Okay, good afternoon, everybody. Thanks so much for joining us today. I guess that sunshine is very brilliant and difficult to stay out of, so we appreciate all you brave learners for coming to our session today. This is our third of six clinical case puzzler sessions. As we mentioned in the sessions this morning, we've been doing this for 16 years, and we really appreciate all of your input, and hopefully it's an educational session for everybody. So just some housekeeping points. Please evaluate your session on the mobile app. Shortly there'll be a slide where you could scan, and not only for the evaluations, but we'll have two interactive questions during the sessions, so please make sure that you are able to answer the questions. These are very informal sessions we try to talk things through. So I'm very fortunate to be here. I thank ACCP for allowing us to continue these sessions. My favorite part of these sessions is the faculty. You get to work with people who are truly giants in their field, and today is no exception. We have Dr. Steve McNickey, who's been with us about seven years now, I think. Steve's been with us seven years. Steve comes to us from Northwell System, and in particular Lenox Hill Hospital, a big hospital in New York City. He has a vast array of knowledge in chest radiology. He's a dedicated chest radiologist. And Steve, we appreciate your great reads and look forward to what you have to say. NRMVP, Dr. Kirk Jones. We always talk about pathology, how it frequently is the final link. And I see one of my colleagues, Dr. Minkin, in the audience with me at Presbyterian Brooklyn Methodist. We constantly say we wish we had a pathologist of the ilk of Dr. Jones. So Kirk, you were saying before how it's a little expensive, the trip and everything here. So maybe Ruth, we can get Methodist because we would save money because every damn sample we take we send out, that we would not have to send out one sample with you. So Kirk, thank you, we're so thrilled to have you. So our disclosures, I have no financial disclosures. I am semi-happy to be in such an extraordinary location. I'm just recovering from jet lag. I basically got here on Sunday. Yesterday I was zombified, I was totally out of it. Today I'm a little better, then of course tomorrow night I'll leave and I'll be re-re-zombified. So next year in Boston, I'm kind of happy about that. And I would be remiss if I didn't thank not only the ACCP leadership, but in particular Lisa Alvarez, who has been our go-to person for these sessions. She has done truly Herculean work in getting all of our slides together. You know, there's always a missing slide or something, someone didn't get an email. And she's been the glue that has held all of this together. A few disclosures as well. I am a Yankee fan who's in absolute mourning. Steve, what the hell happened? Nobody knows. All the New York teams- Fuck, it's a pretty bad time to be a sports fan in New York, I don't know. I may have to get into soccer or cricket. So we've been having some rough goes. So the way the sessions work is that we give each of the specialists gives a ten minute approach. So I'm going to give a ten minute approach as to the clinical evaluation of pulmonary infections. Dr. McNickey is going to give a ten minute approach as to the radiology of chest infections. And then Dr. Jones will give a ten minute overview of pathology of chest infections. And then we have two really interesting and phenomenal cases. We'll dissect them, and in those cases we'll have the interactive session. So without ado, I'll spend a few minutes going over the clinical approach. Now, I don't own anything, so my real estate knowledge is sub-zero. But I know in real estate, they say the most important thing is what, location, location, location. Well, with pulmonary infections, it is exceedingly similar, right? There are infections that in New York City, other than perhaps immunocompromised patients with low CD4 counts, we never see. So for example, I can't remember the last time I saw a conventional valley fever, right? Or coccidioidomycosis. Yet, we have some colleagues who work in Tucson and in Phoenix, and they deal with that not once a day, multiple times a day. So location really plays a pivotal role in terms of infection. Dr. Grona, our radiologist from this morning's sessions, had such a good point when she says, anything can be an infection, right? And the good thing about the vast majority of pulmonary infections, they're treatable, right? The vast majority are treatable. Yes, you may get an overwhelming progressive fungal infection in an immunocompromised patient. They may not make it. But in general, the vast majority of infections are treatable. So really, the onus falls upon the clinician to give the radiologist best history. If there's tissue, give the pathologist the best history, and then try to arrive at a diagnosis. So besides location, what else do we look for in the evaluation of pulmonary infections, timing, right? What's the acuity of onset? Most bacterial infections have a very rapidly progressive onset, a two, three, four day history, although some quote unquote atypical infections may have a little longer history. As opposed to a chronic infection like TB, like MAC. And Steve, I know you must see thousands of MAC scans. We are seeing MAC at an incredible level, not only in New York City, but all over the country. So the timing of the patient's symptomatology plays a big role into what it could be. The more acute tends to be more bacterial, more chronic, chronic infections. Probably the most important factor is the patient's immune system, right? And there's many levels of immunity, there's T-cell immunity, there's B-cell immunity. Many of the infections we deal with both on clinical practice and for board exams are T-cell immunity related, right? Many of you are young, but for those of you that aren't as young, if you trained in the HIV days, right? It was just an incredible amount of markedly immunocompromised patients. And I think the greatest thing about HIV is it shows that medicine can be potentially curative, right? The only people who don't do well with HIV now are the ones who are egregiously non-compliant with their medication. If they take their antiretroviral medication, almost the entirety of these patients do well. So that's a source of great progress. Rapidity of symptoms is really important, right? That sort of goes with the timing, but some patients may have this explosive onset. And when they have those explosive onsets, you worry about overwhelming bacterial infections and you worry about fungal infections. I will certainly defer the imaging and the pathology to my colleagues on the panel. Not only is location important, what city are you in, but there are local differences. So Dr. McNickey works at Lenox Hill Hospital, which is probably nine, ten miles away from my hospital in Brooklyn. It's across the river and a little highway up the road. But yet, his pathology, his organisms may be extremely different from the ones in our institution. And that's where it's really relevant and important that you know your hospital's susceptibility pattern for certain infections, right? And mycobacterial disease, while you can get it anywhere, certainly New York City, we're known for fashion and theater and a lot of great things. Unfortunately, we're one of the multi-drug resistant TB capitals of the world, this too, maybe not quite as good as some of our other things. Immune status, probably the most important entity is someone's immune status. So like we mentioned earlier, there are a whole array of different types of immunocompromise. And many of these people who are immunocompromised can get anything, right? We have patients who get chemotherapy for their lung cancer, who get immunotherapy for their lung cancer. You saw this morning a case of rituximab-induced lung injury. So these patients may have infection, they may have drug-induced lung disease, they may have progression of their cancer. So these are points that you really wanna keep in mind as you're going through your differential. So certain infections may present differently depending on a patient's immune status. And I think probably the greatest example of that is tuberculosis. So tuberculosis in HIV, anybody who has HIV can get TB. But how they present, both clinically and radiologically, is distinctly and unequivocally dependent on their CD4 count. So for example, if their CD4 count is greater than 300, they will get the regular conventional garden variety TB that we see in non-HIV patients. And that being the upper lobe fibrocavitary disease that so many of our TB patients get. So if your CD4 is greater than 300, because you can mount some immune response, that's how they'll present. The time that it's really difficult to diagnose is when their CD4 count is less than 100. Then, because their immune system is so poor and because they really have a paucity of any immune reaction. Rather than getting upper lobe fibrocavitary disease, which requires a healthy immune system to develop, right? That's a very important part of the TB. It's the so-called delayed hypersensitivity reaction. When your immune system is that bad, when your CD4 is less than 100, you'll never get upper lobe fibrocavitary disease. And in descending order, the common radiologic manifestations for these patients are adenopathy, miliary pattern, that's not military, it should be miliary, and that's the so-called millet seed pattern. And I have a feeling Dr. McNickey may be showing us one, so I will leave that to him. And even more frightening, some of these patients may have lower zone opacities, right? So when you have someone who has lower lobe opacity, you may think it's a lot of entities. One entity you usually don't think it's TB, but if their CD4 is really low, it may be that. Now, PJP also depends upon how they get it. There's two ways you get PJP, you get it with HIV, and you get it with non-HIV. Primarily, chronic steroid usage or profoundly immunocompromised patients, transplant, chemotherapy, etc. How they present is quite different. The HIV-associated PJP has an insidious, prolonged, usually weeks of onset. And if you take a good history, they're typically dyspneic for months. Whereas in the non-HIV, they have a very rapidly progressive fulminant disease. I would be remiss if I didn't mention the most recent infection, right? This is the Johns Hopkins data. They stopped collecting in March, but just look at this frightening data. So the amount of people who have been infected and who have died from COVID is truly astronomical, right? Now, I'm happy to report, and I'm sure many of you are finding the same clinical syndrome, so to speak. The worst wave was the first wave, the so-called alpha variant. That was the one that was extremely pneumotoxic and literally ripped through lungs at an alarming rate. Delta variant had some pulmonary toxicity, not quite as much. And as we've gone on between the vaccines and the different strains becoming less virulent or certainly less pulmonary virulent, we rarely. Any of you intubating anyone for COVID anymore? We have not had an intubated COVID patient in a very long time. Is that everybody's experience? That's very good to hear. And finally, just a few words about HIV, right? This slide is a little busy, but when I trained, about 80% of people who had HIV, if they had pneumonia, it was PJP. That has changed now. PJP is still the second commonest form of pneumonia, but it's not the commonest. The commonest form of pneumonia in HIV patients is garden variety, streptococcal pneumonia, but PJP is second. And again, we're seeing less because the majority of our patients are compliant with their antiretroviral therapy and are indeed doing what they're supposed to do. And finally, don't ever forget infections. While this is a section on pulmonary infections, and you always wanna rule out infections, again, because we said they're so eminently treatable, not everything is an infection. So today's topic is pulmonary infections. And here is a scan of a patient who was HIV positive, who had a low CD4, who was referred to us. And everybody said, that's PJP, there's lots of cysts. And the CD4 count was indeed low, and imaging looks similar. And this ended up being LIP, right? So just because you think it's an infection, it may not be. And in these patients, in the immunocompromised patients, we recommend an aggressive approach. And if sputum is not diagnostic, bronchoscopy with BAL and transbronchial biopsy play a big role. I'm gonna stop and we'll turn to Dr. McNickey, who is gonna go over the radiologic approach to pulmonary infections. Thank you so much, and Steve, thank you. Welcome. Aloha, everybody. Thanks for attending this Pulmonary Infections Clinical Case Puzzler. My name is Steve McNickey, as we've said. I'm a chest radiologist at Lenox Hill Hospital in New York City, part of Northwell Health System. Today I'd like to review with you the various patterns of infection that you may encounter on chest CT scans. And I plan to discuss the most common causes of each pattern and the differential diagnosis that you should consider. So we're gonna start with ground glass opacity and consolidation. And specifically on this slide, we'll talk about ground glass opacity. So in this case, there are these bilateral, sort of diffuse symmetric ground glass opacities. And when you see a pattern like this, you should think of infection due to atypical organisms, such as viral organisms or atypical bacterial organisms, as these pathogens are more likely to present with ground glass opacity as the predominant abnormality. As mentioned, over the last several years, we've all seen more than our fair share of patients with COVID. And while COVID had numerous different manifestations on chest CT, a typical pattern is one such as this, with multiple bilateral, peripheral, and rounded areas of ground glass opacity, and that's what this patient had. So moving on to consolidation, here we see a large area of consolidation with air bronchograms in the left lower lobe. Consolidation is a very common manifestation of infection on chest CT. This is an infection that originates in the alveolar spaces and spreads through the pores of Crohn and canals of Lambert, and is usually limited by the fissures to one lobe. And this produces the so-called lobar pneumonia, or airspace pneumonia. And when you see a pattern like this, think of bacterial organisms, such as streptococcus, or H flu, or klebsiella. The differential diagnosis of consolidation could include mycobacterial and fungal infections, particularly if there's an upper lobe predominance of the consolidation. And this patient had a bacterial lobar pneumonia. So for ground glass opacity and consolidation, it's the distribution of the abnormality that gives a clue as to the cause of the organism. Atypical organisms, whether they're viral or the atypical bacterial organisms that I've listed here, are more likely to present with ground glass opacity as their predominant abnormality, and will more often cause a diffuse or symmetric pattern of opacities, as I showed in that first case. On the other hand, bacterial, fungal, and mycobacterial organisms often present with a more patchy, focal, or asymmetric pattern of consolidation as the predominant abnormality. As was mentioned though, even classic findings like ground glass opacity and consolidation have a differential diagnosis, and aspiration, edema, hemorrhage, diffuse alveolar damage could all present with one of these patterns. Another pattern of central lobular nodules with soft tissue attenuation occurs when there's endobronchial filling with infected mucoid material resulting in these central lobular nodules. Notice how these nodules don't extend to the pleural surface as they're limited to the central lobular portion of the secondary pulmonary lobule where the airway resides. This was a patient with a MAC infection, one of several I'm going to be showing. So these central lobular nodules of soft tissue attenuation likely represent infection due to bacterial, fungal, or mycobacterial organisms in the acute setting, and could be an early sign of bronchopneumonia. You should consider aspiration if these central lobular nodules are in the dependent portions of the lungs. In a chronic setting, consider either recurrent infection, or aspiration, or even invasive mucinous adenocarcinoma. Occasionally, pulmonary edema again or hemorrhage could mimic this appearance. The finding of central lobular nodules of ground glass opacity could also represent infection, but it's more typical of infections that produce peribronchiolar inflammation without bronchiolar impaction. So here we see central lobular ground glass opacity nodules. Again, not extending to the pleural or fissural surfaces. And this was an older female with atypical bacterial pneumonia. So in the acute setting, this finding is often caused by infection, either due to viral or atypical bacterial infections, such as chlamydia or mycoplasma. The differential diagnosis, again, could include pulmonary edema, or hemorrhage, or even hypersensitivity pneumonitis, giving central lobular ground glass opacities. In the chronic setting, infection is less likely, and then you consider the other causes of central lobular ground glass opacity nodules, classically hypersensitivity pneumonitis, or respiratory bronchiolitis, or follicular bronchiolitis, or even pulmonary hypertension. A classic pattern of infection is the tree and bud pattern. This pattern refers to central lobular nodules that are connected by linear or branching densities. Again, they don't extend out to the pleural or peripheral surfaces because they're in the central lobular portion of the lobule. And this also represents impaction of small airways by infected mucoid material, and is classic for infectious bronchiolitis. Oftentimes, you'll see bronchiactasis and bronchial wall thickening associated with this finding. So this patient, another patient with MAC infection, classic. So the tree and bud pattern, highly suggestive of infection due to bacterial or mycobacterial organisms in the acute setting, with fungal and viral organisms and aspiration less likely. If there are chronic symptoms, also commonly due to infection, but think more atypical mycobacterial organisms. A rare entity that's been discovered to mimic this pattern is tumor emboli. And if you think about the anatomy of the secondary pulmonary lobule, you'll remember that the artery travels with the airway in the center of the lobule, and thus if there are tumor emboli, it may mimic this pattern of central lobular nodules and produce a tree and bud pattern. The next pattern is that of airway wall thickening and impaction. Usually, airways are penciled in. In this case, you can see that they're thickened bilaterally. There's an airway in the right lower lobe that is impacted with mucus, and this is a patient who had acute bronchitis. A thing to think about is that airway wall thickening and impaction could represent large airway infection. And if it's an isolated abnormality, again, atypical organisms are most likely, such as viral organisms, chlamydia, mycoplasma again. Other organisms should be thought of if there is associated central lobular nodules, consolidation, or tree and bud opacities. Also important to keep in mind that you may find airway wall thickening and impaction on patients who are not infected, patients with just asthma or chronic bronchitis could also have this appearance. We've spoken about smaller nodules so far, central lobular nodules and such. And now, it's important to remember that large nodules and cavities can also be a sign of infection on CT. This patient happens to have both cavities and solid larger nodules. This was a patient who had aspergillus infection. It was an immunocompromised patient. Large nodules and cavities commonly are due to infection, whether it's due to septic emboli, bacterial lung abscesses, fungal or mycobacterial infections, or even nocardia or actinomycosis. If there's an air fluid level associated with the cavity, it could be a sign of a bacterial infection. Of course, there's a differential diagnosis, right, and you always want to make sure there's not malignancy that you're dealing with. You could have GPA causing nodules and cavities or tracheobronchial papillomatosis. A milliary pattern is one thing that we mentioned, and it refers to innumerable small, usually 1 to 4-millimeter-sized nodules scattered in a random distribution. Here you see some of the nodules are up along the pleura and the fissural surfaces, then others are located more centrally. That's what defines a random pattern. This was a patient who had disseminated tuberculosis, which is a very common cause of this pattern. The term milliary refers to these millet seeds, small seeded species of cereal crops or grains used as food. That's where it gets its name. When you see a milliary pattern, though, you should keep in mind that there's a differential and consider whether or not the patient is febrile or afebrile. If you've got a febrile patient with a milliary pattern, think milliary TB, other mycobacterial infections or fungal infections such as histo or coccidioidomycosis. But if the patient's not febrile, you have to make sure you're not dealing with the hematogenous spread of cancer. So there are some cancers that are known to spread this way, and I've listed some of them there, such as thyroid, renal, breast cancer, melanoma, and pancreatic cancer. So with that, I'll say mahalo, and I hope that this review of these imaging patterns helps you remember the most common causes of these patterns and a differential diagnosis that you should consider. Thanks. All right, thank you again for inviting me, and thank you all for attending. I'd say aloha, but as we all know, aloha means hello and goodbye, and I don't want anyone to leave. So story for another day. So I'm going to talk about pathologic evaluation of pulmonary infections. All of these clinical case puzzlers, it's like I get up there and, like, what do you want me to talk about? Pathology of everything in the world, you know, and you're just like, how am I going to narrow that down to ten minutes? So let's go quickly through, and we'll look at some pretty pictures. So considerations at biopsy, when you have kind of any pattern that an infection has, is going to be a lot of things from infection to neoplasm, drug reactions, underlying disease, comorbidities. And the number of infections is also quite broad, viral infections, bacterial infections, mycobacterial, and then a bunch of unusual things that can sometimes show in different ways. And then the pattern of infection is also quite broad. So we could have diffuse alveolar damage, particularly seen in viral infection or in patients with sepsis, alveolar filling by neutrophils, like you would just see in a typical bacterial pneumonia, necrotizing consolidation or a necrotizing pneumonia, which would be more common in things like actinomyces or nocardia, but also in some of the pyogenic bacteria. Necrotizing consolidation with nuclear debris, and so now you've got neutrophils, plus you're seeing little bits and pieces of stuff. That's probably most common in viral pneumonias and would have been seen in patients with COVID as well. I don't have a nice slide of that. Necrotizing granulomas, sometimes called caseating granulomas, which is fine if you're talking about the gross appearance, but we use necrotizing for the microscopic. Fungal pneumonia, mycobacterial diseases, and then miliary pattern disease, either granulomatous or other, and we think mostly about tuberculosis in these cases. Here's a typical granuloma. We can see the central area of necrosis, the surrounding histiocytes, and then one of the findings that we see, not infrequently in infectious granulomas, is that you get these little satellite sarcoidal granulomas around it, non-necrotizing granulomas, around the dominant solitary necrotic granuloma. So this is a case of tuberculosis with these satellite non-necrotizing granulomas. And it's not specific to tuberculosis. So, for example, here's a case of what I see in California, right? Coccidioidomycosis, or valley fever, and again with the little satellite sarcoidal granulomas in the central necrosis. So one of the things that pathologists are faced with when you send a big chunk of tissue, you know, how many stains do I need to do? How many of these blocks do I need to do? And Anna Katzenstein addressed this right at the turn of the 70s to the 80s with this paper, which was that if you have a big necrotic nodule, the place to look is in the necrosis, and you only have to stay in a couple of the blocks. And you might say, well, what stains do we need to do? First we would do an AFB stain, so here's tuberculosis. Do you see it? I don't even see it. I see it now. Ready? Bink! OK. So at my hospital, which covers, like, three or four hospitals, actually, they all send me these, because they're like, you're better looking at it than I am. I'm just like, it's because I take the time. Strangely, we digitize our slides, and they're easier to see digitally than they are on the actual glass. It's funny. So what stains are we going to use? So stains for fungus, a GMS or silver stain is probably the most common. A PAS fungus stain is beautiful. It's magenta and turquoise. It's like the, you know, teenage girl, beautiful color stain. My brother, when he was a teenager, those were his favorite colors, magenta and turquoise. So I shouldn't say teenage girl. It's him. So PASD looks pretty, but misses histoplasmin and pneumocystis, which are two obviously important lung pathogens. Mucicarmin is a stain that we use to demonstrate mucus in tumors, but strangely stains the mucoid capsule of cryptococcus. So it's sometimes used in diagnosing that fungal infection. And then there are some immunohistochemical stains that we can use, such as pneumocystis stains. And those are really helpful, particularly if the patient's been partially treated. So here's a case of cryptococcus. You can see we don't really need the mucicarmin stain. It's got that what's called a soap bubble appearance with that retraction. It's one of the few bugs that's going to look like that. Here's coccidioides or coccidioidomycosis. And you can see, for example, this one with the spherule with the little endospores. Here's a classical case of pneumocystis with the froth and dot pattern. You know, when pneumocystis first was described, it was thought to be a protozoan. And so the terminology in this disease is that the rounded structures are called... I haven't used this in a long time. The dots are sporozoites, and the rounded structures are... I don't remember. Early stages of Machiavelli-Bignami syndrome coming in. The Italian red wine drinker's disease. So here we're staining it up, and you can see the larger forms of pneumocystis on the GMS stain. Trophozoite. Thank you. Sela. You don't need a pulmonologist or pathologist at your institution. You are the pathologist. So this is a disease that I waited years to get a case of and then did not get a case of. So here it is on H&E. I cannot see the bugs, just this kind of necrotizing junk. On the GMS stain, though, we can see these ovoid nodules with what looked like a pill capsule area where it's dividing by fission. And this used to be called penicillium marnifae, and I was looking for a case of penicilliosis for years. I finally got one. I made the diagnosis, and I got a text from the infectious disease fellow. It's like, they changed the name. It's now talaromycosis. So here it is, talaromyces marnifae. I waited for years. This is a case of aspergillus, and when we're looking histologically at fungus, sometimes the clinician will be like, well, what do the hyphae look like? Do they have septa? Are they branching? And sometimes it's really messy, and you can't tell. This is a great case because it has the fruiting heads, the conidia of the fungus here in the upper corner here. Yes. And they're actually kind of pigmented too because this is the stuff that causes the black spots on mold when you're looking at it. A friend of mine just sent me a picture of a jack-o'-lantern and it was moldy, and that's what he would have seen if he had taken it under the microscope. So I have a saying to my residents, which is aspergillus can get fat, but mucor cannot get skinny. So here's aspergillus, and it looks skinny, like a nice bowl of fettuccine, and then this is mucormycosis, which is all wide and undulating, more like a bowl of pappardelle. But if we just use that, is it fat or not, then we're going to over-call cases like this, which is degenerated aspergillus. And so just kind of use all of your clues when you're a pathologist to tell your fungus apart. Viral pneumonias we can differentiate sometimes based on the inclusions, both the number of inclusions, the number of nuclei, and the characteristics of the inclusion, as well as the pattern of disease. So here's cytomegalovirus with its large red intranuclear inclusion, and then its speckled kind of purplish intracytoplasmic inclusions. Here's herpes. Herpes, like COVID, tends to be kind of bronchiolocentric, and it'll cause a necrotizing bronchiolitis, as will adenovirus, when we look at that. One of the clues with herpes is that it shows this kind of glassy inclusion in the nucleus, as well as multinucleate cells. And so we sometimes talk about the three Ms of herpes virus, which is multinucleation, margination of the chromatin to the periphery, and molding of the cells, the nuclei next to one another. This is measles. Measles... When I first started giving these talks, I was like, oh, measles, something we don't see anymore. But since, you know, 15 years ago, we see a lot more measles now than we did 15 years ago because of people not vaccinating. Not at San Francisco, thank goodness. But measles is characterized by these cells, which have the great name Warthen-Finkelde cell, and they're super lazy. They just kind of drape themselves over the alveolar septal wall. It have inclusions within all of those multiple nuclei. Adenovirus, as I mentioned before, showing this necrotizing bronchiolitis, and then this superimposed... This is an alveolar duct branching down into the alveolar spaces, and you can see there's this... Like, we've taken a pink highlighter around there. Those are hyaline membranes. So we have diffuse alveolar damage with a fibrinous organizing pneumonia, acute bronchopneumonia, and a necrotizing bronchiolitis. This is really similar to COVID pneumonia. And there are stains for adenovirus that we can do. Finally, you know, Dr. Salem mentioned that we can see mimics a lot of times of infection, and this is really quite common. Granulomatosis with polyangiitis would be one of the most difficult ones for me to differentiate, and then some others that we'll go over. So here is the classic geographic necrosis, and you'd be like, oh, this looks a lot like the island of Oahu. It doesn't, but whatever. And then, hey, we're right here at Pearl Harbor. Okay, and oh, wow, this looks like the Big Island. Oh, my God, the volcano exploded, and a piece of tissue went flying off. Anyway, geographic necrosis refers to this kind of characteristic angular shape that we see in granulomatosis with polyangiitis and several other vasculitides. Another disease which causes this infarct-like necrosis would be lymphomatoid granulomatosis, which is an EBV-driven large B-cell lymphoma where the B-cells occlude and necrose the vessels. This used to be a pulmonary artery but is no longer one, and you get this infiltrate of neoplastic cells within the vessel wall causing that infarct. And then pulmonary venous infarcts. We see these patients that have atrial fibrillation, for example, that are treated with pulmonary venous sclerosis can end up with pulmonary venous infarcts because of the venous obstruction. So often it'll be almost always left lung, in my experience, lingular to start out, left upper lobe sometimes, the entire lobe, and rarely the entire lung because of this vascular occlusion. This particular case is from sclerosing mediastinitis, but we've seen it... I've seen it more commonly in the pulmonary venous ablation and AFib, but also from Hodgkin lymphoma and from fungal infections causing sclerosing mediastinitis. Another nodular case, and if we zoom in, you can see that this is this amorphous, homogeneous, pinkish material, which is amyloid. This is nodular amyloid. And then those little blue lymphocytes right next to it is a lymphoma, a MALT lymphoma, external marginal zone lymphoma. There, you can polarize it and see the characteristic apple green birefringence. So this is a cool case. This is another case that I waited years and years to get, and I probably came to this conference, and the guy covering for me, Dr. Erisman, sends me a text. He's like, you won't believe what I got. And I'm like, oh, diraphilaria, the dog heartworm, yes. This is diraphilaria, the dog heartworm, the human is a dead-end host. It goes to the lung and makes a necrotic nodule with a classical kind of infarct-like necrosis around it. Now, the only reason I put this in, because this is an infection, is that a few years later, I had a pathologist bring me this slide, and they said, what parasite is this? What worm is this? And I said, well, this worm is the seed of a kiwi fruit. And so there's a lot of things that will look... So this is a mimic of infection, but not... Anyway, it's not exactly... I had diraphilaria was a mimic of something else, and then this is a mimic of the infection. So one of the nice things, it makes me a little bit unhappy in pathology, is that we've had numerous advances in technology that take my job, but it's OK, because at least I can say which things to send now. And so we've got... I wrote array technology, so like the Virochip, where if you have a novel virus that you haven't identified before, you can throw it on a chip and figure out from sequencing what it is most likely to be through various matching programs. We've got next-generation sequencing, particularly done at the University of Washington here on the West Coast, where they'll, you know, tell you what the mycobacterial type is. We've got targeted PCR as well. And then I thought I had GeneXpert on there as well. Years ago, in this session, we had a couple of gentlemen that often come to this conference. I don't see them here today. But they were like, why didn't you just do GeneXpert on this case of tuberculosis in a pregnant woman? And I was like, I don't know. But they were like, we would have done it. And I'm like, so sad. So in summary, infectious disease of the lungs is an enormous topic that requires several angles of approach, including I wrote the following. And then thinking of infection at the time or before the time of obtaining the sample will allow you to use some of these new technologies that maybe aren't performed on formalin-fixed paraffin-embedded tissue, which thankfully most of them are. And with that, thank you for your attention. applause Thank you so much, Kirk. I could see why we so need wonderful pathologists. So you had the clinical, radiologic, and pathologic approach. We're now going to get to two great cases. Our first case comes to us from Jordan. Come on up. Fenicio? Yes. Welcome. Jordan has a very interesting case. Welcome. Hi, I'm Jordan Fenicio. I am a third-year internal medicine chief resident at Wellspan York Hospital in Pennsylvania. I'm going to be giving you a case of a mysterious lung lesion in a teenage athlete. So we have an 18-year-old female. Past medical history, asthma, controlled with Montelukas and an inhaler, depression on citalopram, generally pretty healthy, and she had just started college, was in her first year, and was there on a swimming scholarship. So this patient was doing fine, healthy, went and got some dental work done, was told she needed her wisdom teeth removed, and went through that procedure with no complications. But a couple days later, started having some trouble with breathing, was using her inhaler more often, and started having fevers at night. But she was busy, waited a couple days, and finally went to urgent care. At urgent care, she was diagnosed with an upper respiratory infection. They thought, oh, you know, it's an asthma exacerbation. You're in a new environment, exposed to new things. They gave her seven days of Augmentin and prednisone. She finished that course and still was doing pretty poorly, still having a lot of trouble breathing, using her inhaler really frequently, just things weren't quite right. So after she finished the course and wasn't getting better, she went to her college's health clinic. And there they tested her for mono, because that was going around the college at that time, and it was positive. So they said, okay, it's mono, go home, supportive care, you're going to feel crappy for a couple weeks. Two days after that, she started having chest pain. And told her parents, her parents, like, okay, that's not right, go to the ER. So she went to the hospital. At the hospital, they ran a bunch of work up and tested her for COVID, because we were in that point in time, and she was COVID positive, and this was the first time she had been tested for COVID throughout all of this. So now we have that she's positive for mono, positive for COVID, had her wisdom teeth out, was having chest pain, trouble breathing, and fevers. Physical exam at the ER. She was afebrile at that time, a little bit of a higher heart rate at 93 for her. As an athlete, she usually ran in the 50s, 60s. Respirations were 23, low blood pressure at 99 over 58, and she was saturating at 96% at room air, so not hypoxic. But when you listen to her chest, she did have decreased breast stones on the right and wheezing bilaterally. So we'll get to the imaging that was done later, but some of the laboratory tests we have that came back throughout all of this at different points in time, but just to give you these. She did have an elevated ESR and CRP, so inflammatory process, and we did test a couple other things. You'll see why in a second. But all of these were negative, most notably HIV, fungal workup, and autoimmune workup, and her blood cultures were negative. So we pull up her chest X-ray, and it's not an eye test, right? I mean, huge abnormality with this big area of lucency in the right upper lobe surrounded by this dense consolidation in the right upper lobe, and there's even a smaller infiltrate, more inferiorly, in the right lower chest here. It even looks like there's a piece of right upper lobe projecting inside of this big area of lucency, right? So you think a big area of lucency on a chest X-ray, what could that be? I mean, she's 18 years old and a college swimmer, so she would presumably have normal lungs, so this isn't a big bulla or anything, and it's surrounded by this consolidation with some lung within it here. So, I mean, I think the first thing you have to think about is that this is a cavity due to infection, right? We go on to chest CT scan, and it looks like she had a CTA to rule out P, probably because she was having chest pain. So I don't have soft tissue windows, but I don't see any evidence of pulmonary embolism, but what you do see is, and there are numerous images I'll show you, there's consolidation in the superior segment of the right lower lobe here, and there are also these central lobular nodular capacities, some solid looking, others on some subsequent images look to be a little ground glass capacity, and again, here we are in the superior segment of the right lower lobe, and as we move superiorly, you see that there's this large area of consolidation in the right upper lobe here, the posterior segment, but also spreading more anteriorly, and we see these ground glass capacities, these central lobular capacities as well, and then we get to this big cavity more superiorly that corresponds to the chest X-ray finding. We see this rind of consolidation around this cavity. It's got thick walls, these sort of irregular walls, and then it looks like there's a piece of parenchyma just hanging inside of this cavity, which you see really nicely on the coronal image, which corresponds to that chest X-ray where there's just this piece of lung parenchyma hanging in this big cavity in the right upper lobe, so you've got a large cavity. You've got consolidation in the right upper lobe and in the superior segment of the right lower lobe, and you've got those central lobular nodular capacities, right? So we've got a young, healthy female who just had a dental procedure. The central lobular nodular capacities and the location of these abnormalities in the superior segment of the right lower lobe and posterior segment of the right upper lobe, but then involving the rest of the right upper lobe, I think that you have to think about that this is aspiration from the dental procedure with infection that has led to this large cavity being formed. Other causes of cavities radiologically, I mean, there was a line in there about her having had a pneumonia as a child. You know, did she have TB that has reactivated, and this is reactivation TB? I mean, I think that would be less likely, given her young age and her generally healthy status up until the point where she got the dental procedure and then had this relatively quick onset of infection. And, you know, it's not likely to be a cancer, given her young age and healthy status, and you checked an autoimmune workup, and this is the only cavity, so I think that would be less likely also. I think that this is a lung abscess that has led to a cavity. Thanks so much, Steve. So let's get to our first interactive question. What would you guys do next? You can scan the barcode. So do you want to do a surgical biopsy? Do you want to do a bronc with a BAL and a transbronchial? Do you want to repeat a CT chest in three months? Or do you want to do none of the above? We'll get a few more responses, then we'll... Okay. Let's get to 20. So the vast majority, this is one thing that is extremely consistent during most of our sessions. Pulmonary critical care doctors like to do a bronch and a VAL. I don't know if I do a transbronchial. So let's go back. Let's dissect this case. This is a real difficult case. So Dr. McNickey and Jordan really gave a great history, and there's not much I can add. So this is a young girl, so you don't think she has much, and then you tell her she's a swimmer. So if she's a swimmer, there's very few exercises that use more aerobic capacity than swimming. So she's in good shape. It sounds like her asthma is really trivial, and she rarely uses her rescue inhaler. So then she has this dental procedure and gets this illness. So let's go through some of the points of the case. Whatever she had made her asthma worse, right? So she was well with asthma, then develops this illness post-dental procedure. So the first question, did the dental procedure have anything to do with it? It certainly would appear as though the dental procedure was the inciting event. You can make a case that it was unrelated, but I think with this young, healthy girl, I don't think it's coincident she had a dental procedure and a week later comes in or a few weeks later with this big cavitary lesion. So that would be high. Now there are many other entities that I think you would have to think of. So she's an asthmatic, right? And now she has this big cavitary lesion. She certainly is not acting like a vasculitis, but I would have vasculitis at least clinically in the differential. EGPA, they do have asthma frequently. But I think the imaging goes very much against EGPA in this case. But that's something I would think of. Another, I think, red herring is her COVID, right? I think, I suspect her COVID was just an incidental finding and she happened to be COVID positive at that time. People with COVID, as Dr. McNickey so eloquently showed, typically have those peripheral, ground glass, wispy sort of opacities. This is a big thick walled cavity that I would have great difficulty attributing to COVID. The other thing I would think of, could she have had COVID for a while and now she's having a fungal infection secondary to COVID? That is well reported, post COVID fungal infections. But my suspicion is she would be sicker. She's sick, she's wheezing, she's in bronchospasm, but I don't think this is an overwhelming fungal infection. But I certainly would have it in the differential. And then you did a great workup. You did a whole bunch of tests to exclude other entities. You did a vasculitis panel, you did aspergillus. So you really did due diligence and I think you've excluded a lot of concerning entities, TB. This doesn't, I mean, although radiologically, I guess it could be clinically, it's not TB. It's a little too quick of an onset. So now what do we want to do? I think a bronchoscopy is certainly what I would do. I can add nothing to the description of the imaging. I agree with everything Dr. McNickey said. Of course, it's easy to agree with what he says, so there's nothing else to say. So what are we going to do? You're the clinician, you're faced with this case. I think given the sort of differential and the choices, I would do a bronchoscopy. Now as someone who has done thousands of transbronchial biopsies, I think this is a case I may have hesitated from doing a transbronchial. There's a big cavity there and I don't know that you're going to do anything other than increase your risk for pneumothorax. If I did a transbronchial biopsy, it might have been in one of those lower lobe areas. That might have been certainly less risky. But I probably would have done a BAL alone, assumed it was related to the tooth extraction. However, I certainly would want to exclude fungal and vasculitis, which you did so. Tell us what happened. So, yes, our pulmonologist had the same concerns as you about doing a biopsy, so did do a bronchoscopy with BAL. So initially she was started obviously on broad spectrum antibiotics as soon as we saw that in the CT, got our pulmonologist and infectious disease doctors on board. During the bronchoscopy, the right upper lobe area was very inflamed and actually got a lot of purulent material back. Unfortunately, after the bronchoscopy, she had a little bit of a complication, suffered from some bronchospasm, required oxygen overnight and several nebulizer treatments, but she was weaned off the oxygen within 24 hours and did fine without oxygen after that. We did decide not to do any kind of specific COVID treatment for the same suspicions you had is how long has she had this, she's not very symptomatic from it, she's not requiring oxygen. So after Legionella antigen came back, we discontinued azithromycin and kept her on the other antibiotics. The white count initially up-trended, but clinically she was doing much better. She continued to improve and she was asking us every day, when can I go home, when can I get back to swimming? And we ended up giving her some fluids and then the white count came down nicely. So we switched her to IV ceftriaxone and oral metronidazole. The problem we ran into is the bronchoscopy was done about three days after antibiotics were started for various reasons, so it didn't grow anything. We couldn't tailor the antibiotics to a specific bug. So she stayed on three weeks of ceftriaxone and oral metronidazole, was seen outpatient four weeks later by her PCP, ESR, CRP, CBC, all that had normalized. Clinically she was much better and asking when she could go back to swimming. And then she saw our pulmonologist about two to three months after her admission in the outpatient setting, repeated the CT, which you'll see in a second, and they cleared her to return to swimming. So the CT scan that was done later showed marked improvement in the abnormality in the right upper lobe. I mean, I'll show this image here. The loosened lesion has become, now has much thinner walls and I would say it's consistent with a pneumatic seal at this point. And she's got a smaller amount of consolidation and or scarring left around it in the right upper lobe. So she's got this residual pneumatic seal. Thank you. Thank you. So with lung abscesses, some of the common bacteria in our strep pneumocephalus, Klebsiella, and H flu are sufficient with this patient as did she have COVID for a while, even before the dental procedure, which may have put her at increased risk for this bacterial abscess. And the way she responded really makes us think this was some sort of bacterial abscess, maybe we couldn't isolate the bug necessarily. Dental surgery itself is a risk factor. Now we did have to discuss with her after the follow-up CT that she now does have this cyst and as a swimmer and an active individual, this does put her at higher risk for pneumothorax going forward as well as subsequent fungal infections, especially as an asthmatic. But clinically she's doing better and in the past about a year she's had no issues and not had to be hospitalized or seen for anything. So doing okay so far. Thank you. That's a great case and I think the antibiotic choice was spot on and hopefully she's back to her normal self. I'm curious, Steve, you think that pneumatocele will get a little smaller or do you think she's going to be left with something? It's very large right now, so I think she's definitely going to be left with something. Thank you. So our next case, we have Dr. Kasim who's going to come up and present a really interesting case as well. Welcome. Thank you, Dr. Saleh. Good afternoon, ladies and gentlemen, international SHARES colleagues. My name is Dr. Kasim, pulmonologist from Bangkok, Thailand. It is a privilege to present you with a case of a 72-year-old male with a known CVS COPD, bronchiectasis, who recently recovered from COVID-19 pneumonia two weeks ago. This patient presented to emergency department with 38 degrees, 0.5 Celsius fever, dyspnea and cough for three days. Back three weeks ago, he received 10-day course of IV remdesivir for his severe COVID-19 pneumonia, along with dexamethasone tapering dose. On physical examination on arrival, his body temperature, 39.4 Celsius. Blood pressure, 143 over 83. Heart rate, 114. Respiratory rate, 28 per minute. Oxygen saturation, 93% on ambient air. On examination, he has high fever with dyspnea, hypoxemia on oxygen nasal cannula, three liters per minute. Chest auscultations, bilateral cause crackles without wheezes. Initial laboratory data, CBC show leukocytosis, white blood cell of 12,000 with neutrophilia, 86%. Hematocrit, 36%. Platelet counts, 128,000. Nasopharyngeal swab for RT-PCR. Before admission to the hospital, gene expert detected SARS-CoV-2 with the N2 gene cycle threshold of 41.6. In the ER, we did a urinary antigen for streptococcus pneumoniae. And Legionella pneumophila were negative. OK, so on to the radiology. We've got two chest X-rays. And tell me if I'm correct here. I think that this X-ray is one that was done prior to the other one over here. Yes. The left one is prior. Yeah. So on both chest X-rays, there's an opacity in the left upper lobe. It looks like some volume loss, maybe bronchiectasis. I'm guessing this is the chronic problem due to old granulomatous disease, whether it's TB or something else. But the new finding is that there's a new opacity down at the right base on the current or later X-ray. So looking at this, I'd be worried that there was a pneumonia in the right base. And then we get coronals and axial CT images, which show this consolidation with air bronchograms down in the right lower lobe. So this is not typical for COVID, right? COVID, if you remember, had the bilateral multifocal opacities usually. This looks more like a low-barred pneumonia pattern. And I'd be worried that there was a bacterial low-barred pneumonia after COVID in this patient. Thank you so much, Steve. OK, let's see what the audience wants to do. If you could load up your audience response key. You want to do a surgical biopsy? You want to do a bronch with a BAL and a transbronchial? You want to repeat a CT chest in three months? Or do you want to start prednisone? Many pulmonologists frequently give prednisone, right? It's a good drug. Sometimes. Is that BAL and or transbronchial? Let's say and or for your purposes, yes. OK, so let's see what the audience said. Again, the vast majority wanted to do a bronchoscopy with a transbronchial biopsy. We had one colleague who is either married to or related to a surgeon who wanted to send for a surgical biopsy. That's me because I wanted pictures. All right, he wanted pictures for his not glass slides, but his projected slides. A couple CTs. So again, I think Dr. McNickey, he makes my job almost superfluous here because he's basically telling you everything. So this patient has underlying chronic lung disease, right, who just recovered from COVID pneumonia, who now comes back with what looks like a relatively acute onset of symptoms. So had COVID, got remdesivir, got dexamethasone, certainly got what we would consider standard of care. You didn't mention anything about tocilizumab. It sounds like the patient maybe wasn't sick enough for tocilizumab, so the patient got standard of care, excellent care, got better, went home, and now has a relatively acute onset of three days of dyspnea, fever, and cough. And patient looks relatively sick acutely, not so much from a respiratory standpoint, but has a fever, is coughing, and has crackles bilaterally, which is interesting because on the imaging you only saw what looked like disease on that right base, but did have bibasilar crackles. And labs, again, seem to go for some infectious agent. So this looks to me like a bacterial pneumonia, relatively acute onset, post-COVID. So if you go to our choices, right, if a choice was as it was in the previous question, none of the above, I might have opted for none of the above and just treated with broad-spectrum antibiotics and see how this patient did. So to me, a couple of really important issues here. One, it's post-COVID, and we all know post-COVID, not only bacterial, but fungal infections. This didn't smell to me like a fungal infection. It was relatively localized. It didn't have any of the classic radiologic manifestations of fungus, but I guess post-COVID I would keep it in mind. And the other thing I would keep in mind is organizing pneumonia, right? So organizing pneumonia is really one of the main pathologies of COVID. And in my mind, that's certainly something that I would consider. So of the choices, I would definitely do a bronc of those choices. If there was a choice E, none of the above, I would have opted for that, given antibiotics. However, I would have had a low threshold if that patient didn't get better to bronc to rule out organizing pneumonia. So tell us what happened. This patient, he was a frail gentleman with a severe COPD who just recovered from COVID-19 pneumonia two weeks ago. So we agreed with Dr. Saleh. We started with initial antibiotics as a broad spectrum, which were meropenem and vancomycin, because he had significant comorbidities. However, his condition deteriorated and required oxygen nasal high flow and was brought to a critical care unit. Then bronchoscopy was performed. BL fluid was sent for pneumonia pathogen panel. Okay. You didn't think you were coming up again, did you? I didn't. I was so relaxed. We've got two images here, and it looks like we have... It's a little pixelated. This is not a biopsy from MarioCart, but rather the patient. And you can see that there's consolidation of the alveolar parenchyma. And it's hard to see, but there's filling of the alveolar space here with inflammatory cells in fibrin as well as some blood. So it looks like an acute bronchopneumonia with filling of the alveolar spaces by inflammatory disease in fibrin. I can't go much further than that, but it sounds like you guys did with the serologies. So it's not an organizing pneumonia? I don't see plugs of granulation tissue on that small biopsy. Thank you. And BAL fluid for pneumonia pathogen panel, it revealed Legionella pneumophila. BAL culture show normal bacteria. Fluid for PCR for HSV-1, HSV-2 were negative. Fluid cytology negative for malignant cells. During the hospital stay, this patient developed delirium during the course of his ICU stay. He also had acute liver injury and acute kidney injury. Antibiotics were tailored to only acetylmycin alone. He gradually recovered from this illness, which took him about 2 weeks in the hospital. So the final diagnosis would be Legionnaires' disease. Legionnaires' disease commonly seen in clusters and in certain patient populations can present in a variety of ways and frequently can progress rapidly to respiratory failure. Treatment is macrolides or quinolones. Rifampin may be added synergistically. Some of you might ask, we did a urinary Legionella antigen test, which were negative in the ER. However, it was a false positive, false negative test. And from the literature, it's shown that in about 12% to 20% of the case can have a false negative rate from urinary antigen test. Thank you very much. Thank you. What a great case, and I want to congratulate you. I think your management was impeccable. Well done. I just have one question for Dr. Jones before we break. Thank you. Dr. Jones, we mentioned organizing pneumonia. So in my limited pathology knowledge, when we think of organizing pneumonia, I used to think, oh, well, you have to have the meson body or the intraluminal plug, but that's not true. Tell us what you look for in an organizing pneumonia. We're already over. So polyploid plugs of granulation tissue, the so-called meson bodies, are the classical finding in organizing pneumonia. Now, you can have an organizing acute lung injury, which overlaps with that, where you're going to have type 2 pneumocyte hyperplasia, alveolar septal thickening, fibrin within air spaces. You could have a fibrinous organizing pneumonia with polyploid plugs of fibrin within the air spaces. So there's various different spectra, I guess, of acute lung injury. On one end, with organizing plugs of granulation tissue, the meson body, and on the other end, frank diffuse alveolar damage with hyaline membranes. So the spectrum of acute lung injury is tricky, but organizing pneumonia would have to have meson bodies, in my experience, and DAD would have to have hyaline membranes, and the rest I'm just descriptive. Well, thank you. I want to thank you guys for coming out. Enjoy the rest of your afternoon. We will be back here tomorrow. I think we're in C. We have three additional sessions. Look forward to your coming, and thank you so much. Thank you.

COPD

bronchiectasis

COVID-19 pneumonia

fever

dyspnea

chest X-ray

CT imaging

Legionella pneumophila

antibiotics

bronchoscopy

bacterial lung abscess

Chronic Obstructive Pulmonary Disease