Hodgkin's Lymphoma

foreign what's up Ninja nerds in this video today we're going to be talking about Hodgkin's lymphoma before we get started if you guys like this video it makes sense for you please support us one of the best ways that you guys truly can do that is by hitting that like button commenting down the comment section and please subscribe also do you want some amazing notes and illustrations to help to follow along with me during this process go down the description box below we got a link to our website where you guys can check all that

stuff out but starting off with Hodgkin's lymphoma Hodgkin's lymphoma is a very interesting disease and really it comes down to a very in-depth lymphocyte pathway alteration so there's an alteration or an abnormality that develops within the lymphocyte pathway now I don't want us to go crazy into this pathway I want us to have a basic understanding of the pathway and understand where along the pathway there's disruption or alteration so let's quickly go over the lymphocyte pathway and what I want to start off with is what are the organs involve what is the pathway involved maybe

what are some specific intermediaries that are involved let's talk about that a little bit so the first part here that we have to discuss is we start all of hematopoiesis off in What's called the red bone marrow so hematopoies is the production of all blood cells that includes lymphocytes now in the red bone marrow well we start off with those called A hemocytoplast and A hemocytoplast should differentiate into what's called a myeloid and lymphoid stem cell which is the stem cell that's involved in the production of lymphocytes the lymphoid stem cell so that's the one

that I really care about so let me have right here this is going to be our lymphoid stem cell that's the precursor for basically all your lymphocytes and what it does is is it makes what's called precursor B cells and precursor T cells so what I'm going to push out here into the bloodstream is a precursor T cell and then this precursor T Cell will then move to the thymus and then at the thymus it'll undergo a little bit more differentiation so what I'm going to put is I'm going to put this as a precursor

T cell and I'm going to push this into the bloodstream and this is a precursor B cell and the precursor B cell should move to the lymph node right and the specific part of the lymph node I'll diagram out which part of the lymph node we're actually looking at in a second but this is the process so we have the bone marrow making precursor B cells and precursor T cells the precursor T Cell should go to the thymus the reason why is in the thymus should undergo a little bit more development maturation and then differentiation

into two specific types of T cells and these particular T cells are different based upon the specific type of cluster differentiation protein they express so one I'll draw here and like this pink color so it's got these specific types of cluster differentiation proteins and then another one I'll draw here in like this bluish color here this is another cell with cluster differentiation proteins but it's a different type so these are called your CD4 proteins so these are your CD4 positive cells so what happens is the precursor T Cell which doesn't know what he's supposed to

be goes to the thymus and develops CD4 positive T cells these are also called T helper cells and then the other one has cd8 positive proteins so he doesn't know what kind of cell he's supposed to be goes to the thymus differentiates into cd8 positive cells these are also called t cytotoxic t cells now that's the process of T Cell development the problem is is that not many Hodgkin's lymphoma is really any present with any T Cell Hodgkin's lymphoma it's primarily B cells so let's take our time and focus on this pathway what I'm doing

is I'm zooming in on what's called a lymph node like the germinal center of it so here we have the germinal center and here's the pre-germinal center if you guys want to understand what exactly I'm referring to imagine here I draw a small lymph node here's the efferent lymphatic vessels and you have a bunch of afferent lymphatic vessels going into it right what I'm really looking at is you have these things called trabeculae which separate out the lymph node and then we're looking at these like little follicle Parts here this is really what we're zooming

in on right here this part here so let's actually talk a little bit about this I don't want to go crazy we'll focus and focus on this a little bit more in Non-Hodgkin's lymphoma but what happens is this precursor B cell if you want to think about it it's also naive so we can also call this not only a precursor but we can also call it naive B cell meaning it has never been exposed to an antigen so at this point when it's a naive B cell or a precursor B cell that's naive it has

no antigen exposure what happens is it goes to the actual lymph node and it moves into this area here this area here called the mantle Zone and in the mantle Zone the mantle zone is the zone of antigen exposure it can also occur in the blood we're going to say that this is the area of antigen exposure for simplicity's sake so now here what happens is this is going to be either we're going to move these precursor or naive B cells into the mantle Zone and some of these will actually become exposed to antigens some

of them will not become exposed to antigens the ones that do not become exposed to antigens stay in the mantle Zone the ones that do become exposed to antigens they move into the germinal center so now what I'm going to do is I'm going to represent this antigen let's say on this B cell surface it has little receptors it's called B cell receptors and when it gets exposed to a particular antigen so we'll make this antigen let's make it red here's this antigen so we're getting exposed to a answers I'm going to write with the

right right then says a antigen this is a antigen that we're getting exposed to the B cell once it gets recognized it binds to the actual B cell receptor it takes it in and then once it does that it exposes a piece of it on its mhc2 complex we'll get that into it in a second but it takes it in it gets exposed to an antigen that's the big key here once it gets exposed to a big antigen it becomes a special type of cell and this cell is very interesting in the sense that it's

a really large cell a really large cell kind of a bunch of different nuclei on it and it's been exposed to this particular antigen what happens is this is called a centroblast this is called a centroblast now the centroblast what it's supposed to do is it'll take this antigen right that it bound to and it's supposed to then have a very strong affinity for antigens very similarly to this what happens is there's a kind of a pathway here where you diverge one is if the Affinity that these B cell receptors have for that antigen is

weak so we say a decreased affinity for antigens from this B cell receptor then these are supposed to undergo apoptosis these cells should die that's naturally what should happen is that these cells should undergo apoptosis because if you don't have a strong desire or a strong affinity for antigens then what kind of purpose do you have B cells you don't have a purpose because again the B cell receptor is supposed to be a very good strong antigen attached attachment structure so when it sees antigens you have a strong affinity and bind to those antigens if

it doesn't have a very good affinity for antigens it's not a good cell we should actually kill it and not let it be there because it can cause disease or it doesn't have any effect but if it does have a strong Affinity if the Affinity is strong it has a good affinity for the antigens then what it does it moves down and it moves into something else another cell and this cell is called a centracite this is called a centrocyte and now here's what I want you guys to understand the centracytes is just a little

bit more mature a little bit more developed so it's got these B cell receptors which are primed they're ready they're really good at their job okay they're really good at their job they're good at being able to identify antigens but you know what B cells are also supposed to become they're also supposed to become plasma cells so you can have two different types of B cells one is a memory B cell means it has these B cell receptors which can identify antigen for years and years and years it's it's good at that but you should

also have a type of cell that can produce antibodies that can also recognize that antigen so we should have two different types of cells a plasma cell and a memory B cell so with that being the case these centrocytes become exposed to two other cells in this lymphoid kind of lymph node structure this cell here is called a T Cell so this one here is called a T cell this is a T cell and this one here is called a dendritic cell this is called a dendritic cell now what happens is is the dendritic cell

has a very specific antigen that it exposes and we should already know that this antigen will be very nicely recognized by that B cell receptor so the B cell receptor will be able to recognize the antigen on the actual dendritic cell but the other thing is as T cells have a very special type of molecule on their surface they have like this mhc2 molecule they have these little mhc2 molecule that can also expose an antigen and this should also be able to interact with the centrocyte when the centrocyte interacts with these things it then from

that point decides what it's going to do all right so then what happens is if it's decided okay I like interacting with antigens and being a memory B cell it'll become a memory B cell oh I like becoming a plasma cell and producing antibodies it'll become a plasma cell so this site right here it undergoes a process called class switching so from here when it interacts with these two it'll move right up here into something called the and moving to something called the marginal Zone into the marginal Zone and then from this point here this

centrocyte is differentiated and it says okay I know what I'm going to be from here I'm going to become a memory B cell or I'm going to become a Plasma Blast which then actually becomes a plasma cell so what are the two different things that happen here so at this point the centrocyte once it goes through this pathway right here what is this what happens here at this step here it undergoes something called class switching where it has the ability to produce different antibodies that all it means it switches its antibody production from maybe IGM

to IGG and IGA right so that's the whole point so it undergoes class switching and then it moves into the marginal Zone once it's in the marginal Zone it then differentiates and decides what it's going to become so at this point if it goes this pathway and expresses tons of these B cell receptors which are good at recognizing antigens this is a memory B cell if it goes this way which is going to be leading to the actual formation of plasma cells which are cells that produce amazing antibodies then this is going to be going

in the direction of the plasma cell so this is called a memory B cell and this is called a plasma blast which then becomes a plasma cell which produces antibodies and what do these antibodies recognize these antibodies are supposed to recognize those antigens freely circulating these memory B cells are supposed to recognize any of these antigens freely circulating that's the cool concept of these things so another question you probably have is okay Zach that's a lot of cool stuff but where the heck is Hodgkin's lymphoma involved Hodgkin's lymphoma is involved kind of like somewhere in

this process here it's what's the thought process here is that something is happening we're centroblasts which are supposed to undergo apoptosis do not undergo apoptosis and so what happens is these Central blasts they never actually completely undergo apoptosis so this is where it actually happens this is where the disease process occurs and if the central blasts never undergo apoptosis they continue to keep kind of like replicating and replicating replicating but they never fully differentiate so that's the other problem they never fully differentiate and they kind of just stay in this stage where you have tons

of these tons of these Central blasts but the central blasts look a little bit odd they don't actually have this characteristic shape like you would think they take on this weird kind of shape so what happens is you get a ton of these Central blasts but the central blasts take on a very odd type of shape and you know what this actual shape is let me show you here what happens is they kind of look a little bit like this they have a big nuclei here and a big nuclei here that kind of looks like

two eyes and we call these cells read Sternberg cells so these are called Reed Sternberg cells and that's the problem you get a bunch of these and what's the reason why you get a bunch of these stuck in the lymph node is because the cells won't undergo apoptosis and they won't completely kind of differentiate and so you get a bunch of these like owl eye looking cells that accumulate within the lymph node now the question then comes what is the reason why these cells don't undergo apoptosis that's a great question let's come down and talk

about the reasons as to why that happens the big Point here is that we got these cells right so we talked about how you have your B cell how it's naive goes into the mantle Zone becomes exposed to an antigen if it gets exposed to an answer and becomes a central blast the central blast will then have a very strong affinity and become a centrocyte the Central site after it undergoes so this is a specific process here where you go naive B cell antigen exposure to a centroblast central blast if it has a very strong

Affinity there's something it does it actually switches the variable region of its actual B cell receptor it's called somatic hypermutation so we'll actually quickly write that it's called somatic hyper mutation hyper mutation that's for the central blast then it'll go and become a centrocyte the centrocyte undergoes a very special special process called class switching and then from there it'll move into the marginal Zone and give way to memory B cells or give way to plasma blasts which become plasma cells so that was the basic kind of process here now what happens is we say that

technically at some point here the central blasts were maybe some of them that didn't have that very good somatic hypermutation or they didn't have that strong Affinity that decreased Affinity was the problem right they go this way whereas the ones that have very good affinity for the antigens they go this way and they continue to differentiate and what's supposed to happen to these cells is they're supposed to undergo apoptosis but it doesn't happen so the question then arises like how does this actually happen well it comes down to like the actual like genetic material in

these lymphocytes let's say we zoom in on these actual lymphocytes we're zooming in on one of the lymphocytes here we're going to have the DNA and there's different types of genes that are kind of involved here the one gene that's really been thought to be heavily involved here is called nuclear Factor Kappa beta so it produces a molecule called nuclear Factor Kappa beta so this produces a molecule called nuclear Factor Kappa beta what nuclear Factor Kappa beta does is you know in order for cells to kind of divide they have different processes you have what's

called proto-onco genes and these are genes that want to have a lot of cellular proliferation so we have two different types of genes here one is we have what's called Proto oncogenes and then you have what's called apoptosis genes so in proto-onco genes in these situations this isn't the problem but if they were on what they would do is these help to cause increase in cell proliferation all right cell proliferation if these are hyperactive if you have what's called anti-apoptotic genes so they don't want to allow for apoptosis then we have what's called anti apoptosis

genes these will basically decrease cell death so then the cells will die either way and both of these scenarios the cells continue to survive so what happens is the nuclear Factor Kappa beta will basically go over here and certain particularly turn off some of these actual genes and so what it'll do is is you'll take these anti-apoptosis genes right which you basically if these are kind of like on they'll basically prevent the cell from ever being able to die and so that's what it does it kind of goes over and tells like these apoptosis genes

hey go ahead and turn off so if we turn off apoptotic genes or we decrease the apoptotic genes then the cells won't die and so that's basically what happens is the same kind of effect here and so basically what we're doing is we're turning off apoptosis and if I turn off if I decrease the apoptosis this is the basic concept the cells will not die there's no problem here with the proto-onco genes it's really the cells just refuse to die and so if they don't if they don't die they continue to survive and survive and

survive and used to get a lot of these green Sternberg cells that just accumulate within the lymph nodes and that's really where the problem comes but the question is what actually causes this up regulation so there's a lot of this what's called nuclear Factor Kappa beta what's the reason for this there's not a great answer but what's thought is is that nuclear Factor Kappa beta maybe in these high amounts secondary to what's called Epstein-Barr virus which is the virus that causes infectious mononucleosis and it may be secondary to things like HIV or immunosuppressed States but

again the mechanism exactly of how it does that we're not sure but what we do know is that the nuclear Factor Kappa beta will decrease apoptosis and if you decrease apoptosis you decrease cell death and so that causes these read Sternberg cells to continue to accumulate in the actual lymph nodes and cause disease processes so here's the recap lymphocytes are made in the red bone marrow the precursor ones they get into the bloodstream particularly the B cell type it should then go to the lymph node as it goes to the lymph node it gets exposed

into antigens in the mantle Zone if it gets exposed it then goes into the germinal center becoming Central blast centroblasts now have that B cell receptor which it bound to the antigen it should actually somatic hypermutation in other words it should change the antibodies structure just a little bit to be able to recognize variable antigens once it does that if it has a good Affinity it continues to go to Central sites if it does actually go to Central sites then it'll go undergo class switching it'll then become a little bit more differentiated into either a

memory B cell or a plasma cell the breakdown in Hodgkin's lymphoma is really that the cells refuse to undergo apoptosis because of their poor affinity and they refuse to completely differentiate and become specific cells so they kind of get stuck into this intermediate of like a central blast but looks weird like a reed Sternberg cell and the reason why this happens is you've turned off the apoptotic genes because of an increase in nuclear Factor Kappa beta which may be related to viruses such as Epstein-Barr viruses or HIV okay the question then comes what would it

look like if you get a lot of these weird funky cells these Reed Sternberg cells let's actually draw this one of these funky like little looking Reed Sternberg cells that are accumulating inside of the actual lymph node let's talk about that next all right so now we got a lot of these Reed Sternberg cells just accumulating like rabbits in the lymph nodes and again the reason why is there was a breakdown and the apoptosis pathway so when the lymphocytes are supposed to undergo apoptosis they don't and the reason why I may be due to Epstein-Barr

virus is maybe HIV this could be immunosuppressed States in general like after they got a transplant or they're on chemotherapy whatever it may be but it causes this increase in nuclear Factor Kappa beta which kind of shuts off the apoptosis Gene so they continue to keep thriving and it's again it's kind of like these weird like intermediaries of centroblasts which are called Reed Sternberg cells now if you get a lot of these read cernberg cells that accumulate in the actual lymph nodes what does this look like well here let's say that we get a bunch

of these suckers just accumulating in the actual lymph nodes because they just refuse to die they refuse to die if they refuse to die and they continue to kind of Thrive within this lymph node then what happens is you get something called lymph adenopathy and this is really a problematic issue for these patients so lymphadenopathy kind of occurs when you get like these different lymph nodes that get kind of big and swollen and large and so that's really the problem with this is that this can occur all over the dang place where can this occur

when you get lymphadenopathy the most common areas tend to occur in the cervical region the supraclavicular region the axillary region and then one other region so they can occur on both sides though cervical they can occur superclavicular they can occur in axillary one other area which is kind of an interesting one and that is mediastinal they can also occur in the mediastinal lymph nodes but one of the huge huge things here is with the lymphadenopathy it's usually painless it's a painless lymphadenopathy they're oftentimes slightly rubbery in their actual texture when you feel them and there's

one more big feature here it's contiguous so it's contiguous or continuous what does that mean in other words let's say here that this is the lymph node that gets in fact it gets actually a lot of these Reed Sternberg cells accumulating if it accumulates in this lymph node it'll travel to this one to this one to this one to this one to this one it's a straight shot that it continues to go in the order of lymph nodes in the proximal vicinity that is super super important but again lymphadenopathy is going to be one of

the key features here the questions again come as which area so let's write these down again one of them is going to be cervical lymphadenopathy the other one is Supra clavicular is another really big one another one is axillary and the last one that I really want you to remember here is mediastinal mediastinal and the reason why is the media style is very common sometimes in the patients with Hodgkin's lymphoma and it can present a lot of different ways so think about it it's in the proximity of a lot of different structures here so it

can definitely cause irritation or agitation or compression of structures like the heart the lungs or the superior vena cava so watch out for things like cough and shortness of breath and chest pain and the reason why is this may be compressing on nearby structures so this can cause a lot of different things so it can cause maybe some of the cough and the shortness of breath due to compression of the lungs it can cause chest pain because of compression of the pericardium or the pleura and it also can cause something like superior vena cava syndrome

due to compression of the supravena Cava so watch out for any kind of like edema or bluish discoloration of the neck and the face and the arms that's really really big things to watch out for here now we know lymphadenopathy is key is because these Reed Sternberg cells are accumulating in the lymph nodes and they're just refusing to die because of the increase in nuclear Factor Kappa beta the other problem is that these dang kind of like read Sternberg cells they like to see secrete a lot of different types of cytokines and this mechanism is

believed to be one of the reasons for a lot of different things so one is they can release things like interleukin-1 interleukin-6 tumor necrotic Factor Alpha bunch of different things but what this is thought to do is is these cytokines are thought to go and stimulate multiple different tissues and one of the tissues is the hypothalamus so it may act on the hypothalamus and the hypothalamus is really really sensitive to these cytokines because what it'll do is it'll actually increase the body's thermostat because it's kind of like an inflammatory signal so they try to increase

the body's temperature so this can lead to fevers this can lead to night sweats and what's really interesting about this is that these symptoms oftentimes occur very like sporadically and this is a very interesting term so we have first off lymphadenopathy is a really really big feature here but the other one here is the fevers and the night sweats this kind of stuff can happen really inspirat it's like a sporadically and we call this B symptoms B symptoms and so this is a really really important thing to remember is that you get these kind of

like periodic kind of symptoms here where they can have like a fevers and night sweats and maybe even some degree of weight loss they may even have some degree of weight loss so this can happen kind of continuously or it can occur periodically that's another important thing to remember this can occur this is usually continuous if it's b symptoms but if it occurs periodically where they have these like high fevers and night sweats for like maybe a couple weeks and then they become a febrile no night sweats for a couple weeks and they go back

it's a periodic it's a cyclic process they call that pel Epstein fever so remember that there is a variant of this there's a variant of this b symptoms which is you can have a cyclic let's just call it cyclic b symptoms if it's cyclic b symptoms we call this pel Epstein fevers pal Epstein fevers this is more of a cyclical process of these fevers so just remember that as well okay so so far we have lymphadenopathy in these particular areas that is contiguous painless rubbery we have b symptoms that can be continuous or periodic pale

Epstein fevers another thing that can happen here which is really weird it's it's not as specific and it's actually not it's not very common but it's highly specific for Hodgkin's lymphoma Palpatine fever but there's another one sometimes the lymphadenopathy can actually be painful which the mechanism is not completely understood whenever the patient drinks alcohol so there's a really thing that an additional thing to add on here so sometimes you can get what's called a alcohol induced lymph node pain and this is very rare but highly specific for Hodgkin's lymphoma so if you see this on

your exam don't forget this one okay same thing like the pale Epstein fevers they're very rare but they're highly specific for Hodgkin's lymphoma all right what else with the cytokines the cytokines can also tell the liver to produce things like an increase in the erythrocyte sedimentation rate or an increase in the CRP so these may be lab markers that you could check to see that there's a lot of markers of this liver reactivity it also tells the bone marrow and the bone marrow responds to a lot of these inflammatory cytokines by decreasing the number of

red blood cells and increasing the number of eosinophils so what is the effect here for some weird reason you can see this anemia of chronic disease where you drop your red blood cells but you see an eosinophilia because you increase your eosinophils so these are other kind of weird things to be able to take into consideration as well but the big thing I want you to remember is lymphadenopathy that is contiguous you may see b symptoms due to these cytokines causing the hypothalamus to upregulate the body temperature causing fevers and night sweats and maybe some

degree of weight loss if it's alcohol-induced pain or polypsy fevers are highly specific for Hodgkin's lymphoma but very rare you may see acute phase reactive proteins you may see some degree of anemia particularly anemia of chronic disease really this should actually be more specifically anemia anemia of chronic disease and this is eosinophilia the last particular situation is another one that's highly specific for Hodgkin's lymphoma but very rare this is another one where you can get a lot of these like basophils and these basophils can become hyper activated and what they do is they increase so

the basophils they basically increase their histamine release and if you increase histamine release what this does is this produces something called puritis this Purdue produces something called Puritas so itching of the skin this produce like a local inflammatory reaction if you will and this is another thing that I want you guys to remember so the big things to take away at this point before we move on to the next part which is extra nodal tissues is you're going to get lymph node involvement due to the increase in reinser Mark cells that's going to be causing

lymphadenopathy it's contiguous if they release cytokines the cytokines can cause a bunch of different things such as b symptoms if it's periodic it's Pell Epstein fever if when they drink alcohol it cause lymph node pain it's highly specific but rare seen in Hodgkin's lymphoma you may also saw evidence of acute phase reactive proteins being released you may see evidence of anemia chronic disease and eosinophilia you may also see pureitis due to lots of basophils releasing histamines another thing that you could potentially see here and this is a controversial topic is you could see spleen involvement

and the reason why this is controversial is because sometimes there's what's called extra nodal tissue involved tissue involvement and lymph node tissue involvement which you can see in lymphomas and Hodgkin's lymphoma technically the spleen is considered in many different textbooks it's considered to be a part of nodal tissue so technically if we're really being specific this is a nodal tissue so we can't consider this to be a part of the extra nodal tissue involvement so what can happen here sometimes these lymph nodes can actually these lymphocytes can these Reed ceramic cells can populate within the

spleen and if they populate within the spleen they can cause enlargement of the spleen and cause spleno megaly and if they cause split omegaly they may cause nausea vomiting they may cause anorexia they may cause left upper quadrant pain and the reason why is is as you enlarge the structure you compress on things like the stomach the stomach is right next to it and if you compress in the stomach you make less room as the patients eat they get full really quickly they kind of get nauseous they don't want to eat a lot and that's

another feature that you want to watch out for is split omegaly but again big thing is is it's controversial because some people say oh it should be an external tissue but the textbooks have kind of stuck with it being a technically a nodal tissue so we can't consider that the last thing here is with Hodgkin's lymphoma it is very rare for you to get extra nodal involvement but we need to talk about it because we should understand that this is a possibility it's just not as common this is more common in Non-Hodgkin's lymphoma that's the

big difference but so we are thorough here what could this potentially look like it's very straightforward we said that the Reed Sternberg cells are causing a lot of these like they're just accumulating inside the lymph nodes they're populating like bunnies and so you get these big kind of like lymph nodes lymphadenopathy that we talked about but sometimes they can actually seed into the bloodstream and if they seed into the bloodstream they can spread to other tissues so if it spreads to the Git it can cause a bunch of different problems here so we'll talk about

this a little bit later but it can spread to the git and cause a lot of different symptoms here it could potentially spread to the central nervous system it could potentially spread to the liver and cause hepatomegaly it could potentially spread to the glands like the salivary glands the thyroid gland the lacrimal glands it could potentially spread to the bone marrow so you can see CNS you can see liver you can see glands you can see bone marrow it can even spread to the pleura and the pericardium so it could spread to the pleura and

the pericardium or it could even spread to the skin however these are not as common as you will see and it can be way more common in Non-Hodgkin's lymphoma so the big thing I want you to remember here is it's more common in non -hodgkins lymphoma and that's a really really important thing here you can potentially see it it is just not very common and the symptoms that they will have are dependent upon the tissue that they deposit in so if they deposit it into the GI tissue they may cause things like bowel obstruction they

may cause things like abdominal pain if they deposit into the central nervous system they call things like seizures they may cause tumors it can cause hepatomegaly it can cause maybe decreased salivary and lacrimal gland production dry eyes dry mouth thyroid enlargement if it deposit into the bone marrow can decrease other cell production so it may cause pancytopenia and bone pain if it deposits to the skin and cause skin lesions if the deposit into the pleural and pericardium cause things like cardiac tamponade and pleural effusions so there's a lot of different things that you can see

here it's just important for you to remember and I think this is really really key here this is way more common in Non-Hodgkin's lymphoma but it's still slightly possible now at this point we have covered Hodgkin's lymphoma how it actually develops we covered the causes we've covered what are the effects of having a lot of these like Reed Sternberg cells all over the body now let's talk about how do we diagnose Hodgkin's lymphoma all right my friends so we have a patient who comes in they have a lymphadenopathy as their primary symptom right so they

come in they have some lymphadenopathy maybe it's cervical maybe it's axillary maybe it's super clavicular maybe they have some compressive symptoms from mediastinal lymphanopathy like cough or shortness of breath due to compression of the structures like the pleura and the trachea and things of that effect or maybe they have chest pain to actually involvement or compression of the heart the pericardium maybe they have superior vena cava syndrome due to compression of the SVC so you get the point they can have a lot of those features if they also come in with b symptoms so fevers

night sweats weight loss right maybe due to the cytokine storm if they also have it periodically which is pale Epstein fevers or if they have alcohol induced lymph node pain or if they have puritis these can be highly specific but rare and how Hodgkin's lymphoma also watch out for any spleen involvement like splenomegaly this may cause early nausea vomiting abdominal pain abdominal fullness of that effect and remember extra nodal involvement is possible it's just nowhere near as common as patients who have Non-Hodgkin's lymphoma that is way more common and easier to remember for your exams

but it is possible if that happens especially the contiguous lymphadenopathy you should start right off and say okay I just need to find those read certain book cells if I buy The Reserve or excels we're good problem is is that you can have lymph nodes that are big and puffy and it could be maybe Hodgkin's could be Non-Hodgkin's or it could be metastasis how do I know which one it is biopsy and look for the Reeds third work cells so that's the first purpose of the lymphoma biopsy is here you have this Mass I want

to know is it Mets versus lymphoma so when I take in this piece of actual tissue what I'm going to be looking for is what I'm going to be looking for these goofy looking things what are these called again my reed Sternberg cells so the first thing I'm going to do is I want to be able to find a lot of these so my first question is is it Mets versus lymphoma in other words it's a cancer from somewhere else that spread to a lymph node because that's possible and is it Hodgkin's versus Non-Hodgkin's so

first thing I do is I biopsy that actual area once I biopsy it if I see Reed Sternberg cells or gotta be very very careful read Sternberg cells or a variant or a variant called popcorn cells so these are basically a reed Sternberg variant they are kind of pretty much equivalent to them that if that is present right if these are positive then you have Hodgkin's lymphoma that is really what it comes down to my friends so you start off with the actual okay is it Mets versus lymphoma biopsy once you biopsy it and you

basically say okay once I biopsied biopsy I can say no cancer cells right no let's actually be more specific because like Technically when Hodgkin's lymphoma is a cancer no Mets and then once I see here I go to the next part which is okay I find Reed Sternberg cells if there is no Reed Sternberg cells this is a possibility of being Non-Hodgkin's lymphoma right so that's a really really important thing so we start off with lymph node biopsy and what we're trying to be able to find is is there Reed Sternberg cells or is there

popcorn cells now once we've found Reed Sternberg cells are the popcorn cells we have a pretty good you know suggestion this is Hodgkin's lymphoma so the question comes okay if it is Hodgkin's lymphoma how can I really determine so the next kind of question comes is how do I know if I have these Reed Sternberg cells there's a little Ally looking things or these other cells that are kind of like it but it's called popcorn cells so now the next question is is a reed Sternberg cells or is it popcorn cells because I know that

yes this is both present in Hodgkin's lymphoma but I need to know which one is it so then I go to the next test my flow cytometry flow cytometry will basically say okay I did my biopsy I found read Sternberg cells or I found popcorn cells okay which are basically a variant of Reed Sternberg cells so Reed Sternberg popcorn cells the difference and nice thing between these here is that they have differences in their proteins they expressed on their surface so you guys know it by this point after watching all the leukemia videos that flow

cytometry is great at being able to recognize specific proteins on the cell surface because what we can do is is we can make antibodies that are basically fluorescent and tag these specific proteins and so what I'm tagging here on the Reed Sternberg cell is cd15 and cd30 let me make this bigger so you guys can see this so cd15 and cd30 for the popcorn cells at cd20 and cd45 if if the cd15 is positive and the cd30 is positive we call this classical Hodgkin's lymphoma so we're going to preview this classical Hodgkin's lymphoma okay and

there's four different subtypes from that one you're like what the heck why doesn't it end if this is positive the cd20 is positive and the cd45 is positive this is called non-classical Hodgkin's lymph I mean non-classical non-classical Hodgkin's lymphoma and there's only one subtype for this one thank goodness now the big thing is is that classical Hodgkin's lymphoma is much much much more common non-classical Hodgkins of volma is much less common so that's another really big thing to take away from here this is more common this is less common all right so at this point

what I want you guys to understand then is that if we've gone through we've said hey we got a big old lymph node I biopsy it my question is is it a met is it Hodgkin's Non-Hodgkin's from that biopsy I'll be able to determine oh there's no Mets good is there any Reed Sternberg cells oh there is Reed Sternberg cells or there's a variant of them the popcorn cells oh well if that's the case that's possibly Hodgkin's lymphoma there's no cervix they could be Non-Hodgkins we'll talk about that in a Non-Hodgkin's lecture if I see

Reed Sternberg cells are popcorn cells I have a pretty strong suspicion that this is Hodgkin's lymphoma so then how do I determine which subtype of Hodgkin's the film it is classical or non-classical I go to flow cytometry and I find which one it is if it's Reed Sternberg cell positive it's classical odd Hodgkin's lymphoma that's the most common type if I find popcorn cells or the Reed Sternberg variants that's the non-classical Hodgkin's lymphoma that's the less common type now at this point then the next question is there's subtypes of this one and there's one subtype

of this one how do I know which one it is let's come down for a second so I go to the next part here right either I'm read Sternberg cell positive or I'm popcorn cell positive or if you want to even be more detailed just to recap I'm CD 15 30 positive or I'm CD 20 45 positive this is all the classicals this is non-classical for the classical there's four subtypes and we can identify these based upon their histopathological appearance I'll show you guys each one at a time the most common one is called nodular

sclerosis this is going to be the most common type it looks like this the next one here is called mixed cellularity this is called mixed cellularity this is the second most common so this is the most common this is the second most common and it looks like this the third one is called a lymphocyte rich so lymphocyte rich and then the nice thing about this one is that this has the best prognosis so one of the benefits of doing this test this histopathology is you want to be able to find which one has a good

prognosis and then again lymphocyte Rich looks like this and then you also want to be able to identify the poor prognosis the lymphocyte depleted thank goodness this is one of the least common but it has the poor prognosis or the worst prognosis and it looks like this so it's important for you to be able to realize the classical Hodgkin's lymphoma with the most common type being nodular sclerosclerosis but it's also important for you to be able to recognize the one with the best prognosis and the worst prognosis now it shouldn't be something that you're expected

to be tested on off the histopathology it's just something to give you guys an idea of what this looks like under the microscope now the other one is the non-classical Hodgkin's lymphoma if this is the case there's only one type and it's called nodular lymphocyte predominant and this one actually does have not too bad of a prognosis so that's another beneficial thing so this is the kind of concept that I want you guys to understand the most common one is nodular sclerosis the one with the porous prognosis lymphocyte depleted don't want the best prognosis is

lymphocyte Rich and all of these are the Under the Umbrella of Reed Sternberg cell positive cells are cd1530 positive cells or classical Hodgkin's lymphoma type and the nodular lymphocyte predominant is on the umbrella of non-classical Hodgkin's lymphoma cd2045 positive cells or popcorn cells which are read Sternberg cell variants now at this point we have identified if it's Hodgkin's if it's classical versus non-classical and then what's the subtype which can determine the degree of prognosis for the patient via histopathology there's one more Factor and it's did the actual Reed Sternberg cells or the popcorn cells spread

to other tissues did this have extra nodal involvement are they really really important because are they involving multiple different lymph nodes are they spread everywhere around the body how big are these lymph nodes because that's the next part so then we go into staging so when we talk about staging of Hodgkin's lymphoma it's now going to the next part so we kind of see how we're kind of going in sequence of the lecture here we started off with these Reed Sternberg cells or popcorn cells accumulating in the lymph nodes they cause lymphadenopathy maybe some b

symptoms maybe some of the other like rare stuff like alcohol-induced pain puritis Pell Epstein fevers and then maybe they have some splenomegaly but the next part was they kind of spread so if this leeches into the bloodstream we said that they can spread and they can go all over the dang place they can go to the git they can go to liver they can go to the spleen they can go to the glands they can go to the plural and the pericardium they can go to the brain they go to the bone marrow these were

all possibilities of where they can go but we did say it's much less common in Hodgkin's as compared to Non-Hodgkin's now how would I be able to determine where these spread is there a way absolutely there's two different tests that we can do one is we can do what's called a PET CT scan and we can use something called a radioactive isotope called fluorodioxic glucose and what it does is cancer cells especially these Hodgkin's lymphoma cells they eat up this glucose they consume it and then it lights them up on the actual scan and so

it would light up which areas the actual neoplastic cells have invaded into that's one test an alternative could be a CT of the chest abdomen and pelvis with particularly IV contrast this is another option because it'll basically kind of help to demarcate and highlight some of the masses in other particular tissues so these are the alternative options for finding some of these masses that may have spread to other areas of the body such as the actual git the liver the spleen the glands and the lure the lungs and the Heart now if it's spread to

the central nervous system this is important you want them to have neural symptoms if they have any neuro symptoms or their HIV positive so if they have neuro symptoms or they're HIV positive you should probably test them to make sure it hasn't invaded the brain or the meninges and so the ways that we can determine if it infiltrated the brain is we can get an MRI the way that we can determine if it infiltrates into the meninges is testing the cerebral spinal fluid so we can do a lumbar puncture so those would be things that

you want to consider especially if the patient has any neural symptoms or the HIV positive you should definitely check an MRI to see if it invaded the brain or do an LP to see if it invaded the meninges and subarachnoid space and then lastly what if it invaded the bone if it invaded the bone yeah you met your CBC may have evidence of pancytopenia because it's invaded and kind of taken up a ton of space but the other question is is get a biopsy if there's a lot of these actual Reed Sternberg cells in the

bone marrow then we know it invaded there so another option would be a bone marrow biopsy and that will confirm that you have Reed cernberg cells there okay so these are the ways that you can go about doing that and once you determine this if any of these tests are positive in other words my bone marrow biopsy is positive for read Sternberg cells my MRI or my LP reveal usually you have to do a combination of these because you need to confirm the actual tissue type maybe it'd be a biopsy or an LP if any

of these tests are positive you have confirmed external involvement and that is really important because now that determines okay the Hodgkin's volume is not just in the lymph node now it's spread around the body and that determines the degree of treatment and how aggressively we'll treat these patients so it moves into the next part here because we have to have an idea in order for us to treat patients we have to know how significant the tumor burden is in the body so what we do is we use a system called the Ann Arbor staging for

Hodgkin's and Non-Hodgkin's lymphoma and what it does is we divide this into four stages so we have stage one two three and you guessed it stage four now for this Ann Arbor staging what we do is is we say okay if one of the lymph nodes let's say it's just cervical it could be cervical superclavicular axillary there's one lymph node that is involved here all right and we were able to determine that from a lymph node biopsy that there was one lymph node involvement that's stage one if there's two limp two plus lymph nodes that

were involved and they were on the same side of the diaphragm so now I'm going to put like this imaginary axis here they're on the same side of the Hemi diaphragm that's stage two if I have two plus lymph node regions being involved and they're on opposite sides are both sides of the diaphragm that's stage three and if I have any regions I have two plus regions whether it be again on opposite sides or on both sides and I have a actionodal involvement let's just say for example here I pick the liver I'm just picking

the first one that I think of there's extra nodal involvement there that is stage four so if you have one lymph node region two lymph node regions two plus symptoms on the same side of the diaphragm who plus lymph node regions on both sides of the diaphragm or extra nodal involvement so that's how we identify these so one is one lymph node is positive two lymph nodes positive on same side of diaphragm two lymph node positive on both sides of the diaphragm and then lastly is there any extra nodal positive involvement that involve the pleura

the pericardium that it involve the brain did it involve the bone marrow did it involve what else the liver that involved the git the glands technically technically the spleen is what in the most specific instances in the textbook it's technically not an extra nodal tissue it's technically a nodal tissue all right so now all of this is technically a part of something called the Ann Arbor staging so when you take into consideration all of this information you get something called the an Arbor staging system now you can actually add on to this Ann Arbor staging

system with the subclassification system you're like oh man can we just like make it simple I promise it's not terrible it consists of three subclassifications one is it's denoted by a b and X now a is the absence of b symptoms this is based upon their clinical history so is there negative b symptoms if there's negative B symptoms they get the actual subclassification a if there is positive b symptoms then they get the subclassification B and if the lymph node tumor is approximately greater than or equal to 10 centimeters in diameter then they get the

subclassification system X now with all of that being said this is also called bulky disease there's another way you can describe the X if you've got a bulky lymph node Mass that's another indication so with that being said we start off with an example to kind of make sense of this so here we have a patient two lymph node regions are positive or basically these big old swoll lymph nodes but they're on the right diaphragm side so if we go back here one lymph node two lymph nodes on the same side of the die from

that stage two so so far we can already write that down but before we do that let's make sure that there's no extra nodal involvement and b symptoms for the lymph node diameter of approximately 15 centimeters you had no mention of extra neural involvement so because of that we can already start this off with and Arbor stage two but what's the subclassification is there absence of bee symptoms no there's presence of b symptoms so that's B so 2 b with a lymph node diameter of approximately 15 centimeters that's greater than 10 centimeters that's bulky disease

and so that is stage 2b x so that's how we would denote this Ann Arbor classification system of this patient's Hodgkin's lymphoma at this point we have covered how we've diagnosed Hodgkin's lymphoma from here we need to go into the next step which is how do we treat Hodgkin's lymphoma first stage is one to two meaning one lymph node region right or two lymph node regions on the same side of the dot on the same side of the diaphragm classical Hodgkin's lymphoma so we know classical is read Sternberg cell positive if that's the case we

do something called abvd therapy and it goes adriamycin now adriamycin is kind of like the brand name it's technically called doxorubicin this is what you actually should know it as doxorubicin the other one is called bleomycin now the big thing here we'll talk about is a couple like pathophysiological like Downstream negativities from these drugs we'll go over them in more detail when we do like chemotherapeutic agents like pharmacology but we'll briefly talk about these in a second the next one is Vin Christine then Christine sometimes you see it written as Uncle then so just be

careful you may see it written as uncleven and then the next one is called decarbazine so we have these particular agents that we would use and a patient who has Hodgkin's lymphoma classical type so this would be nodular sclerosis lymphocyte predominant or lymphocyte dominant lymphocyte depleted or some type of mixed cellularity which was cd1530 positive now if they upgrade their stage to stages three to four so again two plus lymph node regions on both sides of the diaphragm or extra nodal tissue involvement plural pericardium brain bone marrow glands salivary thyroid or git skin involvement Etc

they've upgraded to this stages for this one we can technically if you really wanted to you can do abvd again times six Cycles or you could do be a cop so this is bleo mycin this is etopocide this is adriamycin and again adriamycin just be aware that this is the brand name for the general generic drug called doxo rubison you could use cyclo phosphamide cyclo phosphamide ankovan which is again the brand name for vincristine the next one is called procarbazine which is kind of like a form of decarbazine and then lastly is prednisone but this

is just to indicate that you could use any steroid prednisone prednisolone dexamethasone it's just an indication that you want to use steroids so at this point if a patient comes in with Hodgkin's lymphoma stage one two you do abvd adriamycin which is doxoruba symbliomycin or ven Christine and decarbazine if they're stage three to four you can repeat the abvd for six Cycles or do the be a cop regimen bleomycin etopicide Adrian myself which was also known as doxorubicin cyclophosphamide then you have oncovin which is also known as vincristine and then pro-carbazine and lastly is any

kind of steroid we just put prednisone to make sense of the mnemonic now big things to watch out for here that I want you guys to know is that bleomycin can cause a lot of pulmonary fibrosis so when you're putting a patient on this drug you need to make sure that you're monitoring their pfts doxorubicin can cause a cardiomyopathy so you want to make sure that you're monitoring these patients Echoes so again pulmonary function test for the pulmonary fibrosis from bleomycin so again you can see pulmonary fibrosis so just make sure that you're monitoring those

pfts and then doxorubicin can cause cardiomyopathy like dilated cardiomyopathy so make sure that you're monitoring the patient's Echoes all right so for the non-classical Hodgkin's lymphoma again you have to remember that for these ones this is that popcorn cell so with the popcorn cell you have to have those specific types of molecules on their surface so they have to have again what were those molecules that we said cd20 and 45 45 so cd20 and CD 45 positive if that's the case and this really is these popcorn cells for the non-classical type these will benefit more

specifically from rituximab rituximab and again the most common subtype for this one was nodular lymphocyte predominant now the last one here is refractory CHL so you've tried the abvd maybe you've done the be a cop regimen after that they're still not in remission you can consider another drug but they have to test positive so this is for those read Sternberg cells so they have to be read Sternberg cells and on their surface they have to have so there was the cd15 and the CD 30. you have to test positive for the cd30 molecule if you

test positive for the cd30 molecule you can find potential benefit from a drug called Brin hoxumab vidotin and this is a type of monoclonal antibody that you can also utilize so with that being said in this video we've talked about Hodgkin's lymphoma we went over the pathophysiology we went over all the different diagnostic tests we went over how to treat these patients I hope it makes sense I hope that you guys enjoyed it and as always until next time [Music] foreign [Music]