Lung Cancer/Tumors

in this video i'm going to teach you everything that you need to know about lung cancer this is an this is an incredibly high yield and important topic that shows up all the time so my goal in this video is to have a reductionist approach simplify this tell you only what you need to know and nothing more explain confusing topics that trip medical students up all the time and then pepper in some pretty sweet mnemonics so let's get started now when it comes to lung cancer you don't really need to conceptualize this and break it

down into different categories but i know that generally speaking we're all a little ocd so if this will help the way that i think you should think of lung cancers is two big categories and we're going to use the same categories that the world health organization uses because it just makes the most sense on the left we'll talk about large neuroendocrine lung cancers and on the right we'll talk about non-small cell lung cancers there are other ways to categorize lung cancers but to be clear for the purposes of usmle or comlex this really doesn't matter

at all i'm just putting this here for completeness sake and for those of you who are a bit neurotic like me so the cancers that we're going to talk about in this video are what you see on this slide in the large neural endocrine category we'll talk about small cell carcinoma and bronchial carcinoid tumors and then in the non-small cell category we'll talk about squamous cell carcinoma adenocarcinoma and large cell carcinoma just a brief overview on lung cancer and why it shows up on exams all the time this is the leading cause of cancer related

death worldwide and perhaps obviously this is due to smoking it's the second most common cancer in both men and women so because it's such a public health concern obviously test writers are going to put this into exams all the time because not only is this does this topic have a lot of little nitty gritty details they can test you on but there's actually a public health concern and therefore this will be really clinically relevant once you're in residency and beyond now historically lung cancer's affected males more than females typically around age 70 but this has

changed somewhat in recent times let's get started by just going through and talking about these cancers one at a time we'll start with small cell carcinoma but as you can see on this slide we're going to pay special attention to the location of the tumor the histopathology that you need to memorize and on and then all of those high yield associations that will show up and be very buzz wordy on exams so for small cell carcinoma this is centrally located and the big histopathology that you want to look for is kolchitsky cells and this is

what kochitsky cells look like they're small dark blue neuroendocrine cells that at least in the lung tumors specifically in this case small cell carcinoma will lie close to the bronchi and the bronchiolar basement membranes so if you're taking your exam you know it has something to do with lung cancer because of the presentation in the vignette and you see these really dark purple cells those are kulchitsky cells those are neuroendocrine cells but without a doubt the highest yield part of small cell carcinoma and the most important thing for you to memorize are the high yield

associations again all of these different lung cancers have high yield associations they have expressed tumor markers they have associated mutations and they have clinical syndromes that you want to look for and this stuff gets tested the most out of any single item in this entire video so when it comes to small cell carcinoma you want to know that it's highly associated with smoking and that if you're taking your test and you get a question and the question explicitly tells you that the person is a non-smoker you probably want to think about a different type of

lung cancer because small cell carcinoma is just so strongly associated with smoking so that's actually very telltale in the clinical vignette now you also want to be on the lookout for chromogram and a now this is a tumor marker that gets expressed by small cell carcinoma this is a secretory protein that you want to associate with different types of neuroendocrine cells and recall from a few slides ago i showed you that the small cell carcinoma has those kulchitsky cells which are noroendocrine so this is a really useful biomarker and shows up in exams in the

vignette if they tell you that an unknown lung cancer is expressing chromogram and a you want to think perhaps small cell carcinoma the other high yield association is the elmic oncogene okay so this is actually a mutation in a proto-oncogene that leads to or contributes to the formation of small cell carcinoma so if they give you elmic oncogene as far as a proto-oncogenic mutation thinks small cell carcinoma but without question the highest yield part of small cell carcinoma and being able to identify it on exams like usmle and comlex is being able to spot when

they give you a perineoplastic syndrome a perineoplastic syndrome is basically a clinical syndrome and you see some examples below that's due to an incorrect immune response to the cancer and the immune response to the cancer inadvertently causes something that's functionally identical to one of these syndromes like si adh cushing syndrome or lambert eaton syndrome and you really can't differentiate them from their native syndromes in other words you don't know if it's due to cancer or if it's due to like in the case of si adh a problem with adh at the collecting tubule because functionally

they're pretty much the same so if you're taking an exam you want to be on the lookout for these three syndromes again we're talking about si adh the syndrome of inappropriate antidiuretic hormone secretion so if you're taking an exam and they give you a lab printout and you see hyponatremia but you see that in the backdrop of other symptoms that look like lung cancer you know coughing up blood etc you want to think oh they're giving me a peroneoplastic syndrome they're giving me si adh and pairing it with the cancer therefore the cancer is probably

small cell carcinoma likewise they could give you cushing's syndrome so this is hypercortisolism and you should be very familiar with cushing's syndrome so if you see clinical symptoms of cushing syndrome but that's in the backdrop of somebody that's a smoker that's coughing up blood right they're giving you the lung cancer component with the symptoms of cushing's syndrome they're giving you peroneoplastic syndrome and then lastly you can see lambert eaton excuse me lambert eaton syndrome which is due to antibodies against presynaptic voltage-gated calcium channels and those are specifically located in the neuromuscular junction now recall that

this syndrome will create muscle weakness but that muscle weakness will get better with more use of the muscle alright so if you see those symptoms and you see that in a smoker who's coughing up blood who might have lung cancer you want to think oh it's a perineal plastic syndrome it's lambert eaton syndrome therefore the answer is small cell carcinoma so as you can see this is kind of tricky because test writers love to give you a question that kind of sounds like they're going after one of these syndromes maybe you think oh they're asking

me about si adh oh they're asking me about hypercortisolism oh they're asking me about some type of neuromuscular problem and then all of a sudden they're asking you for where else would you find pathology or what might the express tumor marker be and this is really a prime opportunity for the test writer to ask you a third order question that's really challenging so if you've seen my high yield video question bank series you know that i preach being able to answer third order questions by making these connections and neural networks in your brain i.e you

want to be able to think that when you get a question about si adh there's a chance they could ask you about small cell carcinoma in the lung so that you're not blindsided when you get a lab print out it shows you hyponatremia and then they ask you for histopathology in the lung and you're like what siedh and the lung what is this so you just don't want to be caught off guard and that's why this connection in your brain is really important so when it comes to small cell carcinoma how do you memorize this

right what's the dirty mnemonic that you can use well my my method here is that when you think small cell carcinoma you want to think scl small cell lung after all the way that this is you know commonly referred to is small cell lung cancer so scl and scl is a really useful mnemonic because it tells us two things one it tells us that this is associated with smoking chromogram and a and elmic oncogen ocogene mutation but we can also use small cell lung scl to memorize the different paraneoplastic syndromes s for si adh c

for cushing syndrome and l for lambert eaton syndrome so small cell lung cancer scl tells us what we should associate this with and it also tells us the perineoplastic syndrome so this is just a beautiful mnemonic so use it well so that's small cell carcinoma of the lung one of the more complex lung cancers but really honestly if you're going to take one thing out of this video just know the perineoplastic syndromes and you'll be in good shape now let's talk about bronchial carcinoid tumor so these can be central or peripheral and test writers really

aren't going to ask you if it's central or peripheral with small cell maybe they'll want you to know it's central but for bronchial they're not going to care the histopathology here is that you'll see prominent rosettes okay you're going to see prominent rosettes in the bronchial carcinoid tumor this is associated more more so with children it's also associated with chromogranin but the biggie here really is the carcinoid syndrome that this bronchial carcinoid tumor will create and what i want to do is sort of just take a step back here and over explain probably what a

carcinoid tumor is and how they function because there's a lot of confusion i've noticed with medical students and understanding carcinoid tumors but also carcinoid syndromes so if we take a step back and just speak really generally here carcinoid tumors can exist in various different locations most of them are going to be in the gi syndrome but a very small percentage of them will actually be in the lungs and that's the type that we're talking about obviously in this video with bronchial carcinoid tumors and these types of tumors they all regardless of where they're located whether

they're in the gi system the lungs or anywhere else they all share the common feature of being neuroendocrine tumors which is to say that they're comprised of cells neuroendocrine cells that are active in producing neuroendocrine chemicals right noro in the neurologic system endocrine in the endocrine system so it shouldn't be surprising to you to hear that they produce serotonin also known as 5-ht and the effects of serotonin are what you see on this slide it causes flushing diarrhea bronchospasm diaphoresis and gi upset and if you have any trouble memorizing those effects of serotonin i just

want you to think about what do you see in a patient who has serotonin syndrome well you see these symptoms and that should make sense to you because in someone that's got too much serotonin in their body whether that serotonin is due to serotonin syndrome or whether that serotonin is due to the production of endogenous 5-ht by neuroendocrine cells in a carcinoid tumor the effect is going to be the same and lastly if you've gone through your psychiatry section in first aid already you probably know that the side effects of your selective serotonin reuptake inhibitors

or ssris include the things you see on this slide and that's because when we increase serotonin regardless of if it's in a pill if it's due to a neural endocrine tumor or if it's due to serotonin syndrome the effects are flushing diarrhea bronchospasm diaphoresis and gi upset so in a carcinoid tumor it's neuroendocrine cells that contain these little teeny granules and those granules will produce these neuroendocrine products in this case serotonin now i want to explain the most complex part of carcinoid tumors and that's carcinoid syndrome carcinoid syndrome is not going to be present in

every single carcinoid tumor and i just want to take a minute to again over explain this because i see this as a huge point of confusion in lots of different students so here on the slide you see a neuro endocrine cell so that little black cell i want you to pretend for a second that that's present in a carcinoid tumor now because it's a neuroendocrine cell in a carcinoid tumor it's going to have neurosecretory granules that will produce serotonin okay so 5-ht and normally that serotonin will be basically released into our circulation specifically in the

portal circulation and it'll go up to the liver and when it reaches the liver the liver have has an enzyme in it called monoamine oxidase and for short that's mao and what the role of monoamine oxidase is is to basically break down that serotonin it breaks down that 5-ht and it makes the breakdown product 5-h-i-a-a and i don't need you to worry about what that stands for but just know that if you see 5-h iaa that that's a breakdown product of serotonin and then that 5-h iaa will get excreted out into the urine okay so

this is what happens in normal circumstances and this is what happens if you have a carcinoid tumor in the gi tract because even if you have a carcinoid tumor in the gi tract it's going to secrete the serotonin but that serotonin will go through the portal circulation and basically go through the metabolism by the mao in the liver okay so you don't get carcinoid syndrome if you have a gi carcinoid tumor because the liver is basically serving as a safety valve to break down all of the serotonin that the carcinoid tumor is creating now let's

talk about what happens if you get metastasis of your carcinoid tumor so now you see that that neuroendocrine cell that carcinoid tumor now it's red and beefy because it's going to metastasize and if it metastasizes specifically to the liver then it can bypass the metabolism of mao in the liver and what it's doing here is that serotonin is now being released on the liver because the carcinoid tumor has metastasized to the liver and that serotonin will be released directly into the hepatic vein and undergo hepatosystemic shunting and in this case because there's no mao available

to break down what's natively now being produced on the the actual liver itself then what you're going to get is that serotonin being released directly into the circulation bypassing the breakdown in the liver and at this point we have full blo full-blown carcinoid syndrome so you're gonna get flushing diaphoresis all that stuff that we talked about on the previous slide so big takeaway so far is that if you have a carcinoid tumor in the gi tract you have nothing to worry about because the liver will break down any serotonin that gets to it but if

a carcinoid tumor metastasizes to the liver from the gi tract now you're going to get carcinoid syndrome okay now we're obviously talking about lung cancer so let's talk about what happens when carcinoid tumors occur in the lungs now if that cell is occurring in the lungs the lung also has monoamine oxidase in it so basically once anything gets to the lung just like you saw in the liver in that example with the black arrows so too will the lung break down any serotonin but that's actually a problem for everything that happens before the lung so

if you're getting a carcinoid tumor that's secreting serotonin and that serotonin is going through the right side of the heart before it gets to the lung because that's the direction that blood flows then you get something called carcinoid heart disease or right-sided carcinoid heart disease and that clinical syndrome is composed of a few things one right-sided valvular fibrosis two tricuspid regurgitation and three pulmonary valve stenosis and basically what you're seeing here is that there's increased deposition of collagen which leads to all three of these symptoms but you don't see that on the left side because

as the blood flows through the lungs the monoamine oxidase in the lungs will break down the serotonin that's in the blood that was produced by the carcinoid tumor just kind of like you saw with the monoamine oxidase in the liver in the first example so this is a crazy over explanation of how different carcinoid syndromes will present or not present based on where the tumor is located so obviously again we're talking about bronchial carcinoid tumors here and you want to think about these obviously being located in the lung and you can see extra intestinal serotonin

secretion so that is your bronchial carcinoid tumors no good mnemonics here just memorize carcinoid syndromes and know to a greater extent the symptoms to look for and what location your carcinoid tumor will be in and whether or not that will have the full-blown manifestation of carcinoid syndrome all right now we're going to switch gears and talk about the non-small cell lung cancers and we'll begin with squamous cell carcinoma squamous cell carcinoma is located centrally the high-yield histopathology you want to know are that you're going to see keratin pearls and desmosomes and specifically as you see

on this slide due to those desmosomes you're going to see something called intercellular bridging so if you see the buzzword intercellular bridging or you see the buzzword desmosomes you want to stop do not pass go and pick squamous cell carcinoma now the highest yield thing to know about squamous cell carcinoma is that just like small cell carcinoma it is also associated with a perineoplastic syndrome this one's a bit easier because there's really only one big perineoplastic syndrome that squamous cell is associated with and that one is called humoral hypercalcemia of malignancy sometimes you'll see this

written out as the shorthand as pthrp so pthrp stands for parathyroid hormone-related peptide and it has a function that's basically identical to endogenous parathyroid hormone and in humeral hypercalcemia of malignancy due to an incorrect immune response to the lung cancer the body is incorrectly sensing the presence of parathyroid hormone and it's really this parathyroid hormone related peptide now what does parathyroid hormone do well to refresh your memory recall that it is responsible for osteoclastic bone resorption and that has a net effect in the body to basically increase calcium levels and decrease phosphate reabsorption so when

you get this humoral hypercalcemia of malignancy it shouldn't surprise you that some of the clinical syndromes that you'll see are all of the symptoms that we classically associate with hypercalcemia okay and what are those symptoms you're going to see things like nephrolithiasis so be on the lookout for the formation of calcium oxalate or calcium phosphate stones you also want to think about non-specific gi complaints so like abdominal pain nausea vomiting constipation etc you want to think about musculoskeletal injuries and musculoskeletal complaints so myalgia arthralgia non-specific generalized bony pain so all of these items all of

these clinical symptoms are evidence to you that the test writer is going after a hypercalcemic picture and that hypercalcemia is due to the body having an aberrant immune response to the parathyroid hormone related peptide okay and formally that whole peroneoplastic syndrome is known as humoral hypercalcemia of malignancy so it's very very high yield so needless to say squamous cell carcinoma if you're going to take one thing away from this video it's that you want to know the specific perineoplastic syndrome that i just talked about and how do you memorize this my mnemonic here is that

when we think about squamous cell carcinoma we want to really focus in on the letter q because this is the only lung cancer with a q in its name so squamous equals hypercalcemia claritin pearls and cellular connections and of course when i'm saying cellular connections i'm talking about those desmosomes and that intercellular bridging so again just to summarize really hammer this into your brain squamous has the q in it it's the only lung cancer with q q for hyperqualcemia queritin pearls and cellular connections so again desmosomes and intercellular bridging that q can really queue no

pun intended cue your memory into the three things that you need to know and that's it guys really really easy squamous cell carcinoma really know that perineoplastic syndrome and then if you're feeling fancy and you're shooting for that 290 keratin pearls and desmosomes so that is squamous cell carcinoma all right so now let's move on and talk about adenocarcinoma of the lung adenocarcinoma of the lung is located peripherally and the histopathology is that these are featuring mucin-producing cells you should know by now that the prefix adeno means gland so adenocarcinoma means cancer arising from glandular

tissue and therefore in glandular tissue it should be no surprise to you that you're going to see mucin producing cells excuse me mucin producing cells that will stain positive for mucin now the associations are what really are high yield for adenocarcinoma and this is much more of an epidemiology thing than it is anything else the big high-yield points here is that adenocarcinoma is highly associated with women more so than men and non-smokers and that non-smoking piece is really high yield because some of the other cancers that we've already talked about like small cell lung cancer

and squamous cell cancer those are highly associated with smoking but adenocarcinoma is the one that the test writer will go after if they don't give you a history of smoking or if they give you a female patient so you want to know adenocarcinoma non-smoking female patients now as far as the associated genetic mutations you want to think about a few things here the first is epidermal growth factor receptor or egfr the next is anaplastic lymphoma kinase translocation or alk and the last is crass k-r-a-s which is basically just a proto-oncogene you don't need to know

what these are or what they do but just know that if you see them the test writer is going after adenocarcinoma one of the high-yield associations that you do want to know pretty well is what's called hypertrophic osteoarthropathy and this is probably a perineoplastic syndrome associated with adenocarcinoma and regardless of whether we give it the distinction of actually being a peroneoplastic syndrome or not you just want to know this association so hypertrophic osteoarthropathy is going to cause patients to have clubbing of their nails and you can see what that looks like here on this slide

if you're answering a question on usmle or comlex and you have a patient who clearly has some lung problem with risk factors for lung cancer and a presentation of lung cancer and they give you this image they're hinting heavily that this is adenocarcinoma due to this hypertrophic osteoarthropathy and what we think is going on here is that you get fibrovascular growth in the nail bed and that's probably due to these things called megakaryocytes that that go to the nail bed when they shouldn't normally they should be filtered out in the lung but because the lung

is undergoing the adenocarcinoma i.e the cancerous process which is disrupting its normal physiology these things that should be filtered out are not filtered out and therefore these patients will have the accumulation of these substances and therefore some abnormal growth and proliferation in the nail bed the net result and i'll go back to this image for just a second is that if you are doing a physical exam and you palpate the nail bed it's going to feel soft and and some people describe it as sort of spongy and and kind of waxy so this is what

you want to what you want to keep an eye out for if you're taking your exam and the question gives you lung cancer because that's going to be the association of hypertrophic osteoarthropathy and now the last thing you want to know about lung adenocarcinoma is that adenocarcinoma has a relatively better prognosis than the other types of lung cancer that we have already talked about today so if you see adenocarcinoma it's somewhat atypical in the sense that it's peripheral it occurs more in females it occurs more in non-smokers and it has a better prognosis so like

i said when i started the conversation about adenocarcinoma this is more of an epidemiological kind of question so pretty high yield especially on step two and level two but if they go after it on usmle or comlex step one level one maybe they'll go in the direction of these atypical features now because these atypical features are what i believe is the highest yield part of learning adenocarcinoma you need a mnemonic to help you remember that this is somewhat atypical so when i think of adenocarcinoma i think of added non-carcinoma which reminds me two things one

is that this is the cancer that occurs in non-smokers so adenocarcinoma and non-smokers the other thing is that if i look at the letters n-o-n in non not only does it tell me that this occurs in non-smokers but n for non-smokers o for osteoarthropathy which again is that clubbing of the nail that's associated with this and the last n is not a bad prognosis so that kind of reminds me of the atypical features but it also reminds me of that high yield association which may or may not be a perineoplastic syndrome so that's adenocarcinoma of

the lung so here's where we are at this point we've just got one more lung cancer to talk about and that is large cell carcinoma of the lung luckily large cell carcinoma of the lung is extremely straightforward and the name of this lung cancer tells you really the only thing that you need to know so the location is peripheral and the classic histopathology is going to be anaplastic undifferentiated pleomorphic giant cells and this is really the highest yield thing here it's being able to recognize either in the image of the cancer or by the description

or the buzzword pleomorphic giant cell that you're being shown or you're being led to the large cell carcinoma so because the name is large cell carcinoma clearly this cancer involves giant cells so if you see the description undifferentiated anaplastic pleomorphic giant cells or you see this image which has large undifferentiated anaplastic giant cells you want to be thinking about large cell carcinoma now just a few other associations to top us off here this is associated with smoking and large cell carcinoma does have a pretty poor prognosis and for whatever reason test writers do sometimes incorporate

this last fact here it's that large cell carcinoma responds poorly to chemotherapy so if you see that you clearly want to pick large cell carcinoma but again the most important thing about large cell carcinoma for usmle and comlex is being able to recognize this image so if you see those pleomorphic giant cells if you see this slide that's the classic histopathology and you want to pick large cell carcinoma so at this point we've done all of these types of lung cancers and along the way i've pointed out the very high yield bits of information that

you should take away from this slide if you're sort of approaching this topic like dude just tell me what i need to know and save me all the fluff i don't have time for that so for your studying pleasure here is a summary table of these five different types of lung cancer and what you see here is whether they are central or peripheral their associations and the mnemonic that i gave you remember that small cell lung scl tells us not only the associations but the perineoplastic syndromes squamous cell carcinoma is the only one with a

q in the name so just remember that q tells you a lot and then for adenocarcinoma think adenon carcinoma for non-smokers and then a few other things as well the last mnemonic i want to add to this is that it's very important to understand that small cell carcinoma and squamous cell carcinoma are your two big centrally located lung cancers and the way to remember this is that small and squamous are central but if you can memorize my very stupid mnemonic shown in red as well as this last one here shown in blue you're going to

be in great shape to get all these questions correct so i hope this was helpful to you and keep up the awesome work