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Hematomorph Session for FRCPath Morphology

Haematology, Morphology, FRCPath Exams1:15:03

Transcription

So this is the first case. A 8-year-old boy presented to the emergency department with recurrent epistaxis and uh spontaneous bruising. He is an adopted child. To the parents' care, the full blood count shows hemoglobin of 120, white cell count of five, and platelet count of 102. This is the power 10 blood spin, and we will go to power 50. But I need a volunteer on the left side if they want to come in for the blood. Any um uh, I'll give it a try. So, uh, from this power, I don't think I I can see any platelets. And I don't know whether I should like comment on platelets in this power or not, but it seems like there are no platelets. Um, so this is power 10. Power 10 is just for general overview of the blood film to tell you whether there are white cells or not, whether there are clumps or not, or whether there is any worm. If there is, this is an easy. This is a general overview of the blood film. So now I will go to power 50. Then you will find something. Ignore the moving object. So this is 50, and you can see red cell morphology, the white cells, and the platelets. At this point, would you like me, would you like to ask me any question? I think I can see spherites here from this power. Spiroides? Is that right? Spiroides are very dark in pillar and small. Okay, so I see large forms of blade. Large form? Large what? Large forms of platelet. Platelets. Large forms. Okay, so you are seeing large platelets here? Yes. Is this related to the patient's bleeding or not? Yes, yes. Maybe. What do you mean, maybe? Uh, function test we need. I think so. That's why I asked you, would you like to ask me any question at this point among the investigations? Yes, the blood film shows left shift also for the neutrophils. I uh, I see band forms, some activated lymphocytes, uh, large platelets, mild thrombocytopenia. Otherwise, he has normocytic, normochromic. Okay, so if I tell you this patient's mean platelet volume is 15, would it help or no? Maybe point it towards some congenital platelet disorders. Okay, right. So we will talk about congenital platelet disorders. If you are sitting for part two exam, how would you report this blood film? Now you have seen the red cell morphology, platelet morphology, and white cell morphology. Starting from history, taking or you, you ask about management, or just reporting the blood film? Reporting the blood film. So if you are sitting for part two exam, they will ask you to report the blood film or or aspirate or refine. I think today we don't have many clinical hematologists to report the blood film. So you would say, the blood film shows, um, large size platelets or macrothrombocytes. The platelet counts are low in number. You discuss platelets first because the abnormality is in the platelet. So whichever line has the abnormality, you will mention that first. This blood film contains macrothrombocytopenia. No platelet plugs or clumps seen. White cell morphology is normal. Red cell morphology shows few echinocytes, which can be an artifact. The blood film is consistent, consistent with macrothrombocytopenia. This patient needs further investigations to exclude, um, congenital causes of macrothrombocytopenia. This patient is 7 years old, he has recurrent bleeding and bruising, and he has macrothrombocytopenia. The next question would be, what are the different causes of macrothrombocytopenia? One of them might be ITP. Another cause is congenital platelet function disorders. I can't recall now any one of them. Actually, I think ITP is a differential, isn't it? As well? Yes. Uh, ITP has large platelets, but they usually do not present with recurrent bleeding or epistaxis. Your platelet count is low, usually very low. Yeah. So when they ask about possible causes, shall we like mention the causes in in view of the background history, or just according to the blood? Background history, which is the which is the likely cause should be on the top, which is the least likely cause should be at the bottom of the list. So you mentioned that congenital causes of macrothrombocytopenia and ITP. So I would keep the congenital causes on the top and ITP at the bottom of the list. Now, congenital causes are many. Do you remember any name? [Music] Concept of platelet. Can someone ask her to mute the phone please? Or if you muted? Yeah, okay. So with congenital causes. Okay, so right. If they ask you, what are the different causes of macrothrombocytopenia? So there are four congenital causes and one is idiopathic, which is ITP. Congenital causes, you can make a mnemonic. I have made a mnemonic. BMGX. B starts for Bernard-Soulier syndrome. M starts for MYH9 syndrome. G starts for Gray platelet syndrome. And X starts for X-linked thrombocytopenia with dyserythropoiesis. So these are a few causes of macrothrombocytopenia. Then the next question they can ask you in the short cases will be, what further investigations are required to confirm diagnosis? So now you are at congenital thrombocythemia. What further investigation do you need to confirm diagnosis? Maybe some genetic testing. Maybe some genetic testing is not an answer. Yeah, you are sitting for part two exam, you need to answer accordingly. You have full blood count. Look for, um, mean platelet volume, whether it is high or not. Then we have discussed the differentials. According to the differential, you will go down the route to investigate the cause. We discussed that case previously in the last part one session. Hopefully, you will remember something. If not, then full blood count, you have already. Blood film is the second one. Platelet volume is the third category. Then you will send the patient for, you will send the blood for platelet aggregometry, light transmission aggregometry to find out what is the response to ristocetin and other agonists. And then you have flow cytometry because the Bernard-Soulier has a defect in CD42. After that, you can say I will go for genetic test because these these, um, diseases are confirmed on genetic investigation. So what is the genetic mutation associated with Bernard-Soulier syndrome? GP9, GP1bB, or GP1bA. These are the genetic mutations that you can get in Bernard-Soulier syndrome. It can be a part one question as well. They will ask, what is the genetic mutation associated with that? Or whether, what is the inheritance, is it recessive or dominant? And where is the defect? In which glycoprotein you have a defect? Do you remember which glycoprotein is defected in Bernard-Soulier syndrome? 1b95. Glycoprotein 1b95. 95 is the receptor. So if you are working in pediatric department, you will see many such cases of macrothrombocytopenia. You can see this platelet. It is bigger than the size of the RBC. It's quite big. This is almost like an RBC. So macrothrombocytopenia usually comes in short case, or they come in the population paper where they will give you LTA, transmission aggregometry graph, and a scenario, and they will ask you for the management of this patient. In my exam, the board case was a ward case. All right, so this was the first case. Now the second case is a GP blood film about a 70-year-old patient who has been, who has routine blood test. All right, so anyone from the labs side, because the blood film first goes to the biomedical scientist or lab hematologist, if they want to volunteer to comment on the blood. This is power 10 at the moment, and then I will go to power 50. Anyone from the left side? I can see a lot of, um, uh, lymphocytes, monomorphic like lymphocytes, and I can see one smear cell, two smear cells. Count looks like increased, and there are atypical cells, um, on the film, as well as a few, um, neutrophils. And, um, there are reduced number of platelets, and RBCs are mostly microcytic. You are clinical hematologist or lab scientist. Who was that? Who was speaking? All right, so this patient has high white cell count, and as the candidate mentioned, there are many smear cells as well. For example, the, uh, biomedical scientist or the lab staff think that this is a lymphoma or acute leukemia. Sorry, in this case, it has been referred to clinical hematologist, hematology registrar to comment on that. Is there any clinical hematologist who want to report this blood film? What happened? There are 20 people in the session and no one is replying. Anyone? I can't try. I'm really apologize about the background noise. I have, no problem. I have also background noise. It's okay. It's Sunday. Everyone is at home. Yeah, so, uh, I, in the blood film, I will, I will start first, like, by saying there is some red cell changes. Um, I will start with this one, although, like, I know, like, the elephant is in the room. Um, the red cell show some, I can see some microcytes, some spherocytes, and, um, platelets look morphologically unremarkable. And in the white cells, I would say there is some have a prominent nucleoli, and, um, um, few of them have also some like deep cleft or, Mhm. And there are some smear cells as well. It's actually that some have actually like a rosette sort of morphology. So it's likely an acute type of leukemia. And I will suggest further investigation, bone marrow testing, and flow cytometry. Patient is completely normal. He has no symptoms. Yes, some of these cells have prominent nuclei, like in this film. This is the only problem. The rest of the nuclear material is very blue and true. So some of these cells look like a CLL sort of morphology, plus the smear cells do support that. But I'm not quite sure about there are, because there are some like cells which are a bit larger in size, and this prominent nucleolus make me a bit confused about the possibility of some malignant transformation or like will be there. Because if you are suspecting CLL, so CLL can have prolymphocytes, and prolymphocytes will have prominent nucleoli. But the nuclear material is very, very mature. Very dark. In acute leukemia, the nuclear material is very open. Or yeah, yeah. And how can you describe this cell? You just passed through. It has some like blunting and some of these have like a flowering sort of outline. Yeah, like this one. That one. What do you think this is? Acute leukemia? This is, this is, or this? I think we have some dimorphic picture here with this like more mature, smaller, and more condensed chromatin cells, and others are a bit more like medium to large size. Oh, this one is really. Could that be CLL? I don't know. Like, CLL are not like this. There are increased number of atypical lymphocytes with the condensed nuclear chromatin, but some of them are showing clefts or, you would say, twisting of the nucleus. Looks like prolymphocyte. And I would go with a prolymphocytic leukemia. Prolymphocytic leukemia, B or T? B cell prolymphocytic leukemia. There is no BPL anymore after WHO 2022. There is only T. Okay, so I brought this blood film because in the previous morphology courses, our sessions, when I brought this blood film, patients directly, people directly jump to ATL. ATL has a cleft nucleus, see, flower, some people say flower, flower type of nucleus. But the main purpose of this blood is that this is not ATL. All these nuclear material is in the form of flower. Shaped nucleoli. But you never say this is ATL morphology or this is TPL morphology, etc. There are only few cells which are like this, but the rest of the cells, they are quite mature. Their nuclear material is very mature. You only say likely lymphoproliferative disorder. We need flow cytometry for this patient to confirm the diagnosis. Because this patient has almost white cell count is 70. A lot of them are mature. Only one or few of them are having flower-like type of cells. Patient is completely normal. The patient with ATL would have constipation or polyuria, or they have some sort of symptom presenting. But this patient is completely normal. See, you never make a diagnosis on morphology. Always say likely or possibly, then you are saved in the exam. Like, I would report this film like that. This blood film contains leukocytosis with normal platelets and RBC morphology. The white cells or the leukocytes, they have, um, they are small in size, small to medium in size with condensed nuclear material, some of which contain a prominent nuclei. There are few cells which have nuclear material in the form of cleft-like shape. This represents a likely lymphoproliferative disorder. We need flow cytometry to confirm a diagnosis. You would have suggested flow cytometry for this patient. So now, if I tell you that this patient's flow cytometry was CD5 positive, and CD10 negative, 23 positive, 43 positive, 25 negative, what do you think I'm heading toward diagnosis? It's going toward, sorry, CLL. Yeah, CLL. CD5 positive, 23 positive, 43 positive. I mentioned 25 negative because ATL is 25 negative. All right. The main point here was that do not make diagnosis on just on the blood film. If you see cells like this which are cleft-like, and you say that this is ATL, no. Look at the scenario as well. And look at the, and suggest flow cytometry. If they have given you flow cytometry, it will be very easy to confirm your diagnosis and to make your diagnosis. If not, then you have to suggest. There are many cleft-like cells, but this is not ATL. This is CLL, chronic lymphocytic leukemia. Sir, there is a variant CLL in which the prolymphocytes are more than 10% but less than 50%. I think I'm correct with the figures. Uh, could it that, could it be that it has a very difficult name? Clinical formal leukemia with prominent nuclei, but they should have 50% of prolymphocytes. The previously called BPL has been removed now from WHO 2022. If you open WHO 2022 classification, there is no BPL. All right. There is a new category called splenic lymphoma leukemia with prominent nuclei, which contain two categories. One is BPL and another is hairy cell variant. Both of them have been mixed together. And now it is for clinically formal leukemia with prominent nuclei. This is another case. This is a 30-year-old patient who presented to you with worsening back pain. He has a previous diagnosis of multiple myeloma and he has been started on non-transplant eligible category chemotherapy, VCD. This is the blood film of the same patient who has come back to you with worsening back pain. The blood test shows ISS stage 2, hypercalcemia, and hemoglobin is 90. Which say the CLL? No, no, no. This is a new patient. Who is a 70-year-old patient with the previous diagnosis of multiple myeloma on VCD chemotherapy, presented to you with worsening back pain. The blood test shows ISS stage 2, hemoglobin 90, hypercalcemia, and this is the blood film. Any volunteer? The RBCs and platelets seem to be normal with slight rouleaux formation in the RBCs. And I can appreciate plasma cytoid lymphocytes in the blood film. I will make it power 50 for you to make it more clear for you. What is this? Plasma [Music] lymphocytes in the blood film? Why are you calling it plasmoid? They do not have the typical plasma cell morphology. What is the typical plasma cell morphology? Say, medium-sized cell with eccentric nucleus, clock-shaped nucleus, and cytoplasm, which should be basically. Do you think this is plasma cells? Not a true plasma cell. Is this eccentric? A, there is a slightly slightly eccentric. Yes, okay. There is rouleaux formation as well. Sounds are okay. This is also a plasma cell with, um, halo formation. Some more. Right, so now we had more than 5% plasma cells. H, they look like, do they look like more than 5% plasma cells on the blood film? Yes, they are more than. In multiple myeloma, you do not see this much plasma cells in the blood. That would be like plasmacytic leukemia. Why are you saying plasmacytic leukemia? As I have already told you that this patient has previous diagnosis of multiple myeloma. Yes, in general, according to IMWG definition of plasmacytic leukemia, if the plasma cells are more than 5% in the peripheral blood, you call it as plasmacytic leukemia. But this patient has already a diagnosis of multiple myeloma, and the flow cytometry shows he has CD56 positive with other myeloma cytometry. So the main point behind this blood is that you can get a question in the exam which will tell you that the flow cytometry is showing CD56 positive, but when you open the blood film, the blood film has a lot of plasma cells. You would think that whether the initial diagnosis was wrong or now the patient has developed any plasmacytic leukemia, which cannot be possible. This is called spillover myeloma. When the myeloma becomes refractory or relapsed, and the bone marrow is overwhelmed, although your plasma cells have CD56 positive, which is a ligand protein, do not allow anything to go out of the bone marrow because they are overwhelmed. You will see plasma cells appearing in the blood film of multiple myeloma patient. This is called spillover or myeloma. We had a question like that in the exam. Hopefully, it will not come for you. So always, when you see a blood film like that which has more than 5% of plasma cells in a blood film, look at the flow cytometry. If it is given, if it is given, and it shows that CD56 is positive, then it is likely a spillover multiple myeloma. If the CD56 is negative, which is a case in plasmacytic leukemia, then it is a plasmacytic leukemia. Hopefully, now you would be able to differentiate what is spillover multiple myeloma and what is plasmacytic leukemia with the flow cytometry. Uh, how will we report this blood film? Only on the morphology. Okay, so on a safe side to report this blood film, if you have no flow cytometry and no history, then you say, this blood film contains leukocytosis with multiple rouleaux formation and normal platelet count. The blood film has multiple plasma cells, which are likely more than 5%, representing plasma cell dyscrasia, i.e., plasmacytic leukemia. But we need to confirm this diagnosis on flow cytometry. In the bracket, you can write, if it is CD56 negative, it is plasma cell leukemia. If it is CD56 positive, it is multiple myeloma. But this particular patient has multiple myeloma history already. I would say this blood film contains leukocytosis with red cell rouleaux formation and normal red blood cells. The, um, the plasma cells have a typical morphology in the form of eccentric nucleus and halo formation around the nuclear material. This still represents plasma cell dyscrasia, and the history of previous multiple myeloma represents that this patient has likely developed a spillover multiple myeloma. When you say spillover multiple myeloma, it means the patient has either become refractory to the current treatment or the patient has relapsed after going into remission. So be ready for such cases in the exam as well. If I haven't told you that this patient has multiple myeloma previously, then this is plasma cell leukemia. And if you do flow cytometry, it will be CD56 negative. If I told you that this patient has previous history of multiple myeloma or CD56 is positive, then it is likely spillover multiple myeloma. Because multiple myeloma has CD56 positive, plasma cell leukemia has CD56 negative. And CD56 is a ligand protein. It does not allow plasma cells to go outside the bone marrow. Hopefully, it will be clear now. Yes, sir. Such cases do appear in the exam. So be ready for such cases as well. And if you are working in a treatment center and you have myeloma patients, then you must see a spillover multiple myeloma or ask your lab, they would have such blood films as well. Now, the fourth is a 60-year-old patient with eczema, profound eczema almost covering the whole of the body. All right. Is there any volunteer to go through this question? Uh, sir, please zoom a little. Okay, I will go to power 50. Let's see a few cells, and then you can comment on that. [Music] Any idea about the nature of this cell? Uh, sir, they look like lymphocytes. They are lymphocytes, but we want to see the characteristic morphology of these cells. Do you have any differentials in your mind? Uh, sir, the first one that comes to my mind is Sezary cells. What is the morphology of Sezary cell? Cerebriform nucleus. These cells also have something like that. Do you think this is a Sezary cell? Yes, I haven't seen before, but, uh, what I read about the morphology, so I think, yes, this is. Can you focus more? The, yes, yes. I'm searching for a typical cell. Uh, that the cell has scanty cytoplasmic projections. Scanty cytoplasm, but there are projections. Am I right? They are very, very scanty, very, very few. So I'm, I'm searching for a typical Sezary cell to show it to you so that you cannot forget in the exam. For me, this looks like mature cells, like CLL cells. Generally, they are. Is it a new differential? Like, when you have first look to the blood film, do you think about probably just mature, like B lymphocytes for CLL? But they are bigger than the CLL cell. CLL cells are a bit small, and these cells are a bit bigger. The nuclear content is mature in both, but the Sezary has typical form appearance or what is this? A dry fruit? Then you open it and it has a c-form appearing, some type of. Not, I know the name in my language, but I do not remember it in English. Please tell in your language. My language is Punjabi. So you do not understand. Yes, sir. I also put on that. So I was asking, maybe I would know in English too. Maybe do we need to give differentials while looking at morphology only? If they ask you in a separate question, what are the differentials, then you have to give differentials. Otherwise, not. So I think this a bit resembles to the Sezary form appearance. If I make it more, this compartment is it cerebriform? Cerebriform? Is it do you mean like the brain? Like the brain? Cerebriform. And this patient has a history as well of eczema. So if there is eczema history and you have cells like this, it most likely goes with the Sezary syndrome. Like this one. But not all of them looks like cerebriform nucleus. So some of them are like Sezary cells. Or do you think all of them are Sezary cells? Not all of them. Obviously Sezary cells. Not all of them are Sezary cells because not all of them has cerebriform pattern. Okay, so there are some mature lymphocytes then? Yes. Sorry, can I comment? It might be like hyperchromatic type of cells. It's not just mature. Hyperchromatic. What do you mean by hyperchromatic? Yeah, usually the T-cells, usually the maturation of the cytoplasm, like hyperchromatic. So it might be pointing a clue like, it's likely one of the T-cell neoplasm. Never heard about hyperchromatic terminology. Sorry about that. No, that's okay. I think maybe that is more used in histology. Now, these three cells, if I make it more clear. So the percentage of these cells in the periphery for diagnosis? No, no. There is no need of any percentage of the cells. It is only the morphology of this nuclear material which is mature and, um, and has ups and downs in the nucleus. Like someone put water in the flow and then put a hand in the flower, before making the bread has appearance like that. So it has quite a lot of Sezary cells. But the typical appearance in which it has a central line in between and has c-form appearance on both sides, they are not. Yeah, but I think ask question. Mhm. Is it easy to differentiate or you need to be like suspicious to look specifically to see Sezary cells? Or it should be obvious? Because what I saw now, you have to be on a high power to judge that this is Sezary rather than just mature lymphocytes. Am I right? If you have given a history of eczema, so eczema either goes with eosinophilia. So you will be thinking that maybe this is, um, there is eosinophilia or associated with any allergic disorder. Another, you would think maybe this is some type of worm. So you will see the slide on power four first. And the third, third cause of eczema in the hematology, the widespread eczema in hematology is Sezary syndrome. So you would prepare your mind to see these type of cells. Now, this cell which is in front of you, um, has a central line in between and folds on the other on each side. It resembles more to a cerebrum than to cells of CLL. In CLL, you do not expect to have eczema or erythroderma. And these cells are a bit larger than the cells of CLL. In CLL cells, they are almost the same size as that of the RBC. The CLL cells are very small. And Sezary cells has smear cells as well, plus prolymphocytes. This one has no smear cells and no prolymphocytes. All of the cells are mature and half of the cells has morphology like that. I think this cell which is in front of you is more clearer toward cerebriform nucleus. Now, this one as well has lines inside. So the nuclear material is not uniform. There are a lot of indentations in the form of cerebrum, and they have a central line as well in between. And the history of the patient, they would guide you that these are Sezary cells and a diagnosis of Sezary syndrome. If you are working in NHS, your laboratory must have Sezary syndrome collection. They should help you with that. But do see them before the exam because they always come in the exam. All right, so you will describe this blood film findings as a medium to large-sized cells with a cerebriform nuclear appearance. Yeah, most likely consistent with, um, Sezary syndrome. We need flow cytometry to confirm this diagnosis. Sezary syndrome flow is usually exclusion of other T-cell lymphoma because there are no typical markers to suggest that this is T-cell lymphoma. Like for ATL, you have specific flow. For LGL, T-LGL, you have specific flow. For TPL, you have specific flow. For PTCL, you have specific flow. But for Sezary syndrome, you have symptoms and exclusion of other T-cell lymphomas. Right, so this is the last case. This is the thank you so much. This is the aspirate of a 30-year-old female who presented to ED with epistaxis and bruising. This is power four, just to see if there is any particle in this aspirate or not. Looks like there is no particle in this aspirate. You will go to power 10 and you can see the cellularity now. This is power 50. What type of cells do you see on this aspirate? Like the promyelocytes. And what is promyelocyte? Just for the audience knowledge. Yeah, it is, um, one of the cells of granulocytic lineage in mature form. White cells. Mhm. Usually it's, um, big cells and could be hypergranular. Okay. Malignant. Right. Yeah, these are malignant promyelocytes. Mhm. Medium to large in size, with the adequate cytoplasm, a convoluted nucleus, may have nucleoli, and the cytoplasm, when it's granular type, it has the granules. And in both the granular and agranular type, we can appreciate Auer rods. Have you seen Auer rods? If you haven't seen, then do not mention it in your answer. Yeah, so far, it's mainly hypergranularity. I can't appreciate Auer rods so far. So this is granular. And this, this cell is bi, this is one lobe, and this is another. That's a lot of granular cells. And the blasts and pro, and promyelocytes. I think it is easy to diagnose APML on aspirate than on blood. But sometimes the APML variant is hypercellular, and you can miss the APML on on blood. So, yes, this patient has epistaxis and bruising, and you can see the aspirate is full of myeloid lineage, large promyelocytes. They are hypergranular, some of them are bilobed, and there are few with nucleoli as well. Yeah. How would you treat this patient? Arsenic or with arsenic and OB? What was the patient's age and comorbidities? Patient is 30 years old and has no comorbidity. Yeah. And what is the white cell count? Excellent. You have asked the question that I was hiding. White cell count is 20. Sorry, how much is the count? I didn't get that. 20. Yeah. So arsenic and, yeah, yeah. And obviously to treat the underlying, if there was any coagulopathy, supportive and treatment. Yes, this patient has epistaxis and bruising, so the patient may be in DIC. Usually these patients have very low fibrinogen levels, and you need to check the fibrinogen level twice daily to make sure the fibrinogen is above one, and some trusts about 1.5. In other, yeah, so different trusts have different ranges. Our trust has 1.5 range. And, uh, yeah, also we say 1.5 in our trust. Yeah, yeah. And if this is a patient in your part one exam or in part two exam, you need to start treatment as soon as possible. Do not worry for fertility preservation, because you don't have time to wait for fertility clinic appointment. Just mention, I would have considered fertility preservation, but this is a hematological emergency. I need to start treatment as soon as possible. I will prioritize my patient and I will start treatment. This is another kidney-shaped or bilobed nucleus. Right, so this is for the last case. Do you have any questions? Sorry, I just have a question for the case number four. What is, you mentioned usually is the differential for, if there's a history of eczema or skin condition? Yeah, what is the differential again? Apart from the Sezary cells? So if you have a scenario like which says that there is eczema in the patient, so mild eczema can be in any T-cell lymphoma and in Hodgkin's disease. But a severe eczema which comes as an erythroderma, the whole body is covered with eczema, and they have given you a peripheral blood film, it means either there is a, this is a case of eosinophilia or this is a case of PCL, leukemia, Sezary cell, mycosis fungoides. And if it was a Hodgkin's disease, they would give you a lymph node biopsy because you have to see the Reed-Sternberg cells in the lymph node biopsy. In peripheral blood, you cannot see cells or in the aspirate, very rare. Okay, so that's why I say the exam is a little, need skills. And all of you have knowledge about Hodgkin's, Sezary, everything. But to save your time in the exam, in the nine minutes, if they say this patient has a full blood count shows eosinophil count of four, and patient has no travel history, nothing, this may be eosinophilia or if you see the blood film, it can be associated with acute myeloid leukemia. If this patient has, um, erythroderma all over the body, refractory, pruritus, does not responding to any medication, likely a T-cell Sezary syndrome. If this is a young female, 24-year-old female with lymph nodes as well, and the blood film and a full erythroderma and the symptom is pruritus, then you would think that it can be a Hodgkin's disease. So they would have given you a lymph node biopsy for that. So the stem of the question and the patient symptoms and age relate them, then you will get the answer. For example, if they give you in an exam that this is a 19-year-old male patient or female patient with cervical lymphadenopathy, most likely it is an infectious mononucleosis. You will see a reactive blood, reactive lymphocytes. If they say that this is a 2-year-old boy with B-cell count of 50, the most likely they are talking about acute lymphoblastic leukemia. Either B-cell or T-cell. B-cell has high count, T-cell has less count. Um, again, if they say that this patient is unwell, he had travel to Jamaica, or this patient has polyuria, or this patient has constipation because of hypercalcemia, so they are talking about ATL. ATL has high calcium. Or if they say this patient has rheumatoid arthritis and now he is persistently neutropenic, and you see the blood film and you see large lymphocytes, the lymphocytes would have a structure of large peripheral lymphocytes. It is either T-LGL or NK cell. And if they say this patient has high count and with infusions or with prolymphocytes, you will see lymphocytosis in the blood, just like CLL. But if you observe the cells, they would have blasts. So it would be a TPL. TPL comes with infusions, either lymphedema or swelling. So, scenario helps you a lot. Scenario and sometimes might be a flow cytometry as well in the stem. If you are lucky, if you are lucky, you get the flow. In my exam, they had given you only one flow for CMML case. In the other question, they asked us what is the expected flow. So if you are lucky, you will, and you get the flow, you can make a diagnosis without going without seeing the blood. Combination of things. Yeah, yeah. Right, yeah. Thank you. Automatic makes the diagnosis very easy. You are then confident what you are seeing. Okay, so this was about the session. We will continue slowly and slowly our sessions and subscribe the channel more. And if you want to join the group, I'm not active over there, but people do discuss morphological cases. You can scan this and join the group. And thank you. Have a nice sunny Sunday and see you next week. Thank you very much. Thank you.