Welcome back to the Ninja Nerd Podcast. Today we're talking about lung cancer. We're continuing our conversations throughout oncology and next up is lung cancer and I'm pretty sure it's going to be a behemoth. Yeah, this one's a huge one. Very common one but I think the biggest thing to remember about lung cancer, and this is why it's actually a really scary one, is the most common cause of malignancy related deaths. So when we think about any kind of cancer that could actually kill you and cause that higher chance of mortality, this is the one. It's more common in men, but there is an uptick in women for this condition. And when you put lung cancer under a big umbrella, how would you go about breaking this topic up? So I think the biggest thing to think about when we talk about lung cancer is really breaking it into kind of screening, because obviously just like we talked about breast cancer, when we think about it, it's like, how can we potentially know, the way that we can prevent breast cancer from when we identify it from being stage three, stage four. How can we catch it a little early and then come up with the next steps? So that's the same thing for lung cancer. We should know which patients are at the highest risk of lung cancer. How do we screen them if they end up getting an image for some other reason? And we see something weird on their chest x ray or on their CT. How do we know what to do with that? That's the first thing. And then the second thing is to know if it's super, super aggressive, very rapidly developing lung cancer, such as small cell carcinoma, or if it's one of the other ones that aren't as rapid, but it can still be problematic and that's non small cell lung cancer. How do we screen patients? How do we know how to follow up on a nodule that shows up on an image? What do we do with it? And then second is how do we really think about small cell and how do we really think about non small cell lung cancer? So those are the two arms of this discussion is non small cell and small cell. Exactly. All right. Yep. Let's get into it. All right. Case one We have a 58 year old male presents for routine annual lung cancer screening- Hey, now getting an annual screening, is that something you do after a certain age or is this like, Hey, we should be doing this every year? I don't. So the USPSTF gave guidelines on this and actually recently changed a little bit, but 50 to 80 years of age is the timeframe. The risk like population is those who are smokers, whether it be current or former. Yeah. But you have, if you're a current smoker. It usually needs to be greater than or equal to a 20 pack year history. And the way that you determine that is You look at the number of packs that are usually smoked within a day, and then you multiply that by the number of years that the individual has been smoking. So let's just give an example. You smoke two packs a day, and you've been smoking for 15 years. That's a 30 pack year history. they had greater than or equal to 20 pack year history, 50 to 80 years of age. Their current smoker or former smoker and still meets that greater than or equal to 20 pack your history. The little caveat to the former smoker is you had to have quit within the past 15 years after 15 years, you don't really fit that high risk population. So current or former greater than or equal to 20 pack your history. If you're a. Former than it needs to be less than 15 years. And the age range that we start screening annually is 50 to 80 years of age. Yep. So with our patient again, 58 year old male presents for his annual lung cancer screening. Okay. So he falls within this range. Yep. It's because he is asymptomatic but has a significant smoking history. This patient has a 35 pack year history. He had quit smoking five years ago. No previous imaging is available. He denies cough, shortness of breath, hemoptysis, or weight loss. For our past medical history, hypertension, type 2 diabetes, medications, he's on metformin and amlodipine. Family history, his father was diagnosed with lung cancer at age 60. For his exam, vitals are normal. Nothing out of the ordinary here. Exam, lungs are clear bilaterally. Otherwise unremarkable. So we're not really noticing too much with this patient. He's overall asymptomatic. He's doing his annual screening. He has a pretty extensive history of smoking. Yeah, and he had quit five years ago. Yeah. All right. So at this point, Zach, what do you do? What's the recommendation at this point for this patient? Because right now he's looking so far so good. Yeah. So we with this patient with the concern I have is there a chance that I'll find like a nodule or find a lung mass? And so they meet the criteria, as we discussed, 50 to 80, current, former, greater than or equal to 20 pack year history, if you're a former, had to quit within the last 15 years. So he fits all the categories. He's between 50 to 80 he's been smoking, he's got a 35 pack year history. Even though it's, he's not a current, he is a former and it's within the past five years. So he fits the category to, to get a screening question is, is how do we screen them? Yeah. So we need to get chest imaging. We don't want to hit them with higher radiation, especially if they're getting annual screens. So we do a very low dose radiation chest CT. And that's the first way that we have to go about this is we need to say, let's get a low dose annual CT scan. Look to see, do I see oh my gosh, there's a goober hanging in your chest or is there nothing or, oh man, this looks a little I don't really know. Is it good, bad, ugly? There's a nodule. So that's figuring out is that there are nothing, is there a nodule or is there a big honking lung mass? For our patient here, we get the low dose CT. It does reveal a new solitary. 10 millimeter nodule in the right upper lobe. No previous imaging is available. What's your thought process here? Yeah, that's a concerning one. So when- it sounds like we're catching it early though. Yeah, you are. And that's really good. So when I hear solitary 10 millimeters, that's a little bit on the bigger side. It's not crazy, but what we do is, is once we get a nodule. And if it's new, so always on the exam, I'm telling you when you hear the exam, patient has, let's say that they didn't even mention that this was their first screening. They got a chest x ray or low dose annual CT, found the nodule. How do you know if it's new? You have to compare to prior imaging. This one doesn't have any prior imaging. So we're going to consider it new. So in this case, when it's a new nodule, we have to determine it based upon risk stratification. So I'd probably have to get a CT. So I'd probably get a normal CT for this patient first to better quantify, better take a look at it while they're doing that. I'm going to go into my calculator and I'm going to look at their risk and see where do they fall. Are they low, intermediate or high risk? The way that we determine how they fit in a risk category is based on age. If you're less than 40, low risk. 40 to 60, intermediate risk. Greater than 60, high risk. So he would be intermediate. So this one would be within the intermediate range. Second, is does this patient smoke? If they don't smoke, low risk. Current smoker, intermediate high risk. Another thing that we look at is the location of the nodule. And he was a right upper lobe. That's concerning upper lobes, more likely to be more malignant, lower middle lobe. Those are likely to be more possibly benign or they're low risk. Now with a upper lobe, is that where you get a Horner syndrome involvement? You definitely can. If, especially if it's near the apex, like near the superior sulcus, you can get some compression of a lot of different things like nerves and vessels and stuff like that. So 100%. The other thing here that's really important is the look. So what does it look like? The fact that it's solitary what we want to look at, is it round, smooth borders? Or is it more scalloped? Where it looks like it's like wonky. Is it irregular and has like spiculations? So if it's smooth and round That's like the lower risk. If it's scalloped, if it's got irregular borders, it's like poky and looks like it could really stick you. That's more high risk. So what I see here is I'm really seeing a patient who fits age range of intermediate. I see a location that suggests more like the intermediate range to high range. I see also another important thing here, which is the current smoker that fits them into the intermediate high range. The size, if it's less than eight millimeters, that's low. If it's anywhere between eight to 20, that's intermediate. If it's greater than or equal to 20 millimeters, that fits them within the high risk category. So the big thing for me right here is everything screams a intermediate risk. Next thing, upper lobe. A little bit concerning for intermediate risk and what I would do here is I would probably get a PET CT scan before referring them to a surgeon to get a biopsy. Some people, they may want to go to a biopsy, but I think that this person fits more of that intermediate risk and I don't want to put them in a need to get a procedure that's not necessary and put them at risk. So I'm going to do a PET CT. It's going to take a better look. At the nodule. And so it's really cool when we do PET CT, we use this thing. It's called FDG. It's called fluorodeoxyglucose and we take that thing and we it's like a radio tracer and basically cancerous lesions take that and they light up like a Christmas tree. And it shows up that this, Oh, this area is really has a lot of metabolic activity, which you would see with a cancerous mass. If it's really likely to be malignant. If it's benign, it won't take up as much of that. So can you see why if I say, all right, I'm going to have you get a biopsy of this lung, this like this suspicious appearing nodule. That poses risk. If I do the PET CT and I say, Oh man, this thing's lighting up. That's really concerning. Now I think we should go to do a biopsy. It just really makes sure that we don't do something that could harm, iatrogenically harm the patient. So that's what I would do is I get the PET CT scan and go from there. We don't want to just go for being completely aggressive, especially as you said, he's in that intermediate stage. So what we do is we get the PET CT, like you said. Now this PET CT does however show an increased uptake of that fluorodeoxyglucose. would you go to a biopsy now? Yeah, I'd biopsy. And so depending upon the location of it right upper lobe. You this is where a surgeon has to get involved and your pulmonary team has to get involved. So there's a lot of interdisciplinary involvement here, but you have to figure out the best target to get that biopsy. If it's like really close to the periphery, you can actually stick a needle through the periphery and it's guided by like CT or sometimes even like ultrasound or fleuro and stuff like that. But we guide a needle to show that going into where that mass is and we can aspirate off some of that. If it's more centrally located and I can actually get a bronc down there to find that mass and it's endobronchial or it's even maybe a little bit outside, I can use ultrasound in the bronchus and go in there, take some of that if they had a plural effusion. Believe it or not that stage four, this was terrible. But if a big pleural fusion, you can stick a needle right to the pleural effusion, pull that off and send it off for cytology and see if there's cancer cells. But that's definitely what I would have to do. And it just depends on where it's located. Hopefully this won't be a little bit more peripheral given it's the right upper lobe. And maybe I could do like a CT guided FNA for this one. All right. That kind of discusses what we would do in this scenario of how we would go about. That diagnostic procedure there. Exactly. I think the whole goal to take away is if it was low risk, let's say that this patient was low risk, like they fit, like they were younger, they weren't a smoker. It was round. It was smooth. It wasn't like huge. It was less than or equal. It was less than eight millimeters. I would just do another follow up CT in six to 12 months. If it came back worse than this, like the worst case scenario is if it came back and it was like, this thing's. 22 millimeters. It's they're a heavy smoker. They're greater than 60. They have speculated all over it. It's speculated and it's very irregular appearing and it's upper lobe. I probably wouldn't even bother with the PET CT. I would just say, let's give a biopsy of this. At that point you could be aggressive. Exactly. And then to add one more thing, cause we didn't see this in this patient in your exam, you can't forget this. Let's say that this patient had another, let's say that this wasn't as bad. Let's say that we had the patient who was the low risk 10 millimeters. I'll say that was fine. We did an annual we do to repeat CT in six to twelve months. If that thing increased in size or doubled in size, I got to go to biopsy. Yeah. So that's another thing is that you have to know if the actual mass or the nodule got bigger, usually we say, did it get bigger and I'm doubling size, did it get significantly bigger? So there was the rapid growth within the past two years. If there's been rapid growth in the past two years. You don't even want to, you probably just go straight to biopsy that day. I want to move on to case number two now. All right. We have a 64 year old male presents with chronic cough, hemoptysis, weight loss, and a new hoarseness to his voice. He has had a persistent cough for four months now, recently with blood streaked sputum. He had an unintentional 15 pound weight loss and hoarseness over the past two weeks. He has a heavy smoking history, 50 pack years, occupational asbestos exposure for 25 years. Oh my gosh. That's not good. For his past medical history, pertinent for COPD, hypertension. Medications. He takes an albuterol inhaler and lisinopril. For his family history, his father died from lung cancer at age 67. Let's get vitals, BP is 130 over 80. Heart rate is 84. Temp is 37 degrees Celsius. For pulmonary, we have decreased breath sounds, dullness to percussion, right upper lung. Hoarseness is noted. What would that be significant for, Zach if hoarseness is noted? That's a good one. You remember he brought up like a Pancoast tumor? Yes. So sometimes if like, apical tumors are near the recurrent laryngeal nerve, they can smash that puppy. If you, if I had a tumor near the apex, the recurrent laryngeal nerve actually, you get a right vagus and a left vagus. The right vagus comes down and swoops underneath the subclavian artery. The right subclavian artery comes back up as the right recurrent laryngeal nerve. The left vagus comes down swoops underneath the aortic arch and comes back as the left recurrent laryngeal nerve. And as they come up, they go and they supply your larynx, which is your vocal cords and controls the movement of airflow across those with your speech. If I had any point mash on one of those, I decreased the supply to my vocal cords. And so sometimes you can get vocal cord paralysis, which is scary, or you could have hoarseness of the voice. With the next part here, labs and imaging, we get a CBC, CMP, normal. Chest x ray, we have right hilar opacity. Chest CT, we note a four centimeter central spiculated mass, ipsilateral hilar nodes. Not too good? No. Okay. Where do we go from here? We have a lot of information, we've got some rough diagnostic imaging. What's the next step? You gave me everything that I would have started off. So if the patient just came in with cough, hemoptysis and weight loss I would have done everything you just did, which is. Get a chest x ray first, see what's going on there. And it doesn't always have to be lung cancer. So this could patient could have pneumonia. They could have something else weird tuberculosis. So it's always good to start off and just get a chest x ray with the past military of CFPD. So initially it's always important to just get a chest x ray, take a look. It's not the best test. It's just the best initial test. It showed some abnormalities. But the best test is the chest CT that was concerning when I see a mass that's four cents. So usually anything greater than three centimeters. That's probably where I'd start getting concerned. Because that's now considered a mass, a lung mass and on a nodule. The fact that it's a regular, it's speculated, that's concerning. And then you told me that they got some node involvement. So MC lateral higher nodes that put them in one stage in the TNM staging. This is pretty concerning, man. So I think like with all of this right here. I have a lot of confidence that at this point we just need to start getting ready and say, Hey, we need to do a biopsy of this mass. I was going to say, we've done an x ray. We've done the CT. At that point, you kind of have to. Yeah. At this point, this is a central lesion too. So remember the last one, it was upper lobe, maybe peripheral. I could do a CT guided FNA. This one is, it's central. You can't do that. So for this one, you do a bronchoscopy. You go down bronchoscopy. Sometimes you can do it with an endobronchial ultrasound. And I would try to get to that mass and biopsy the mass there. And I would even try to get to the lymph node there. That's why you use the -they call it EBUS: Endobronchial Ultrasound. So you can take this thing down and you can say, Oh shoot, there it is. There's that lymph node pop right into it and take some of the tissue there as well. All right, cool. We do the biopsy. Okay. All right. We note the biopsy for squamous cell carcinoma showing keratin pearls, Intercellular bridges and a positive P40 stain. How do we stage it? Yeah, so this is a good also talking point because when you see central, at least for your exams, central screams squamous cell or small cell. Peripheral tumors are usually adeno and large cell. So we'll talk about this a little later because this one is definitely what's called a non small cell lung cancer. So non small cell lung cancer consists of adeno, large cell and squamous cell. So those are the three most common ones. And so squamous out of those, the only one that's usually centrally located and it's usually cavitary. And then as you said here, the keratin pearls squamous cells are like epithelial cells and they love to make keratin. So that's probably why you're going to have a lot of keratin, but and then they stain P40 positive. If it was like Adeno, that has mucin staining with the TTF-1 positive staining. If it was large cell, they don't stain with anything. They're just weird looking cells. You're like, I don't know what the heck these cells are. So that's kind of the nice thing is this definitely tells a squamous, but at this point my concern is, okay, I got an Olymp know what if it's somewhere else or what if it's in lymph nodes that I can't even see? Like I see the lymph node that's involved there. That ipsilateral hilar. What if it's higher up in a supraclavicular? What if this is in the contralateral nodes? What if this is in the liver, the adrenal, the bones? I don't know, right? So a PET CT would probably be what I'd go with to see. So here's the tough thing. Some practitioners, and you're not wrong, you can do either. It's just you have to be careful. CT scan of the chest, abdomen, and pelvis with IV contrast. It can be an alternative instead of doing a PET scan. So you could do that. And as long as you do a contrast, you may be able to pick up an adrenal met a liver met. Maybe you can pick up some lymph nodes or, Oh shoot, the tumor was here in that, or was it their right side? Oh, there's another tumor in the left side, and I didn't see that one. So you can still do that. It's just the evidence has shown that PET CT has a higher sensitivity for identifying distant metastasis and It's better at identifying node involvement And it's better at identifying bone mets. So that's why I would probably just go with the PET CT to stage this patient and figure out, is this anywhere else? Because right now, all I have is they got a node involvement. They got a size. So I have the T and M of my TNM staging. I don't have the M, which is there distant metastasis or not? Because that's going to change drastically how I treat this patient. But with a PET CT, you could check for distant metastasis. Exactly. You could do with the CT. of the chest abdomen pelvis with IV contrast. It's just, it may miss something so sometimes even if the chest CT abdomen pelvis comes back negative with the contrast study, we may still just do a PET CT to be safe to make sure we didn't miss anything. That's why it's just oftentimes just get the PET CT. Let's say that there is no distant metastasis. Okay. Then how would you stage it? That's a good question. So now staging is always a son of a gun, man. I always hated it when I was in school. I'd be like, Huh, how the frick am I going to remember these things? It's a lot of information. And so the easiest thing to remember is don't, size is important, but not as important in this case. All right. The nodes are the important thing. And that's what I want you to remember. For example, N0 means that no nodes are involved. There's just a tumor that's isolated into the lung tissue, lung parenchyma. N1 is if you have a tumor on the right side, the ipsilateral hilar or like peribronchial, which is all the ones that are in that lung tissue, those got involved as well. N2 is you spread here to the central part. So now the tumor started here, went here to your parabronchial, and to your hilar, and then it moved into the mediastinum. So that's now N2. N3 is from here, it could have gone to this mediastinum, and it could have spread. Up to your supraclavicular, or it's spread to the other side, so now it's contralateral. That is the best way, because the way I look at these is it just makes it easier for me to figure out. For example, stage 1, I just look at what's the N. In this case, stage 1, it could be N0 or it could be N1. Stage 2, is it's N1, right? And then stage three, it just varies a little bit. So there's stage 3a and stage 3b and that depends upon the end as well. Right here, this patient is in one that fits stage two. So I would say that this patient has stage two non small cell lung cancer, and it's the type is squamous cell carcinoma. If they have a lung tumor, I'm not going to worry about the size of it, the T part. I want to know the node involvement. In this case, it's N1. N1 will fit with my stage 2. And then the TNM, of course, we said before, there is no distant metastasis. So we know that's not even involved. So we're good. Cause if it came back, I had some distant metastasis we're stage four, done. Okay. So that's why we look at the end. The end tells us if we fall really within stage 1 to stage 3. And then that metastasis tells me if I fall in that stage 4, you're up to the 4 immediately. Exactly. For our patient now, since you have considered this to be stage two, non small cell lung cancer, what is the treatment? So stage two is actually potentially resectable. Okay. So you can still cut this thing out and then you can go in there and cut the nodes out too. So the first thing I would do is I do some usually we do PFTs on these patients first. We want to know what their lung, function is. Because if we're cutting out tissue, we need to make sure that what they're left with is enough for them to properly function. So we have to determine if they're medically operable or inoperable. And so that's the first thing I would do. If they're medically inoperable, I may not be able to do surgery on them. And then sometimes we, there's a newer thing, it's called Stereotactic ablative radiation therapy. And so they can use that and it's a focused high dose beam of radiation that just jams right into the tumor and it could potentially kill it. You sometimes have to follow up with some adjuvant chemo. But that's an alternative if you can't get operated on. Okay. But I would do PFTs, make sure that their PFTs, their FEV falls within a predicted value that's acceptable afterwards. And if they, Oh, they're medically operable. Okay, let's send them to get a surgery, cut that thing out. And then potentially depending upon the amount that we want to do, sometimes you can just do a little wedge resection. Sometimes you have to do a lobectomy depending upon how big it is. This would not warrant pneumonectomy is you remove the entire lung. But it seems for him, it's still somewhat localized to a certain extent. And so it depends. I, you'd have to obviously have a surgeon at this point, really decide on what's the best course of action, but sometimes you may just have to do a lobectomy and that might be the way to go about this. And when you do the lobectomy, you also get rid of those nodes that were involved. Sure. So cut those puppies out so that it doesn't continue to spread along the other lymph node passages. How about any complications associated with non small cell? Anything in particular? Squamous cell has its own kind of complications. Okay. Any lung cancer, you can have, sometimes they're asymptomatic, sometimes you just don't know. Sometimes it's very mild, like a weird symptoms, like just a cough. Yeah. Sometimes you can actually cough up blood, right? Which I think this patient did. They had hemoptysis. He did. Sometimes you can obstruct the airway and then get wheezing. So any kind of central mass is more likely to obstruct airflow. Funny enough, the most common presentation of a patient with a central mass is recurrent pneumonia. So let's say that a patient had, pneumonia in their right middle lobe. Three times this past year, bro, what's going on? You know what I mean? It's not normal. Sometimes if the tumor is in one of those bronchi and it's big enough that it's obstructing the bronchus, you can't pass mucus and bacteria across that for you to spit that up. And so if you obstruct the mucus and like the ciliary flow of things that will cause an obstruction just post or after where that tumor is. And so it's called post obstructive pneumonia. We see it a lot of time when people get a big enough obstruction and you get no airflow. What would you think would happen to the air sac? It would shrink. So it's called post obstructive atelectasis. In this case, they just let all the bacteria and mucus sit there and it gets infected. And so they get a post obstructive pneumonia. So recurrent pneumonia is in the same lobe. For your exam, it's always going to be concerning and suspicious for malignancy. So that's something that I would think about. The other thing is compressive effects. So they had recurrent laryngeal nerve compression, right? So there's a shat ton of nerves that run through this area into the mediastinum, right? So you can think about it. You got the phrenic nerve running down. That could get compressed. So then you get phrenic nerve paralysis. That's not good. No, it's because your diaphragm is dookie now. Yeah, so that's a tough one to diagnose. but the right phrenic nerve, imagine that thing got compressed. So then what would happen is this diaphragm, it, when it's supposed to contract, it's supposed to drop down. It won't be able to do that. And so when you get a chest x ray, what happens is this diaphragm is elevated a little bit. Because the diaphragm, if it, when it's contracting, it drops down. If it can't contract, it's going to be boop. And you're going to have an elevated hemidiaphragm. So you know what we do? It's called a sniff test. You have them under floral, and you have them go like this. And if you do that, your diaphragm should do what? Naturally drop down. One this one will drop down this one will not and so that's a way that you can see phrenic nerve paralysis This one doesn't have it, but that's one. Yeah. Another one is you could compress the sympathetic chain ganglia, and so that's the ones that are this particular one the superior cervical kind of stellate ganglia They go up and they supply your eye, particularly the, levator palpebrae superioris and then this supplies the pupil and then some of the eccrine sweat glands. And so if you compress them puppies they smash what I was talking about. Yeah. If you smash them bad boys, then your pupil won't be able to dilate instead, it'll constrict. And so it's called meiosis. The levator palpebrae superioris won't be able to contract so you'll get a droopy. Right. And then you can't sweat. Yep. So ptosis, and then you can't sweat. So anhidrosis. So the mnemonic is Pam, Pam, Pam, Pam, Pam, this is for the office people in there, but it's a ptosis, anhidrosis, and meiosis. Another nerve is going to be the recurrent laryngeal nerve. Talked about that with our patient, hoarseness. Yep. And then one more would be the brachial plexus. That's really a tough one, but if you have your nerve roots right around that thoracic outlet it's, I think it's C8 to T2 nerve roots can get compressed. And so you can get shoulder pain and then it hits the ulnar nerve distribution. But those are the biggest things with the nerve compression. If it's really big and in the center the superior vena cava comes down and so it could mash in the superior vena cava and then blood can't drain into the right atrium. So you could get like a JVD, you could get swelling of the face and some right heart failure. Yeah. Except a lot of it will stay in the upper extremities of the lower. So that's another one is SVC syndrome could be a pretty scary one, but those are the biggest things. And then the last thing that's important is that these tumors, they're funky. They may gain the capacity to make hormones. And so you remember hypercalcemia bro? I sure do. So hypercalcemia malignancy, you always think PTHRP, vitamin D or lytic lesions. This one can cause high PTHRP secretion. So the tumors literally make PTHRP. Tell the bones to resorb calcium and then they also tell the kidneys to reabsorb calcium so they can get hypercalcemia. All I know is the stones, bones, groans, psychiatric overtones. That's all you got to know. That's all I got. That's all they could present with stones, bones, groans, thrones, psychiatric overtones. You like that one, huh? I like, yeah, I know my stuff, but that's one thing there. So that, that would be what I would look at. Actually, I'd actually order a calcium on this patient. If I had any kind of concerns like that. And did they get a they got a CMP. It was normal. So the calcium would have came up, normal on this. Oh, true. True. Yeah. So with adenocarcinoma, one of the things about this one is it can release transformative growth factor beta. And now this guy, this one acts on like fibroblasts and periosteal cells. And it makes, I'm not even kidding, man. It makes your fingers look like. Like spoons, you could literally like scoop mashed potatoes with them bad boys. You don't need utensils. You got them on your freaking fingers. Oh gosh. But in all seriousness, it is really terrible. It's called hypertrophic pulmonary osteoarthropathy and it's where I'm not even kidding. You get like finger clubbing. And that would be one potential sign of adeno. I can't say this is all too common with adeno, but sometimes adenocarcinoma, certain tumors, especially pancreatic tumors, they can pump out a lot of tissue factor. And tissue factor is a part of our extrinsic pathway for coagulation. They can activate factor VII, they can trigger a lot of clots to form. Sometimes this can be in form of superficial thrombophlebitis. So you get these red, tender cords that are clothed within veins in the extremities, usually in the arms, or it could be full on DVTs, PE. The last one is a paraneoplastic syndrome is large cell. Especially for the non small cell lung cancers. And this one, they can actually release HCG. This can cause breast tissue enlargement. So you end up with orangutan titties. You know what I mean? The torpedo titties. Yeah, exactly. So that's another one. Gynecomastia is a pretty concerning feature that can happen with large cell. So that's, I'd say the biggest things to take away from this is what happens if they're central and they obstruct an airway, right? You can get pneumonia. What happens if they're peripheral? You can get pleural effusions. A third is what happens if these things are secreting hormones, you can get perineoplastic syndromes. So those, and then also if they're a little bit more central and apical, you can get nerve and vessel compression. All right. That does it for case two. All right. We got one left and it's on the big mama, small cell lung cancer, small cell lung cancer. All right. So we have a 60 year old male. With acute facial swelling, severe dyspnea and persistent cough. That sounds like SVC syndrome right away. 100 percent though. Okay. Now this patient has rapid onset. He notes to be less than two weeks of facial swelling, shortness of breath and worsening cough. He is a heavy smoker, currently 45 pack years. Past medical history is pertinent for coronary artery disease and hyperlipidemia. He's currently taking aspirin and atorvastatin. For his exam, his vitals, BP is 145 over 92. Heart rate is 92. Respirations is 22 per minute. SpO2 is 91 percent on room air. General, we note significant facial edema and a prominent JVD, SVC syndrome to the max. Yeah, for real. In this scenario, this patient, his SVC is just getting cut off. there's probably massive like central compression somewhere in the mediastinum for this bad boy. And then for pulmonary, he has mild bilateral wheezing, diminished breath sounds bilaterally. We do labs and imaging. We get the following back, CBC, BMP, normal. Chest x ray, we have a central mediastinal mass. We follow that up with a chest CT, and we have a large central mass compressing the superior vena cava. Look at you, dude. You're a diagnostician. I'm pretty good. I'm not going to lie. I'm pretty good. I'm the real deal. So Zach, our final case, 60 year old smoker, 45 pack years. We've got facial swelling, prominent JVD, dyspnea, and this pretty large central mass compressing the SVC. Yeah. Thoughts. What do you do? I think you said, I think like you got definitely a concern for SVC syndrome. So this is like somewhat of an oncologic emergency. So that's definitely one of the things that makes you start working up what's going on in the chest. You already got that already started. You get the chest x ray that showed that there's a big mass inside of the mediastinum. Followed it up with a chest CT that shows us, there's a really large central mass that's compressing the superior vena cava. The thing that's concerning me is the rapidity of how this formed. Like they got SVC syndrome in like less than two weeks. It was really quick. And then usually SVC syndrome with central masses. You can get it with a squamous cell because that's also a central tumor.

squamous, small cell.

adeno, large cell. And so this definitely could be squamous, but I think usually squamous doesn't get as big to cause, and then it does not that rapid to, to be like this. So this is definitely just I don't know, scream small cell lung cancer. And really the only thing I got to do with this one is I got to go and do a biopsy. And so this one, it's central. So a bronchoscopy with a biopsy via that route would probably be the way that I would go here. And I look to see what that would show. The big thing here is whenever you do a biopsy for a small cell, what you would want to see is these poorly differentiated cells. Very like small, round filled with like height, like lots and lots of chromatin. And so it just shows that they're not really like very well differentiated. The cells that these form from are what's called neuroendocrine cells. So when you look at the lung epithelium, there's always the Pseudostratified ciliated columnar epithelial tissue. Then you got these little basal cells, which are like the progenitor cells. And then you got a lot of your cells that produce mucin. So you have the goblet cells. And then you also have neuroendocrine cells, and they make some hormones. Whenever you have a malignancy for a small cell, it's a malignant transformation of those neuroendocrine cells. They're called the Kulchitsky cells. And so whenever you have rapid proliferation of those, they like poorly differentiate, they stain with particularly on immunohistochemistry. You use immunohistochemistry to look for a very specific protein called chromogranin A. And so that would be what I'd be looking for here. So that's what I'd be looking for is the staining positive for chromogranin. I'd look for like the a small, round, hyperchromatic, poorly differentiated cells. And that would really be the way that we would confirm small cell lung cancer. We do the biopsy. It does confirm the small cell lung cancer. Okay. What would be your next diagnostic steps here? The big thing here is you gotta know if it's like limited or extensive. So we see that it's like large, it's central. I don't really know how many lymph nodes are involved. If they're pretty extensive in that sense. So I'd probably do a PET CT. That'd be the first thing. It would show me like if it's isolated to the hemithorax. If I got like limited, that's you're lucky. You caught this early and there's more that we can do. If it's extensive, that means it's beyond the, this ipsilateral thorax, hemithorax. It's in the other one. It's in multiple lymph nodes on the other side. It's a spread to the brain. It's spread to the adrenals, the liver, the bones. I start with a PET CT and then you have to do an MRI of the brain. The reason why is that this spreads, you can remember the mnemonic BLAB. So with lung cancer, it metastasizes to the brain, the lungs, the adrenals, and the bone. Those are the locations that I'm concerned about. The one with the highest risk of mortality is the brain. Because if that thing gets into the brain small cell lung cancer can bleed in the brain. So you can get hemorrhage. It can also cause seizures. It can increase intracranial pressure. So there's a lot more chances of neuro deficits, et cetera. So that's the things I would do is I would start off, get a PET CT, see how extensive this thing is. If it is extensive or did I get lucky and it's limited to that ipsilateral hemithorax and get a brain MRI to make sure that it's not spread to the brain. For our patient must've been caught a little earlier. It does show limited stage small cell. What's our best treatment approach knowing this information? So it's still going to be aggressive. So the diagnosis of small cell lung cancer, it's, again, you can catch it limited. That's a great chance that you can maybe prolong survival, but the prognosis is still poor overall. So you're going to do probably some type of platinum based chemotherapy for this patient. So usually cisplatin is a common one and then you're going to combine that with another agent like a toposide. And so that's usually you're going to be doing those things in combination with radiation therapy. The point of this is that you're going to use these agents to try and kill some of the cancer and prevent it from continuing to grow. The radiation therapy is also going to try to kill some of that micrometastasis as well. You're just trying to hopefully improve their chances of living a little bit longer. And trying to limit the spread. The other thing is when you try to limit the spread, again, a very important area is the brain. So sometimes we do prophylactic cranial irradiation. see how they respond to the chemo and the radiation. If they had a pretty good response, I think no matter what you should try to prophylactically cranially radiate to prevent that potential metastasis to the brain for this patient. So that's the way that I would go about this one. How about high yield complications? Anything we need to know, big complications for small cell lung cancer? It's all the same stuff that you get with a central mass. So with the central mass, you can get post obstructive pneumonia, you can get wheezing, you can get coughing, you can get hemoptysis, right? If it's big enough and it's in the central portions where the superior vena cava or some of those nerves run through you may get compression symptoms It's not peripheral. So you don't get plural effusions with this one too often unless it spreads and it spreads it can but the last thing is paraneoplastic this one has the most like variations of its paraneoplastic syndrome and it's funny because It's derived from neuroendocrine cells. Neuroendocrine cells make hormones. These make a couple of them. First one is ADH. I know you remember from the hyponatremia, or the sodium disorders lecture, right? Of course I do. You thought I forgot? So, SIADH. Syndrome of Inappropriate ADH Secretion. A common cause of malignancy. It could be drugs, right? That could definitely be one. Sometimes pain and lung diseases can cause that, pituitary to produce ADH. But sometimes it could be ectopically produced from a cancer. Small cell lung cancers actually can make ADH. If you make too much ADH, it goes to the collecting duct. Acts on those vasopressin receptors and reabsorbs tons of water. Water gets into the bloodstream, dilutes down the sodium, you can get hyponatremia. And so that's one thing that we can see is SIADH in these patients via the presentation of hyponatremia. Hyponatremia can present variably. Maybe headaches, maybe nausea, maybe vomiting. Sometimes it can cause enough edema in the brain that it can cause the ICP to go up. If it's severe and acute enough, it can cause seizures. That's a big concern. Another one is Cushing's. So not Cushing's syndrome, even though people want to call that it's Cushing's disease. So Cushing's syndrome is when it's coming from the adrenal gland. That's the problem. It's the one pumping out cortisol. Cushing's disease is when it's coming from another source that's producing ACTH. Usually that's the pituitary. It's like a pituitary adenoma. Those micro adenomas can pump out ACTH. If I were to do this patient, what I would have is I'd have a patient who would have high cortisol. So they would present with a swollen moon face. They present with a buffalo hump. They present with the abdominal striae and a lot of central obesity. Maybe even like high blood pressure. You would check their cortisol. It'd be elevated. And you do all those workups that you would be doing for Cushing's syndrome, you do your low dose dexamethasone, you do the urinary cortisol, you check all these things, salivary cortisol, and then once you find that, okay, cool, let's figure out, is it coming from the adrenal, or is it coming from the pituitary, or is it coming from somewhere else like the lung, you check the ACTH levels, alright, and so the ACTH levels in this case would be through the roof. And then what you would do is you would then say, okay, how do I know if it's coming from the pituitary or coming from the lung? And so then you do what's called a high dose dexamethasone suppression test. And if you do that, you would suppress the pituitary, but you would not suppress the lung tumor. And so the ACTH levels and cortisol levels will still be high. That would make me think about a Cushing's disease due to an ectopic ACTH secretion. The last one, I've never seen this- is Lambert Eaton syndrome. It's just something that's been associated with lung cancer. Lung cancer has antigens and these are abnormal tumor antigens. And so your plasma cells will see those antigens. And what will happen is you'll have interaction with other cells that will communicate to the plasma cells. Let me make antibodies against those tumor antigens to try to get rid of them. Those antibodies that you make towards the tumor. Antigens may mimic. or look similar to some of the antigens that are present on nerves, especially the nerves that go to our muscles. There are the voltage gated calcium channels that are on the axon terminal. Those antibodies can go and attach onto them, block them. Calcium can't come in. Your nerve can't release acetylcholine. Your muscles can't contract. You get proximal muscle weakness. You'd be like, Oh, shoot, this looks like myasthenia gravis. It's kind of like myasthenia gravis except with Lambert Eaton syndrome, it gets better with exertion. Myasthenia gravis, it gets worse with exertion, the weakness. So that's something that you would also be thinking about in this one. All right. In summation, Zach, that covers all three cases we had today on lung cancer. If you had to send our audience away with a final high yield recap, What would you say? I think the biggest thing is to make sure that you follow the screening protocol. According to the 80, greater than or equal to 20 pack your history, current, former, and former less than 15, you screen them low dose annual CTs. If you get a nodule, risk stratify them, get a CT scan to get a better characteristic of it. So you want to look at the characteristics of it to know, is it smooth, round, irregular, speculated, things like that. You want to look at their risk. Do they smoke? What's their age? And then also take into consideration of all of these things and the location as well and say, what should I do? Are they low risk? Just get another CT in six to 12 months. Are they intermediate risk? Let's be safe. Let's do a pet CT. Are they high risk? Just go straight to biopsy. So that's really important for non small cell. Remember that there's only three. There's squamous cell, there's adeno, and there's large cell. They all have their distinct kind of characteristics in the sense that squamous is central, adeno, large cell, peripheral. When you think about these, it helps you think about the way that they would present, but perineoplastic syndromes are commonly utilized on exams to differentiate these squamous cell, hypercalcemia, adeno, clotting, and also consider clubbing, the hypertrophic osteoarthropathy. Large cell, tits. Gynecomastia, so those are, I'm just trying to help you remember, but that's a, that's something to think about here. Small cell, super, super aggressive, rapid, central mass that causes massive presentation almost all the time for your exams- superior Vena Cava Syndrome. Remember the paraneoplastic syndrome for this one, SIADH, Cushing's disease, Lambert Eaton syndrome. The other thing for these ones is that non small cell, it has a chance of being treated a little bit better based upon if it's stage 1 and 2. You can actually surgically resect those. Stage 3, it depends. You might have to do chemo before it to shrink it, see if you can resect it. If it's not, It's chemo radiation and you're probably doing targeted therapy depending upon the type of if there is any oncogenic drivers there for small cell, you just need to determine is it limited. If it is limited, chemo radiation, prophylactic cranial irradiation. It's extensive. You don't really got much help. It's probably just chemo. All right. That wraps it up. That's all I had as far as questions for lung cancer. That was a great episode. Thank you. Yeah, man. Thank you. And I hope that you guys liked it and I hope you liked this episode and you learned a lot and enjoyed it. 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