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Weekly Morphology Session for Lab staff and Clinical Pathologists-DLBCL, IDA, CML and Sepsis

Haematology, Morphology and FRCPath Exams1:01:01

Transcription

Hello everyone. Can you hear me? Yeah. Is the screen visible? Can you see the screen? Let's not first.

This is a 40-year-old man admitted to the emergency department with high-grade fever and productive cough. His hemoglobin is 120. White cell count is 70 and platelet count is 210. This is power 10. And I will do now.

Do we have any lab scientist in the audience? Okay, if there is no lab scientist, for example, I am the lab scientist. I have seen this blood film and reported as leukocytosis with NRBC, likely CML. Refer this blood to clinical hematologist. You are the clinician and you have to report this. The first on the list is How many Godwin? How many? If you have any comments on this, but we have a short hello. So, do you have any comment on this blood?

Okay, sorry. Please brief history again. Sorry, my this is a 40-year-old man admitted to the emergency department with fever and cough. The full blood count shows hemoglobin of 120, white cell count of 76, and platelet count of 220. Lab scientists have seen the blood film and he has reported as leukocytosis with NRBC, likely CML. The blood film referred to hematology, clinical hematology. If you can report this blood film as a clinical hematology.

Um, so the red, the red blood cells, um, so the red cells, I would say, aniso, an isocytosis. Um, they are neglected red blood cells, neglected RBC for the red cell. And then for the white cells, I will say nucleocytosis, um, with complete myeloid spectrum. And for the platelets, so for the platelets, I say, feel, I'm looking at now, uh, reduced on film, but not, yeah, and that's what I can appreciate here. Yeah.

What is your impression? So my impression with this would be, would be CML. And what opinion you will, what suggestion you will give to the team? Because they will contact you shortly from the ED that the patient has high white cell count. Is this a leukemia or what is this? So this is, this looks like this, this CML. So I'll go with CML.

So for this [Music] um, the immediate care for this patient would be, uh, I could get some cycle reduction for the patient while waiting to get, um, a more definite diagnosis. Uh, so I could give some hydroxyurea, give hydroxyurea and then ensure patient is hydrated. Then give, um, [Music] allopurinol to prevent, um, in case of TLS. And then for patient having fever, so we could also do the sepsis workup, get a chest X-ray, uh, do the blood culture, get the full blood, uh, do blood culture, do urine, and then start empiric antibiotics. Um, yeah, so that will be the immediate care, care for this patient. And then eventually, um, we try to get a more definitive diagnosis. Although for CML, we could still send blood sample for FISH to get the BCR-ABL. But, uh, we will still need to do a bone marrow so as to help us do the staging properly and also for cytogenetics. And then for this patient, we also need to look at, uh, other comorbidities. Is the patient diabetic? Does the patient have any, uh, cardiac concerns? Because that would eventually determine the treatments that we would offer this patient.

Okay. Is there anyone in the audience who disagrees with Godwin? Ravia, what do you think is Ominy correct in reporting the blood? Raj. Hi Aish. Um, do you agree with Omi Goodwin or do you disagree with Omin? Yeah, I think, um, I saw a couple of blasts, um, but just I would like to see more, um, like tight of the film just to decide like if, like in blast crisis or not. I agree that it's CML is the probability, but obviously we just, we need to make sure that there is no significant, uh, number of blasts, like it's not in blast crisis. Um, so far in this film, I can see like it's, uh, I agree that there is variation in the, in the granular sites at different maturation stages with, um, mainly myelocyte peak, many neglected red cells in this field. Um, is there anything missing in this blood film? If you are saying the visual field is missing, then why are you saying that this is blast crisis or? Yeah. Yeah. I couldn't appreciate any. Yeah. There was no battlefield as far as I can see. Yeah. Did you see any? You see nothing? No. No. No. No, I couldn't appreciate, um, any basophil or eosinophil. Yeah. So then what, what could it be if there is no basophil? No, and there is myeloid peak and this is the picture. Yeah. Um, action. Yes. Patient has sepsis. Yeah. And there is, yeah, definitely left shift neutrophilia. So this is a common case that appeared in the partat exam and people write it as CML. Both reaction and CML has high count, but the difference is basophilia, and we didn't see any basophil here. We didn't see any here. Also, all other components of myeloid series are present here with NRBC as well, and the patient is febrile, having pneumonia symptoms. This is a septic blood, not for CML. You should see eosinophils, you should see basophils as well. Yeah, that's true. Yeah. So reactive blood film is a must thing in the exam, and people write it as EMF. So you need to see, uh, blood picture, blood films of septic patient in your hospital, and also the CML patient blood as well, so that you could know what is the difference between the two.

Okay. This blood film contains a lot of NRBC. There is anisocytosis. We could see many, uh, teardrop cells here in this picture. You can see target cells as well. There were few Howell-Jolly bodies in the red cell. There's myeloid peak in the white cell. Okay. You can see also of, uh, myeloid series there. Platelet count is low, which is low because patient has pneumonia, as evident by the target cells and by the whole GIB body. So this was the septic blood.

Now, the same patient presented to hematology department after 5 years. Okay. The GP referred the patient to hematology department because of persistent leukocytosis. This is instruction. This is power. His full blood count shows hemoglobin of 105, white cell count of 400, and platelet count of 100. Okay. Now I will go to power 50. Okay. So, what do you think about this blood? The same scientist has seen the blood film again, and he says that this patient has leukemia and likely leukemia. The blood film has come back to you again. Now you have to report it. Ravia, are you there? So Ravia is hiding today. Uh, next one is Rashag Guda. Okay. Samir Abas. Hi. Hi. So I, um, I can still see like very large number of left checked, um, granular sites with with all stages of maturation and and I think it is still with some like rouleaux formation in the background as well, which might be like suggesting possibility like of a severe infection again. So, um, I, I couldn't appreciate any basophils or eosinophils still in this film. So I would still go with, um, reaction.

Can you see my? Oh, yes, this one. No, this is, um, there were many things like this and this look that we have seen. Is that a basophil? This is a basophil. [Music] Basophil is a very, very adrenaline. And there are many leukocytosis reaction will not give you white cell count of 400. This is another reason. This is the business. This one. See this. Yeah. This film is full of these. So now this is a CML. This is a PML, but we don't know whether this is blast crisis or how would you differentiate? So between the two. So the blast percentage, um, is the most important here. Mhm. We don't have now in the classification anymore the accelerated phase, but, um, which will be like a 15 to 29% of blast. And if more than 30% it will be blast phase, otherwise it will be chronic. More than 20% blast, if you have now in CML, you will treat it as AML. Okay. So for CML and for the SEA mutation, BCR-ABL, and for SEPA mutation, you need more than 20% blast, treat them as AML. For others, if you have just mutation or translocation present, irrespective of the blast percentage, you will treat them as AML. This is according to WHO 2022. Okay. All right. The chronic phase, the blood, how, um, I think then it will be anything less than, than the 19, 10 to 19%. Yeah. Because now the accelerated phase has been removed. Yeah. So anything less than 20, we consider as in a chronic case. Previously 10 to 20 was accelerated and less than 10 was chronic. But now most of the hospitals in they use WHO 2022.

What are the major root abnormalities in KML? Was it the K? Um, there's no KOS in CML. Anyone who knows which of the major root abnormalities in the CML? Try eight and others, there's also additional chromosome X8, 19, and chromosome 17 or consider as major root abnormality. Okay. What is the progress score that you use in your hospital for CMI? The ELA score. ALTS score. If the care score is high in this young patient, which medication you would like to offer to this patient? Yeah. Uh, second generation KKI, um, like the satinate. The certain highs, young patient, you can offer them second generation, the certain. What are the contraindications of the certain? Um, I think pleural effusion, edema, or pericardial effusion. Yeah. Anything which desaturates is the contraindication. Sorry. Contraindication for the detert. Um, got already pulmonary or pericardial disease. Yeah. So D for the certain, D for desaturation. Anything which desaturates the person means cause hypoxia can lead to, uh, or the contraindications of, um, inter 20 female. Okay.

Uh, so presented to ED with fatigue. Okay. The full blood count shows hemoglobin of 90, white cell count of four, and platelet count of 150. The lab scientists have reported the blood film as thrombocytosis, likely essential thrombocythemia. The blood film has been referred to you for your comments. So this is the power 10. Now I will go to power. Okay. Any comments from your site? How to report this blood film for the exam purpose? I think I will say, um, RBC is showing a need for cytosis, um, with some, um, with Mhm. Okay. Um, I think in the previous film, I appreciated, um, some pencil cells, but I can't see them here. Um, um, there are, um, occasional fragments. Mhm. Okay. There are, there is some mild platelet clumping. Um, platelets. Um, aniso, an isocytosis. Yeah. So here there are some, um, I think, uh, there are some pencil cells here in this field. There are few cells lacking the central pallor. Looks, I don't want to commit myself to spheres here, but, yeah, and my thrombocytosis, lymphocytes. So there is lymphocytosis in the middle here. And if we compare the size, the red cells is slightly microcytic. Um, yeah, but I think I will say feature suggestive of, um, iron deficiency anemia.

Do you think this is iron deficiency anemia or combined deficiency or this is ET? So, um, the cell sizes, um, some of them are smaller, some of them are smaller than the size of the side nucleus, but there are few a little bit bigger cells like this one on top here. Yeah. And another one here at the middle. So it could be mixed. Yeah. You're right. It is not ET. I don't think so. Well, I can't say for sure, but because we need to do further testing, check the iron stores, check the inflammatory markers. Um, and if all negative, then I can check the JAK mutation. And, yeah, but initially we need to exclude reactive causes. Your approach is correct. First, they have to exclude the methemoglobin deficiency and the, uh, infection marker. If they are normal, then we have to send blood to SMDS or, or yes, this has a lot of anisocytosis, both microcytic, macrocytic cell. One of the cell has Howell-Jolly bodies. And I bring out this nucleated red cell for you so that you can compare the size of the RBC with the lymphocyte. And he is a female and can have anemia as well, leading to iron deficiency. So yes, we cannot jump straight to ET. We have to exclude iron deficiency and, uh, infection first, according to the BSF algorithm to exclude, exclude the rejected. For example, this patient was diagnosed as ET. What treatment you would like to give to this patient? So, she is a young lady. Um, I need to check her, um, uh, if check if she had any previous history of thrombosis. Or, um, yeah, VTE before. Um, if no. So, if not, she's, uh, then that means she's low risk. Uh, so I will start now on aspirin and keep monitoring. How cows? No need to start cytoreductive therapy at the, like currently. Better to check your hospital guidelines whether they would like to give aspirin or not, because her platelet count is about 1000. I've seen some of the trusts do not give aspirin if the count is above 1000. Some of the trusts do not give aspirin if the count are above 1500. So check your hospital guideline or discuss with your myeloid consultant. If they say yes, you will give, then okay. If they say no, then in the exam, you can mention to them. According to my first guideline, they usually avoid aspirin when the platelet count is about, because of the risk of acquired von Willebrand. So practice according, practice studies in terms of aspirin, but below 1000, yes, everyone will get aspirin and no indication of reductive therapy.

So this is a 70-year-old man presented to ED with a large neck mass on the left side of the neck. CT scan neck, abdomen, pelvis shows lymphadenopathy above and below diaphragm. The full blood count shows hemoglobin of 110, white cell count of 12, and platelet count is normal. He has weight loss, night sweats, and lack of appetite. The night, the neck mass is quite big and it is causing discomfort to him. This is power 10. Let's go to power 50. Now there are some droplets in the slide. No. Okay. So I have seen this blood film as a biomedical scientist and I have labeled this case as a lymphoma because of these abnormal cells in the patient's lymphocytes in the blood. I don't know about the history of the patient because we do not have access to the patient record. I was trying to preserve the blood by keeping a slip on it. And this has created all the. So when I saw this slide, I thought this is some kind of neoplasm. I should refer it to clinical hematology. Do you know the story of the patient and this is the blood? Next on the list is Imbraim. Im said Ahmed Ibraim is silent. Then we have top on the list is Doc D O C Doc. Yes. Yes. So what do you think is going on with this patient? The biome, the biomedical scientist think that this is some lymphoma in this patient. He has not mentioned which lymphoma, but after seeing these cells, he thinks maybe there is lymphoma in the patient. Okay. Um, um, these, uh, these cells are, uh, large and, um, maybe it could be a leukemia too. I don't know the exact count of the cells. I don't, uh, recall the DLC. What cell count is 13? 13. Is hemoglobin is 105, count is normal, and the age of the patient is 70. Is there any history of fever? Patient has no fever, but he has a history of weight loss, history of, uh, night sweats, and he has a big, uh, neck mass. Okay. Um, what is the ESR of the patient? And, um, we don't do ESR here. Okay. Um, I would like to rule out plasma cell or plasmablastic. This is your blood cell. You have to report it. Okay. So, uh, the, the WBCs show large, uh, large cells with abundant cytoplasm and few vacuoles and nuclei also prominent in the large nuclei. Mhm. Um, I could not decipher how, how many these cells are because it really counts. I would like to know the exact DLC, because if these cells are like around greater than 10% or greater than 5%, then I would, because these are very big and, um, they are definitely not reactive lymphocytes. They are a little more bizarre looking than those. They have here, yes. Mhm. And also I wanted to see whether there is rouleaux formation, but I don't think there is any rouleaux formation on the, on the smear. And the RBCs, uh, are showing some kind of, uh, maybe some kind of fixation defect, some, the, and the platelets look normal. So, um, I'd like to advise flow cytometry on this, since the patient has a mass in the neck. So, and also there should be, uh, FNAC or, um, biopsy of that mass to rule out any lymphoma or, uh, what do you think call it neoplasm?

What is your impression? Yes, you have commented on the blood film. You have given your plan as well. But what, what is your impression? I don't know. But I had seen one case of plasmablastic leukemia somewhere, and I don't know why these cells are reminding me of those cells. I have no idea. But somehow it is giving me that sort of look. Leukemia comes with a mass. Come. No, I'm the, just the cells. Just the cells. If I'm just looking at the cells, then I'm, it's giving me that sort of thing. It's very big and they're very aggressive looking. Could be DLBCL, but the DLBCL does not have so much cytoplasm. Mhm. Or, um, anaplastic large cell would be one of the differentials. You would see any plastic large cells in the aspirate or in the fine. They rarely appear in the blood. Yes. Fine. True. Okay. So the flow cytometry results have come back. It is CD5 negative, CD7 negative, CD10 negative, CD19 positive, CD20 positive, CD23 negative, CD43 negative, BCL2 positive, BCL6 positive, TP53 positive, MYD88 is positive. Do you have the cold immunohistochemistry result? Yes. DLBCL. So you think this is DLBCL? Yes. These are not blasts. You can see the size of the blast with the surrounding RBC. And some of them have a single prominent nucleus or some of them have two prominent nuclei or more than that. Okay. And if a patient has a big mass in the neck as well, that is telling you that it can be a high-grade lymphoma because Burkitt lymphoma or DLBCL will always present with huge masses either in the groin or in the tummy or in the axilla or in the neck, compressing other structures and putting the patient in agony and and the mass appear very quickly, in a matter of days, because they are aggressively proliferating. If the mass appear over months and the cells in the blood film are small as well, small to medium size, then I may think that maybe this is low grade. But these lymphocytes are quite big with a very prominent nuclei in the center, as you can see in this picture. You always worry for a high grade. If it was a Burkitt, Burkitt has different morphology. Um, the cytoplasm is very deeply dissipated if they involve the blood with some vacuolation as well. Um, so this patient's age is 70, LDH is 5,000. He has lymphadenopathy above and below the diaphragm, and his performance status is two. Do you think which regimen of therapy he would be fit for? Okay. I, um, are you asking me? Yes. Um, I'm sorry. I do not remember the drugs right now. Okay. So anyone can, if this patient is aging 70, LDH is 5,000, he has a disease below and above the length of the diaphragm, his performance status is two, what regimens do you have in UK to offer to this patient? I would ask Ravia or AA. Okay, Samir, you can talk if you have an answer. I was thinking that maybe his IPI score could be three plus. Mhm. Because of the age and the high LDH, um, and the performance status, and then, um, and he's double hit, um, so we can give him R-CHOP, like, um, or, uh, or R-Polar-CHOP. Mhm. Plus we can consider like, um, the radiotherapy to the neck mass to reduce like the symptoms of of the pressure. Radiotherapy is an option here, but because of many vital structures, [Music] um, people may avoid it. They would like to see the response to chemotherapy first. Because if you offer him any chemotherapy, um, the mass reduces very quickly. But if it is, it does not reduce, he fails the chemotherapy, then we go for radiotherapy of the neck. So what regimen do you suggest? CHOP or POLAR-CHOP? You mentioned his IPI is more than three. So in high IPI, you give them POLAR-CHOP. If the IPI was 0, 1, or 2, then you would have offered R-CHOP. This patient has no other comorbidity. So he can take POLAR-CHOP with high RPL. There are two other things about which we need to be careful in DLBCL or in in this patient. What are they? Can we consider them in every TBC? CNS involvement or if they were like high for that? Yeah. CNS IPI, you have to calculate. And second, TLS profile, because these patients, they have high, uh, tumor burden, and they can go into TLS very quickly. All right. Do you have any question? Oh, thanks. No question. Then we can. Sorry. Um, just a quick one, please. I, I have thought question on the last one. So sorry to take us back for the patient with ET, low-risk ET, and a young patient. Um, if you're thinking of acquired von Willebrand, so what would we now offer the patient since we won't be giving aspirin? So if the patient has ET and can you please repeat? So ET, um, young patient, less than 60, high platelet count, and we are, we are bothered about acquired von Willebrand disease. So what would be the treatment option? So the risk of acquired von Willebrand is high, most if the platelet count is above 1500. In that case, you can give this patient cytoreductive therapy because you will not always follow what is written in the guideline. The case scenario sometimes get different according to the clinical situation. If this patient's platelet count is, for example, 2000, I know that he can bleed, any she can bleed anytime. I will cytoreductively reduce the patient because without cytoreduction, you cannot reduce the platelet count of the patient. In that cases, in such cases, offer them cytoreductive therapy. Okay. Thank you. And then you, and you avoid the aspirin as well. In our trust, we usually avoid aspirin if the platelet count is above 1000 and because we are at high risk of, um, bleeding related to acquired von Willebrand. Okay. So still in a young patient. So once we've been able to cytoreduce, um, this patient, would we continue it long-term or would there be an option of stopping it after some point? Can you please my question? So I'm saying, so I'm saying yes, we know that for younger patient, we would usually want to opt for aspirin. Yes, in this patient, patient, because of the high platelet count, we opted for cytoreductive to reduce the platelet count. So we've had a platelet count going far less than a thousand, maybe in 600 thereabouts. Would we still carry on the cytoreductive long-term or at some point get to stop and only give aspirin? If the platelet count is 600 and patient has no VTE, no hemorrhage related to to the ET, you only give them, you only give them aspirin. If the patient is young. If the patient has any, uh, if the patient has any VTE event or if the patient has any hemorrhage related to ET, you will start profile, you will start cytoreductive therapy even at low platelet count as well. So what I'm asking, I'm not talking of a new patient. I'm saying the patient that initially had cytoreductive therapy, then the platelet has now gone down to 600. So are we to carry on with the cytoreductive or we get to stop at that point? Yes. So once the platelet count is in normal range, 150 to 400, at this stage, we can pause the hydroxycarbamide and see whether whether the patient can maintain the platelet or not. If the platelet count start to rise again, we reintroduce the hydroxycarbamide because if you continue hydroxycarbamide, it is cytoreductive. It will continue to destroy your red cells and platelet and it may go down dangerously low. Because if you open the hydroxycarbamide algorithm in the BSH, they have mentioned if your platelet count goes down below 100 or hemoglobin goes down below 45 or neutrophil count goes down below 1.00, you have to stop the hydroxycarbamide and you have to repeat the full blood count after a week. And if they are above these values, you can reintroduce hydroxycarbamide with a lower dose. So once they reach the normal values, you can give a pause. But we know that we follow these patients regularly and, uh, we check their full blood count, uh, every month or in the control patient, every 3 months. Uh, if they, if the count increase again above 400, we will start a small dose of hydroxycarbamide again. So if you open the hydroxycarbamide algorithm in the BSH, we always manage our patient, patient hydroxycarbamide according to the guidelines for hydroxycarbamide, and this is the algorithm. In any case, if it, if it is a polycythemia, if it is ET, if it is any other MPN, we follow this algorithm. Where is that? This one. It is on the screen. Count less than 1.00, platelet less than 80, hemoglobin less than 45. Stop hydroxycarbamide and repeat full blood count weekly until neutrophil is above this level, platelet above this level, hemoglobin above this level. Once stable, dose is established. So this is the hydroxycarbamide algorithm that we follow in our MPN patients. All MPN. Okay. Okay. Right. Thank you. Okay. If nothing else, then we will see you next week. Thank you. Thank you very much. Thank you. Take care.