Everybody, welcome to our session on Caught in the Cavity. My name is Sebastian Kurz. I'm a pulmonary physician at Tübingen, Germany. And my co-chair is Amy Petrovalla, who's right there. We're going to moderate the session. We'll have three junior faculties going to present cases to this esteemed panel of experts. Do you guys want to introduce yourself? Good morning, everyone. My name is Vivek Murthy. I'm an interventional pulmonologist at NYU. And I've known Dr. Kurz since 2011. Very glad to be here. Good morning, everyone. I'm Sarah Tamor. I'm one of the infectious disease doctors coming from New York. And I've known Sebastian since 2017. I'm Andy Berman. I'm from Rutgers New Jersey Medical School. And I am the pinch hitter radiologist, though I am a pulmonologist. I've known Dr. Petrovalla since 2011. And we have just met. So this is not all about me, of course. And of course, good pulmonologists are always good radiologists. So we're very happy to have you here on board. All right. We'll start with the first case. So Vanessa Suetanto, who is a fellow at NYU School of Meds in New York, is going to start with the first case. OK. Hi, everyone. My name is Vanessa Suetanto. And I'm a pulmonary and critical care fellow at NYU. I have nothing to disclose. I'll be presenting our first case today. And this patient was actually seen and cared for by Dr. Sebastian Kurz. So I want to thank him for sharing this case with me. So this is going to be our audience response session. But it'll come up again, the QR session. So this patient was a 67-year-old man who was diagnosed with right upper lobe non-small cell cancer, was also found to have mediastinal and cerebral metastases in 2019. At this point, he was started on chemotherapy, which included carboplatin, pemetrexed, pembrolizumab, as well as local radiation and removal of brain metastasis. After four cycles, he was noted to have a good response and was continued on maintenance therapy with pemetrexed and pembrolizumab for two years. In 2011, this was his PET-CT, which is shown here. As you can see, there's a little bit of PET avidity. However, you'll just have to take my word for it that it's better than before. So in February, he was found to have new bone metastases. And he was started on docetaxel and nintenidib. This continued for a year. Now we're just going to speed through time a little bit. So here's his CT in August 2019 prior to initiation of treatment. And then in February 2022, docetaxel and nintenidib was initiated. In July 2022, he started to have febrile neutropenia and a cough with worsening peripheral consolidation and small cavitary lesions. He then underwent bronchoscopy with transbronchial biopsy of the right upper lobe apical segment, which revealed no more lung. BAL cultures at that time showed haemophilus influenza for which he was treated. So in October 2022, he had a repeat CT test, which showed worsening dense consolidations peripherally and more apically. It's very, very much denser and a little bit more kind of around circumferential now. At this point, he went under another bronchoscopy with cryobiopsy of the apical and posterior segments of the right upper lobe. And it only revealed bronchial mucosa with necrosis. BAL cultures were negative. So the team decided to wait and observe to see if the cultures grew. But in January 2023, a little less than three months after, he had come back for progressive dyspnea on exertion. And the chest X-ray showed this. Let me just pause here for a second. I just want to ask the panel, when you see what happened between July and October with this persistent infiltrate and the bronchoscopy that was done, are you actually satisfied with essentially the diagnostic results of that? Vivek is shaking his head. What do you think? This is a very peripheral area, and so accurate sampling is inherently going to be a little bit challenging. Particularly, I don't know if a robotic approach was used in the bronchoscopy. No robots in tubing it. OK. I didn't want to assume. But yeah, so those types of biopsies can be a little bit more directed. But in this case, I would be worried about something that wasn't addressed with the biopsy, unfortunately. Do you think the initial haemophilus that was found that we thought corresponded well to that infiltrate, was it just a contaminant, a bystander, or could that have explained the findings at that time? And maybe Sarah can help you. Yeah, no, hard to say. I think it needs to be put in clinical context. Like you mentioned that the patient had febrile neutropenia and cough. Certainly, in an immune-compromised host, presentation can be protracted, et cetera. But yeah, I certainly would not attribute these persistent radiographic findings to H. influenzae. It shouldn't be a contaminant, but it can certainly be just a respiratory colonizer. It's one of the commensals. All right, and a question to a radiologist. That infiltrate, how it evolves, does it raise any concern that could be something else than just community-compliant infection? Yeah, so this is a situation when you have a known tumor, and then there's a chemotherapeutic intervention and neutropenia. So we're left with the situation, is this something to do with cancer recurrence? Is this something to do with the toxicity of one of the chemotherapeutic agents? Or is this a consequence of the neutropenia, and are we dealing with an infectious cause? So right now, it's very unsettling that we do not have a diagnosis. OK, so I'm going to continue by showing you the CAT scan here as best as I can. It's not a video, so just bear with it here. No video, too. OK. So as you can see here, there is a thick-walled cavitary lesion that's coming into view. And some bronchiectasis. And no, that is not his diaphragm. It's only just approaching the level of the carina here. And we start to see a very large loculated pleural effusion and compressive atelectasis. And in the coronal view, we see it's in the shape of a mitten. All right. So a thoracentesis was done. Any thoughts on what this could be? Or is it a whole question? No, not yet. Actually, can I ask a question? Yes. Do we know the details of the second bronchoscopy when a cryoprobe is used with respect to the size of the cryoprobe, or how many biopsies were obtained, or anything? I don't have that information. So there were five biopsies. I cannot tell you the size, but there were, you know, you could see them. Yeah, I have a question. So at this point in time, how is he feeling? And does he have any constitutional symptoms, you know, like fever, et cetera? And is he still neutropenic? I think my understanding is that he was still having some dyspnea and some fevers. I'm not sure about whether he was having neutropenic. No, the neutropenia was resolved shortly after that initial episode. And was there any CNS symptoms at the time? Headaches. Why do you ask? I think nocardia is a potential pathogen here, and just thinking it through. That's great. Okay. So the thoracentesis was done twice, and it showed a neutrophilic exudative effusion with no malignant cells on cytology. So we're going to have some audience response session here. What would you do next? Would you treat this as an empyema with TPA and Dornase? Would you consider this a malignant effusion at this point and place an indwelling pleural catheter? Consider this a malignant effusion and proceed with a VATS discordication right away? Repeat a third large volume thoracentesis to increase cytologic yield for malignant cells. So culture positivity on an infected pleural space, in the best case scenario, is around 60 percent. So the absence of a positive organism doesn't exclude the possibility of an empyema. However, this is a space where there's been instrumentation. The possibility of malignancy exists. And so I think that empiric therapy with intrapleural fibrinolytic therapy, it's a little tough because it may limit your diagnostic options, and it may also not achieve the goal. We see that there's a thickened visceral and parietal pleural peel. This has been present for at least several weeks, if not longer, based on the imaging. And so while I do understand kind of the rationale for considering intrapleural fibrinolytics, I think this is a tough case to make an argument for that up front. And the question of malignancy, I don't know if you want me to comment on this as well, but the diagnostic yield of thoracentesis in the context of cancer really depends on the underlying cancer subtype. So for breast cancer, for example, there's an almost 100 percent yield. It's around 90, 95 percent yield for one thoracentesis. For lung cancer, that's much less. And the yield plateaus after the third thoracentesis, going from around 80 percent sensitivity for the first to 85 percent, and sorry, from like 60 percent to 70 percent to 85 percent as your final plateau. So a third large volume thoracentesis might be helpful, but two negative ones, you probably want to start to think about getting tissue. Yeah. No, I agree completely. This has gone on too long, and I think the less invasive approaches are likely to be non-diagnostic as well, so I think it's time to push forward. Okay. So what happened, actually? So an indwelling pleural catheter was placed, and due to persistent poor lung expansion, a vast decortication was done, during which a biopsy was also done at that time. We don't have the results yet. And then the persistent air leak started to happen, and then here's an X-ray afterwards. This is actually artwork chalk on black paper. I'm just kidding. It's diffuse subcutaneous emphysema. So here's the CAT scan that I will start to show again. It's a really thick-walled cavitary lesion, a chest tube that was attempted to be placed after the persistent air leak and pneumothorax coming down, and here's our pleurax catheter that's there. So at this point, the pathology comes back, which showed this. Any takers? It looks like there's granuloma formation here, and it looks like actually well-formed granulomas and giant cells. So it's tickling the sarcoid diagnosis, but sarcoid, as everyone knows, is a diagnosis of exclusion, and I would really fight that diagnosis at this point. So I would have to think, in the setting of all this, that I'm probably looking at some kind of fungal infection, or a reaction to the chemotherapeutic agent, I guess, of those two. Yeah, no, I would agree with that. This is all a very, very indolent process, and even though, you know, the effusion, like the neutrophilic inflammation, you know, can throw you off, like, but, you know, really putting it all together, this really is speaking to an atypical infection, if this is one. So you know, we'd like to see what the tissue stains show, and we really try to get biopsy tissue itself, like for AFB fungal cultures, et cetera, to maximize diagnostic yield. Yeah, so this is exactly that. It's granulomatous changes, and if I said, you know, it has a necrotic center, that kind of rings a bell for everybody, even though the Zeal Nelson stain here does not actually show any organisms. So what's our final diagnosis? It's actually cavitary pulmonary tuberculosis, also pleural tuberculosis. Great. So another question for everybody here, which cancer drugs are associated with TB reactivation? Actually pembrolizumab, which he was on, is also associated with reactivation of TB. Actually, as I was learning about this case as well, this man is actually from Vietnam, and he came from an endemic area. I didn't want to give that away. It would have been too easy for everybody. And then he was also on antenanib for quite a while, as well as when he started to have symptoms, and this also could cause reactivation of TB, which I thought was very interesting and a good learning case for me. Great. So what interventions happened? So we did bronchoscopy with balloon exclusion to localize where the air leak was coming from, and you could see here a beautiful image of where the bubbles were coming from in the right upper lobe. Subsequently, a surgical sponge tamponade was done and placed in the interior and posterior segments of the right upper lobe. And then it was replaced by four endobronchial Watanabe spigots with stability of the pneumothorax and improvement of the subcutaneous emphysema. Fourteen days later, the spigots were successfully removed, and I'm happy to say that he's doing quite well on antituberculosis medications. He culture converted after four months, which is delayed usually. Hopefully it's two months, but given his extensive disease, it's okay. And his carcinoma was stable on further imaging. Thank you, everyone. Thank you for the presentation. So I can just give you an update. I just saw the gentleman in clinic two weeks ago. He's doing fine. His Burkitt's catheter liberated itself, as Josh pointed out. So he's still under surveillance. He's completing his TB treatment. If there had been progression of his cancer, we would have elected to re-expose him to therapy, to cancer therapy, since his TB is well controlled, but so far he has been stable. Jamie Felzer, who's now an assistant professor of medicine in Emory University, Atlanta, is going to share the next case with us. Thank you. Thank you. Good morning, everyone. I'm Jamie Felzer. I'm a brand new faculty at Emory University. So I will get started. We will also have some audience response questions. So this is a 75-year-old male. He is a current smoker of 100 pack here. He lives in the Midwest. He has diabetes. Oops, sorry. And he lives in the Midwest. He has diabetes, COPD, some esophageal dysphagia, chronic kidney disease, and severe protein calorie malnutrition. He's quite cachectic when he presents. He was previously admitted with weakness and altered mental status. So he comes into the hospital. He's admitted, or the week prior to his admission, he was also admitted to the hospital. At that point, he was found to have a cavitary pneumonia and a new pulmonary embolism. At that point, did have some hypoxia with that, was started on anticoagulation and antibiotics. He was admitted to the hospital at that point for three days, discharged home, and then presents again now with some weakness and altered mental status. During his further evaluation in the emergency department, he again was found to have a pulmonary embolism. And he was found to have this cavitary lung lesion. So he was switched over to Heparin drip and started on broad-spectrum antimicrobials with piperacillin, tazobactam, and vancomycin. At his last hospitalization, they had suggested, due to this cavitary lung lesion, that he undergo a swallow evaluation. But the patient didn't want to do it and wanted to do it as an outpatient. So that's why he was discharged at that point. When he presented to the hospital, we didn't really have too many records on him. He gets most of his care at the VA. And so that was a work in progress, trying to get all of those records. His wife also noted that, you know, with this protein calorie malnutrition that was previously undiagnosed, she just noted he really didn't have much of an appetite. And so he'd been losing a lot of weight in the past couple of months. So I have a CAT scan. This is essentially, we'll call it day one. This is his first hospitalization. So I'll kind of throw this over to our esteemed colleagues. So I'll show you this cut first, and then I'm just going to switch to a video. So I'll let you guys view this, and then I'll have our panelists tell us what you think. Just to clarify, this is at the time of diagnosis of the PE or the subsequent? At the time of diagnosis of the PE. And let's see if I can replay this again. Yeah, let me just. All right, so. So for a question, where's the PE? We'll focus more on the lung parenchyma for this one. So do you guys want to kind of tell us what you're seeing and I guess we'll throw it to the radiologist for the group. I'll put on my radiology hat. So there is mostly in the left upper lobe. I was just trying to see, at first I thought there was some ground glass opacities also in the lower lung fields, but I was just trying to kind of follow the anatomy down. But there's certainly a large cavitary lesion with some surrounding ground glass. And that in and of itself raises this finding of the halo sign where we think of maybe some hemorrhagic focus around the cavitary lesion. And that doesn't really land us in any one camp. The differential diagnosis of the halo sign is quite large. We think of fungal infections, invasive fungal infections, but really we could see that with tuberculosis. We could see that with tumors. We could see that with treatments of tumors. We could see that with a pulmonary septic emboli and pulmonary infarcts. This I don't think is a pulmonary infarct. We would just not really follow the anatomy and such. So the other part of this is that you're telling us you received these really broad spectrum antibiotics, which I think are appropriate and we'll hear in a second, and perhaps you did not respond to that. So it would raise a concern for other organisms. Yeah, I will say, so this was the CAT scan, sorry if that was slightly unclear, but this was the CAT scan, his initial presentation. So at that point he had just presented to the emergency department. He was diagnosed with the pulmonary embolism and then they saw this cavitary lesion. The broad spectrum antibiotics were a couple of days later. I'd say some other observations, considering the very broad differential of his exposures would be, there's also some bronchiolitis, not a lot, but bronchiolitis and some airway thickening. So there's some chronicity to probably recurrent aspiration given everything we've heard. And the fissure between the left upper and left lower lobe is respected, which is important. It's bulging, but it is maintained. So when we think about his cancer risk with the 100 pack year smoking history, it's absolutely on the differential with a lymphangitic adjacent process potentially. But the fact that the fissure is respected does raise the question about whether this is more likely infectious or not. Very good. Thank you, everyone. So we will do a quick poll. So for the audience, at this point we have this gentleman and he's come back a couple of days later. He's failed his outpatient management. What would you guys do now? So. I was gonna say, please don't call me. No, this could also be one of those. You go to the barber and you get a haircut. Yes. Yeah, so I think a lot of people chose bronchoscopy. I think this is a tough situation and I'll kind of let the panelists comment on that and then I can jump in, but yeah. Yes, I mean, I'm an infection doctor. So as you guys know, I will ask for a bronchoscopy. For cultures and all kinds of studies. But you know, as you rightly pointed out, like I mean, we have a large cavitary lesion. There's really nothing specific about the halo sign except that it shows angio-invasion, you know. So it just has to be put in clinical context and the differential can be really wide. So I think some tissue like, you know, deep cultures, et cetera, like would be helpful here. I don't think the SWALA study is a bad idea. You did mention that he had esophageal dysphagia. Like, so I think there are a few options here like which are correct. You'd probably get a SWALA study and also a bronchoscopy. Yeah, the two things I would say. One is that the timing of bronchoscopy is very important. We have an acute PE that was just diagnosed and so pausing anticoagulation in the event a biopsy is needed is probably inadvisable for the first two weeks at least, depending on the clot burden and the urgency of the procedure. And secondly, just given the breadth of the differential, there are plenty of non-invasive evaluations that can be done while we're allowing anticoagulation sometime. Exactly, so that's, you know, again, I think there are lots of right answers here. And so, you know, at that point the team decided to start with a non-invasive workup because we can start non-invasively. This is an elderly gentleman. He was just started on anticoagulation. He's altered at this point. I will note that he's DNR, DNI. And so, you know, that was a large discussion and that will come into play later as well. And so we started with the swallow evaluation, the non-invasive workup, and then said let's see how this goes and then if we need to and we don't get good non-invasive laboratory workup, then we can transition to a bronchoscopy. So at that point, you know, things like vasculitis, penile aspergillus, blood cultures. He was made NPO until the swallow study and had an NG tube placed. So just kind of a timeline because this is a little complex. So day one, we'll call that when he first presented to the ED, he was found to have the pulmonary embolism and the pneumonia. He was discharged a few days later on antibiotics and anticoagulation, then readmitted about a week after his initial presentation at that point with failure to thrive and put on broad spectrum antibiotics on heparin and a pulmonary consultation was obtained. MRSA was negative, VENCO was discontinued and he continued to have significant electrolyte abnormalities. A lot of the non-invasive workup was negative at that point. ID was then consulted and the zosyn was switched to muropenem at that point in thoughts of transitioning to outpatient management for ease of administration. He had a swallow evaluation. It showed that maybe he had some micro aspiration but no frank aspiration. And then he was discharged to a SNF with a repeat CT close follow-up due to this cavitary lesion, of course, counseled on tobacco cessation and modified diet. And he had a TTE, I didn't mention that as well, and that showed moderate aortic stenosis but no vegetations or anything, no other lesions. So a few days after he was discharged, he developed worsening mental status, presented back to the emergency department. He was found to have a spontaneous psoas abscess. Remember, he's on oral anticoagulation. A repeat CT was performed. So I will show that again. And I will have our panelists briefly comment on that. I apologize if I misspoke, it's a psoas hematoma, not an abscess, sorry. So there's the large cavity now has an air fluid level in it concerning for obviously infection. There's also what looks like bilateral pleural effusions left a little greater than right and some scattered ground glass opacities. So ongoing infection and even with an abscess, the vascularity around the abscess is so destroyed that it's so hard to get the antibiotics to do what they're intended to do. So it doesn't necessarily mean that this is a non-bacterial problem, but it does increase the differential diagnosis of this expanding problem on antibiotics to other organisms. He also appears to have a new right middle ovum infiltrate that he didn't have before and his esophagus is pretty full for most of its course. So it raises the question of despite the negative swallow study, ongoing aspiration. Exactly. Yeah, I would agree with that and I wanted to ask you if the patient was expectorating and if that's part of the non-invasive workup like sputum cultures, simple things like that could have helped us direct, target the antibiotics. Right. So he was not expectorating much and he was fairly altered at this point. So of course, sputum cultures were ordered and minimal cultures were obtained, but that was definitely part of the non-invasive workup and agree that, yeah, we noted the esophagus as well. So another question for the audience. Again, there's not really any particular right answer, but just kind of wanted to see what the group thought about all this. If you called me now, I'd be okay with it. It's been two weeks. Yeah. Excellent. Well, thank you everyone for your participation. So yeah, I think at this point, you know, like everyone has kind of pointed out, we've exhausted a lot of the non-invasive evaluation and so at this point we need to get a better evaluation. So that was the team's thought as well as to proceed with bronchoscopy. However, there was a lot of discussions with the patient, the family, the interventional pulmonary team and the concern at this point, he's hypoxic, he's on oxygen, he's very altered. And as we mentioned before, cachectic and he's probably aspirating even with the negative swallow study. So after extensive discussions with the family and the entire team, we voiced concern that he may not be able to be extubated after the procedure. And the family was insistent that that would be not in line with his wishes. And so at that point we decided to forego a bronchoscopy at that point. And so there were discussions about doing a thoracentesis. We did bedside ultrasounds and it was very small pleural effusion. So it really, with the anticoagulation at that point, with the very small pleural effusions, the diagnostic yield was felt to be, the risks outweighed the benefits. So he was kept on broad spectrum antibiotics, an MRI was suggested to be obtained. But again, due to his altered mental status, inability to sit still, there was the concern that he would not be able to sit in this MRI scanner for 30 to 45 minutes. And so then it would be, again, involving our anesthesia colleagues to safely sedate him and with his altered mental status, that would also probably involve an airway. So just to kind of continue the timeline, we're now kind of at day 21, readmitted for that altered mental status. There was a thought that maybe the ertapenem could have contributed to his altered mentation. So he was switched over to ceftriaxone and metronidazole. He had the psoas hematoma and this increased cavitary lesion, the MRI we just discussed. And then ultimately, a couple days after he was readmitted, he had a rapid response for hypotension bradycardia, and he was transferred to the ICU requiring pressers, blood cultures obtained. And at that point, the pleural effusion had increased, so thoracentesis was performed, and we started on pressers. There the noninvasive workup expanded, and he had urine blastoantigen that was positive but quite low, and a sputum culture was obtained, and it showed some stenotrophomonas. So one last audience response question. So we'll have our infectious disease physician weigh in. Yeah, I mean, it's hard to know what to make of this, you know, like, putting it in clinical context, it's certainly not, like, you know, blastomyces, of course, like, can cause pulmonary infection. Is this, like, the typical, like, presentation for that? Like, not really. You know, the urine antigen, as you said, like, was positive, like, but very borderline. And a little bit, I'll say a little bit about these molecular diagnostics that we now have to turn to to make some of these, you know, to diagnose, like, these endemic fungal infections and whatnot. They are pretty specific, like, I will say, like, you know, there tends to be very little cross-sensitivity between fungi, like, you know, could this be blasto? I guess it's possible, like, although I wouldn't have expected, like, you know, it to present quite this way. Yeah. What do you think of that stenotrophomonas? Yeah, yeah. Thank you for reminding me of that. So, it's hard to say, like, I mean, at this point in time, like, how long has it been, right? Like, since all of this started. Right. It's been three weeks, right? Yeah, yeah, yeah. Since he presented to the hospital. I mean, I think it's been going on for a lot longer. Yeah. So, I mean, hard to say. And he came from a nursing facility, right? Correct. Like, yeah. So, I mean, it is possible, like, that he's had this all along, like, I don't know. I would have to take a look at how he, whether he responded to the antibiotics he was receiving or not, like, to understand, you know, if he was getting better, but doesn't seem like he got any coverage for stenotrophomonas, right? And this is, of course, the classic bug, like, that shows up on meropenem. Like, you have somebody on meropenem, like, stenotrophomonas shows up. So, hard to say, like, if this is what's been going on. But I would definitely target the stenotrophomonas. Okay. Yeah. So, I guess I'm going to, like, recognize the aspiration risk, but I'm going to just take the move and toss it out. And I'm just, I'm just thinking, you know, he's from the Midwest. And usually, just for test takers, if you say you're from the Midwest, I mean, otherwise, every other question doesn't say you're not from the Midwest. So, it's a real tempting. May have been a key point. Right. So, it's a tempting morsel. So, I think I'm going to chew on that and wonder if there's a fungal pathogen related to that. Fair. Excellent. So, further cultures were done, and blastomycosis ended up growing everywhere else, essentially. So, at that point, he was started on aspergillus, or sorry, on amphotericin. And so, because there was concern at that point for CNS toxicity, and that was the thought of his altered mentation was this CNS blasto. And so, he was started on amphotericin, he was kept on the meropenem, also on levofloxacin. And eventually, you know, when ID weighed in the following morning and all the cultures, everything else started to come back, the thought was increase the dose because he wasn't responding. He was also started on posiconazole, minocycline, due to resistance to levofloxacin. At that point, unfortunately, he continued to have an increasing oxygen requirement. The family was still pretty firm that, you know, he had been declining for quite some months and he did not want to be intubated. And so, at that point, the family decided to make the transition to comfort care. And so, he passed peacefully. So, just very briefly, blasto is a dimorphic fungi found in the Mississippi and Ohio River Basin. So, that tip-off as to, you know, living in the Midwest, that was an important tip-off as it is in most of our board questions, right? It's a broad-based budding yeast. It's inhaled from spores. Most people are asymptomatic. Those that are symptomatic, about half of them are in pulmonary cases. But half of the cases are asymptomatic. So, pulmonary is the most common. There are lots of other endemic fungi, as you can see, blasto, cocci, histo. There's kind of an overlapping portion. Definitive diagnosis requires culture. It can be obtained through many different mechanisms. And antigen detection is fairly sensitive and specific, upwards of 80% for both. But the urine antigen is going to be more sensitive than the serum. Just a couple of quick pathology slides. This is on GMS. You can see the broad-based budding yeast. And then, oops, sorry. And then just, you know, itraconazole is going to be the treatment of choice for mild to moderate disease. Once we get into severe disease or any type of disease involving the CNS, we want to have amphotericin on board. And sometimes the corticosteroids will be considered. So, thank you. Great job. So, I know blasto is out there in the Midwest, but not everybody living in the Midwest is getting blasto. Was there any kind of, in his history, any risk factors? I think he was not portrayed as being like cave exploring, bat hunting, and things like that. Correct. What do you think he got it from? So, he was a farmer as well. And so, he spent a lot of time outside. And he, you know, lived his life outside. He was still working outside. He had relinquished a lot of his farming responsibilities to other people, but he spent the majority of his time outside in the farm. So, that was his major risk factor. Thank you. In this case, this patient has active ongoing exposures, of course. So, this could, you know, like be primary infection. However, it's important to keep in mind that a lot of these pathogens reactivate. You know, and even in someone like without cancer or any form of formal immune compromise, like, you know, immune senescence as you get older, et cetera, our ability to keep those pathogens that are lying dormant in the dormant state gets compromised. So, you can certainly see reactivation in the elderly. All right. Thanks for that additional clarification. So, our next presenter is Richa Nahar. She's a Pulmonary Care Fellow at Rutgers University, and she's going to take on the next case. Thank you. Hello, everyone. I'm Richa Nahar. I'm a Pulmonary Critical Care Fellow at Rutgers University, and I'm here to talk to you about a patient who has been diagnosed with a cancer. So, I'm going to introduce you to Richa Nahar. She's a Pulmonary Critical Care Fellow at Rutgers University, and she's going to talk to you about a patient who has been diagnosed with a cancer. So, I'm going to introduce you to Richa Nahar. She's a Pulmonary Critical Care Fellow at Rutgers University, and she's here to talk a care medicine fellow at Rutgers University, New Jersey Medical School, and I have nothing to disclose. So this is also a presentation where we will have the audience responses. So my case is of a 66-year-old woman with, thank you. My case is of a 66-year-old woman with a chronic productive cough. She was diagnosed with Hodgkin's lymphoma in 1970s and had mental radiation to the neck and the chest. And about a decade later, she had worsening of bronchiectasis and had severe bronchiectasis of her right middle and lower lobe with hemoptysis for which she had right middle and lower lobectomies done. About a decade later, she had another cancer diagnosed, which was the right-sided invasive ductal carcinoma and had right mastectomy done. And it was in remission after which she developed a second primary left invasive ductal carcinoma and had the left mastectomy done and was on anestrozole. In 2022, she had a worsening of her productive cough and she was brought to our attention in 2023 from the community. So over the year where she had worsening of her productive cough, she was started on albuterol and acetylcysteine nibs. She had exacerbations for her bronchiectasis for which she was on chronic infection suppressant with sulfamethoxazole and trimethoprine combination for 20 days in a month and azithromycin for 10 days in a month. But her productive cough continued to get worse. It was whitish and throughout the day and she had worsening exertional dyspnea. She also started to notice like noisy chest and like squeaks and had trouble sleeping on the right side because of the noise. And when she presented to us, she also had wheezing. Okay, so I have a question for you all. Okay, awesome. Are panelists think differently? No, okay. Okay, all right. So as we have the CAT scan of her chest, this is the sagittal view and the transverse view. And then I'm going to ask Dr. Berman, our radiologist, to comment on the CAT scan. And I'll say that even though we are from the same institution, there was the only thing that she said was good morning and that's the only thing she shared with me. So I do not know anything about this case, which I will get back at you later. So we certainly, we have a complex right upper lobe cavitary lesion with a small cavity at the right base as well. I also see a significant loss of lung volume on the right side. I don't see anything to point out on the right side and I can't really comment on lymph nodes. So here we have someone who lost the volume but we have a history of both a right middle and right lower lobe. So in fact, what we're seeing is just all of the remaining hyper-expanded right upper lobe and with multiple cavitations in its place. It's very thick-walled cavity. In the old literature, they used to say thick-walled after a certain number of millimeters, you should always think of neoplasm and that was based on x-ray data. That really has not panned out in our current evaluation of cavitary lesions on CT scans. So we don't really use that at all and infections can easily have this appearance. I guess with the history, concerned about the effect of radiation and radiation can definitely cause changes in the lung which can result in cavitary lesions. One of the forms of radiation that is more classically associated than perhaps whole beam is the radiofrequency ablation RFA and RFA lesions typically can produce those halo or reverse halo signs and it's part of that differential as well. But I don't believe that that was probably the case here. So at least at this point, I have some wheezing so I'm thinking of airway disease. That could be a component of the bronchiectasis. Certain infections can be associated with eosinophilia and wheezing response or even urticaria and we see that with some parasites and other pathogens. And if I can add, I'm a little concerned about the right main stem bronchus. I don't know if there's older imaging to demonstrate evolution of changes but it looks very threatened, very narrowed, potentially due to recurrent infection but I would be curious about, you may not have it but whether old imaging showed a similar central airway anatomy. So I don't have the images but it did not. So this was a new development and to that, Dr. Murthy, what would be the diagnostic workup that you would suggest? Yeah, so a lot of reasons why in this context we would expect narrowing of the right main stem bronchus. I think the mantle radiation from 45, 50 years ago is probably less involved in the kind of acute changes that are occurring. It may have a role in changes in the overall ability of that airway to heal. It's all very centralized, right? But with recurrent infection, we can sometimes see a kind of a ball valve effect where mucoid impaction and infection occurs. It's not able to clear effectively and now all the airways distal become recurrently inflamed, infected and then cystic changes over time. And so that would be my chief concern here is are there changes that are evolving over a long time where now the right upper lobe is just really compromised because the right main stem is damaged. Having said that, she's also at risk for many things and I don't wanna ruin your next multiple choice question but there's something I'd like to hear from her. The answer is many things. I just wanna also ask Dr. Tamer about the chronic suppressive antibiotic regimen and whether that raises a specter of any particular infections. Prior to this time, we don't believe she really had any sputum cultures. Yeah, no, thank you. I was gonna make that comment. This is a patient with a lot of structural changes in her lung like bronchiectasis, mucociliary clearance impairment. So these patients are sitting ducks really for environmental infection due to environmental pathogens. NTM, of course, are common but then also other water-borne bugs like pseudomonas, et cetera. I certainly would worry about resistant pathogens and really they could be any. This is a patient on chronic suppressive antibiotics, two of them, the azithromycin. So you have to worry about macrolide-resistant NTM depending on how long she's been on that and then you would also worry about something that's breaking through the bacterium and that really could be anything but I'd worry about something from the environment, you know, water or soil-borne. Great, great. Thank you for that. So as Dr. Patravala mentioned, the cultures so far have been negative or presumed negative. So with her findings on the CT scan and the concern that she probably had some compromise of her right main stem, bronchus, she had a bronchoscopy performed which showed constriction of the right main stem, bronchus and sort of a necrotizing exophytic lesion. We would sometimes describe this as a pseudomembrane where you have recurrent infection or inflammation and the granulation tissue is there but it's granulation that you would be concerned it's either related to radiation or to infection, that yellow appearance. Right. And then we had the interventional pulmonary attending perform the tissue debulking and tracheal dilatation for the patient and then the tissue was sent for histopathology which showed chronic inflammation, necrotizing debris, granulomas and it was negative for malignancy. And this particular, like the pseudomembranes that you're describing and the granulomas certainly raise a concern for an aspergillus pseudomembrane formation. I just wanted to also ask Dr. Murthy, is there advantage, disadvantage to doing this kind of debulking if you're worried about infection? Is it the right time to do it or is there a right time to do it? It's a tough question to answer just because it's hard to generalize. In this specific case, I think it absolutely had to be done because no amount of antimicrobial therapy is gonna be effective without source control and that's what this is gonna achieve, symptoms aside. It probably won't help address your cough on its own because there are many layers of airway that are compromised, unfortunately. But from an airway clearance standpoint, no acetylcysteine is gonna get through it, right? So you need it to debulk. I think it was the right move. I don't think NAC really does much on a good or bad day. Perfect. Just another comment that tissue cultures can be very helpful in these situations. So oftentimes we do see histopathology sent which doesn't give us the specific diagnosis. So we end up with something that doesn't show malignancy, suggestive of infection, but we don't get information beyond that like without cultures. And for anyone who's interested in intervening on these, I would exercise caution. These tend to be very neovascularized, very sensitive. Even touching these with a bronchoscope can induce significant bleeding. So you'd wanna be prepared before approaching a case like this. Great. So at this point, what do we think is the differential diagnosis for this patient? Okay, so this certainly could be infection. Like, I mean, that would probably be my first guess. And you have a patient like who has a chronic cough, looks like she's been coughing for at least a year, right? Like if not longer. So we certainly have to think about like atypical pathogens, like so fungi, mycobacteria, alongside, you know, like routine bacterial pathogens, of course, you know, yeah, I think you have a good differential on there. Aspergillus is certainly one of them that I would think about, you know, with that appearance that was described. And just to add, some of the other non-infectious etiologies can cause fibrocavitory lesions like granulomatosis with polyangiitis, cryptogenic organizing pneumonia, sarcoidosis, Langerhans histocytosis, and sometimes septic emboli can cause this picture shift. And then as Dr. Tamer was mentioning, what are the cultures growing? So this is the next question for you guys. What do you think is the culture growing? Guess the bug. This patient had mycobacterium xenope. As Dr. Tamer was mentioning, something like indolence, low-growing, you know, non-tuberculous mycobacterium, something which is like opportunistic infection could be causing this kind of a slow progression of symptoms. The disease is usually insidious and onset, and in patients who have pre-existing pulmonary disease, they can have apical cavitory lesions with mycobacterium xenope. This patient was seen at our Global TB Institute at Rutgers. So I'm just gonna skip through this. There is paucity of data on the combination of a regimen used for mycobacterium xenope treatment, and there have been a couple of systematic reviews which have used multiple regimens, and there was a prospective randomized open-label study with like only 34 patients, very small population, which looked at the regimens between, comparison between rifampicin, etambutol, and ciprofloxacin versus rifampicin, etambutol, and clarithromycin groups. They got this regimen like daily for two years, and then the follow-up was at five years to see if they had any treatment response or failure, and they saw no difference in both the groups. And per the most recent ATS, ERS, IDSA guidelines for fibronodular disease for mycobacterium xenope, azithromycin, and or amoxifloxacin, along with etambutol and rifampin, daily or three times weekly regimen can be given. If patients have cavitary lesions, you can add amikacin IV three times weekly, and we are aiming for a 12-month sputum culture conversion. Patients who have, who can undergo surgical resection of the cavitary lesion, they have a higher sputum culture conversion ratio, and patients who have the mycobacterium xenope infection usually have higher all-cause mortality, and it's not particularly related to the mycobacterium infection. They're just very sick patients. And for our patient, she was on the airway clearance measures for her bronchiectasis, the flutter valve, albuterol nabs, hypertonic saline nabs. We started her on amoxifloxacin, rifampin, and etambutol, but she had a viral infection, adenovirus infection, and along with that developed an idiosyncratic rash, and so the regimen was held because we couldn't discern if this was because of the regimen or because of the viral infection, and we aim to gradually put her back on the antimicrobacterial treatment regimen. So thank you so much.

productive cough

bronchiectasis

CT scans

necrotizing exophytic lesion

granulomas

mycobacterium xenopi

antibiotics

airway clearance measures

idiosyncratic rash