Online Morphology Session for Lab Staff and Haematology/Pathology

Okay. So this is the first case one. So this is a 19-year-old female patient who presented to the emergency department with headache and confusion. Hemoglobin is 97. MCV is 61. White cell count is 132 and platelet count is 61.

If you can please allow the people waiting in the lobby, I will be thankful to you.

So this is the 19-year-old patient with uh 98 hemoglobin, 67 MCV, white cell count 132, and platelet count of 60. Do we have any biomedical scientists in in our session? If there is any, shout out any biomedical scientist. No, for example, I'm the biomedical scientist. I have seen this blood film. Very high white cell count, and I have seen these few large cells and uh some of them are small, looks mature as well to me. There are NRBCs, right? And I am the first-year BMS, for example, I am a trainee BMS. I have seen these few NRBCs as well, and I think that this is CLL, okay? Because I'm a first-year trainee BMS, I haven't seen blood films before, so I think that this is CLL. So I have referred this case to a clinical hematologist. So now I need a clinical hematologist to comment on this blood film. This is power 50. Dr. Ramir, can I go ahead?

Yes, please report the blood film.

Yeah. So, uh, this is a neoplastic blood film showing uh very high white cell count, and the white cells consist of a largely monomorphic population which are large in size with abundant cytoplasm. Um, some have prominent nuclei. So some, some cells are uh also showing uh cytoplasmic vacuoles. Uh platelet count is reduced, and uh MCV is also uh as you already said that it is a low MCV. So most likely uh hypochromic microcytic red cells, and uh overall the picture is concerning for uh acute leukemia and most likely belonging to the monocytic lineage, maybe acute monoblastic leukemia.

Okay. So as I mentioned to you, I am a, I am a first-year training BMS. So I would be asking you, why do you think that this is acute leukemia, not CLL? What, what, what difference is there in the blood film to you that is suggesting to you that this is leukemia, acute leukemia, not chronic leukemia? How would you tell me?

Uh, so firstly, the cells don't uh look like the CLL cells. They, they don't look like mature small mature lymphocytes. They are big in size. Uh, I can't see much of, although there are some uh smear cells, but not huge. So they, they are not lymphocytes, basically. They look monocytic, and platelet count is reduced. The other thing that uh goes more in favor of a leukemia is the age.

Okay, good. Age also goes in favor of a good leukemia as well. Yeah. Right. So now, and the cell morphology, most of you know them are because they have abundant cytoplasm. The cytoplasm has vacuoles. The nucleus is also kidney bean shaped. So, um, they're more in keeping with uh the monocytic than the lymphoid.

Okay. Right. Right. So now you think that this is acute leukemia. What next step would you like to do? Your report does not finish at yesterday. You need to tell somebody something else as well.

Yeah. So, uh, I will, uh, uh inform the consultant who is looking after the lab on that day, and I'll send the blood, the blood sample immediately for uh immunophenotyping, and uh I'll call the patient where the patient is at the moment. If it is a GP film, we can actually call the patient immediately uh to hospital uh and then we can admit the patient, do uh bone marrow, and send urgent cytology in the hospital because she presented with headache and slight confusion. So, yeah.

So if the patient is coming with headache and confusion, then with such a high white cell count, there is a risk of, you know, leukostasis. And so, uh, we would like to, I don't know if we can do. I'm sorry.

Okay. So this, this patient, you, you think that this is acute leukemia. So most likely, uh, this is as suggested from this picture, even the presence of you as well, and you mentioned as well. This patient needs admission under hematology, blood film cytometry, um, imaging of the head for any uh ischemic event or or hemorrhagic stroke, and urgent bone marrow biopsy. Okay. This patient's count is very high. You need to reduce the counts by hydroxyurea. Okay. And if the CT scan shows any uh any findings, if it is ischemic stroke, you need to know immunology. If it is hemorrhagic stroke, you need to know neurosurgery. High white cell count, acute leukemia, and headache. Usually they have something in the head, either stroke or hemorrhage. Most of the time it is hemorrhage. And she's 19 years old. So you need to involve the. If there is a B. So I could see there was someone, Farhan Halid, your hand was up.

Yeah. So, uh, basically, pretty much echoing uh Romana's thing that this, this patient does have, have predominantly monomorphic appearance of of of the cells favoring more blastoid, a more blast-like picture rather than anything else. And I, and I don't think it's CLL simply because they, they are not CLL cells are more small and mature. These don't look mature at all. They do look very uh large, and there are some uh some kidney shaped among them. Yes, acute leukemia would be a diagnosis in this one. Um, one of the things, and it depends center to center. I think if the white blood cell count is more than 100, you can technically send cytogenetics from the uh from the peripheral blood itself. But it's, it's very specific. So not all centers do that. You can also send w, you can, you can send for for flow and cytogenetics from the peripheral blood if the white blood cell count is more than 100. And, um, obviously, but if that's not the case, do an urgent bone marrow, as everything which you said.

Thank you. All right. So we are suspecting that this is myeloid category of leukemia. So again, the same question, according to WHO, according to BSH 2022, what gene panel or myeloid panel would you like to send for this patient? What would you like to pick?

So, so, so this will, first you'll, you'll start with your flow. Your flow will guide where it is. It is obviously, you, although it is very likely to be myeloid, but you can be proven wrong. So, you start with your flow, and then you send your myeloid gene panel. I mean, looking at it, I would send the myeloid panel on its own, the entirety. Uh, so, so in NHMDS list, you can have an, you can send the entire myeloid panel in one go, which includes pretty much all of the cytogenetics.

What cytogenetics? The BSH has mentioned four categories in the exam as well. What, what's the minimum genetic test you would like to send for a new acute AML?

That's a good question. No, m, um, no, I don't know the answer to that. I think probably, if I'm guessing now, I'm guessing now, it would be 8;21, inversion 16, NPM1, FLT3, s, uh, BC, translocation 9;22, 8;16. Yeah, I'm guessing now. Sorry, this one I'm guessing now. I'm guessing. First category is karyotyping. The second category is FISH/PCR for 8;21, inversion 16, and NPM1, KMT2A. Platelet 3, NPM1 is a third category, and the whole genome sequencing is a fourth category. If there is a blood of acute leukemia in the exam, this question will be there for two months.

Sorry, Dr. Amit, can you kindly repeat?

It will be karyotyping, number one. Number two, FLT3 with NPM1. Number, number three is the inversion 16, 8;21, and KMT2A. And then the fourth one is whole genome sequencing for the mutation NGS.

Thank you. Thanks. There is, there is a table given in the BSH chart, and but this question is a must-ask if there is any type of AML given in the.

What treatment option do you have for this patient? Do you want me to try? Yeah. Anyone?

Yeah. So, uh, so assuming that this is acute myeloid leukemia. So, first we will need to do a, um, we need to know its cytogenetics first, like right now, the bigger picture is the bigger picture, and the patient is confused. We need to know why. So, uh, if does this patient have any evidence of, um, uh, hyperleukostasis? Do we need to do leukapheresis? These are the second question. Or hydroxyurea can reduce the count if there's nothing else going on. And neurology, as we said. Now, based on the cytogenetics, we make a decision on what to do next. So our options of treatments include, uh, either trying, if it is high cytogenetics, we can even consider going FLAG, um, FLAG, um, FLAG-IDA plus, if, if there is FLT3, we can add midostaurin. If that's not the case, we can consider local protocol depending on on the, on the, uh, depending on the trust, you can consider if there, if the standard risk cytogenetics, you can consider giving cytarabine plus daunorubicin plus go, um, if, if your trust guideline allows, or or otherwise, if clinical trial, then go for clinical trial. But actually, first, you should mention clinical trial.

Well, then everything else. I should rephrase. So, uh, yes, cytoreduction is a must, but if there is any intracranial event, then leukapheresis. We have to, we have to, intensive treatment which is DA and the FLT3. If it is a standard risk AML, then then it is DA, but if there is any other genetic mutations involved, then FLAG.

This case, by by morphology, it is acute monocytic leukemia, but but we know that we now follow the follow the genetic mutations as per the WHO 2022. This patient had no genetic mutations. Um, so we, we treated this patient with DA and then followed by followed by transplant as per MDT decision. Although in standard risk AML, we do not do transplant, but she was very young, we did allograft. She's in remission though.

Dr. Amir, I just have a question. I have heard that you can, we can do the nuclear reduction with the cytarabine as well. Is that also something to consider, or it's only the one scene has been used sometimes?

Yeah. Okay. Um, but if there is any intracranial event, uh, then we have leukapheresis machines. We leukapheresis them, and then the counts come down to double figures very, very quickly, or high doses of hydroxyurea, but you may not use it in all patients because they may have cytopenias, and there is a contraindication for them. So either leukapheresis, um, cytoreduction with hydroxyurea or daunorubicin. Yes.

This is another 40-year-old patient admitted with fever and uh productive cough. He's on oxygen as well, supplemental oxygen. His white cell count is also 132, and, um, hemoglobin is 108, and platelet count is 98. This is the blood film, power 10. Let's see if we can figure out the difference between this one and the previous one. It has neutrophils and lymphocytes. It has all. There is a biomedical scientist who would be happy if a biomedical scientist commented on this first, because the blood film goes to the biomedical scientist first.

True. Anyone from lab? No one from the lab.

I can try. Yes. Go on. What do you think?

Okay. Uh, first of all, the peripheral smear showed uh leukocytosis with left shift and mostly neutrophilia, but these are uh dysplastic with uh hyposegmentation as well as hypogranularity. And I, I haven't seen any blasts here yet. And, yeah, this may be, this is looking like immature cells here on 1:00, and RBCs, there are, um, several nucleated red cells along with anisocytosis with spherocytes and, uh, teardrop normochromic and macrocytes as well. And, uh, platelets are reduced. Uh, in the field overall, these are reduced. There is thrombocytopenia. So based on, uh, based on history and, uh, smear findings and counts, my suspicion, uh, my suspicion is, um, this can be, uh, this can be clonal or this can be reactive. So I, I, uh, give a DD, differential here for infection. It's, this can be secondary to the infection, or this can be secondary to a clonal cause, MPN, most likely CMML. So advice for further investigation like, uh, flow cytometry and infection serology.

You mentioned you are from lab, you will refer it to clinical hematologist, right? Okay. So, I will refer, refer, I don't know whether he was male or female. Uh, I will refer her to the clinical hematologist.

Okay. All right. So now we request the clinical hematologist to report the blood film, because she, as a lab person, thinks that this is either reactive or CML. So you need to report it and tell her whether this is reactive, CML, or something else, because as a clinical hematologist, you teach your lab people as well. Dr. Amir, can I go ahead?

Yes.

So the blood film shows leukocytosis, and and the leukocytes, it is a leukoblastic blood picture with the leukocytosis showing dysplastic neutrophils with the left shift, and then there are some occasional blasts as well, along with dysplastic monocytes. Red cells also show dysplastic changes. There, there is anisocytosis with some teardrops, spherocytes. There are quite a lot of stomatocytes as well. Uh, platelets are reduced, and, uh, given the history, I think the overall findings are, uh, suggestive of, uh, CMML based on the dysplasia as well. And, uh, since the patient has a history of some infection, we should also check for infection markers. But the blood film findings overall are suggestive of, uh, MDS/MPN, and most likely CMML.

Why CMML? Why CML?

Mhm. Because there's a dysplasia. Dysplasia. Uh, I can't see, uh, any striking basophilia to call it CML. Okay. And where are the monocytes? Have you seen monocytes or promonocytes?

Uh, not really.

Then how can you call it a CMML?

Yeah, I, I haven't seen it much, but it is quite dysplastic. And, but you know, I can't call it a CMML. So, okay. Right. So, asir has hands up. Um, do you want to add anything?

As, yes, sir. Uh, I just wanted, I, I was just thinking that there is leukocytosis with dysplasia and blast cells, but we cannot see an increase in monocytic cells, like, uh, dysplastic monocytes or abnormal monocytes. I cannot appreciate it, and there is absence of basophilia. Can it be atypical CML?

Okay. You think this is atypical CML?

May I ask one thing? Is this, is this the first, only time that the cell counts are increased? Or because you said the patient came in with an infection? So is this the first time the white cells have jumped all of a sudden? That's the first question I have. Is there any previous bloods to compare? Second question. Third question is, these, these look quite reactive to me. Although they are, I agree there are dysplastic cells everywhere in the peripheral blood cells. Um, there is anemia, but I would say it's a leuko-erythroblastic picture, um, with with neutrophilia and or left shift with dysplastic features as well. So, yeah, it, it is suspicious of a, of a, of a hematological disorder, but I wouldn't call it CMML.

So, first of all, in the exam, they will not give you such information. How was the pre, the patient was previously? They have given you a story that the patient has a high-grade fever, chest symptoms requiring oxygen. This is the count 132, and this is the blood film. Some people are sending messages in the Teams. I cannot read the messages. Please speak what you have.

Danish? Well, different ideas. Hi. Uh, I think it's definitely not CML. CMML, sorry. So this is a leukocytic film. Based on the history, I would say this is likely a reactive picture. Or I don't know, obviously in an exam setting, it's difficult to compare as you say. So I would just say if persistent, and my underlying diagnosis, well, it could, why can't it be MDS? As well, if obviously, if the history is, uh, currently is an infection, but, uh, why can't it be MDS? MDS with cell count of 32, 132? Oh, yeah, sorry. I missed the counts. Yeah, sorry. Maybe, yeah, counts are very high. So it's not CML because there is no basophilia. It's not CML because there is no promonocytes or monocytes. Leukemoid reaction. So many of you said, many of you said that this is a leuko-erythroblastic picture. And I am a first-year BMS training. This is my first day in the lab. I'm asking you, what is leukoerythroblastic? What is a leukoerythroblastic picture?

Presence of dysplastic features including nucleated red blood cells or presence of blasts, but not a very high count of blasts, can indicate that this patient has, um, um, has leukoerythroblastic feature.

Dr. Well, I think it, it is the left-shifted myelopoiesis as well as the presence of nucleated red cells, which, which we can call leukoerythroblastic blood picture. NRBC plus myelocytes plus al has.

Hello, you can speak.

So, first of all, the history. This patient is admitted with infection. Okay. He has severe chest infection which is requiring oxygen. Right. There is no basophilia in this patient. Okay. And no monocytosis. There are a lot of NRBC and myelocytes, neutrophilia, dysplastic neutrophilia. Okay. Um, all this picture belongs to sepsis, acute sepsis, and severe sepsis. Okay. So that's how you can be tricked in the exam. Some of the people will say this is CML, CML, because the counts are very high. But there is absence of basophilia. Some say that this is CML-2, but there is no promonocytes or monocytes. This patient has the history tells you that this patient has severe infection. In CMML or in CML, the patient is normal. They do not have any infection. They would have told you that this patient has abdominal discomfort, which means there is splenomegaly. If there is MML-2 or if there is CML, they will tell this patient has abdominal discomfort. They will not tell you that this patient has big spleen. They say abdominal discomfort.

Dr. Amir, but what about the dysplasia? Can the infection also explain the dysplasia?

Yes, infection can lead to NRBC. Your bone marrow is under stress. It can lead to. It's okay. But, but the neutrophils are dysplastic. I mean, in the infection, we mostly see neutrophils with toxic granulation, and you know, the picture is entirely different. These are dysplastic neutrophils, hypolobulated. When the bone marrow is under stress, you get a dysplastic picture. You say that this is a leukoerythroblastic picture. So one of the causes of leukoerythroblastosis is sepsis. When the bone marrow is under stress, it can lead to a leukoerythroblastic picture.

Dr. I agree. I agree with you with the leuko picture can give the dysplastic feature. Uh, my question is that the background RBC, many of the RBCs are like stomatocytes. And, my second question, can we give a differential diagnosis in that case if we are not confirmed about the, uh, leukemoid reaction, whether any clonal cause? Which clonal cause? Again, this is, you are raising the same question. Which clonal cause? No, I'm not, uh, saying any specific clonal cause. I'm, I'm saying about the MPN. So, which MPN? PN, MPN is a big category. CMML, but there is no monocyte, no promonocyte. Why are you calling it as CMML? Okay. Atypical CML can be considered here, but, uh, whichever component is also more than 10% here. Uh, whichever component should be less than 10%. So it, it is not fulfilling the atypical CML as well. There is no more after the WHO 2022. You can say MDS/MPN with neutrophilia. Okay. Uh, but this patient's history is clear. This patient has severe infection. If there are stomatocytes, it is because maybe he is heading towards DIC. Liver is involved. When liver is involved, there will be stomatocytes. Okay. Yeah, I agree with you. I mean, so because they are predominantly neutrophilia, I don't think we can technically say it's anything else. I mean, the only thing is which is, if you, if you really think there is something going on, it is like, as you mentioned, MDS, MPN, or or a chronic neutrophilia, leukemia, but that's a rare. This is not happening in a patient with sepsis. So that's not happening in a patient with sepsis. So, yeah, it is sepsis. And this slide can be given to you in another form as well. They can only ask you, write the findings in the blood in this blood film. Okay. And you have a lot of findings in this blood film. You have myelocytes, you have metamyelocytes, you have band forms, NRBC, you have neutrophils, dysplastic neutrophils, uh, teardrop cells, hypochromia, um, the stomatocytes, low platelets. You have a lot of findings in this, in this blood film. So this can, this blood film can be given to you in a different form as well, which does come in the exam. We had the same question, and many people after me had the same question. They will give you a blood film. Say, write only the findings in a blood. 1, 2, 3, 4, 5, 6. Or they may ask you, write six findings in this blood.

Right now, we have the same 40-year-old patient, a different person, but he is also 40 years old, and you have received the blood film, and his white cell count is also 132. Too. Where do you find these 132 WBCs, mate? More of a joke. This is my specialty. So the people refer it to me. What I was meant. And when you sit in the FRC Path exam, all the scenarios and blood look the same. Remember this. I believe you make.

So this is again a 40-year-old man with a white cell count of 132 and uh platelet count of 98, platelet count of, sorry, 198, and hemoglobin of 110. All right. The blood film goes to the biomedical scientist first, because they are the ones who deal with the blood first. Do we have any BMS here?

So we don't have any biomedical scientist. Uh, again, I can try. Yeah. Okay. Give us your preliminary report, and then if you are suspicious of anything, refer it to the clinical hematologist. What do you think about this blood?

So, um, based on, uh, this peripheral blood film, as, uh, showing leukocytosis and, um, leukocytosis, uh, mainly myeloid in hypoplastic myeloid cells, like, uh, neutrophilia, uh, and, uh, I also, uh, I also see a blast, one to two blasts, and these are granular with all the stages of maturation. And, uh, I haven't seen any blast here in this field. And, yeah, one to two cells are suspicious, maybe atypical cells, and maybe blast-like here in the center. And there are all stages of maturation. And platelets are, can you move? Another thing, platelets are adequate. Platelets are adequate. Cytopenic? I don't know. I have a suspicion. And NRBCs are there in the background. So, yeah, blast is also there. So it can be, uh, yeah, this is a cytopenic. So, based on, uh, these findings, my, uh, conclusion is, uh, most likely MPN, like CML. So I will refer the patient, uh, to the clinical hematologist.

All right. Now we need a report from the clinical hematologist. Eosinophilia is also very prominent. Yeah. So, what does the clinical hematologist say? Do you want me to have a go?

Yes.

Yeah. So, um, looking at the blood film, it shows all predominantly leukocytosis with metamyelocytes, myelocytes, uh, eosinophilia. I can see, I saw only, yeah, basophilia as well, and, uh, with blasts as well, but the blast counts are not very increased, at least from what I, what I saw in the pictures. Um, this is suggestive of, um, so among the red cells, it does look like some of the red cells do look hypochromic. Platelets are normal. This is favoring a diagnosis. It's, it's favoring a myeloproliferative disorder in the form of CML. Suggest further investigation of flow cytometry and BCRL, and obviously, the patient needs to be seen in clinic or, or if the patient is admitted, I didn't hear the, the, the, the initial presentation, so sorry. So if this patient is admitted, then needs review, but suggest, um, suggest, uh, flow cytometry and BCRL, and subsequent bone marrow.

Flow cytometry? Why flow cytometry? Mainly BCRL, but yeah, but I, if I would, I usually write the same way. It's sort of a habit. I shouldn't write it technically. You're right. If you're suspecting that this is CML, then, uh, BC, mainly BC. It's a sort of a habit. I always write flow cytometry. I shouldn't write it. You're right. You have a point. Yes.

So what's the difference between this film and the previous film?

So the previous film has, uh, previous film has neutrophils. The history, I think it would be the main, because I didn't hear the history of this guy, sorry, I apologize. But the first one was a guy with severe sepsis. There was neutrophilia. There was, um, there was, um, different types of cells. If you notice in this one, these cells are sort of clustered together, which is more seen in in hematological disorders, such as like, as we always used to see in morphology, blasts and and metamyelocytes are sort of clumped together in in form of groups or chunks, as you can see here in this picture that you've shown. In in sepsis, usually they're more scattered out. The other thing is the history is the most key defining element here. In that one, you did see a lot of neutrophilia. In this one, we are seeing a lot of neutrophilia. We're seeing eosinophils, neutrophils, basophils. In the previous slide, we didn't see any basophils. We saw pretty much every cell line, but not basophils. And the history was the target thing because there, this, that guy was admitted with sepsis. Now, in an, in an, in an real, in practical world, obviously in the exam is a different situation, but in practical world, if you had seen a previous, a day or two blood count, and if you had seen a dry jump, we would say it's leukocytoid. But obviously, in the exam purposes, that's not the case. So I think this one more favors a disorder rather than the previous one.

Can I add?

Yes.

Yes. Who is am? Yeah. Dr. Artika, sir. Dr. Go, sir. This, if we talk specifically about, about this, uh, film, how it is different from the previous one. Uh, there's a bimodal peak. We can see there are so many myelocytes along with the neutrophils. Point number one, which favors the CML, as we can see they are metamyelocytes, but the peak is by this, a bimodal peak. The second thing which I can see is the predominance of the eosinophils, as, uh, the previous doctor said, and along with the basophils. And, and on the, in RBC, I can also see, uh, macrocytes, uh, due to the increased turnover or cell turnover, and due to secondary folate deficiency. So these are the specific, uh, things which favor the CML, and it is different from the previous term.

You mentioned everything, but you forgot to mention this basophil. Basophils also.

Yes, sir. I said these are the key, and basophils, they are key features which differentiate from the leukemoid reaction.

Hello, Dr. Hay. Yes. Yeah, this is, um, May. I'm just listening in on my phone from the ward. All right. Okay. Uh, which score would you use for prognostication in CML?

It is ELTS. ELTS. ELTS is one of the three scores that you need to remember for the exam with its components.

What is included in ELTS?

Okay, ELTS, the DBCL IPI, and the Henneke score of information. These are the three scores that you need to remember for the exam.

Okay. So, and what are the major chromosomal abnormalities in CML?

Uh, it is trisomy 8, trisomy 19, isochromosome 17q, and extra Philadelphia chromosome.

And if this patient has a high-risk score, what drug would we?

Uh, we will go with the second-generation TKI.

Which one?

Dasatinib. Dasatinib. Dasatinib. Dasatinib. Dasatinib.

And what are the contraindications to dasatinib?

Any pulmonary features? Any cause that can lead to deeperation? Effusions. Okay. Pulmonary hypertension, pericardial effusion.

Sorry, why did we choose dasatinib? Sorry. Just a question. Why did we choose dasatinib over everything else?

It's a second generation, more potent than imatinib. Okay. And he is a young patient, and secondly, the important thing is that his ELTS score is high. So he's a high-risk patient. Okay. If your patient has a high ELTS score, if your patient is a young female and she wants to get pregnant in the future, and you want to bring her quickly into remission, then you can start with a second-generation TKI. If there are no contraindications.

This is a 19-year-old boy with headache. Came to ED, and this is the full blood count. Looking at the full blood count, his count is 600. White cell count is 600. His platelet is, his platelet is uh 68, and hemoglobin is 110. I need a different biomedical scientist than the previous one, and I need a different clinical hematologist than the previous one to report it. Anyone from the lab? Um, biomedical scientists. There should be someone. There are 36 people. Okay. If there is none, then let's say I am the biomedical scientist, first-year trainee, and first day in the lab. I saw this blood film. I thought this is likely CML. I have referred this to, um, clinical hematologist. I need a clinical hematologist to report this thing. Dr. Can I go ahead? Have you reported before?

Yeah. Yeah, I have reported.

No, I mean, have you reported in this session?

Yes. Yes. Yes.

Iana, I would like to give a chance to another person if there is any, if you don't mind.

I will. Sorry. Uh, I will go. I will, uh, well, this is, this is seems like leukocytosis, uh, with monotonous, all the population. But I will see the low power for you. Yeah.

So, uh, there is the, uh, mainly the leukocytosis and, uh, with, uh, blast. Yeah, blast cells, uh, with the high N:C ratio, with scanty cytoplasm, and prominent, uh, this, open chromatin, and prominent nuclei. Right. And it's, sorry, initially I have to mention medium to large size blasts, and you cannot see any granularity, very scanty cytoplasm with the basophilic cytoplasm. And, okay, in the background, RBCs are, uh, anisocytosis, microcytosis, and platelets are reduced. Seems reduced. Yes, platelets are reduced. So, uh, my findings, like the diagnosis, this findings are suggestive, uh, suggestive of what?

Yeah. Okay. And most likely seems maybe I need, I need a confirmation from my cytometry and FISH analysis in this case to categorize it. Is it myeloid or lymphoblastic? Is it medium to large size? Cytoplasmic blasts?

Could be lymphoblastic. Okay. This is most likely leukemia. Leukemia because the cells have a lot of nuclei and the cytoplasm is clear. So likely acute lymphoblastic leukemia. But you will confirm that on flow.

Yes. This patient has a CT scan and there is intracranial hemorrhage. What would you do next?

Uh, yeah. Uh, so, patient has a CT scan and, uh, if it is not diagnosed yet. So, um, uh, first we will, because there is intracranial hemorrhage, we will, uh, call the neuro, neurosurgery also, and neurology to be involved, and we will start immediately. And our differential is ALL. So we will start immediately dexamethasone or dexa, 6 to 16 mg per day for 5 to 7 days, and we will send all the workup, and, uh, we will go for the hydration. We can start with TLS, um, prophylaxis, respling, and we will avoid any, uh, procedure because there is hemorrhage, so intracranial chemotherapy or other, we can avoid it. And, um, uh, the main thing is we will start initial steroid and initial vincristine for this patient, and TLS, and of course, monitoring of all the labs to see the DIC and to,

The patient died the next day. Died. Yeah. Why did he die the next day?

So due to leukocytosis because of the extension, extension of intracranial hemorrhage. Yeah. Because you gave her steroids, and steroids take many days to show its effect. You will be, so you will be sued. Okay. Then you will appear in court. So should we go for for leukapheresis at this stage? But, uh, admit the patient and start, we cannot go for the chemotherapy first in all patients. Uh, yeah, leukapheresis can go. Leukapheresis is 600 count, right? So you need to do leukapheresis in this patient because this is an emergency situation now.

Skip the WBC count. Yeah, you need to involve the neurosurgeons urgently to to do any evacuation or not. You need to check the one antigen in this patient because they, they are all blasts. Okay. The one antigen may have attached to these blasts, and there is no one brand present in the body. You need to check the fibrinogen in this patient as well. Close fibrinogen. This patient may need triac precipitate or one concentrate, um, as well. These are the urgent actions that you need to do in this patient. But the most urgent thing is first should be leukapheresis. Remove this white cell from the patient, otherwise, his, um, um, intracranial hemorrhage will extend, and he may die. Right.

So I had made a video recently about the hematological emergencies. Okay. If you had heard that video, okay, you heard that video? If not, you need to hear that video. What are the hematological emergencies? And the title was, failing to recognize hematological emergencies means failing the exam. Okay. It is on this website. All right. So, um, if they give you such a scenario that the patient has a high white cell count and CT scan shows intracranial hemorrhage, you need to, uh, reduce the white cell count. Leukapheresis may not be available everywhere. Practically, it is only present in the, um, tertiary centers and those district hospitals where they are doing autografting. But your answer should be that this patient ideally needs leukapheresis to reduce the cell count. If none, then high doses of, um, cytoreductive, cytoreduction, or transfer of this patient, uh, to to a tertiary center by blue light or this should be your answer. Okay. In hematology, the emergency is not only TTP, APML. These are not the only emergencies. There can be a lot of emergencies. 16 or 17 emergencies are there in hematology that are present in the video that I posted a week earlier on the website.

The last blood film, and then you can go.

So this is a 60-year-old male patient with white cell count of 32. Sorry, what's the age? Sorry. Uh, this, this blood film is a bit defective. I'll remove that and put another one. This is our T. This is a GP blood film. Okay. The patient's white cell count is 32, and he is 60 years of age. This is our 50. Any biomedical scientist, just shout out because we are near the end of the time. I'm so sorry. What the age of the patient? 16.

Looks like we don't have biomedical scientists now. So, for example, I am the first-year biomedical scientist. Somebody told me that if the cytoplasm is clear, it is lymphoid. I think that this is lymphoblastic leukemia. I have referred this to you guys. You're the clinical hematologist, and you need to report that. So tell me, what is this? I am a first-year biomedical scientist. Today is my second day in the hospital. You are the professor, consultant, senior registrar in hematology. Please tell me, what is this? Dr. AI, can I go ahead?

Okay. So, uh, this blood film shows, uh, leukocytosis, mainly lymphocytes, which are which appear small and mature, uh, with, uh, mature clumped chromatin, uh, alongside many smear cells. Mhm. And, and, uh, the red cells mostly are, uh, normocytic, alongside a few, uh, spherocytes. I can't see any fragments. The, the platelets, uh, the platelet count looks, uh, okay to me. Sorry, I didn't actually follow what the blood count you, you told. Uh, there are some, uh, 152. Okay. So, uh, there are some lymphocytes which are bigger in size, but the proportion of those lymphocytes is not much. Mainly they are small, mature, uh, lymphocytes. So, uh, the overall picture is concerning for an LPD, most likely CLL. But, uh, we need to send a flow cytometry to confirm the diagnosis. And if you, you told me that it's a GP film, so I think if we are suspecting CLL with with this count, and the patient is must, must, must have been well. That's why I think we need to refer the patient, tell the GP to refer the patient to hematology on a two-week pathway.

What is mature? You mentioned mature lymphocytes. What do you mean by mature?

Uh, Dr. Ramir, I am small. I am a first-year biomedical science. I don't know what is. So please tell me, what is a mature nucleus?

Doctor, uh, they are small in size, uh, compared to the size of a red cell. They are roughly the size of a red cell with a slight rim of cytoplasm, which is clear, and they don't have any prominent nuclei. In between, the chromatin is clumped, more bluish.

Yeah, I got it. And you mentioned some smear cells. What is a smear cell?

Uh, the smear cells are when you can't, uh, uh, see the boundary of the cell, and you can't actually make out if it is a complete cell with nucleus and cytoplasm. You just see, uh, some blotches of color, just like we can see in this film as well.

Okay. Just like the cell is broken during preparation.

It is broken during preparation. It is not present in the patient's body.

Uh, yes, I think it is broken during preparation because they are, uh, very delicate cells. So they are broken during preparation.

So what flow cytometry are you expecting?

So if it would be CD19 positive, 79B positive, uh, CD20 weak positive, surface immunoglobulin weak positive, CD5 positive, 23 positive.

All right, doctor, you said that the CLL cells are small and mature and they don't have nuclei. But I can see one cell here, it has nuclei. What is this?

Uh, so, uh, in CLL, we, we can see actually some, uh, cells which are, um, prolymphocytes. They are larger in size with abundant cytoplasm, but they shouldn't be, um, I don't know the exact, sorry, the exact percentage. Otherwise, we call them, um, PLL. But less than 15% I think are present in CLL.

Dr. Sam said the other day that PLL has been eliminated after. Yeah, yeah, it is now called splenic. So can I comment on this?

Yes. Dr. Um, I think, um, uh, I appreciate any prolymphocytes on this film because the size is enlarged as compared to the mature lymphocytes. So I will evaluate the whole film for the percentage of the prolymphocytes. If it is more than 15%, then according to the WHO 2022, that is a prolymphocytic progression of CLL. But I need to look over the film to get it exact. And if it is more than, if it is more than 55%, then it will become SLL/PN, just like the case that we did on the last session. Yes.

Right. So what treatment you want to give to this patient?

Uh, Dr. Amir, it is, if it is, we will need to check it with the patient. If the patient wants, uh, continuous, no. So firstly, we need to do the cytogenetics as well. The TP53 mutation, unmutated or mutated. Oh, it is unmutated. Okay. Um, there are two options. 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