in this video I will explain almost everything that you need to know about lymphomas so as a brief overview lymphomas are a heterogeneous group of malignancies that arise from clonal peripher of B cells t- cells NK cells at various stages of maturation not to make it sound stupid or to dumb it down too much but lymph oite cancers equal lymphomas and so if you understand the basic Immunology and physiology of a lymphocyte it makes understanding lymphomas much more easy to understand so I would encourage you before you view this video make sure that you understand the basics about all your different types of lymphocytes now lymphomas may arise from lymph nodes or extranodal tissue non hodkin lymphomas are much more common than hodkin lymphoma and if this is your first time learning about lymphomas settle down because we will talk about the difference and the different types of lymphomas that fall into different categories so don't worry about this distinction just yet note though that lymphomas arise most commonly from chromosomal translocations and or associations with various infections and more on that to come so broadly when we talk about lymphoma we separate them into two categories one category shown on the left is hodkin lymphoma or HL the other category shown on the right is non- hodkin lymphoma or NHL and this distinction is made pretty much by the presence of something called a reed Sternberg cell so if there's a reed Sternberg cell you're dealing with a hodkin lymphoma if there's no Reed Sternberg cell and alternatively if you're mostly looking at lymphoid cells then you're dealing with a non- hodkin lymphoma readed Sternberg cells are very important to know what they look like you will see this image either on your in-class exams or on step one or level one these are large binucleate sometimes referred to as quote aled giant lymphocytes that have eosinophilic nuclei and a lot of cytoplasm so stare at this image burn this image into your brain this is a reed Sternberg cell you have to know what this looks like because if the test writer shows you this picture you have to infer that you're dealing with a type of hodkin lymphoma so when it comes to hodkin lymphoma there are both classical and non-classical subtypes of hodkin lymphoma when it comes to non- hodkin lymphoma we generally separate these into B cell and t- cell non- hodkin lymphoma now I want to pause for a second if you're watching this video because you are taking USMLE or comlex the majority I would say 90% or more of your questions will come from the right hand part of this slide you need to know the non hodkin lymphoma the B cell non- hotchkin lymphomas include burket lymphoma diffuse large B cell lymphoma follicular lymphoma mantle cell lymphoma marginal Zone lymphoma and primary CNS lymphoma the te- cell non- hotchkin lymphoma includes adult te- cell lymphoma and mosis fungoides if you're watching this video again solely because you want to do well on step one or level one this is what you need to understand and I'm not even going to bother talking about the different types of hodkin lymphoma although I will type them out for completeness sake so this video will focus on the right hand part the non- hodkin lymphomas because that is 90% if not more of all of the questions that you'll get on step one or level one so let's go through these one at a time we'll talk about all the different types of non- hotchkin lymphomas and then at the end of this video I'll talk about the clinical presentation the difference between hodkin and non- hodkin clinically and then some Associated syndromes that you need to know for USMLE and complex so we'll begin with burket lymphoma this is more common in children and young adults it is due to a chromosomal translocation 814 this is a reciprocal translocation where the cic gene on 8 and the heavy chain IG Locus on 14 are involved so what happens here is after this translocation you have increased activity of cik which is a Proto onco Gene that incre increases transcription factors which increases transcription so you have an increase in Aerobic glycolysis and subsequent cell growth and that's how this cancer forms you have increased cell growth now burket lymphoma is divided into several subtypes you have endemic sporadic and amuno deficiency on your exam the one that you want to know is endemic this is associated with EBV occurs most often in Africa and South America it classically involves the maxillary and mandibular area and this occurs predominantly in areas where there is malaria and what happens here is that malaria decreases one's resistance to EBV and therefore EBV is associated with burket lymphoma know for completeness sake of course that we have a sporadic subtype where the abdomen and pelvis is involved this actually is the most common subtype but on your exam chances are the exam writer is going to go after endemic and I'll tell you why in just a moment and then lastly there's an imuno deficiency subtype which is associated with HIV and patients who are posttransplant again if you're just taking USM or complex you got to know endemic and the reason you need to know that is because the maxillary and mandibular involvement has a classical image that looks like this so if you see this image you have to know burket lymphoma this image equals burket lymphoma so again if if you're looking at this slide endemic highest yield second highest yield amuno deficiency third highest yield which interestingly enough happens to be the most common but on exams not that important so what I want you to take away so far burket lymphoma equals 814 translocation increased activity of cmic endemic subtype associated with EBV in areas of the world where malaria is present because that decreases one's resistance to EBV and this image equals burket lymphoma because this is the endemic subtype that involves the face now histologically you're going to see something called a Starry Sky pattern and this has become quite a hot buzzword if you see Starry Sky the answer is burket lymphoma now the description that you could see are tingible body lated macras with fagos tumor cells that may or may not show up but Starry Sky is the buzz word that gets thrown around all the time so know that equals burket lymphoma now there are two pneumonics that I can offer you that might help you on your exam when I think Burk it Burk it lymphoma I think burke8 lymphoma instead of burk it so Burk it burke8 and that cues my brain that I'm dealing with an 814 chromosomal translocation because unfortunately sometimes the exam writer wants you to pick the chromosomal translocation associated with whatever lymphoma they're describing and because you have all of these translocations as you'll see as I go through this video it's kind of difficult to memorize luckily I have a pneumonic for almost all of these and then lastly you can remember the E with burket lymphoma e for endemic e associated with EBV and E for eating which reminds me of that facial involvement e endemic EBV eating the most important thing from this slide again though is burke8 lymphoma 8 814 translocation now let's talk about diffuse large B cell lymphoma this is most common this is the most common non- hotchkin lymphoma in adults and this one is the one where you don't need to memorize a chromosomal translocation because it's due to a mutation in bcl2 BCL 8 and p53 now just recall we won't go too deep into this but recall that bcl2 is a protooncogene that is involved in apoptosis regulation bcl6 is a transcript repressor that regulates cell maturation and p-53 is a tumor suppressor Gene so when you mutate these things obviously you're going to affect cell function cell division cell regulation and when you have that at an unchecked level you get cancer and that's what you're dealing with here now luckily there's not a whole lot you need to memorize for exams when I think dlbl for diffuse large B cell lymphoma dlbl that kind of sounds like BCL there's a lot of L's and B's and it it doesn't rhyme but it almost Rhymes dlbl BCL and that just you know in my brain makes the association that with dlbl we're dealing with things like bcl2 and bcl6 and if you can take that one step further perhaps you can memorize p-53 but if that doesn't seem worthwhile to memorize you know if you're cramped for brain space or you're just like dude I I I can't memorize anything that I don't 100% need to know that's super high yield then just move on to follicular lymphoma follicular lymphoma is the most common lowgrade B cell lymphoma it is due to a chromosomal translocation between 14 and 18 so you have the heavy chain IG on 14 and bcl2 on 18 and what happens is when you translocate then you have bcl2 increasing or overexpressing its product and when that happens you have decreased apoptosis which prolongs cell survival anytime you pathologically prolong cell survival you get subsequent malignant progression so that's follicular lymphoma now histologically you need to know that there's going to be the presence of something called cyes these cyes have small cleaved nuclei occasionally they might really throw you a curveball and give you a central blast Central blasts are large lymphocytes but do not have the cleaving so if you see either of these terminologies cro site or Centro blast think folicular lymphoma if you see small cleaved nuclei think folicular lymphoma now when I think of follicular lymphoma the way that I've always memorized 1418 translocation is follicular 14 14 begins with f follicular 14 keep it simple because this is the only translocation where the first number in the translocation is 14 now let's talk about mantle cell lym this is most common in adult males and this is due to a chromosomal translocation between 11 and 14 pause for a second I just told you in follicular lymphoma no other translocation had 14 as the first number but here you see 14 as the second number so just keep that straight in your brain this involves cyclin D1 on 11 and the heavy chain IG on 14 when you increase the activity path logically of cycl D1 you increase replication because you're essentially going through into S phase more than you should this increases cell proliferation and we have pathological malignant progression now usually when it comes to mantle cell lymphoma this spreads pretty rapidly so it unfortunately generally gets diagnosed when it's already reached in advanced stage but for USM or complex you really just need to know the chromosomal transl location not a whole lot of other high yield details that's mantle cell lymphoma I have a pneumonic for you but we'll come back to it after we talk about marginal Zone lymphoma so marginal Zone lymphoma is due to a chromosomal translocation between 11 and 18 now occasionally they'll write out something after the 1118 translocation and it might say q21 q21 don't worry about that this is an 1118 translocation that's what you need to know if you're studying for boards now marginal Zone lymphoma is very high yielded because it is associated with autoimmune inflammation and something called a gastric malt lymphoma now this confuses medical students so let's just say what malt is malt Mt stands for mucosa Associated lymphoid tissue and basically in certain mucosal tissues there's this sub mucosal lining and that that material is actually lymphoid it serves a lymph function and so in this instance gastric malt lymphoma is a lymphoma specifically associated with that mucosal Associated lymphoid tissue in the stomach so because of that it is highly associated with hpylori gastritis so in patients who have hpylori infections and hpor gastritis there's some connection between that inflammation and that malt tissue isssue becoming cancerous and the important thing to know is one there's the simple Association where gastric Mal lymphoma is a type of marginal Zone lymphoma and it's associated with H pylori but what's high yield to know especially if you're taking step two level two and Beyond is that this lymphoma actually may remit if the H pylori is treated so that's high yield for step two level two and beyond for step one level one just know that gastri malt lymphoma is a subtype of marginal Zone lymphoma in that mucosa Associated lymphoid tissue in the stomach connected somehow to hpylori inflammation as far as the autoimmune Association goes marginal Zone lymphoma is associated with Hashimoto thyroiditis and shogran syndrome so this is a really tricky opportunity where the test writer can start you off on a question that maybe gives you Labs or buzzwords that have to do with thyroid or shogan and then they'll ask you which of the following is the patient at increased risk for and the answer is going to be marginal Zone lymphoma so you're going to have to connect lymphoma with these and more endocrine rheumatological diseases now the pneumonic for both marginal and mantle because if we go back to mantle mantle starts the the chromosomal translocation starts with 11 and in marginal it also starts with 11 these are the only two trans locations that begin with 11 and so what I want you to think about when you think about 11 is if you've ever seen stranger things there's a character named 11 and 11 is played by Millie Bobby Brown Millie beginning with m so both mantle and marginal begin with m both mantle and marginal begin with 11 in their translocation so I associate Millie the m in Millie Bobby Brown with the character that she plays 11 and the two chromosomal translocations now let's talk about primary CNS lymphoma and I want to point out that depending on the textbook that you read or the lecture that teaches you at your school this technically is a subtype of diffuse large Bell lymphoma but it kind of gets carved out because it's its own thing so the what you need to know for your exams is that primary CNS lymphoma is associated with EBV and HIV AIDS now EBV Infection may be required for pathogenesis in imuno compromised individual so it's not like it's Associated necessarily with one or the other it is highly associated with both EBV and HIV AIDS almost concurrently and what you see here is a Neuropsychiatric presentation that is important to know what I think is even more high yield for USM or comlex is being able to do a differential diagnosis between toxoplasmosis CNS lymphoma abscess and metastasis and I've I've tried as best as I can to simplify this for you but admittedly it's not an exact science and the test writer is going to try to trick you but when it comes to looking at these differentials the reason that you need to know this is because these all cause ring enhancing lesions in the brain so you're going to be taking your exam they're going to give you the results of Imaging and there's going to be one or more ring enhancing lesions and then they're going to ask you which of the following is responsible for this presentation and all four of these things are going to be potential answer choices and so how you can think about this and again not a not an exact science so this isn't a 100% way to get this correct but in general you can think about someone's immuno compromised or not status and then other associations so with CNS lyoma chances are on the exam the patient's going to be immunocompromised because again it's associated with HIV AIDS there is a chance that they will give you a patient with autoimmune disease and if the test writer really wants you to pick CNS lymphoma they're going to tell you that the patient was tried on treatment for toxoplasmosis but failed that treatment some people think that when it's a solitary or single ring enhancing lesion that the answer is CNS lymphoma and that's not really helpful on exams anymore because they can give you one and it could still be an answer Choice that's not CNS lymphoma or they could give you multiple and you just don't know toxoplasmosis chances are on the exam the patient will be immuno compromised because that's associated with HIV Aids on the exam if the test riter wants you to pick toxo they're very likely going to give you Associated risk factors or exposures to things like you know cat feces raw raw meat or goats milk so your classic buzzwords associated with toxo they don't have to but generally they do if the test raater wants you to pick an abscess you can't go by the imuno status because the patient could be imuno compromised or immunocompetent what they will give you in most instances is that the patient had a recent infection and it's the entry of the pathogen through that infectious route that leads eventually to the abscess ly for metastasis chances are on the exam the patient will be immunocompetent so they're not they're very unlikely to have HIV Aids on your exam and if they want you to pick metastasis on the exam they will either give you that there are multiple ring enhancing lesions although again solitary versus multiple doesn't really necessarily tell you metastasis but metastasis is usually multiple lesions and usually they will either give you the cancer history or insinuate very strongly that the patient has a history of cancer so again not a complete science but as far as differentiating CNS Lymphoma versus toxo versus abscess versus metastasis this is a very broad way to conceptualize this now let's talk about mosis fungoides so to be clear we've talked about the B cell lymphomas and now we're moving into the the few te- cell lymphomas that you need to know mosis fungoides is the most common low-grade T cell lymphoma it involves malignant CD4 plus t- cell infiltration of the skin so because of that the clinical presentation is pretty unique you see patches plaques and nodules so a lot of Dermatological findings and what you will see described are cesari cells now cesari cells you see an image here they have cerebra form nuclei that is a very hot buzzword don't worry about the term cesari cell no cerebra form nuclei you can also see intraepidermal neoplastic cell aggregate so basically that is a fancy way of saying that in the epidermis there's aggregations of cells and those are called I may be butchering the pronunciation here potri microabscesses if mosis fungoides involves the blood it is termed cesari syndrome so that is a leukemic form of mosis fungoides so high yield to know that this t- cell lymphoma has it basically can can be leukemia because it can involve the blood it can progress to that form now let's wrap up by talking about adult T cell lymphoma so this is neoplastic proliferation of mature CD4 plus te- cells what you need to know when it comes to adult t- cell lymphoma are its associations with htlv1 and IV drug abuse that's really important to know on your exam if the test writer is going to give you a vignette or a presentation with adult te- cell lymphoma they'll give give you either the htlv1 or a history of IV drug abuse and then they'll give you some labs and clinical findings the labs will be in elevated lactate dehydrogenase elevated calcium level and all the symptoms that come with that hpat spin omegal and of course because we're dealing with lymphoma likely they'll give you lymph anop so know that elevated calcium and the elevated LDH of course know all of your symptoms of hypercalcemia in particular those liic or punched out lesions now we've just gone through a number of different lymphomas this is sort of the summary of how this looks clinically so clinically you really can't distinguish hodkin versus non- hodkin lymphomas on the basis of symptoms because generally these present with what are known as b symptoms fever night sweats unintentional weight loss where you can differentiate these are what you see in age cells spread and Association so in age hodkin lymphoma tends to be more bimodal so young adults and those age 55 and older whereas non- hodkin lymphoma on your exam it's very likely the patient will be 55 or older but the risk increases with age the cells we already talked about really high yield to know that hodkin you see Reed Sternberg cells non- hodkin you see lymphoid cells spread this is one that can really help you get the answer correct if the test writer describes clinical findings or physical exam findings or nodal findings and when I say nodal findings I mean what lymph nodes are involved and where are they located on the body so in hodkin lymphoma it's more localized the spread is contiguous so it's kind of node to local node and the prognosis is better in non- hodkin lymphoma it tends to be more extranodal it's non-contiguous so it's not really localized and for these reasons the prognosis is worse associations hodkin tends to be more associated with immunosuppression and EBV although clearly we've talked about immunosuppression and EBV in non hodkin so this is one that you you can't really go off this to get the answer correct in non- hodkin we're dealing with chromosomal translocations very high yield as I've pointed out autoimmunity and not only EBV but also things like htlv1 and HIV this is your high yield clinical summary now I want to finish this video by talking about some Associated clinical syndromes these include tumor liis syndrome and superior vena syndrome and so on your exam the test rator might give you findings of these syndromes because these syndromes are associated with lymphomas now to be clear it's not just limited to lymphomas these findings these syndromes are also associated with other malignancies but I'll include them here because they do tend to show up and they can get lumped in with the big package of symptoms that you'll get on your exam so tumor liis syndrome is a syndrome that occurs after cytotoxic tumor cell destruction so let's just simplify this you've got a tumor cell the patient gets treated the tumor cell explodes and it releases its intracellular components it is the release of those intracellular components that causes tumor liis syndrome The Big Three are phosphate potassium and nucleic acids now with an increased phosphate phosphate will bind up all the free calcium and cause calcium phosphate crystals with potassium increased levels of potassium alter the resting membrane potential which can cause cardiac arhythmia and with nucleic acids these get converted to uric acid which causes hyperuricemia now what you'll see on your exam of course on the left here we've got our lab findings and on the right we have some Associated clinical features on the left we deal like I said increased levels of phosphate increased potassium increased nucleic acids and by extension increased uric acid and decreased free calcium again that phosphate binds up the calcium so you actually get hypocalcemia if you're looking at labs this can present very heterogeneously so there's it's not just these symptoms but I've included the you know the big six so to say so you could see cardiac arhythmia from your elevated potassium because of your calcium you could see tetany trtic sign tro sign you could have seizures and because of various Pathways that ultimately cause kidney injury right hyperuricemia and calcium phosphate crystals you get obstructive uropathy so these are things you want to look for on your exam each of these clinical findings will have third order findings and third order symptoms so tumor liis syndrome is really a big thing that they could go after on USMLE or comlex lastly we have superior vena syndrome so as the name implies this is a syndrome that occurs when the SVC is blocked or congested because the malignancy the cancer is locally kind of either pushing on that area or metastasizing to that area or involving the blood flow through that area and so what you see are symptoms where you have decreased flow in that region so things like upper extremity and facial edema jugular Venus distension orthostatic hypotension you can get neurological symptoms including headache uh difficulty with vision altered mental status and things like renal failure and a host of ENT symptoms if you're looking at this now I think tumor liis syndrome is a lot more High geld than SVC syndrome but both of these again can be associated with lymphoma and other malignancies so that was a pretty long one a lot of good information that I think you should know for your exams know the chromosomal translocations know what a reed Sternberg cell looks like know some of the more Buzzy words in there but that is lymphoma