DIP Episode 81 - USMLE Step 1 Hematology Review Part 3 (Oncology)

Okay, welcome. My name is Divine. I'm a PGY1 transitional year resident. I'll go into diagnostic radiology and in today's podcast, like this is the first episode, I'll continue a review of hematology and oncology for the USML step one. This is going to be primarily an oncology podcast. I'm going to be talking about the more focusing more on with this. And again, a lot of the material I'll try to introduce it with case scenarios. I think that'd be in general pretty helpful with regards to our exams. So let's begin. So let's assume you get a question about, you know, like a 70 year old guy has like many let's you over the past six months, he has had like five bolts of pneumonia. And then serendipitously, you obtain a blood smear. And when you obtain that blood smear, you see neutrophils with two loops. Remember, usually neutrophils, right? They usually have like, you know, like anywhere from three to five, three to five like nuclear loops, right? But if you see neutrophils with say like six, seven, eight loops, right? That's a hyper segmented neutrophil. Hopefully that gets you thinking about a B12 or fully deficiency. But in this question, I'm talking about a neutrophil with two new clear loops, right? So like a by loop neutrophil. If you see that, that, that's something that's actually known as the pseudo pelga hue. So pelger P, L, G, E, R, Hue is H, U, E, T, anomaly, okay? And it's pathonomonic for my low display syndrome.

So this guy has something known as a my low display, my low display syndrome. And really, the thing is my low display syndrome, my low display syndrome, they are like sort of like poorly understood. But the, in fact, let me just go ahead and say this right now. Many of the topics I will discuss today, they are just certain key things you need to know about it. So I'll try to highlight those key things, but try to give you again, some pathophysiology, we're appropriate. And really, the thing with the my low display syndrome is that it's basically, I think of it as like a stem cell disorder, where essentially your hematop, your, your red blood cell, your white blood cell precursors, they just don't work right. Let's put it that way. And they, I mean, there are many reasons why they may not work right. So what me happen is, they may die early, right? So you may have like early apoptosis of those cells. So they may like die off in the bone marrow. Alternatively, you can just have them having certain mutations, where they just do not differentiate. So the both phrase you're looking for in examples is ineffective, erythropoicis or leukopoicis or whatever. But basically, like those cells, like you have, don't get me wrong, you have the precursors, the all hanging around in the bone marrow. In fact, classically, if you do a bone marrow tap for these people, you'll see like a hypercellular bone marrow.

You have all these, you have all these stem cell precursors, like all these stem cells, but they just do not work right. So because they don't work right, they don't differentiate appropriately or they die too early, right? So they have like early apoptosis. And then because of that, you're not differentiating to like your terminal cell lines. If you don't differentiate to your terminal cell lines, then guess what? You begin to have side opinions in the periphery, right? So you can have like thrombocytopenia. So these people can have a lot of bleeding. You can have leukeopenia. So this book can have lots of infections. Like this guy in the question I gave, right? He's having like many recurring bolts on pneumonia. And they could also have anemia, right? So again, just again, precursors not working right. And one key boss phrase pathophysiology is that the cells die too early, right? So the precursors, you find them in the bone marrow, the bone marrow is hypercellular, but the die early from like intramedularis are so right? Like within the bone marrow, like intramedulari apoptosis, and then they don't survive. So what are the key things you want to keep in mind with your myelotus plastic sentrums, right? So one thing you want to know is that being exposed to benzene is a pretty classic risk factor on exams.

So they can describe a person that works for like an all servicing company or a person that like works at an oil well or something like that, getting a myelotus plastic syndrome. In general, it's super rare, but it's, it may be super in the real world. You may never see it in your career, but trust me, it is not super on NVME exams. And again, classically, right, when they give you a question involving a myelotus plastic syndrome, the patient will likely have like a pan sideopiniac. So the hemoglobin will be low, the applied leg count will be low, right? So a normal pleated leg count is usually like above 150,000, it may be less than 150,000 for these people. Their white cell count can be low as well, right? And then those in the setting of those sideopinias, right? They also tend to have like blood elements that have like weird morphologies, right? So like weird shapes. So the classic ones that shop on exams, right? So you can see like red blood cells that are sort of like oval shaped, right? So like macrovaluocytes, those are classic in myelotus plastic syndrome. And I'll just go ahead and see this that myelotus plastic syndrome is actually one of the causes of anemia with a lower retic count, right? So their reticulocyte count is low again, because they have this ineffective erythropoesis. And then like I said, if you look at the blood smear, you may see like a by-lobed neutrophil, okay? That's the pseudo-pelga hueway.

And normally that's pathonomonic for myelotus plastic syndrome on exams. And the thing is, there are many things that cause MDS, right? So I just basically the wear memories is that they have like mutations in odd numbered chromosomes, right? So they can have like mutations in chromosome five in chromosome seven. I would not worry about knowing the specific mutation. I mean, there's one that there's one classic one that if you speak to any hemonc physician, they'll say, oh, if a patient has like like, oh, myelotus plastic syndrome, the patient has like a five-queue deletion. It's just the reason that it's highlighted a lot in hemoncircums is that there is a specific treatment. There's this drug that looks a lot like a phallidomide. It's called a linolydomide. It's actually pretty good for treating myelotus plastic syndrome that arises from the five-queue deletion mutation. And one thing I would encourage you to pay attention to if they give you labs in a patient that has MDS on an exam, look at the MCV. The MCV is usually greater than 100 on MB Ms, right? Because myelotus plastic syndrome, yes, you can cause any kind of anemia, but classically it causes macrosidic anemia on exams. So that's one thing you want to look out for on tests. And I mean, it can ultimately progress to like AML or something like that. So I mean, obviously, it's not a it's not a great, not a great disease to have.

So I think that's all I, all I specifically want to say about this, the myelotus plastic syndrome, but really, I think if you know those things I mentioned, you should be good to go on exams. So let's go to our next case, right? So let's assume, you know, you get a question about a guy that's like, I don't like 70 years old, sort of presents to the ED has like, you know, severe left upper quadrant pain. Your check is hemoglobin and you're like, man, this guy's hemoglobin is five, right? The normal hemoglobin is like 12, 13, something like that. But this guy's hemoglobin is five. So he has a bad, bad, bad anemia, right? And again, this guy has been admitted for multiple, multiple times for pneumonia, right? And then you again, serendipitously, you check your performance blood smear and you see red blood cells that look like tear drops. If you see this presentation, right? So like tear drop sheep red blood cells, I'm really, really hoping that you are thinking about something known as a primary myelofibrosis, right? So primary myelofibrosis. And in fact, primary myelofibrosis represents the first myeloperolyfreeative neoplasm that I'm going to talk about. So please on your exams, please do not confuse myelodisplastic syndrome, which is what I talked about first. That was the first case with a myeloperolyfreeative neoplasm, which is what I'm talking about now. There's like four myeloperolytive myeloperolyfreeative neoplasms. I'll talk about all four of them.

But really, the first one I want to talk about is like primary or sometimes they call it idiopathic myelofibrosis, right? And this one, again, just few key things you sort of want to keep at the back of your mind, right? So it's usually like a disease of old people, right? So chances are a 30-year-old will not be getting primary myelofibrosis on on your exam. It's usually like in a person that is more than 65 years old. In fact, like the median age of presentation is like 65. And basically, the thing that happens is at least the pathophys, like what people think causes this condition is you have like a weird like myelod precursor that basically gives rise to weird male carocytes. And then those weird mega-carocytes begin to release things that stimulate fibroblast, right? So like TGF beta or pleitleid derived growth factor beta, right? So they release those things, it stimulates those fibroblasts, and what do fibroblasts do for living? They lead down collagen, right? So they go, they lead down collagen, and effectively fibros the bone marrow. So think about it. If you fibros the bone marrow, I sort of remember ribloxels you make them in the bone marrow. If your ribloxels are trying to get out of the bone marrow and you have to squeeze through that collagen, you can already sort of build a mental picture that they will look like tear drops when you do a blood smear, okay? So tear drop shape ribloxels, I believe those are known as dachrocytes if I'm not mistaken.

That's pathonomonic again. Can you see tear drop shape ribloxels in many other disorders? Absolutely. But on MBM Es, if you see a tear drop shape ribloxel, I only want you to think about in this case primary mylofibrosis. And if you notice in the question I gave you, I said that, oh, this person has a hemoglobin of five, right? So the reason they have that low hemoglobin is again, the site of production of hemoglobin of ribloxels, the bone marrow is basically gone because it's been replaced by collagen. So those people, again, they don't have a good location to produce ribloxels. And you may also notice from the question I said that this guy has severe left upper quadrant pain, right? That's because this person is having extra medallary hematopoesis, right? So it's like, oh, bone marrow is not available anymore, okay? Well, that sucks. Let's start producing our ribloxels like in the spleen or in the liver. So these people tend to have like massive hepato spleen omega-le because they're just trying to produce ribloxels by hook or crook, because again, their bone marrow has been replaced with collagen. So, so again, classically on exams, I will say that, like probably like nine times at a 10 on exams, if you get a question about primary myloy fibrosis, the patient will have like hepato spleen omega-le. Again, because the bone marrow has been replaced, has been replaced with collagen.

And the thing is, they may even tell you in an example question that, oh, they did a bone marrow aspirate and they got a dry tap, right? Again, remember, the reason they get a dry tap is because the bone marrow just basically does not have ribloxels, okay? And again, what are the things that would cost primary myloy fibrosis? It could arise from like a jack-to-mutation. It could also arise from like, there's this protein that's beginning to make its way to the USML is this called chal reticulum. So, a chal reticulum mutation can also be indicated, have been implicated in the pathophysiology behind our primary myloy fibrosis. And I mean, how do you treat this? I would probably not worry about treatment on exams. Probably not super high you to know. Although there's this drug known as Rookson-Litinib, it's an inhibitor of that jack pathway, right? And remember, I just said that a jack-to-mutation is indicated in certain cases of primary myloy fibrosis. In fact, you know what I'll just say this. For most of the myloy prolypharative neoplasms, except CML, a jack-to-mutation is effectively implicated in all, I mean like in most of them. Yes, polycyphemia vera has like the highest incidence of the jack-to-mutation, right? So it's like 97%. But lower percent, I guess you can say lower percentages of the other myloy prolypharative neoplasms associated with jack-to-mutations. So Rookson-Litinib, it's a tyrosine-kinesine inhibitor.

I hope you remember from one of my from ecology podcast, right? I said that if something ends in Nib, it basically tells you it's a tyrosine-kinesine inhibitor, right? So like a matnib is a tyrosine-kinesine inhibitor. And a lot Nib is a tyrosine-kinesine inhibitor, okay? So you can give Rookson-Litinib, it's a jack-to-mute, jack-to-mute inhibitor inhibits that pathway and you can use it to treat a primary myloy fibrosis. Every now and then you're probably into transfuse these people because of the anemia they have and you may occasionally have to give them like like radiation therapy, but that's probably going to detail. I don't suspect you'll ever see anything like that on an exam. So and again this can actually progress to AML, okay? And again if you do the bone marrow tap, you get the dry tap, you'll see a lot of collagen in the bone marrow and you may also see like giant or like weird-looking mega-curious sites. Okay, so I think you think that's enough for that. So let me go on to my next case, right? So let's assume you get a question about again a 70-year-old guy and he has like the sudden onset of like very severe, right upper quadrant pain and then he tells you that oh you perform an abdominal exam and you see a fluid like a distended abdomen with a fluid wave, right? That's like pathonomonic for ascites. And then let's say you know what because you're the teaching hospital, you measure the sag gradient, right?

So the serum ascites are being gradient and you determine it to be greater than 1.1. And then this guy says, Doc, you know what? Whenever I take a hot shower, let's step out of the bathroom, I just begin to each of ton, right? Hopefully if you see all these things I'm talking about, I really, really hope you're thinking about the next myeloprolyphreative neoplasm, polysiphemia vera, right? Polysiphemia vera. So polysiphemia vera, right? Classicly on exams, it presents with, it can present with something called aquagenic preridus, right? So basically the person like takes a hot shower and they begin to each, the reasoning behind that is they believe that it's arising from like mast cell degranulation, right? So as those mast cells, they release like histamine, for example, you get a lot of itching. That's why anti-histamine can actually help patients with polysiphemia vera. But if you notice, I talked about my sodium onset severe opaquodron pain and acides and the sag gradient is greater than 1.1. I am really, really hoping you're thinking about like a botcaric syndrome. I will say that polysiphemia vera is one of the most common, if not the most common cause of botcaric syndrome on USMLE exams. Notice I did not see the real world on USMLE exams. Botcaric syndrome, in fact, I'll go ahead and see this right now. The most common cause of botcaric syndrome on USMLE exams is polysiphemia vera.

So if a person has polysiphemia vera, then botcaric syndrome, remember botcaric syndrome is like thrombosis of the hepatic vein, right? Or thrombosis of the portal vein, right? So when you have thrombosis of those veins, right? You can basically have like really bad portal hypertension. That's why the sag gradient is greater than 1.1. And you can have a lot of assignments, right? Because again, a lot of things are just sort of backing up proximal to the proximal to the liver. So polysiphemia vera, right? So classically right, on USMLE's, they'll give you labs, right? They'll give you like a CBC. And when you check the red blood cell mass, it's like super, super high. And one thing I guess I'll go ahead and see with this myeloprolypharative neoplasms is that in general, you name the myeloprolypharative neoplasms based on the thing that is like super, super elevated, right? So for example, in polysiphemia vera, it's your red blood cell mass that's super, super elevated. But the truth is, in many myeloprolypharative neoplasms, other cell lines may also be like elevated, right? So like the platelet count may be super high, the white blood cell count may be super high. So just one of those weird things, you kind of want to keep at the back of your mind, for example. Don't think that it's only one cell that will be elevated, right? So in fact, the boss phrase for that is panmylosis, like everything is elevated, like every cell. And again, don't forget that, right?

So they check the red blood cell mass, you'll be like, let's say a normal red blood cell mass, I guess hemoglobin is like, oh, like 12 or 13. Where you see it's like 2022, 23, you're like, this person's hemoglobin is like 60%, 65%. That's abnormal. That should make you think about polysiphemia vera. And classically, right? Polysiphemia vera, I think about it as a cause of primary polysiphemia, right? It's actually very high, you know, that in polysiphemia vera, the levels of ipo, because it's like the very high levels of red blood cells, right? That sort of sends like negative feedback, remember to like the paratubola capillaries of the kidney, right? So the levels of ipo alo, in fact, that's a very useful means of distinguishing between primary polysiphemia, of which polysiphemia vera is like the main cause you want to think above on exams, from like secondary polysiphemia, where those people tend to have elevated ipo, right? So let's say like a COPD patient that is chronically hypoxemic, so they release a ton of ipo so that they can make more red blood cells because they are sort of like oxygen deprived, or you can think about a person that lives on a high innovation, right? That is like an acronic hypoxic state, because they are just living at very high, this very big elevation above sea level, right? Or if a patient has like an ipo secretive malignancy, right?

So classically like a paratubola carcinoma on exams, or like renal cell carcinoma, those are causes of like secondary polysiphemia if you may, right? So it's just again, one of those rare things you want to keep in mind. And the thing is the jaqtumutation, right? Basically, if you see jaqtumutation on your test, the very first thing I want you to think about is polysiphemia vera. So that should already tell you that oh, roxolitinib may be a great treatment for polysiphemia vera, because remember that's a jaq pathway in hebertra, and again, like I said, aquagenic parriders, they may have something called erythromyalgia. Basically erythromyalgia is like like just pain in the extremities, from platelets just getting like super activated, because again, I remember I told you that in these myeloperiferative neoplasms, it's not just the red blood cells that increase, other things increase, right? So like platelets. So if your platelets, if there's just too many platelets and you activate a bunch of them, right? You can begin to have like kind of like microvascula thrombosis, right? Of like small vessels, right? So they can get like intermittent, like burning pain in the extremities, like their fingers, their toes, their legs, and things like that. So that phenomenon is known as erythromyalgia. And again, remember on exams, right? Again, they can have like botchiaris syndrome. They can infect sometimes, they can tell you on test that oh, they have like a rody complexion, right?

Like facial plethora, right? So like red face, basically that's what that means. And if you see that again, think about a polycythemia there. And because the erythromyalgia blood cells have been turned over like a lot, gout can actually be a presentation of polycythemia there, okay? Gout can actually be a presentation of that, right? So a patient of polycythemia very may benefit from like alopeurinol, so that you can inhibit xanthinoxidase so that they don't a ton of your acid. And I mean, how do you triplecythemia there? Yeah, you can try phlobotomy, right? So you can sort of bleed them out to sort of like, you know, give your hematocrit to like a reasonable level. And if you really try to like do phlobotomy until the hematocrit is like less than 45 percent, for that erythromyalgia, right? Because it's like caused by platelets that have been activated, you can give an anti-plitlet agent, right? Like a coxone and twin-hyper and irreversible coxone and twin-hyper like aspirin that can help under those circumstances. So I think that's what I'm going to say about the polycythemia vera, but those are sort of like the key things you want to be able to identify on exams. So let's go to my next case, right? So let's assume you get a, actually, you know, before you go to my next case, good idea just sort of pop to my mind, right? So there are just certain high eu thrombosis syndrome that are good to know for exams like step one, step two, step three.

So I just talked about like hepatic vein thrombosis being a balkyri syndrome, having an association with a polycythemia vera. There is this disorder, it's known as thrombosis of the splining vein. So splining vein thrombosis, that's classically associated on USM Ls with like acute pancreatitis. So that's again another high euphid you want to know, that's another high euphid venous thrombosis syndrome. And then if they give you a question about like thrombosis of the reno vein, I really hope you're thinking about nephrodix syndrome, because remember writing nephrodix syndrome, you dump antithrombin three in your urine. So you no longer inhibitor factors 10 and 2, right? So you have a high risk of thrombosis. And I will say that on exams the most common nephrodix syndrome that is implicated in a reno vein thrombosis is actually membranosnephropathy, remember that's associated with auto antibodies against the forceful lipids, a two receptor. Just one of those weird things you want to keep at the back of your mind for exams. So those three thrombosis syndrome like hepatic vein thrombosis balkyri syndrome with polycythemia vera or if a lady is on like chronic ocepes and then explaining vein thrombosis in the serum of acute pancreatitis. And then reno vein thrombosis in the serum of an euphrodix syndrome classically a membranosnephropathy on exams. Okay, so let's go to our next next uh uh uh next myloprolyphreativa neoplasm, right?

So I guess now I don't really have a good case for this because usually the exam presentation is pretty pretty classic. I guess I'll talk ahead and talk about CML, right? So CML, remember, right? It arises from the 922 translocation, right? Like the BCR able 922 translocation, um, uh, able I believe is like from chromosome 9. And then BCR is uh from our chromosome 22. And when you have that translocation, you'll form like a fusion tyrosine kinase that is constitutively active. And the unfortunate thing that happens with that constitutively active tyrosine kinase is that basically um the person's um uh the person's um myloid cells don't die, right? So it's like you're preventing apoptosis. And then the person's myloid cells just proliferate at time, right? So it's like you have something that is progrov and you have something that is anti-apoptotic. Those are basically like the two key things that happen when you create that constitutively active fusion tyrosine kinase, right? And again, because you know that you're creating a fusion tyrosine kinase, uh so like the Philadelphia chromosome, um that can essentially tell you that you know what if you want to treat this disorder, it probably makes sense that the drug that treats this disorder ends in NEP, okay? Like a MATNEP, right? You can give drugs like a MATNEP, uh you can give like the SATNEP, you can give NETLOTNEP, those are all inhibitors of that BCR Ebola tyrosine kinase.

So CML, I mean it classically occurs like you know people that are like 50s, I mean it actually can occur at any age, um but classically on exams it occurs in booths like in their late 40s or 50s or 60s, um and again like I said BCR Ebola, right? So uh Ebola, like the C-A-B-G, I think of it as a proto-oncogen, right? Because it prevents a poptosis and it encourages a cellular proliferation, right? So when you have that constitutive activation from that, um, from that, what is it called? From that uh, translocation, the 922 translocation, uh you're running to trouble, uh you're running to trouble and the person basically gets a CML. So um one weird thing, actually you want to think, actually a few weird things you want to think about with CML is classically in CML, BASO fields I elevated. Um, I mean there are some disorders that can cause BASO failure, but I'll say basically if you see BASO failure on an MBM exam, really the only thing you should really think about is a CML, okay? CML is the most like BASO failure is just unusual for the most part. So if you see it on MBM exam, you really do want to think about, uh, you really do want to think about CML. And the thing is I sort of think of CML as being in three phases, right? So the thing is, right? So because it's a chronic disease, right? So like chronic myeloid leukemia, right?

So the thing that's happening is that you know, you have this, this person has this hematologic malignancy, but their myeloid cells still have the ability to differentiate, right? Uh contrast that with like the acute leukemia as well, it's like, oh, the precursors, right? They've lost the ability to differentiate. So the person gets like side opinions in CML, at least in the early phase. In fact, that early phase is called like the chronic phase. Um, the cells still have the ability to differentiate. They have like zero issues. But as the person as the, as the cells begin to accumulate more and more mutations, you then go to something called the accelerated phase, where you begin to lose some of that ability to differentiate. So you then begin to build up like blasts in the peripheral blood, right? So, but the blast usually are less than like 20% right in the, uh, in peripheral blood. And then after that, this is where the, it now goes like, alright, like just go super bad really fast. It's when they get to like the blast crisis, right? So when you get to the blast crisis, you've effectively lost the ability to differentiate. So it no longer becomes a CML. It becomes like an AML basically, right? And actually, I'll just go ahead and see the CML does not always progress only to AML. It can actually progress to ALL as well. Again, all these are just arising because you are creating more mutations.

And as you go from the chronic phase to the accelerated phase to the blast crisis, you're basically one accumulating more blasts, right? And you're basically losing the ability to differentiate to like the terminal cell lineage, right? So that's why you're going from like bad prognosis to an even worse prognosis, because you then begin to have side opinius. And I'll say usually the bisophilia sort of raises for the most part, like in the accelerated phase of the disease. And again, the presentation is very non-specific. They may have like a pardospelino megaly. I, to be honest, I really won't hang my hat on the presentation. I mean, pay attention to the age range. A person that is like 78 years old on a USMLA exams, probably does not have CML. Remember, I think I believe I've probably talked about this in a prior podcast. So if I've not, forgive me, I guess I can go ahead and say it now, right? But basically, there's like this nice age algorithm, you can use to determine if you're dealing with LL or CLL or ML or CML, right? So basically, if the person is like a young kid, like a five year old six year old on MBM exams, you need to bother about the rest of the question. It's LL. That's the end. And classically, right, that can be like a Down syndrome patient on test. Now, if the patient is like super old, like in their 70s, their 80s, and they're having like recurring infections, and usually the white count is like crazy, high, like 80,000, something ridiculous on exams.

You really want to think about CLL, okay? Remember, that classically has like smudge cells on on his stology. I'll talk about that in the next podcast, God will. And then in the middle, right? So like ML midlife, you want to think about CML or ML, right? If they want you thinking about ML, they would have to show you like a picture with our rights, right? So if you don't see a picture with our odds, it's CML. And if you say a picture with our odds, it's ML, right? So again, just think of the LL as being the extremes of age, right? And again, like early alphabet A, going with young kids, a little alphabet C, going with older people, right? So again, five years old LL, 70, 80 years old, lots of infections, white blood cell count, that is crazy high, like 70, 80,000, that's CLL. Midlife, so person in there like late 40s to like 60s, think about the M Ls. If you see our odds, it's ML. If you don't see our odds, it's CML. That for the most part can actually get you the right answer like 80 to 90% of the time on MBM Es without you even doing any of kind of thinking. Just literally following our age ranges. So I think those are the big things I want to go ahead and see with with with a CML. And again, I already talked about how you should do with with a magnet. I mean, the other things you can do for treatment, but those things are not necessarily important for purposes, right?

So again, you identify the BCR, abl mutation, and you're although I guess I guess I should go ahead and talk about this. All we think that my purple point is sort of being able to differentiate between a CML and something called a locomoid reaction. A locomoid reaction is just something that happens where you know what, you have like a crap ton, a white blood cells, building up in the circulation as a response to like a severe infection, right? So your white can can be like 40, 50,000 like you'll observe in CML. Although one thing that kind of helps on exams with CML is that they'll usually give you like multiple like fractions of like white blood like myelot cells, right? So they'll say like, oh, they're myelocytes elevated, the metameloocyte elevated and all that stuff. But contrast, locomoid reaction, right? Or locomoid reaction, it's usually like in the setting of like a severe infection, right? And obviously right, a locomoid reaction will not have the BCR abl fusion tyrosine kinase that I just mentioned that's observed in a CML. And then there is this thing actually known as lucosite alkaline phosphatase. Lucosite alkaline phosphatase, it's like something that's expressed in like good like legit lucosites. So if a patient has a locomoid reaction, they will actually their white cells will stay positive for LAP.

But if a patient has multiple myeloma, they will not necessarily stay, I mean, sorry, the patient has a CML, they will not necessarily stay positive for LAP, right? And then I guess you can also hang your head on the basophilia, like basophilia, you don't find that in a locomoid reaction or basophilia, it's pretty common on USM Ls with a with a CML. So I think that's all I'm going to say about the CML. And I guess I can sort of jump to my next myeloproliferative neoplasm. This one is very, really tested. So I'll just say a few words about it because it kind of occasionally pop up on exams. And this will be like essential thrombocytemia. Basically, the thing that happens with essential thrombocytemia, right? Like I said, every other myeloproliferative neoplasm, it's just one cell line that is predominantly elevated, but others will also be elevated. In the case of essential thrombocytemia, it's the pleatlets that I elevated, right? So you can see like a pleatlet count of like one million something ridiculous like that. Think about essential thrombocytemia. If you do like a one-mile tap, you may see like giant mega-carrier sites like with pleatlet morphologies. And again, this like I said can have like the Jack II mutation or the caroticulin mutation. And to be honest, again, like I said, this is very, really tested.

I mean, you can try to with aspirin because if you have like such high pleatlet numbers, that could potentially cause potentially cause like thrombosis and like organischemia. But there is really not much in the way of like uniqueness with essential thrombocytemia. So it's really tested on exams. And I guess one thing I will just go ahead and say is that Kawasaki's disease is actually another weird phenom disorder that because like massive thrombocytosis on a test. So just one of those weird things you want to keep at the back of your mind or the I suspect that will be more for a pediatric shelf. But that can actually be a USMU presentation. Like Kawasaki's disease, they'll have like the lateral anterior cervical lymphatic anopathy, the strawberry tongue, the russian the palms and soles. They can have like red apple quadrant pain from like hydropic swelling of the gallbladder. Or they can also have thrombocytosis. And the fact that's one of the reasons why aspirin is pretty good in the treatment of a Kawasaki's disease. So I just thought I'll go ahead and throw that in. And hopefully that helps you out with your exam. Okay. So let's assume you get a question about, you know, a young kid that has like recall that has like he's had like recurring infections. And then let's say you you know, you you do a physical exam and he has like very severe pain behind the pinna. So like his outer ear. And then you also look at the scalp. You see just this red nasty looking rush.

And then let's say by some magic you up decide, you know, you say, okay, you know what I'm going to go ahead and obtain a bite like a dual biopsy. And when you do that biopsy, you see like a tennis racket shaped structures. So what's your diagnosis on that those are circumstances. I really hope you're thinking about Langehands cell histiocytosis. I mean, there were like some old terms for this disorder, but they're no longer commonly used like you probably heard of this in pathoma like like hand. What's it called? I think it's like hand-tooled Christian disease. And then there's one called like ladder C weight disease like weird stuff. But now everyone just calls it a Langehands cell histiocytosis. The thing is no one really knows what causes Langehands cell histiocytosis. But people believe that it's like proliferation of like dendritic cells remember your dendritic cells are kind of antigen presenting cell. So they sort of proliferate and classically on histology, you see like the bearback granules right. So they're like tennis racket shaped structures that you may see. And the classic presentation on exams is like bone pain because they tend to have like a little bone lesions and they may also have like a rash and the rash is classically on the scalp on exams. So those are like key unique differentiating features. And then unfortunately these are this is one of those he monk whatever's where you probably want to know the like some cell markers right.

So the thing is in Langehands cell histiocytosis on biopsy we actually see like cells that are like S100 positive. Sometimes they may be like CD1 A positive. And then this one is lower your body may pop up on a test they call it like Langeharing CD207. But I'll say really probably the most important one to remember for tests is S100. But S100 is found with many other like disorders. So I would encourage you to also try to remember like CD1 A that's another fairly common one that pops up on exams. And to be honest I think that's what I'm going to say about Langeh and cell histiocytosis. I mean like if you consciously would not recommend this but let's see if you say like you know what divine cat of all this crap I just want to remember one thing don't forget your bearback granules. That will almost certainly be the thing that will pop up on an exam that will tip you off towards a Langehands cell histiocytosis. So let's go on to our next case and again I promise today's podcast will be will be short. I'm not going to make it long really really hoping I can keep it to like 45 minutes or less.

So what if you get a question you know about an old guy this is like 75 years old you know keeps getting recurring infections and then he keeps complaining of like back pain especially like a long-kiss like spinos processes and then he also says dog it's difficult for me to breathe my ribs hurt and then you're like like a reasonable doctor you obtain labs right and you notice that the person's hemoglobin is like eight which is pretty low and you check their creatinine it's like two right they're like these are the crannies and it's not very good and then you notice that the blood calcium is like 13 right hopefully this tips you off pretty quickly that I'm talking about multiple my Loma okay so this patient has multiple my Loma because I mean basically in the question I am giving you the the crap symptoms right so hypercalcemia high calcium renal failure so the creatinine is high anemia right so low hemoglobin and then bone pain right so multiple my Loma so what's multiple my Loma basically you have plasma cells that are proliferating a ton okay and as these plasma cells are proliferating a ton the make I mean what do plasma cells make plasma cells are antibody factors right so they make like one kind of immunoglobulin okay and the thing is as they make that one kind of immunoglobulin you begin to get complications from just all those immunoglobulins that are being made okay so again don't forget your crap symptoms hypercalcemia renal failure so the creatinine will be high anemia so they'll have low hemoglobin and bone pain okay bone pain and the lesions are usually like little lesions right so usually they may have pain along the ribs or like back pain right usually along like the spinal processes so those are key things you want to keep in mind so I guess if you want to think dig more like oh okay what's the pathophys behind that multiple my Loma right so again like

I said it'll be a plasma cell like lineage that produces a ton of one kind of antibody right so the secret like basically a monoclonal antibody and the thing is that antibody that be make that is what is known as because I feel like one thing that sort of like trips people open multiple my Loma is just terminology so that antibody that they make is what is known as the M protein okay that is what is known as the M protein and the thing is the most common immunoglobulin that is over produced in the setting of multiple my Loma is IgG I'll say like 50% of people in multiple my Loma that have like the monoclonal production of antibodies it's usually IgG but people can actually have IgA multiple my Loma and I mean some you can say like some other weird ones but I worry too much about that but IgG is number one because I actually believe it or not the occasionally put questions and exams where you say like what's the most likely antibody that's overproducing this special multiple my Loma think about IgG as number one IgA is number two so just think of like Georgia right so like GA that helps you remember the order and then the thing is it is not all cases of multiple my Loma that are raised from producing immunoglobulin the thing is there actually some people multiple my Loma where they just overproduce like light chain only remember and immunoglobulin is made up of a heavy chain and a light chain but there are people that actually have like light chain multiple my Loma where literally all the produce is light chain and the thing is those light chains they can be filtered at the level of the nephron and then they shop in the urine whenever you see light chains in the urine those light chains in the urine are what are known as Benz Jones proteins okay so N protein is the immunoglobulin that's been overproduced and then those light chains when they shop in the urine that is w

hat is known as Benz Jones proteinary okay so again how you think how you think to know that right and again classic features of multiple my Loma they have the bone pain right because remember these plasma cells these secret like osteolytic factors so some of them make like interlooking one I believe another name for interlooking one is like osteoclast activated in factor right so they can have hypercalcemia from that because they're just resorb in bone some of these plasma cells can actually make a pT-hit related peptide right so again that basically is related to pT each right so you should work like pT each and resorb on right and then some of these plasma cells they actually make a like rank ligand remember rank ligand is released by osteoblast and when that rank ligand binds to the rank receptor that is what activates osteoclast for uterusorb on right so from this plasma cells they actually express express like make rank ligand and that basically again can cause like the bone pain and the bone resorption and then one other thing that some of these cells could actually do is they may actually increase the production of or the expression of osteoportagrin if you remember from indochrain I don't know if I actually am almost certain I mentioned this in a prior podcast but osteoportagrin I sort of think of it as like a dummy receptor for rank ligand so if osteoportagrin comes and binds up rank ligand guess what rank ligand will never be able to see the rank receptor and you will never have activation of osteoclasts and you will never have bone resorption in fact so actually I think I just made a small mistake so in multiple my loma you actually have a decreased production of osteoportagrin right so you have a decreased production of osteoportagrin so if you have a decreased production of osteoportagrin rank ligand interacts with the rank receptor more and you resorb s

orry about that now um I guess let me just bring in some more integrations there right so basically estrogen increases the production of osteoportagrin right so that's why women that are less than 50 years old they really get osteoporosis right because um I mean as long as you're less than 50 overs are working great cigarette crap ton of estrogen and make it a crap ton of osteoportagrin so you're binding up rank ligand so rank ligand is not interact with the rank receptor so you're not resorb your bone so your bone is great and healthy right but once you get past the age of 50 your ovaries die as your ovaries die I mean they don't necessarily let's just say that they don't work as great as when you were younger so the ovaries get out of the equation you don't make as much estrogen anymore and if you don't make as much as estrogen anymore your synthesis of osteoportagrin will go down rank ligand will now begin to interact with the rank receptor more and you begin to resorb your bone some more and voila osteoporosis shows up in fact this is why bino bis I mean bino bis is not a good thing but bino bis is actually protective against the osteoporosis because if you have more dipose if you have like more fat right like more diposeite hyperplasia remember fat cells express aromatees so they can make like an estrogen like molecule so that actually sort of helps with sort of helps with osteoporosis and alternatively remember one way you can sort of fend off osteoporosis is by being like weightbearing so if your bis you're like chronically weightbearing it's almost like your joints are going to the gym like all day every day right so that again also decreases your risk of osteoporosis and I guess if you think of this drug I mentioned in the endocrine pharmacology podcast then assume ab then assume ab is a is a dummy recept it's like a monoclonal antibody against rank ligand it

's actually used to treat osteoporosis because by binding up rank ligand rank ligand does not interact with the rank receptor and you don't have like a bone resorption so those are just sort of like weird high-yode usml integrations you want to know around like rank ligand rank receptor sort of deal okay so back to this so back to multiple myeloma right so through all these mechanisms I just described that's how you can get a like the bone pain and the hypercalcemia and what not with with multiple myeloma and the thing is these people tend to get like you know recurring infections because the plasma cells they produce don't work right okay so they tend to get a lot of problems right then again because these plasma cells sort of like overpopulate the bone marrow these people can have like like anemia right because again there's not enough space for them to make red blood cells they can have like thrombocytopenia because again not enough space to make to make platelets and the thing is these people may have like symptoms of like hyperviscocity in fact I'll talk about that I'll actually talk about that shortly but one actually high-yode thing you want to know is that multiple myeloma is a high-yode cause of amyloidosis so basically right the immunoglobulin light chain can begin to deposit in organs right so you can deposit in the heart for example and cause like a restrictive cardiomyopathy or it can deposit in the tongue right so usually people that know those is have like very big tongues and in fact sometimes you see them they are not able to close their like sort of close the amounts because their tongues are just that big sometimes they can have my absorption because the myeloma light chain can sort of deposit in the GI tract and they can also have like renophilia right so like myeloma nephrapathy because those light chains deposit in the reno tubules and cause a lo

t of trouble and again if you want to make the diagnosis of multiple myeloma right so you can do something called an S-PEP right so like the serum protein electrophoresis S-PEP basically helps you detect that M-protein right so the the the monoclonal immunoglobulin and then you can also do something called the U-PEP right so the U-PEP your in-person electrophoresis that basically helps you detect the Benz-Jones proteins right so the light chains in the urine and if you want to say okay you know what this is exactly the immunoglobulin I have on my hand like oh this is IgG or IgA you can do something called like immunofixation that basically helps you identify the exact immunoglobulin or the exact light chain and I guess one other thing I'll go ahead and say is that if you check the bloodstream of patients with multiple myeloma they tend to have like red blood cells so the stock like coins that's known as the Rulo formation that's like a pathonomonic sign of multiple myeloma on on histology on like a blood smear just so again one of those high yield things you sort of want to keep at the back of your mind you may literally give your picture of that on your test so how do we treat multiple myeloma right so multiple myeloma you can give like thalidomide let me see how divine thalidomide that causes like badness right yeah it causes badness but it causes badness if you're pregnant people that get multiple myeloma like 60 70 years old they're not probably they're probably not thinking about getting pregnant at those ages and then one high yield like this is actually mega high yield to non-exams one of the high yield that you can actually use to treat multiple myeloma is of something called bortezomib I already talked about it in the in like the hemonca pharmacology podcasts but basically bortezomib is like an inhibitor of the preezom like the 26s subunit of the preezom and

think about it right if you inhibit the preezom you basically stop breaking down proteins it so happens that I mean cancer cells are really smart right so cancer cells one thing they do is they actually operate leads are proteisms because by operating proteisms you can basically destroy proteins that can cause hipoptosis of those cancer cells so if you basically degrade proteins that can cause hipoptosis of cancer cells and those cancer cells basically become immortal because they don't die right so if you inhibited the preezom with bortezomib well those pro-ipoptotic proteins don't get degraded so those pro-ipoptotic proteins can actually like do their job for once right they go to the multiple myeloma cells and basically kill them off okay and that's how a bortezomib actually is used in the treatment of multiple myeloma there's like more specific stuff involving like iKAPA B NFKAPA B I discuss those more extensively in the human-cafama-cology podcast so I'll sort of refer you to refer you to that and please don't forget multiple myeloma right they can have something called like a plasma cytoma so basically like a mass of plasma cells that's something that is not uncommon in multiple myeloma and one other thing I'll say about multiple myeloma is I know I said 45 minutes and it's like almost 53 minutes I apologize I work really hard to keep this on there an hour right so let's try for that easier go so there's something that's called like it's almost like a precursor to multiple myeloma it's called like M-Gus that's like the monoclonal gamapathy of on-determined significance basically I'll tell you this these people don't have crap symptoms that's one thing you want to know so they don't have like the hypercalcemia the renal failure the anemia the bone pain they don't have any of that okay and the thing is if you look at the abon marrow they have like less than 10% pl

asma cells in the abon marrow okay so if you see less than 10% plasma cells in bone marrow no crap symptoms your diagnosis is M-Gus okay the end that's literally all you need to worry about but if you see crap symptoms and you see more than 10% plasma cells in the bone marrow or like let's say like the m protein concentration in the serum is greater than 30 grams per liter that basically gives you the diagnosis of multiple myeloma and one I guess close causing of multiple myeloma is something called a Walden strums macroglobulinemia so in fact some people call it like lymphoplasmacetic lymphoma that's another term but I'll say probably on the example you probably see more like Walden strums macroglobulinemia basically the thing that happens is again kind of like M-Gus these people have no crap symptoms okay so no again very high you to notice no crap symptoms but the immunoglobulin that is elevated in these people is not IgG is not IgA it's actually IgM okay and the way I remember that is like IgM Walden strums macroglobulinemia has so many M's right in the term so again no crap symptoms but the monoclonal immunoglobulin that's elevated for these people is IgM okay now why do we care about this the thing is what does Drums macroglobulinemia causes something known as a hyperviscocity syndrome right it's called hyperviscocity syndrome because you have I mean think about it IgM is the largest immunoglobulin remember IgM exists as a pentamer that's one second thing is IgG IgA yes you can find them in the bloodstream but they can also hang out in tissues so there's like many different places where they can hang out in the body but IgM is almost exclusive to the bloodstream okay it's almost exclusive to the bloodstream because think about it has a lot of trouble crossing like membranes and barriers right so it's for the most part to look alive to the bloodstream so if you h

ave a crap ton of IgM right for example like in the setting of waters from the macroglobulinemia you can begin to have like hyperviscocity syndrome so these people usually they'll have like like nosebleeds they may have like headache they may have like renal phenomenon right because they essentially having like those IgMs right they can sort of like agglutinate and begin to occlude a begin to occlude blood vessels right that's a classic presentation of a hyperviscocity syndrome and I'll say this on exams the most common cause of hyperviscocity syndrome is is wardenstroms macroglobulinemia and I mean I guess one thing I'll just go ahead and talk about right just to sit around the solution take too long but if a person has like cancer and you give chemotherapy let's say like CML or whatever for example right and all these cancer cells begin to die as they die remember potassium is an intracellular ion phosphate is also like an intracellular ion right so those people as those cancer cells die and also DNA is also kind of like intracellular right so when those cancer cells explode and you release those things into the serum those people can get into trouble really quickly right so they can get like a hyperkalemia right and they can cause like dangerous arrhythmias right the DNA as it's released into the circulation guess what can happen to those purines those purines can be broken down okay to uric acid right so they can get like like kidney failure that's why for patient is getting chemo they need to be hydrated vigorously and they need to be placed on like alopeurinol that's like a xanthin oxidis inhibitor or like raspberry case I already talked about as barricades in a different podcast it's like a uricase analog that converts um uric acid to something that's more soluble alan toin um and then you also put them on like telemetry right because you want to you want to ma

ke sure they're not getting like bad arrhythmias from hyperkalemia right so like the yqrs um the sine wave EKG and then ultimately a flatline that's obviously not a good thing right and then uh all that phosphates they are sort of releasing into the circulation that phosphate can actually bind up their calcium remember calcium and phosphate they love each other so much so they bind up all that calcium and they can become hypocalcemic and that can again begin to cause EKG abnormalities okay so those they basically this cluster of things I'm describing is something known as uh as a tumor lysis syndrome okay so um I think I've probably said I know for today um to be honest when I plan these lectures I'm like oh it's gonna take 30 minutes like thinking of it in my head I'm like oh this is not gonna take long and then I start talking and then all these other ideas come to my mind because these are basically freestyle lectures and um it ends up taking a while but hopefully you're getting actually getting something from these lectures so as I round up um as I always say I offer one-on-one private tutoring for the USMAD exams so step one step two CK step two CSTEP three after a tons of people that have done extremely well on these tests people have gotten like 30 40 50 point increases uh that I've worked with and I also prepare people for like uh internal medicine exams like uh in training exams board exams um med school exams shelf exams um and I also prepare application because I've been on an admissions committee um before for like a med school so I can prepare like ERAS applications and AMCA's applications I also help with like edilian applications and doing more interviews and all that stuff and then if you rarely have a relative that has troubles with organic chemistry I can also help with that so um but I'm gonna round up here um so in the next podcast I'll want you to

add discussion of uh onc and I wish all the best have a wonderful day and I really hope the leakers make the playoff so see you in the next podcast uh god bless and thank you for listening bye

Pseudo-Pelger-Huët anomaly (neutrophils with two distinct nuclear lobes).

Megakaryocytes.

CRAB criteria (Hypercalcemia, Renal failure, Anemia, Bone pain).

Waldenstrom's Macroglobulinemia.

The Philadelphia chromosome ($t(9;22)$), creating the BCR-ABL fusion tyrosine kinase.

Budd-Chiari Syndrome (hepatic vein thrombosis).

Tear drop shaped red blood cells (dacrocytes), massive hepatosplenomegaly, and collagen replacement of bone marrow.

IgM (due to its large pentamer structure).

Hypercalcemia, Renal failure, Anemia, and Bone pain.

Tyrosine Kinase Inhibitors (TK Is), such as Imatinib or Nilotinib (drugs ending in -nib).

Birbeck granules (tennis racket shaped structures) and positive staining for S100 protein.

Budd-Chiari Syndrome.

Tear drop shaped red blood cells (dacrocytes), massive hepatosplenomegaly, and collagen replacement of bone marrow.

IgM (due to its large pentamer structure).

Hypercalcemia, Renal failure, Anemia, and Bone pain.

Tyrosine Kinase Inhibitors (TK Is), such as Imatinib or Nilotinib (drugs ending in -nib).

Birbeck granules (tennis racket shaped structures) and positive staining for S100 protein.

Budd-Chiari Syndrome.