Good morning, everybody. Thank you for coming to our session today. This is Clinical Case Puzzlers. Diffuse lung disease is so popular, we needed two sessions. We just had our first session. Just a couple of quick housekeeping points. Please evaluate, if you can, all the sessions. Soon you will get a scan, a bar scan, that you could use, not only for the interactive questions that we perform, but also for the audience response key. In this case, there'll be two questions. So, this is actually the 16th year we've been doing Clinical Case Puzzlers. And basically, what we do is, we have a world-renowned faculty, right? Dr. Kevin K. Brown, who is the Chairman of Medicine at National Jewish, is exceedingly well-known through all the pulmonary circles for his remarkable work in interstitial lung disease. We'll ask him some questions about controversial topics in ILD, and his insight is truly phenomenal to have. I think you'll really learn quite a bit. We have a new member to our faculty, Dr. Lauren Groner, who comes to us from NYP, Weill Cornell. For years, I've been saying I wish I had a radiologist like Dr. McNickey, who's in our audience, who will be joining us later today, or Dr. Shah, who does a lot of the Fellows courses. For years, I've been longing for a radiologist of that ilk, and I'm so happy to report we now have it in Dr. Groner. You'll get to hear some of her beautiful descriptions on the radiology of diffuse lung disease. And again, our MVP, Dr. Kirk Jones. Dr. Jones has been with us from day one, Philadelphia, 2008, I believe. And what you will see with Dr. Jones is, yes, the clinical is important, the radiology is important, but many times, the pathologist is the one who connects the dots and tells you this is what it is. And to have Dr. Jones's insight, which he has been doing for years for us, is such a treat. And unfortunately, we don't have a Dr. Jones at my institution. If I did, I think we'd save a lot of money from sending samples elsewhere. So maybe, Dr. Jones, you could command a big salary and we'd end up saving some money. Welcome, Dr. Jones, thank you. So, I have no financial disclosures, right? As I was saying earlier, I'm happy to be in such a nice location, although my jet lag is improving. Yesterday, I was drunk without even drinking. I just felt horrible. But today, I'm feeling a little better. So, of course, then tomorrow night when I leave, I'll feel awful for another day or two. I never thought I'd say this, but I'd be happy to get back to New York. And I wanna thank ACCP leadership. This has been a real difficult few years. And in particular, Lisa Alvarez, who has been so helpful, not only to myself, but to the entire faculty. We email her presentations literally at the last minute. And she just seamlessly is able to upload them. And we've never once had an issue. So I wanna publicly thank her, even though she's not in the audience. She's done really Herculean work in getting our sessions running. My other few disclosures, I am a big Yankee fan, although we are hurting badly over the last 14 years, I think. I do root for the University of Wisconsin, primarily because my older daughter went there. And if you like basketball and you don't like Michael Jordan, you should have a brain exam. So what we're gonna do with our discussion, we're gonna have a 10-minute discussion. It'll just be sort of a one-on-one discussion with Dr. Brown. You'll see his insight is truly remarkable. And we're gonna ask about topics that are controversial in the field of diffuse lung disease. Then Dr. Groner is gonna give you her radiologic approach to diffuse lung disease. Dr. Jones will go over pathologic approach. And then we have two really interesting cases that you'll get a chance to have us dissect. So let's get started, Dr. Brown. From when I started my fellowship till today, probably the hardest diagnosis for us to make as pulmonary critical care physicians is hypersensitivity pneumonitis. I can tell you I've been humbled. Once I had a gentleman who ended up on the transplant list and we thought he had IPF. He was a little young, he was 58, but he wasn't 35 and his serologies were negative. And we really thought he had IPF. And he never had a surgical biopsy because he didn't need one because he had typical honeycombing. And as he was being evaluated for transplant, he had a flare, he got admitted. And so a medical student, a medical student, not a resident, not a fellow, was presenting the case and said, oh, well, what do you think of his job as a janitor, he works as a janitor in a church. And I said, well, I'm not sure there's that much risk. And then she said, oh, no, not with that. She said, did he tell you that in the basement he takes care of 100 pigeons? And I said, no, he didn't. But then, quite ashamedly, I said to myself, no, I didn't ask. So I find no disease in pulmonary critical care more difficult to get a good history. Not every patient tells you there's mold, there's black mold encrusting from the ceiling in my house. The vast majority of times, it's much more subtle. And so, Dr. Brown, I'd like to get your insight as to what you look for. And what's interesting, and Dr. Jones so rightfully mentioned it earlier, the imaging and the pathology could look like anything. Early, it's central lobular nodularity. It can proceed to NSIP, and it can proceed to UIP. So, Dr. Brown, how do you stop them in their tracks? How do you stop that sort of inexorable march to UIP? What do you do? So just that small question. Yes, that small question. So number one, for those of you who don't know Dr. Sala, he's prone to hyperbole, but I can honestly say having known him for all these years, you will not find a more consummate physician or a more thoughtful human being. So thank you for inviting us, Anthony. So hypersensitivity is a big problem, right? And so there are two things. Number one is the patients don't know what they don't know, and you don't know what the patients don't know and don't tell you. So we're thinking about exposures, and there's one or two ways to approach that. One is to give them a 13-page questionnaire that includes all potential exposures anywhere in the world, which turns out not to be particularly useful, and nobody does it, though I've tried. The second thing, the second way is to try to approach it both with common exposures that you might anticipate and exposures that you've been burned by in the past as you have. Singed is more like it. Singed is more like it. One day I'll tell you the story of my patient with fibrotic hypersensitivity pneumonitis, so I said, you gotta get rid of your bird. He said, that's fine, my daughter lives in Alabama, so I'll take the bird to Alabama and drop it with my daughter. So of course, he put the bird in the car, he got in the car, drove to Alabama, made it to Missouri, had an acute flare, and died. So, I mean, those are the things, right, that keep you up at night and you remember. So what do I do? Number one, so I ask about birds in the very beginning. Birds are extremely immunogenic. Lots of us have antibodies to bird antigens if we've been ever exposed to it. If you've had a bird, you almost assuredly have antibodies to bird antigen, but only some of us get the lung injury associated with that. I also ask the question about birds specifically and pets in general because I've been burned by people who tell me that I don't have pets, I have family members who are non-human. So, and I'm not kidding. I'm not kidding about that, right? You call them on the phone and you can hear the birds in the background, but they failed to mention that too. So I've learned to ask about those specifically. Secondly, I think about water, all right? So what does water get you? It gets you pools, hot tubs, saunas, et cetera, but it also gets you water damage in the house and mold contamination. And mold contamination where we've been burned in the past is with people who've been in flood prone areas whose homes have been flooded either internally or externally where they don't have visible mold, but the mold has existed within the walls. So we've looked for mold. I personally don't find environmental hygiene evaluations particularly useful, putting plates out in houses. We haven't found it particularly useful, but every now and then you will see a case where enormous mold contamination will have occurred in a house and people won't know about it. And the third thing I would say is when you ask about occupation, not to ask in general terms about where you work, but specifically what do you do in your job? And I remember the patient that reminds me to do this was somebody who worked in a drug manufacturing plant and I understood her to be sort of an executive type in an office, but in fact she was an inspector and she would go and look at and inspect the essentially powdered penicillin that the factory produced. And it was quite clear after further investigation that she was sensitive to the powdered penicillin and probably a carrier in that. But the specific job that one does turns out to be particularly important. Two more brief questions. One, what about the hypersensitivity pneumonitis panel that many labs offer? Is it useful? I think in the older times maybe it was more useful. I'm not so sure. What's your feelings on that HP panel? Yeah, I'm old enough now that I can just be blunt. So I find it not, I do not find random hypersensitivity panels to be useful because they're generic antigens and the specific antigen that a patient might be responsive to is likely not in that panel. So when you take a very low pretest probability based on a generic panel and a random patient with hypersensitivity and then you include the intrinsic variability of the test, any positive seen in a random HP panel is likely to be a false positive. So I find it much better to spend a little bit extra time asking about what they could be potentially exposed to. And our place doesn't and I know that there are other places do if there's something you're specifically concerned about you can actually get them to bring in for example down from a coat or from a pillow and actually look for antibodies to that specific exposure. And finally before we get to Dr. Grone, a tissue. Are you more apt to send these people because many times we don't know what they have and their imaging can be so vast. It can be central lobular nodularity, it can be NSIP, it can be UIP. Are you more likely to send them for a biopsy? So the more confident I am in the exposure and the more characteristic the chest imaging pattern, the less likely I am to require tissue. I often will do a bronchoscopy with at least a BAL and probably a transbronch in many of those circumstances just to confirm the lymphocytic predominant BAL and then the biopsy is less concerning for me. But in a patient in whom I'm not confident in the exposure and the chest imaging pattern is not characteristic for HP, the more likely I am to end up with a surgical lung biopsy in order to find a positive diagnosis. And how helpful is that BAL lymphocytosis? It's all about the pretest probability, right? So somebody's got birds and a CT scan that sort of looks like HP, but you're not completely confident of lymphocytic BAL, particularly with an antibody to a parakeet antigen and somebody who's got parakeets. I'm good with that as a diagnosis. Thank you so much. Okay. Having swept that under the rug, so to speak, and that is a difficult diagnosis we all struggle with, we're gonna go to Dr. Groner, who's gonna give us a radiologic overview of diffuse lung disease. So happy to have you, Dr. Groner. Thank you. Hi, everyone. I'm Lauren Groner. I'm an assistant professor of clinical radiology. I am thrilled to be here. I thank Dr. Saleh for inviting me. I'm honored. And I have no financial disclosures other than what I pay Dr. Saleh to say very nice things about me. So people think that I'm as good as he says I am, and it's in the mail. And when I do all of the Friday conferences with the pulmonology fellows and attendings, I usually just say what Dr. Saleh said. That is what, that's my differential. So we'll briefly review kind of a definition of diffuse lung disease, indications for imaging, appearance of the predominant abnormality, distribution and pattern, temporality, and how clinical history can help us. I am going to try to bless you. So diffuse lung disease is an umbrella term for a heterogeneous group of diseases with diverse etiologies. Typically we're talking about either interstitial lung disease or a parenchymal lung disease or a combination thereof. And these diseases can be acute or chronic, and of course you can have, bless you, acute diseases that can recur, and then of course you end up with chronic findings. I think imaging is really helpful in either detecting diffuse lung disease in somebody who is symptomatic or in somebody who is not symptomatic but has a disease that is associated potentially with like interstitial lung disease such as rheumatoid arthritis and UIP or systemic sclerosis and NSIP. Someone who has exposure to birds or other antigens. Full disclosure, I had two parakeets growing up, so I hope I'm okay, but I probably have the bird antigens now. It was weird, yeah. And then also formulating a differential diagnosis and then following these patients longitudinally to see if they have progression of disease, if they're responding to treatment or if they've had an exacerbation. So when I open a CT, I ask myself, is it normal or is it abnormal? And if it's normal, well then I say that, and if it's abnormal, I try to craft in my report a story so people can picture in their heads what I'm looking at on the screen. And so if I see something is increased in density abnormally or if there are too many lines or holes or if the lung is abnormally lucent, I say those things and then in my impression try to put that all together and say what I think it is. So consolidation is really filling of the alveolar spaces. You shouldn't see the normal architecture of this lung in which it's superimposed on. So this is a contrast enhanced scan. You can't see the vessels running through this area of consolidation. This is, oh, cryptogenic organizing pneumonia and then, oh, I forgot about this, yeah. Thank you. Adalectosis is incomplete expansion of the lung or alveolar collapse. Ground glass opacity can be partial alveolar filling or cellular infiltration of the interstitium as well as thickening of the interstitium or fibrosis. And then, of course, nodules and masses. Nodules being round densities that are less than three centimeter and masses being greater than or equal to three centimeters. I was told by a very famous chest radiologist that you always have to decide if something is a nodule or a consolidation. You shouldn't call something a nodule or a consolidation. I break that rule very rarely and whenever I do, it's because I can't decide and it always ends up being either lymphoma or fungal pneumonia. And so if I see something and I want to call it nodular consolidation, that's what it ends up being. This is a patient with peripheral T-cell lymphoma. You can see that there are nodules, some of them like some sort of consolidations. There is actually a reverse halo sign, which is kind of rare. But you can definitely see that in lymphoma. And then a patient with acute pneumonitis who has a combination of DAH and DAD. And whenever I see opacities that are fluffy or ground glass and consolidation that's fluffy, again, not a technical term, but something that is almost always, really always for me ends up being hemorrhage. So consolidation and ground glass often occur together. Pulmonary edema, of course, is a very common cause. Acute lung injury in the appropriate clinical setting, alveolar hemorrhage, pneumonia, very common cause of ground glass and consolidation. Inflammatory diseases like organizing pneumonia, eosinophilic pneumonia. So in neoplasm, so if you have a patient who had some sort of consolidation and then 10 years later they come back and the consolidation is bigger and they are alive, it is lymphoma. And it's in the exact same place, it's lymphoma. It's every single time for me. So and then, of course, drug-induced lung disease. So this is a patient who is on, with rheumatoid arthritis on rituximab and presents with acute shortness of breath. They have this kind of bat wing ground glass opacity, basilar predominant consolidation, very classic DAD pattern. And then, of course, sarcoidosis, alveolar sarcoidosis is a misnomer, it's actually not consolidation. It's alveolar collapse and then organizing pneumonia where you have reversed halo configurations. Nodules and masses. So this is a patient with respiratory bronchiolitis, so very faint central ovular ground glass nodules. I kind of divide nodules and masses by where they're living and we'll get into the pattern and distribution later. But things like cancer, whether it's primary lung neoplasms or metastases, smoking-related lung diseases, inflammatory disorders and infection. I mentioned this in the prior study. If somebody comes in and they have a nodule or multiple nodules and there are signs of infection, I almost never mention cancer off the bat just because A, you don't want to alarm people and also something like a fungal pneumonia will kill a patient long before their cancer does. So it's important if you see nodules and you think that it could be fungal pneumonia or severe viral pneumonia in this patient with bronchopneumonia and influenza or tuberculosis, it's important to mention that. 90 plus percent of the time, if you have tree and bud nodules on a CT, it's going to be infection. So that is sort of what I lead with. And then when you think about too many lines, I like to ask myself, do I think that this is reversible or irreversible? There are exceptions to, there's a gray zone there, but things like pulmonary edema can cause reversible interlobular septal thickening. Lymphangitic carcinomatosis can cause interlobular septal thickening that may or may not be reversible with treatment. And then sometimes it's asymmetric, whereas pulmonary edema will be symmetric. And then of course, if you have like interlobular lines superimposed on ground glass with interlobular septal thickening, we call that a crazy paving pattern in this patient with pulmonary alveolar proteinosis, which is sort of like the classic case, but we rarely see it. Things like hemorrhage as it evolves can absolutely cause a crazy paving pattern. Lipoid pneumonia can cause a crazy paving pattern. There are other things that are differential. And then of course, reticulation in the setting of connective tissue disease. This is a patient who has RA and a UIP pattern of fibrosis. And so in connective tissue disease, when the upper lobes are involved, the anterior upper lobes are most prominently involved. And so that's one of the signs of a connective tissue disease related UIP pattern. So when I see holes in the lung, I ask myself, do they have walls or do they not, right? Emphysema doesn't typically have walls unless there's superimposed fibrosis. Cystic lung disease. So cysts do have walls. They're typically thin walled and they can rupture into the pleural space and cause a pneumothorax like this patient with LAM. And then of course, the cysts or holes that we see in fibrosis, which is honeycombing, and those are kind of blown out airways. We found out several years ago that these are all connected with airways. And then of course, in severe bullous emphysema, so you have destruction of the lung and upper lobe predominant severe bullous emphysema in this patient who has smoked for many, many years. And then of course, abnormal lucency. So there are two things that determine the density of a lung. One is blood flow and the other is air. So if you have retained air, that causes increased lucency, or if you have decreased perfusion, that causes a hyperlucency. So this is a patient with bronchiolitis obliterans who has severe air trapping and then a patient with mosaic perfusion from pulmonary hypertension. And actually, yep, okay. And then so distribution and pattern. So then I'm asking, so once I figured out, okay, what am I looking at? Then I asked myself, where is it? So either you can divide this into cranial caudal distribution, which is like upper, middle and lower thirds. I mean, you can kind of just divide the thorax into thirds or you can use from the anterior tip of the second rib and above is the upper and between the second and the fourth is the middle and below the fourth is the lower, but I think probably we're busy, so we just kind of divide it into thirds and use our best judgment. And then of course, things that are central or involve the axial interstitium or peribronchovascular interstitium or peribronchovascular structures, and then the subplural or peripheral lungs. So things that are upper lobe predominant, we're typically thinking about are inhalational lung diseases, so smoking-related lung diseases, hypersensitivity pneumonitis, sarcoidosis, you know, it involves the lymphatics, and our lymphatics tend not to be as effective in the upper lobes, so we typically clear things faster in the lower lobes. And then, of course, post-ARDS fibrosis is classically anterior upper lobe predominant in our pneumoconiosis, lower lung predominant, so, of course, pulmonary fibrosis with the exception of hypersensitivity pneumonitis, and metastases because cancer loves blood flow, and your blood flow, because of gravity, predominates in your lower lungs, and then lymphoproliferative disorders, LIP, aspiration, just because, again, gravity and the orientation of your bronchi, and DIP is really the only smoking-related lung disease that is typically lower or mid to lower lung predominant. And then, of course, I didn't put this on here, but PPFE, also, you would have upper lobe pleural parenchymal fibrosis and thickening, and then lower lobe predominant, sometimes either an NISAP pattern or UIP pattern, and then variable. So I actually find that OP tends to be lower lung predominant, and CAP tends to be upper lung predominant, but, you know, it can be a bit variable. Malaria infections can run amok anywhere, and then, of course, pulmonary edema is usually upper lung predominant, but if somebody is laying on their side or on their back or that sort of thing, it can go with gravity. I see the radiologist in the audience, so I'm just trying not to tell any lies here. And so then, in terms of the axial distribution, so things that are central are things that are, you know, usually cardiogenic processes, things that involve the mediastinum, bronchovascular structures, things that we, like, can aspirate, right, things that are airway-centered or inhalational. So your pneumonias that are central are usually, again, those that involve airways, those that are, you know, more of a bronchopneumonia pattern. Actually Kaposi's, oh, sorry, this thing's very sensitive. So we have alveolar hemorrhage, typically spares the outer thirds of the lung and is kind of fluffy, and then you have this patient with Kaposi's sarcoma, where you have the classic kind of, like, flame-shaped peribronchovascular consolidations. We don't see this often, but I've seen a few cases over the last couple of years. And then a patient with strikingly peripheral consolidation and chronic eosinophilic pneumonia, so other things that are peripheral, ILD, and organizing pneumonia. And okay, so we had our abnormality, our distribution, and now we'll ask ourselves, like, you know, where more specifically in terms of the structures of the lung is this living? Are they, you know, is this a central lobular pattern? Like, do we see that this involves the center of the secondary pulmonary lobules? Or you know, I guess, let me take a step back and say, when I'm trying to decide any pattern, because it can be very hard, first I ask myself, are the fissures involved? And then I know if the fissures are involved, then this isn't central lobular. So then I've narrowed it down at least to random and perilymphatic for whatever that's worth. And I think this is where some of the other points that we made, you know, the density and ancillary findings and cranial-caudal predominance, those things really help. Of course, clinical history. And so then, you know, if things are sort of in a nice uniform way following the bronchovascular structures or along the interlobular septa, the subplural interstitium, and even actually in the center of the secondary pulmonary lobule, all of the radiology books that I've read, one of them mentioned that lymphatics also run in the center of the secondary pulmonary lobule. And it's a devastating blow when you're trying to figure out why sarcoidosis can have central lobular nodules as well. It took me years, but I figured it out. And then, of course, random patterns. So things that are central lobular, again, these are airway-centered processes. Perilymphatic are things that, of course, involve the lymphatic systems and your occupational lung diseases. And then random patterns are things that spread hematogenously, so metastases and then miliary infections. Okay. And so how are we doing on time here? Okay. All right. So temporality. So then I try to figure out, is this acute or chronic? Radiologists' best friends are prior imaging, hopefully not their only friend. I have one sister. She's my friend. And then my prior imaging is, of course. And then all of our panelists are my new friends. So then, okay, so I'm looking and I'm trying to decide if I don't have, let's say for some reason I don't have prior imaging, you know, I think there are signs that can certainly point you in one direction or another. Obviously, if I see something like architectural distortion, I know that this is not something that's hyperacute. I also think about my common things, right? So now based on the density, the distribution, the pattern, if I'm seeing a patient with like a bat-winged ground glass opacity or consolidation, I'm thinking, you know, in a big heart, pulmonary edema, effusions, things like alveolar hemorrhage, you don't always but you can have a drop in H&H, pneumonia, very, very common, right? Aspiration, is this lower lung predominant? Is it involving the airways? Does the patient have a hiatal hernia or dilated esophagus? And then acute eosinophilic pneumonia certainly can present with fairly diffused ground glass, septal thickening, some consolidation. Acute nodules, again, this is really important. When I see nodules in the acute setting, tree and bud opacities, I'm thinking always infection first, and then, you know, one or two nodules in a young patient, maybe they traveled. I'm thinking fungal pneumonia, peripheral predominant, you know, sometimes cavitary lesion, septic emboli. We saw a case, actually, I think last week, right, a patient had used intravenous drugs and, you know, came in very, very sick with septic emboli. And then inflammatory nodules, so rheumatoid nodules are common, but I've seen a few cases, and vasculitides, hypersensitivity, pneumonitis, certainly, lines, so we're thinking interstitial edema in the acute setting, holes, again, things that cavitate, so septic emboli. I actually might include PLCH in this, only because you can have a nodule that then cavitates, but technically it's chronic, but it's new cavitation. And then abnormal lucency, so, of course, PE, decreasing perfusion, and then air trapping. So, basically, I've seen, like a more, we don't use the word subacute hypersensitivity pneumonitis, but I have seen a more, I've seen a nonfibrotic pattern of HP present with air trapping as well. And then chronically, so consolidation, we're thinking then, you know, if it's waxing and waning, I'm thinking more organizing pneumonia, and, you know, chronically airway centered, we see a lipoid pneumonia, which can be tricky, and as we saw in our last case, it can be hypermetabolic, PAP, sarcoidosis, other things, we talked about lymphoproliferative disorders, primary lung cancers, fungal infections, TB, NTM can all present with chronic nodules, and, you know, rheumatoid nodules, which can, you know, develop, regress, stay the same, get bigger, usually they're peripheral, and then vasculitities, so things that are acute, but then often recur, can cause chronic lung disease as well, so recurrent aspiration, recurrent pulmonary edema, which causes hemocytic or inlaid macrophages, and can cause fibrosis, which is something my mentor pathologist in medical school taught me, and I never forgot she said, if you guys can't learn to think critically, then I cannot help you, and I always remembered her, and then, of course, too many lines, lymphadenic carcinomatosis, sarcoidosis, why did I not put UIP on here, or NSAP, of course, fibrotic lung disease, holes, you know, emphysema, honeycombing, cystic lung disease, and then abnormal lucency air trapping from HP, COPD, bronchiolitis obliterans, and decreased perfusion in the setting of like a mosaic perfusion pattern with pulmonary hypertension. So then, of course, last but not least, we love a good clinical history, I get so excited when I get a good clinical history, so how did the patient present, you know, do they have a white count, do they have a medical history that is, that would be helpful, you know, what is their social history, do they, you know, do they let loose by injecting intravenous drugs on the weekend, you know, you never know, or like, you know, are they on a medication that might cause some drug-induced lung disease, have they traveled recently, so, you know, we don't judge, we just get very good clinical history, and that helps us as, I mean, I don't, you guys do, of course, but I trust all of you, so in some, you know, first sight aside, is this normal or abnormal, if it's abnormal, I look at the density, and, you know, so what am I looking at, are there lines, are there holes, is there consolidation, is there ground glass, is the lung too lucent, what is the distribution, the craniocollar and axial distributions, what pattern, if there are nodules or the abnormality, what pattern is it following, and then temporality and clinical history, and that is it. Thank you. Dr. Gronin, thank you so much, we're so happy, not only you came here, but I'm happy you're with us in our institution. So, you got to hear from Drs. Brown and Gronin, now we're going to have Dr. Jones go over a pathologist approach, which really is exceedingly helpful for us clinicians. Kirk, welcome. Thank you all again, and thanks for coming. It's funny with the tables out, because I keep waiting for, like, someone to ding a glass and say kiss the bride or something, but it looks more like a wedding reception than a meeting. So, in the first session, I talked about patterns of fibrosis, and so in this one, what I want to do is just look at three interesting cases and kind of talk about how I, as a pathologist, approach cases. I'm not trying to make you into pathologists, these are just interesting cases that you'll see, that you can see what I see during the microscope, when I'm looking through the microscope. So, the first guy is a 48-year-old man who worked in a stone fabrication business for nine years, making kitchen countertops, you know, bathroom countertops, etc., and he has stopped working in the past two years because he's been so sick. This is his lung at autopsy, and you can see that instead of everything in the lung should be this kind of brownish alveolar tissue, not brown, Dr. Brown, but brown alveolar tissue, the color, but instead you can see it's all white and fibrotic and scarred. It's predominantly in the apices, but this large central component as well. When we look at this under the microscope, we start seeing multiple nodules, and we can see that there's disease in the subplural region, there's disease along the interlobular septum here, and there's disease basically obliterating the bronchovascular bundles in several areas. So, even though it's starting to coalesce, this is a lymphangitic pattern, and so we're like, well, lymphangitic pattern, is it cancer? No. Does it look like sarcoid? Kind of. Are these granulomas? And in fact, the last case that I had of this, the pathologist sent it to me with the diagnosis of granulomatous lung disease. These are not granulomas. These, while they are histiocytes, they're not the classical epithelioid histiocytes with giant cells we would see in granulomas, and this isn't central necrosis like we would see, say, in tuberculosis or coccidioides. That's laminated fibrosis, and that appearance, that post-cellular layered fibrosis, is what we see when patients are exposed to silica. So, this is silicosis. Now, on top of his nodular disease, he also has filling of alveolar spaces by this granular proteinaceous material with these hyper-eosinophilic globules. This is silica proteinosis. So, now, what is going on here? Because this is a disease that we've known about since the 1500s. This is Bernardino Ramazzini's Treatise of Diseases of the Workmen, and if we read this, there's Ramazzini himself coming in to read it for us. We come next to the diseases of stone hewers, statuary stone cutters, and that sort of workmen. For in hewing marble or stones out of the rock and polishing, cutting them, they oftentimes, there's a child in the audience, suck in, by inspiration, the sharp, rough, and cornered small splinters or particles that fly off. And at the end, he writes, and in dissecting the corpse of such artificers, the lungs have been found stuffed with little stones, which are those nodular areas of fibrosis that we're seeing. So, the pattern and the distribution in inhaled dust diseases varies according to kind of what is being inhaled. So, pure coal would just make these little macules. It's somewhat inert and not fibrogenic. The way that they mine coal now, stripping off large areas of the mountaintop, exposes these patients to silica and silicates, and we get what looks more like a mixed dust pattern of fibrosis here, as opposed to SiO2 silica with these laminated nodules. And we call this pneumoconiosis, which is a long word, but in German, it's even longer. The guy who coined the term pneumoconiosis used to call this Staubeinflationkrankheiten der Lungen, or pneumoconiosis for short. Now, but when we're in Hawaii, when we're in Hawaii and we're talking about pneumoconiosis, we need to talk about pneumono-ultra-microscopic-silico-volcanoconiosis, which my nurse in the Interstitial Lung Disease Clinic told me was the longest word in the English language. It turns out it is, but it was invented by this guy who was the president of the National Puzzlers League. None of us in pathology would say pneumono, we would just say pneumo. And ultramicroscopic? Please. You know, this is just sad. What does this gentleman have, though? Well, he has silicosis, and it is having a massive resurgence because of engineered stone. So now, you know, do we want to get Carrara marble from Italy? No. We want to now get this, make sand out of various stone fragments, take the sand and mix it with resin to make beautiful designs, and that's engineered stone. So now the stone cutters are cutting sand and making sand dust. It's worse than if you were just cutting regular stone and making sand. So these guys are exposed to this compound, which is greater than 90% crystalline silica, and we've been seeing several of these patients and wrote some of them up in MMWR. So there was just an article in the Los Angeles Times about a week ago showing one of these gentlemen, and it's quite sad because they're dying, and they're like in their 20s and 30s. The second patient that I want to talk about is a case of granulomatous disease. So it's a 50-year-old man, increasing dyspnea over several months, multiple nodules on CAT scan. He was employed at an optical technology corporation. Here's the CAT scan, and you all, because you have heard Dr. Groner's lecture, know that this has a peripheral, or excuse me, a lymphangitic pattern with peripheral nodules, interlobular septal nodules, as well as some scattered central lobular nodules. And what I see under the scope looks identical. So here's a bronchovascular bundle with the artery in the lower left and the bronchus kind of in the upper middle, and we can see that there are these rounded pink guys, which are granulomas around it, also in the subplura and also in the subepithelium of this bronchus. We can see the rounded histiocytes. They're coalescing. There's a giant cell. This is great for sarcoidosis. In fact, I had it on my desk, best case of sarcoidosis, as you know, waiting for sectioning. But if you go down to the library at Parnassus, and you find this book, Pseudo-Tuberculosis in Man, and you open it up, there's the old PubMed search, and we focus in on this article from the Trudeau report. We find that in the 1940s, there was a group of patients that worked at a light bulb factory, a fluorescent light bulb factory in Salem, and this was known as Salem sarcoid or Sylvania sarcoid. These were investigated. This is a case from Dr. Carrington's collection by Harriet Hardy, and now we know about chronic beryllium disease of the lung because of her work. So this guy doesn't work with beryllium, but he does work with these front-switching mirrors, and what he did was he would use a glove box and spray this aluminum dust to polish the mirror. Well, is this aluminium disease? No, it's actually the mirror had cerium in it, and he was exposed to cerium, not with the glove box, which never failed, but they would take the box at the end of the day and dump it into a dumpster and shake all the sand without respiratory protection. So like chronic beryllium disease, this is cerium disease. I'm going way over, I think. Should I do the last case? Let's do one more. Interstitial inflammation with granulomas. 39-year-old man, worsening dyspnea over several months, and the CT scan showed ground glass opacities, and a surgical biopsy was performed. Here are the granulomas. It looks a lot like HP. There are small granulomas. They're scattered around. They're singletons, unlike sarcoid, which tend to coalesce, but some of them are in air spaces, and so when I see air space granulomas, it's a special type of HP. Here's a close-up view of that granuloma. So HP, right, reaction of the lung to inhaled antigen, and we see the characteristic CT findings of the triple density or three density sign, which I used to call the HEDGES sign because it looked like charcuterie when I'd look at it, and histologically what we see are diffused lymphoplasmicytic interstitial infiltrates with the bronchial eccentric accentuation that I pointed out in the last lecture, poorly formed granulomas, and you often see foci of organized pneumonia. So now we're in Hawaii. This is a picture I took years ago in Hawaii, still as pale as ever. I'm risking getting bagasosis by inhaling bagasse, right, which is moldy sugarcane fiber, so this is a tour of the sugarcane factory when it was still operating in Maui. So this patient, though, has hot tub lung, and that's what is causing those weird air space granulomas instead of interstitial granulomas. So hot tub lung, reaction of inhaled MA via antigen in an immunocompetent host, first described in CHEST in 1997, and it's a form of HP that looks a lot like HP to the radiologist but looks a little different to the pathologist. So in summary, the lung reacts in a variety of ways to the various insults it meets as we breathe, and as we sit here in the Hawaiian islands, pondering the possibility of volcano ash, moldy sugarcane, and hot tubs, it is satisfying to know that we work in such an interesting profession. Thank you. Kirk, thank you. Kirk, while we load up the first case, in terms of, you know, many of us pulmonologists don't know a whole lot about pathology. Typically, we're taught that with HP, other than hot tub lung, they're poorly formed granulomas in a bronchiolocentric fashion, whereas with hot tub lung, they're more tightly formed. Is that accurate? Yeah, it is. So one of the clues that you're dealing with hot tub lung is that the granulomas are better formed than in HP, which sometimes is just a single giant cell or a cluster of small giant cells. Often in hot tub lung, you're thinking about sarcoid because they're so well-formed, but the distribution is just different, and they tend not to coalesce, as I mentioned. So, but yeah, you're thinking along the right way. And the other thing is Henry Taslar, Dr. Taslar at the Mayo Clinic wrote a nice paper on HP talking about how the granulomas can be in airspaces, but the ones that I've seen in airspaces, 90% of those end up being hot tub. So I like using that as one of the criteria associated with organized pneumonia often. Thank you. So you got to hear the clinical radiologic pathologic. So now it's time we delve in to our two cases. Is Dr. Kang here? Welcome. So Dr. Kang comes to us from Nassau University Medical Center, which is actually Dr. Raouf's first institution he worked in before we were fortunate enough to have him at NYP Methodist. Dr. Kang, welcome. Come on up, present your case. Okay, very good. Hi, everybody. My name is James Kang. I'm from Nassau University Medical Center. I'm a second year fellow in the Pulmonary Critical Care Program. So we have a 29-year-old African American male who, with no significant past medical history, presents to our ER complaining of a two-week history of intermittent subjective fevers, chills, and night sweats. He reports a five to 10-pound weight loss in the last 30 days and multiple non-tender bumps on his skin across his chest, back, neck, and arms. For the past year, he has been incarcerated in the general population. Previously, he lived in Georgia his entire life with no occupational history. He denies any sick contacts, recent illnesses, smoking, vaping history, or any family history of medical issues. Also, we did ask about the pets. No pigeons or anything like that as well. Not in the general population. Physical examination, skin examination is significant for multiple papules scattered throughout the neck, upper extremities, and upper chest. The papules had no fluctuants, were approximately one centimeter in diameter, skin colored without indentation, and were not tender to palpation. The remainder of the physical exam was unremarkable. Routine labs are within normal limits. Thank you, Dr. Kang. So I think the clinical history is really helpful, but because I'm a radiologist, I'm going to look at the imaging. But I do have, you know, some, well, I guess before I do, I mean, the combination of pulmonary or respiratory symptoms and, of course, like some sort of skin rash immediately makes me think that this is some sort of like inflammatory systemic disorder. So, you know, that's kind of the differential. I'm going down whether like sarcoid or, you know, a connective tissue disease or something like that. But I think imaging is always helpful. So this is a patient, we have a coronal chest CT, and we can see that the lungs are, the lung volumes are either hyperinflated or normal. There are little like micronodules studying the fissures and the interlobular septa. And, of course, you see little nodules along the bronchovascular bundle. So this is, there are nodules in a perilymphatic distribution. I think the upper lobes are more affected than the lower lobes. And then there's some degree of air trapping, which, you know, so I think this is consistent with parenchymal sarcoidosis. I don't see the lymph nodes yet, so I don't know. So on the axial CT, you can see kind of more of the same. You see these little teeny tiny nodules studying the fissures. And then you can see nodules along the interlobular septa. And along the subpleural interstitium. So again, perilymphatic nodules, upper lung predominance, some degree of mosaic attenuation, which is likely due to air trapping, which you can get from nodules or like granulomas blocking the bronchioles. And so I think this is consistent with sarcoidosis.

African American

fevers

night sweats

weight loss

bumps

skin

chest CT

micronodules

sarcoidosis