respiratory bronchiolitis with interstitial lung disease, I would expect central lobular nodules, predominantly in the upper lobe. This is more than a central lobular nodule. This is really almost the size of a secondary lobule. Then we could go further on to go to DIP. DIP is ground glass. But this is not the DIP I know. The DIP is more in the media part, in the ground part, basal part of the lung. It's more in geographic distribution. It's more confluent. It's not really a predominantly upper lobe disease. So I'm not happy with that, I have to say. I was even thinking about some malignant diseases. It's a man. It's not a woman. So that's a little bit unusual. I would think, because therefore, I said there might be some sort of components. Maybe there is something like an atypical adenomyotic hyperplasia, AAH. But why not so strikingly in the upper lobes? And why so many of them? Normally, we have, let's say, four and five, but not so many of them. So it's a challenging case. I think it is that, oh, is it Lange-Hans-Zellner osteoarthritis? No, I don't think so. I don't see any cysts. I don't see any cavitating nodules. I wouldn't put that in my differential diagnosis. So I think it is somewhere in the spectrum of inhalational smoking disease, but I don't really have a good final diagnosis between RBILD and DLP, but I don't really have a good diagnosis. So I'm very curious what Terry says. I was curious very, because she showed this to me and I thought, oh, I'm not sure what this is. And I had the same problems you were. You know, most chronic inhalational lung diseases are upper lobe. The person did have emphysema. I'm not used to seeing respiratory bronchiolitis with such big ground glass lesions. That was worrying. I didn't know if some of these could be, as you say, T1 lesions and malignancy here. I think if the literature were to be redone, this whole DIP, RB thing would go away, that there was such selection of cases that people only showed things that looked good in some ways to fit these categories. And I think that all of those categories would go away. And we'd just be talking about smoking related inflammation. So Terry, what did you see? Well, thank heavens, you guys don't have the answer all the time. No, yes. And so what would... Sorry, sorry. Say that again, Marie-Pierre. No, I agree with Cornelia that it's a problem not to see any holes, any cavitation in these nodules, but I would not rule out lung hand cell histocytosis. Okay, all right. So starting with the lesions that are ground glass that Jeff has outlined here, these are smoker's airspace macrophages. The cytoplasm contains finely granular hemocytarin, very characteristic, we don't do any stains there. We see them on multiple cases a day. The solid nodules that you pointed out, Cornelia, that are quite abundant here, they are not only fairly discreet on imaging, but they're well demarcated on histology. In this case, oh. Yeah, we took it out. Oh, we took it out? Yeah. So we had a CD1A stain in here, which is a stain, an immunohistochemical stain for lung or hand cells. So these are PLCH nodules. Now for us, we typically don't divide up the smoking-related diseases, because there's a spectrum on histology of probably seven or eight findings, emphysema, small airway injury, fibrosis, longer hand cells. So these cases go out as smoking-related diffuse parenchymal lung disease. And then we end up saying what was in that. So I think the problem that you went through is exactly the problem that all of us have, is that these separate categories were great for the literature, but are not reproducible. And that if you have macrophages around an airway, it gets called RB, but how far from an airway should they be before you start to call them DIP? And if you have all of the most experienced pathologists in one room, which I have seen at times, and the arguments between how many cells do you need in an alveolus before you call it DIP, I think one of the reasons that the disease has gone away is that people have stopped, didn't want to argue with each other. And if we were to really redo all this, we would just say smoking-related inflammation, and sometimes it's around the airways. And like you, I had never seen a case in which the ground glass lesions were so big. I didn't know what this was. And so, and we rarely, you and I see cases of PLCH where it's the earliest phase, just in the nodules before they begin to get a hole in the middle of them. And so this was just very difficult. I think you nailed it completely. This was a chronic inhalational lung disease likely related to smoking. And the thing you bring up is, we had a biopsy from a couple of years ago where it said PLCH, but then next to it, there was an adenocarcinoma. So which of these ground glass lesions actually is RB, and which of these is AAH? And I think we don't know, and I think it's a nightmare for the patient. But I think your discussion was very, very good. Thank you very much. So again, so what I thought was, I thought it was smoking-related diffuse lung disease, but I wasn't sure. And I, like you, had never seen such big ground glass lesions. I wondered about if some of these could be malignant. Histologically, this is how we deal with it these days. Cigarette-smoking related diffuse lung disease then will enumerate what the diffuse lung disease is. And I think biopsies would have been hard to avoid in this case. Okay, gonna finish up for us, Santiago? Yeah, why not? Okay, here we go. You've got a chance here. So 26-year-old male. This was one of my favorite cases. I got shown this, it was a number of years ago, by Terry. And she said, take a look at this. This is a young person who was here for a pre-employment physical and had this imaging. The problem with this case, that it looks too straightforward. But I bet you it's not an easy case. Oh, come on, Santiago. But at least the image, it's quite typical. Okay, we have the plain film, we have opacities, bilateral opacities, and there is higher adenopathies, and bilateral higher adenopathies. With those bilateral opacities was in the plain film. When we look at the coronal image, we see those nodules that are more dense, surrounded by very tiny little nodules. And some of the nodule, the main nodule, looks a bit speculated. So although it's prominent in the right upper lobe, there's also some in the left lower lobe. But when we look at this, this is a galaxy sign. So we need to think first, it would go straightforward. The first thinking is sarcoid. But when you start looking at the case, you can also think in other diagnosis. In my country also could be TB. We can also look at PMF, when you have pneumoconiosis, but this is not the, at least the distribution that you usually see in PMF. And also there are some rare cases of neoplasms that could appear with this image. What it took me first to sarcoid was maybe the adenopathies plus the galaxy sign. But that's too straightforward, and I bet you that you're not gonna bring your case too straightforward today. So I had the same discussion you did about a year ago when Terry showed me this case. And then I said, why are you showing me this? And she said, well, what do you think this is? I said, oh, I don't know. It looks like sarcoid to me. And then I heard that the history, they were asymptomatic. I said, I don't really have a differential for this. This looks like sarcoid. And what did you say to me? I said, show Bob. So show it, I have a compatriot, Bob Bugach, who I work with, who are the oldest people in the department. And so we were there in the morning. He said, show it to somebody else, will you? I said, showed it to Bob. And he looked at me, he said, why are you bothering me with this? This is sarcoid. And I thought, well, so like you, Santiago, this was a cruel case to show you. I understand that. I mean, it's like showing you a normal X-ray on an exam and saying, well, what do you think about that? You find yourself struggling to look at it. I didn't know why I was being queried in this way. So you want to tell us what this is, Terry? Just one thing before. Before your execution. No, no, I know I'm going to be executed. I started to read. Oh, that's bad. One of the things that I started to read said that the galaxy sign, you have to look if the borders are being speculated or not. That could take you one side or the other. We usually don't do that, whereas this is a panel that went to look at this. And I think that the right upper big nodule is a bit speculated. Yeah, stop worrying. Okay, here we go. If I may, I don't have any experience of it, but I've been told by my colleague, Michel Brunet in France, that there's a mimicker of sarcoid, which is berylliosis. I've never seen any true case of berylliosis, but he told me that really, it can really be a mimicker. Good point. Yes, for sure. All right, Terry. So what was the story here? Okay, so it was important for me to know from Jeff how confident he was of the radiographic diagnosis because I had a real problem. So this is a transbronchial biopsy. This is alveolated lung here, but then separate from this. This was not connected to this. This is a carcinoma. This is a pancytokeratin stain. This is malignant. There's no question about it, which of course left me with a real problem because obviously I don't want to deliver a diagnosis of cancer on a 20-some year old. So I talked to the pathologist. I said, please go back through all of your cases for the last two weeks, week or two weeks, and see if you had another case that histologically looked like this. They did not. So we sent this out to the DNA lab and compared the DNA signatures between the tissues. The DNA for this was different than the DNA for this. So this was a floater from the lab. So there are various stages in the processing of tissue where tissue can float off and get stuck either when you're cutting the case or when you're floating the case on a water bath. So cross-contamination is important. This is the laboratory that it was sent to. So this young man in fact did not have cancer. Right, so again, I think it's important when you see something, it's important to go back when you're fairly certain about it to make sure that there isn't some other issue with the histology. This was a floater from another case. And Santiago, you did great. Thanks for being a good sport, Santiago. So I'm going to tie this all up. These were our cases. The final assessment here is typical sarcoid even though it was histologically malignant. These were all these cases which you did such a marvelous job. I want to thank you all.

HRCT

Interstitial Lung Disease

Idiopathic Interstitial Pneumonias

Idiopathic Pulmonary Fibrosis

Usual Interstitial Pneumonia

Nonspecific Interstitial Pneumonia

Chronic Hypersensitivity Pneumonitis

Diagnostic Criteria

Imaging Patterns

Prognosis

Treatment Options

Clinical Radiology