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Good evening everyone. Um I see a few of you here. I'm just gonna start in a couple of minutes. Can someone please just let me know if you can hear me? That would be great. Yeah, someone could please just let me know. That'd be great. Thank you. And then we'll get started. Perfect. Thank you. Cool. Ok, so uh welcome everyone to today's talk on hematological malignancies. So for those of you who haven't been here before, um welcome to teaching things. Uh This is a organization that we have at University College London and we do weekly tutorials open to everyone on the medical platform and we focus on core presentations and teaching and all of these things. It's done purely by medical students and it is reviewed by doctors to make sure that it's accurate information. Um So yeah, please keep an eye out for our future tutorials. So let's go aside. So what are the main hematological malignancies we're gonna cover? So we've got Leukemias, lymphomas and then a few other disorders here. Um and we'll be going through these today. So first before we get started a bit about the normal physiology. So, understanding this diagram helps you the kind of understanding of especially leukemias. It makes things really, really easier to understand. So we have our main um hemo hemato hematopoietic stem cell which splits into our myeloid progenitor cells and our lymphoid progenitor cells. Now, when you think about are types of leukemia, we've got myelocytic leukemia and lymphocytic leukemia. So that is relating to the myeloid side for the myelocytic and the lymphoid side for the lymphocytic. So this is really useful to understand what's happening. And in terms of investigations, when you're looking at blood tests, seeing things like neutrophilia, eos eosinophilia, et cetera. Um compared to lymphocytosis is makes a big difference as to what diagnosis this might be. Ok. So, first on leukemia, so, leukemia is the abnormal proliferation of the white blood cells. So these are in the myelocytic form is the myeloid cells. So these are your thrombocytes, your erythrocytes, your basophils, neutrophils, eosinophils and monocytes. Ok. Whereas the lymphoblastic leukemia or lymphocytic as some people call it is the abnormal proliferation of specifically your lymphoid cells, which is your B cells, your T cells and your NK cells, your natural killer cells. Ok. So just going back to this diagram, your myelocytic is your proliferation of all of these extra, um all of all of these cells here. Whereas your lymphocytic or lymphoblastic is you, is more your t lymphocytes and your B lymphocytes. So this is really, really useful. OK. Also at any point through, through this t tutorial. If you have any questions, please do drop them in the chat and I will try and keep up with them as much as possible. Ok. So first we're gonna talk about the pathophysiology. So let's first look at our myelocytic leukemia. So we've got acute and chronic myeloid leukemia. Ok? Or myelocytic leukemia. So, the acute leukemia, this is associated with the translocation of to 17, the chromosome 15 and chromosome 17. And this is specifically your fusion of your PML and your RA R alpha genes. Now, you don't need to know what those specifically mean. Um Unless you're really interested in the biochemistry in which case, you can go look at it afterwards. But essentially what's happening is it's blocking this differentiation of the precursors. So, if we go back to our diagram, it's kind of blocking the differentiation into all of these things. Ok. So what this happens is you at least an accumulation of your immature myeloblasts. So that's these ones here. Your immature myeloblasts, you're not getting the full um er differentiation into all of these extra in, into these white blood cells here. So you have immature myeloblasts though, ok, your chronic myeloleukemia. Now, this one is associated specifically with your Philadelphia chromosome. Um So this is the translocation of chromosomes nine and 22. And in this case, what's happening is it's resulting in the fusion of the B cr and A BL genes which results in uncontrolled tyrosine kinase activity and this leads to an overproduction of your mature and your immature granulocytes. Ok. Now, looking at the lymphocytic leukemia or lymphoblastic leukemia. Now, acute lymphoblastic leukemia, this is very typically and very commonly seen in young Children. You will very rarely see this in older um in older people or even adults. So this is very, very common specifically in young Children. And this is as a result of genetic musa mutations causing a proliferation of your immature lymphoid precursor cells within the bone marrow itself. Ok. Now, the chronic lymphocytic lymphoblastic leukemia, this is clonal proliferation of the small mature incompetent b lymphocytes. Um and this is the most common leukemia seen in adults and it has a very slow progression. So sometimes they might not even be treated because it might not cause too many symptoms. It's a very slow progression. Now, let's look at the symptoms. So, first are lymphoblastic leukemias. So a lot of these will present very similarly, you know, they're gonna present with fatigue and pallor. Um increased infections, increased bleeding risk and easy bruising weight loss, bone pain. Now, the bone pain in A ll you can imagine is because you have this um you know, you have this proliferation within the bone marrow and the chronic one. Again, this is actually it can be often asymptomatic and it is just an incidental finding on blood tests which are performed in the elderly population. And this presents with can present with B symptoms. Um which as you, I'm sure a lot of, you know, is weight loss, night sweats and fever and fatigue. And it also just presents with bleeding and infections. Ok. And the clinical signs for this. So, in the young Children, for a LL, you'll have lymphadenopathy. So you'll have um a raised lymph nodes, hepatosplenomegaly. So, enlarged spleen and liver, a mediastinal mass, um petite and purpura. So this is like kind of your uh bruising and uh your blood clots under the skin. You may have testicular swelling and you may also see some cranial nerve palsies and meningism on the cll side. You can see an incidental lymphocytosis. So this is like we said, it can be asymptomatic. So this is incidentally seen on a blood test and you'll see a loads of the, the white cell count will be through the roof and there will be no reason for it. There's no infection, inflammatory markers might be normal. Ok. You'll have painless lymphadenopathy and that's really important is painless lymphadenopathy, cos if it's tender, that's usually a result of uh acute infection. Again, you'll see hepato splenda megaly and you'll see pallor on the patient, they'll seem quite pale. On the other hand, the myeloid leukemias. So as you can see, it's similar things, it's fatigue and weakness, increased infections. Um In the, the myeloid leukemias, you have specifically gingival hyperplasia. So, what this is is um increased growth of your gums and increased bleeding in the gums. You may see some menorrhagia, some. So that's increased bleeder bleeding, um, increased vaginal bleeding, uh leg bruises and then bone pain as well. And the chronic side again, your b symptoms, lethargy and tiredness, abdominal fullness and early satiety. Now, this one's really specific to CML and this is as a result of massive splenomegaly and hepatomegaly in chronic myeloid leukemia. Ok. This is very, very specific to CML they usually present with, oh, I'm just ii feel really full all the time and I'm not being able to eat as much. OK. And again, a ML, you'll see these things again. So pallor pete ecchymoses, gingival hypertrophy um and some of this leukostasis symptom. So, leukostasis is like um leucocytes just being very sitting abnormally in the blood which can result in headache and dysnea and vision changes. Ok. Any questions, please let me know guys. It's amazing. So, what would you do to investigate this? So, of course, for all of these things, the main thing we're gonna think about is a blood test. And so in a LL, you'll see anemia, thrombocytopenia and neutropenia. Now, this is overall, those three together is called pancytopenia. Ok. And you have lymphoblasts there as well. And on the chronic side, you have a lymphocytosis of very mature lympho lymphocytes. Um and he was again, see thrombocytopenia, which is low platelets, anemia. So, obviously, low hemoglobin and reduced immuno confidence and on the other side. A ML, again, pancytopenia, but this time, there's high myeloblasts instead of lymphoblasts for the A LL. Ok. Whereas in chronic myeloid leukemia, you'll see.