Hematomorph Session for Morphology

Let's start today. We have four blood FMS and one aspirate. Yeah, so this is a 48-year-old male who was referred to us to hematology by a GP because of persistent and worsening anemia and thrombocytopenia. On examination, he mentioned that, um, he mentioned that he has some abdominal discomfort as well. And on examination, he has plum Al 17 cm. His hemoglobin is 60 and his platelet count is 90. White cell count is 7. Anyone wants to volunteer, comment on the blood? This is power. Okay, any volunteer? No one today. Yeah, could, could you focus in a bit more? Yeah, I will move to power 50 oil. Sign HP cell. Um, this is a, uh, AR. So this is not a, but a significant cell is this one, this one, and this one. We will see some more, uh, sections as well. Why go time and some features here. This one, this drop kill site. This one, toxic granulation, maybe of the neutrophils. Has granulation and MC here. Drop again. All this is going on now, especially here as well. Can we see a couple of neutrophils, please? Neutrophils. Okay, yes, please. Yeah, this is a bit of bend for. Yeah, Ben, the a normal with Dr. What was the HP 60? Constitutional symptoms as well and splenomegaly. Yes, patient has 17 cm of spleen. Okay. Yeah. And sorry, aplastic. Anyway, yes, I agree with that. This is leukoblastic blood. You statocytes, few statocytes as well. Yes. What about the red cells? Hemeolysis. The blood film contains red cell and aspherocytosis with few polychromatic macrocytes. There are deyes or here. Drop cell, you can say that. Multiple NBCs. I'd expect a few more to be multiple, multiple F. MF, sorry. It should be few more te adoption there. Yeah, this one is a te drop. Yeah, this is going to be a te drop soon. And we have seen quite a lot, um, in this patient. Only one thing which I was searching was for any Howell-Jolly body because the patient has clean. Yeah, or maybe this one, but not very clear. So this patient has both polychromatic macrocytes. We have seen few pycytes as well. There are, uh, multiple te drops in this patient. Leukoblastic feature. This blood film is most likely consistent with MF. And MF does not come alone with the hemolysis or spherocytes or polychromatic macrocytes. So this patient has most likely dual diagnosis. One is likely MF because we have to confirm that on bone marrow biopsy. That's why we are saying likely MF. Yeah, because of the leukoblastic picture and here dropping. And there is some hemolysis going on, which is evident by the presence of spherocytes, polychromatic macrocytes. So what would be the recommendation? Like in your report, you have to write some recommendations. This patient needs bone marrow biopsy to confirm diagnosis of myelofibrosis and hematinics to see for any B12 or folate deficiency. So this patient on biopsy had myelofibrosis and had low folic folic acid. So this was a case in the recent, uh, in the short case of hematology morphology. So reporting the blood film. The blood film contains multiple NRBCs and te drops along with the presence of spherocytes, polychromatic macrocytes. The platelets, the platelet count is low. No platelet clumping seen. White cell shows, um, multiple band forms of neutrophils, toxic granulation in the neutrophils, and some neutrophils without granulation. The picture is most likely leukoblastic, which is consistent with myelofibrosis and, uh, some ongoing hemolysis. The patient needs bone marrow biopsy to confirm the diagnosis of myelofibrosis and hematinics to look for any henic. This patient hemoglobin was 60, platelet count was low, and the blood film does not show any blasts. We don't know about the bone marrow biopsy result yet. White cell count was 11. And let's say he's transfusion dependent as well. Anyone knows which DIPPS category he would be? DIPPS low, DIPPS intermediate one, DIPPS intermediate two, or DIPPS high? So he will be DIPPS intermediate category, uh, two. It is a high DIPPS score. And, uh, in intermediate two DIPPS score, we first address the spleen because this patient has 17 cm of spleen and he is in discomfort because of the spleen. So he would need first a treatment with JAK2 inhibitor, which is Ruxolitinib. But if the platelet count drops to less than 50, then we cannot give him Ruxolitinib. Then there is a new drug called Fedratinib to give to this patient. According to the NICE guidelines and V guidelines, Fedratinib is now NICE approved. You can give it to your patient if their platelet count is below 50. But if the platelet count is above 50, you can try Ruxolitinib first as well. For the anemia, because the patient is now symptomatic, you have to give him blood transfusion. But, uh, you need to check the EPO level of the patient as well. If EPO level or erythropoietin level is low, try, uh, erythropoietin stimulating agent EPO first. If the patient responds to that, it's okay. If no response by EPO, and check the response in, uh, few months time. If he responds to Darbepoetin, it is okay. If no response to Darbepoetin, then you have to go to transfusion program. And then because it was a high risk in, uh, high, I mean, the DIPPS score is intermediate two, such patients we usually discuss in transplant MDT. If the patient has no comorbidities, patient agrees for transplant as well, and Transplant MDT also agrees, uh, for transplanting him, then such patient fate is allogeneic stem cell transplant. Is there any question that you want to ask about myelofibrosis? The new thing in myelofibrosis is that Fedratinib has been NICE approved recently. You can use it as a first line. You can use it as a second line. The price of Fedratinib is the same as Ruxolitinib. The side effects up till now, they are very less. They are only gastrointestinal side effects. Patient develops diarrhea or vomiting. Up till now, there is no other serious side effect. In case of Ruxolitinib, you need to wean it down. You cannot stop it at once, otherwise the patient will develop inflammatory response. You need to wean it down under cover of steroid or the RO. We do not use Plerixafor in UK because of the, uh, risk associated with, uh, paraneoplastic deficiency and leukoencephalopathy. So most of the consultants do not use Plerixafor here. Yes, go on. Dr. Can you please explain what is the role of Ruxolitinib in increasing the HP? Does it reverse the fibrosis or what? So the Ruxolitinib is for, according to the Comfort trial, for symptom control only. It will help in reducing the spleen for the anemia. We will check the erythropoietin level of the patient. If it is low, you start the patient on EPO. If the patient responds to that, it's okay. If the patient does not respond to that, then you transfer to Darbepoetin. If the patient responds to Darbepoetin, that is fine. If no response, then you have to think about other options, which is Fedratinib these days. But Ruxolitinib does not improve hemoglobin level. It reduces the spleen size only. And according to Comfort trial, it is for symptom control. Okay. Hopefully you guys would know what were the cases in part two exam philosophy. This was one of the, sorry, Amir, can I ask whether we are required to know about the scoring system and how to calculate them? No, but you should know the names of the scores. Yeah, okay. Uh, because it is very difficult to remember the components, components of DIPPS score. It's very difficult. And there are multiple scores for myelofibrosis: DIPPS score, U MIPS score, MTSS. The transplant, those patients who are going for transplant, the transplant MDT will calculate DIPPS score, the MTSS score for the patient. But in routinely, in routine, the majority, the most of the score which is used in practice is DIPPS score for the. Okay, thanks. So when you see any clinic letter of a myelofibrosis patient, on the top, you will always find what is the DIPPS score of this patient. That he is a low risk category, intermediate one category, intermediate two category, or high category. In the recent exam last week, there were a bit, uh, few changes in the short cases as well, which were, they asked about the management of a disease in a short case, which is very unusual. So people has a lot of management problem in this exam. This is the second case. This patient again, this is a 50-year-old patient admitted under respiratory team because of the plural effusion. When they did the, uh, bloods for the patient, the white cell count was high. The white cell count, you can see from the picture, it is more than 80. So I would like any of the EMS or, uh, lab scientist or lab fellow comment on the blood film. What they think? Well, there are leukocytosis. There. Yeah, can't make the cells out. Yes. So this is power 10, just overview of this slide. Yeah, high, very high. And now I will move to power 50 to make them more clear. Bling on the lymphocytes there. Yeah, that stands out. Lot of BL, P, something like that. Sorry, which dis? A PLL. Yeah, as well. BPL or TPL? T. T. What was the platelet count? Platelet is 97. Okay. Since it's reduced. Yeah. A lot of bling. Yeah. Right. So you have referred this blood film to the clinical hematologist. Any clinical hematologist want to report this film for the purpose of the exam? Any clinical hematologist? What happened today? Everyone is, yeah. So no second. Um, so, um, the blood film is showing a population of mononuclear cells with increased NC ratio. The nucle, there is clear, uh, nucleoli in most of the cells and the chromatin. You can't focus and put some oil on it. Yes, this is power 100. Um, the nuclear chroma appears a bit clumpy. I think I'm not clear whether does that's that's, uh, like this is mature cell. So this is mature. Okay. On the cytoplasm is showing, um, um, cytoplasmic bling, a granular, a granular cytoplasm is something. Okay, that's it. Um, so features suggestive of, uh, LPD, lymphoid proliferative disorder. Further assessment and investigations are needed. So I will do bone marrow biopsy and send flow cytometry. Okay. So the, the blood film contains leukocytosis. The white cells are small and mature with, with multiple cytoplasmic bling. The neutrophils, the platelet count is low and no platelet clumping seen. The red cell morphology is normal. Most likely consistent with proliferative disorder, likely TPL due to the presence of cytoplasmic bling. We need to send the flow to the lab for urgent flow cytometry to confirm the TPL. What flow do you expect in this patient? So you said it is TPL. So T cell markers will be positive in this patient. But can you tell me two markers only which are specific and strongly positive in TPL? T cell markers with strongly positive CD7 and CD52. If positive and this confirms that this flow cytometry belongs to TPL. Do you know what is the mutation or translocation in TPL? Inversion 14 and what mutation is involved? TCL1. Yeah. This is the mutation that is involved in TPL. Remember these things for both part one, part two exam. It can be an MCQ or it can be a one or two mark question in short case. All right. So this patient has a lot of plural effusion. He has thrombocytopenia as well, because of which he is now symptomatic. He has shortness of breath, productive cough, requiring oxygen, and, uh, there is spontaneous bruising in him as well because he has thrombocytopenia. What will be the first line of treatment that you would likely to suggest to this patient? Is it to zoom up? This is half answer. Allogeneic stem cell transplant. Allogeneic stem cell transplant. And in remission, this is the complete. You will get full marks if you mention like that. Allogeneic stem cell transplant and first. Okay, right. So the third case is about a again, 50-year-old lady who has a previous diagnosis of MDS with excess blasts. She is admitted because of the lower respiratory tract infection requiring oxygen. And the white cell count from the analyzer is 42. Usually his lost, his white cell count will be around 11 or 12 as a baseline. But today when she is admitted, our white cell count has jumped to, uh, 42. This is power two, uh, 10, just an overview of the blood film. Too much clumping. It's transforming probably. Yeah. This is the first thing which comes into the mind of every person, I mean, from hematology, that this patient is transforming to AML. But let's see whether he is transforming to AML or she. Right. So the lab scientist or your lab colleague has mentioned this patient is likely transforming to AML. Film, film referred urgently to hematology registrar for reporting or for expert opinion. So I need a clinical hematologist to report on this. There are nine people in the meeting and there is no clinical hematologist. Hello. Yes. Hello. Yeah, I'm Abdul. I think the myeloid series shows a lot of dysplasia. And there are a lot of, probably more monoblasts and promyelocytes. So some of I think I saw some Auer rods also in some of the cytoplasm. So on this film, NRBC, NRBC, myeloid series, I can say that either this is metamyelocyte or a big band form. Myelocyte with granulation. Metamyelocyte and we see here. Band form from metamyelocyte. Yeah. I am seeing many blasts there because the patient has previous history of MDS with excess blasts. Okay. This one has granules, but a lot of granules as well. Maybe pro series, but not full-fledged blast. But we will expect blasts in this patient because patient has previous diagnosis of MDS with now your BMS is with you in the lab and he wants you to teach him or tell him, is this AML or not? What would you say to your lab colleague? I think we'll have to do a differential count, differential blast. Blast. But from the picture, what do you suspect whether this is converted to AML or not? Convinced. Yeah. What do you think is the reason of this myeloid series and ANC? And why the analyzer says that the white cell count is 42? It's probably counting the nucleated red blood cells as lymphocytes. Yes, the RBC has been counted as white cell count. This patient has a lot of NRBC in the background. There are a lot of, there is a myeloid peak. You can see band forms, you can see metamyelocytes, metamyeloid. Some analyzers, some analyzers don't count the nucleated red blood cells. Although the newer ones sometimes do count them. But this is where the film comes in. You'd have to do a manual differential. We have, we have. Yes, I do. They, they pick up NRBC as sometimes. But they don't give you. Well, depends if the analyzer has been set to do nucleated RBC. Ours haven't. Yeah, we'd have to do a manual differential to correct the white cell count. Yeah. When the differential came out, it says that 39% of the whole blood cell is NRBC. And the reason for this, a lot of RBC and myeloid peak, myeloid peak is because the patient was septic. The patient has lower respiratory infection and requiring oxygen. Because of the sepsis, the bone marrow is under stress. And that's why you are seeing a lot of NRBC in the blood film. Yeah. There is no transformation in this patient. There is a septic response in this patient. That's why there is a lot of NRBC and myeloid peak in the blood. So we didn't marrow this patient looking at the full blood count report. We think that this patient has gone into AML. We should marrow it. But when we see the blood film, when we saw the blood film, the blood film was different than AML. So he reported the blood film contains multiple or loads of NRBC with myeloid peak containing neutrophils, band forms, metamyelocytes, and blasts. Low platelet count is low. No clumping seen. Most likely, uh, a bone marrow response to, uh, to the infection. The patient needs blood cultures and treatment of the underlying infection or and treatment of the underlying cause of bone marrow under pressure or stress. Treat patient needs treatment of stress bone marrow. Substance was a case in the recent, uh, exam. Right. Yeah, you send out a manual differential count every few months. So this would probably be a good one to do. Yeah, I agree. So the white cell count here is 42. Can it, can this be CML? Oh, not. I can't see any basophils. The basophils there. Yeah. So this differentiates from the from the CML because CML has myeloid peak as well. But here we cannot see any basophils. And eosinophils. The next question is, can this be a chronic neutrophilic leukemia? I don't think so because of the presence of dysplasia. Yes. So chronic neutrophilic leukemia contains, according to WHO 2022 guidelines, contains a mature neutrophils. The white cell count should be above 25 and 80% of these white should be mature neutrophils. Then you complete the criteria for a diagnosis of CNL. And CNL means chronic neutrophilic leukemia. And chronic neutrophilic leukemia has a specific mutation as well. CSF3R. Which one? I forget the, the four digit. CSF3R S1 or CSF31 something like that. Check it in the Google or the book. So this is another 50-year-old patient referred to the hematology department from the GP because of the eosinophilia since two years. The GP has investigated the patient thoroughly for a reactive cause, but he has not found any reason for his eosinophilia. So he has referred the case to you for further consideration. The patient is completely asymptomatic. We travel history, no travel history. The GP has investigated the patient for a secondary cause. All the secondary causes or reactive causes of eosinophilia has been ruled out by GP. That's why he has referred the case to you for consideration of clonal causes of eosinophilia. This is power 10 and we will go to power 50 now. So the kind of cells, ignore these kind of signs, these are not trial cells, they are just the artifact because of the old sample. You can see the eosinophils here, they are irregular and larger than the normal degranulated. That could be because it's an old sample too. The eosinophils are quite large and they are irregular as well and they are degranulated and some of them are like first burst as well. So what do you think whether these eosinophils are dysplastic or not? Yeah, nucleus does look abnormal, some of them. Yes, their nucleus is abnormal and they are vacuolated as well. Normally, the eosinophil does not contain vacuolation. When they are vacuolated, it means there is something going on. Along with these, they are, they contain a lot of vacuoles. Yeah. Anyone to report this blood film? The clinical hematologists are sleeping today or what is the reason? There are many now. Shak Nting Hospital, Saha Ali, King's Hospital. Think I guess apart from these dysplastic eosinophils, I can't see any significant feature. There is no features to suggest an MPN or LPD as cause of the clonal eosinophilia. Likely first. No, no blasts as well. Report the blood. There is an increased eosinophils with dysplastic features, vacuolation, an abnormal nuclear separation. The blood, the blood film contains eosinophilia. Yeah, eosinophils are abnormally large with multiple vacuolations and dysplastic nuclei. Red cells. Yes. Go about neutrophils. Does he have neutropenia? There is no neutropenia. We haven't seen any neutrophils yet. So he has, he has. Yes, okay. What's the HP? HP is 10.10, sorry, 110. Okay, this is okay. So you have mentioned that the blood film contains leukocytosis and the blood has eosinophilia. Eosinophils are abnormally large with multiple nucleations and abnormal nuclei present as well. There is no platelet clumping and platelets look normal. No red cell changes in the blood film. Most likely consistent with eosinophilia. The GP has excluded reactive causes. We need to investigate this patient for clonal causes of eosinophilia. Right. And for the clonal causes, you will suggest some tests which I will ask. But first of all, what are the causes of clonal eosinophilia? Do you know any cause of clonal eosinophilia? PDGFR alpha, PDGFR beta, and FGFR1 mutation. This is one category. The other two are CHS, hypereosinophilic syndrome. And what is the third one? Chronic eosinophilic leukemia. Chronic eosinophilic leukemia. There are three categories of clonal. I was about to ask you about the molecular targets in eosinophilia, clonal eosinophilia. But you have mentioned PDGFR alpha, PDGFR beta, FGFR1, they are correct. There can be JAK2, ABL, ETS6, 3 as well. Okay. So this patient has eosinophilia since two years, 20, since 2022. No reactive cause. The eosinophils are dysplastic. No molecular targets are found in this patient. Means there is no PDGFR alpha, PDGFR beta or anything like that. Patient is asymptomatic. What diagnosis will you give to this patient? Syndrome. So you said idiopathic hypereosinophilic syndrome. If you write this in the exam, I will give you zero marks because I told you this patient is asymptomatic. The word syndrome will come only if there is a symptom in the patient. And syndrome, Dr., means you will start treatment for this patient as well. While eosinophilic leukemia alone means there is no symptoms and you will watch and wait for the patient only. Let's say this patient is diagnosed with idiopathic hypereosinophilic syndrome. Now patient has developed symptoms. What is the first line treatment for idiopathic hypereosinophilic syndrome? Sorry, according to tissue damage. If, no, no. What is the treatment? Treatment of idiopathic hypereosinophilic syndrome. What you will give to this? Steroids. Yeah. And he did not respond to steroid in three weeks time. What is the second line? Steroids. He did not respond to steroid in three weeks time. Low dose imatinib. 100 mg. It's not low dose. It's a normal dose. 400 mg. You will try low dose only if there is PDGFR alpha rearrangement in the patient. Right. Okay. So the last case is an aspirate. So this is power four. I don't know why there is so much light on. So this is again a 40-year-old young man who is admitted from emergency department under hematology because of anemia, high white cell count, low platelet count, and pain in the right groin. On examination, the right groin has a big mass. Because of the anemia, thrombocytopenia, this patient was marrowed to see for the underlying etiology. So this marrow has particles which is shown here under power four. So it is a particulate. Patient is 40 years of age and the aspirate is very, very cellular. Now power 10. Do you have any differential in mind for this patient or not? Patient has constitutional symptoms, anemia, thrombocytopenia, and a big mass in the right groin. It could be a lymphoma. Yeah, it is a lymphoma because he has a mass. What type of? DLBCL. DLBCL usually comes with widespread lymphadenopathy. And this patient has only a mass concentrated in the groin area. Right. If I go to power 50, you will recognize the diagnosis. I was just asking whether you have any, uh, anything in mind from the scenario or not. Is it lymphoblastic lymphoma? Lymphoblastic lymphoma. What is lymphoblastic lymphoma? I said so because of the hand mirror like morphology. Maybe I may be wrong. What else do you see? Smart said. What else? Again, if the first candidate mentioned lymphoblastic lymphoma, lymphoblastic lymphoma comes with is usually either in very young patient or very old patient. But they come with mediastinal. This patient has a most concentrated in the groin area. I can see some vacuoles in the cytoplasm as well. Okay, good point. Therefore, I say this patient is HIV positive. Is it going towards Burkitt? It is. You can see there are multiple vacuoles in these blasts. Patient has a single large mass in the groin area. And I have given you a clue as well that the patient is having HIV positive. If it is a DLBCL, he would have widespread lymphadenopathy all over in the body. B-NHL does not come usually with. It's very unusual. These cells are very, very basophilic. For some reason, this slide is lightening a lot under the scope. I don't know why, but they are very basophilic. And you can see some of the cells has vacuoles here. Patient has a single HIV positive. It is most likely Burkitt. I'm saying most likely Burkitt because you need to confirm your diagnosis on flow cytometry and cytogenetics. What is the expected flow in Burkitt? Positive for mature B cell markers like surface immunoglobulin, CD19, 20, CD20 positive. CD5 negative. CD10 positive. What about BCL2 and BCL6? BCL2 negative. BCL6 positive. This section contains a lot of vacuoles. But I don't know why there is, uh, too much light on this slide. Otherwise, you would have seen a lot of degranulation here. Remove the condenser. There's no condenser here on the microscope. There's no condenser here. All right. But I don't know why too much bright. Maybe now that's better. That's better. I don't know why this slide is too much lightening, but you can see this is full of vacuoles here. Listen, too much basophilic. A lot of speculation under the microscope. This is very better. An excellent to see. But see here, the camera. These are all vacuoles. This line, whole is vacuole. This section is vacuole. Um, I don't know how to make this more clearer, but you have seen now a lot of speculation. Yeah, that's that's perfect picture now. Straightforward. Yeah. All right. And what is the karyotype or translocation in Burkitt lymphoma? 8:14, plus 8:22, 2:8 and 2:8. This is a young man with diagnosis of B lymphoma. Do we want to treat? Would you like to treat Burkitt or come on guys, clinical hematologist. Would you like to treat Burkitt or not? Yes. Yes, you have to start the treatment as soon as possible because this is one of the fast-growing lymphoma, high-grade lymphoma. The patient will die in two days. Do not start treatment. Delay. What do you need to consider in Burkitt while treating the patient? Are you worried about anything? Tumor lysis. Tumor lysis syndrome because they have high tumor burden. And as soon as you start any regimen for this patient, if it is R-CHOP or R-EPOCH, the patient will start responding to the chemotherapy and the risk of TLS is high. So better to be careful about it. Is there anything you want to ask? Any question? Sir, can you please guide on the thing that how do we go about the preparation? Like there is coagulation on one hand, then there is oncology on the other hand, then we have RBC pathology. So how should we proceed basically? Should we do everything simultaneously or something system we should pick up like that for the part two exam? You mean for part one? For part one, in there was a session last week. How to prepare part one? Did you attend that session? Or yeah, I attended that session, but I just wanted to ask, should we study everything simultaneously or should we finish off coagulation completely, then we should go to the other thing? Okay. So when I was studying for part one, I used to study weekly on weekly basis. One week coagulation, one week transfusion, one week oncology, one week general. I would repeat it like that so that everything is in touch. Secondly, we are doing essays in our part one group. There are 300 people and I receive only five answers. That is a normal thing now. But if you can practice those essays, then we discuss these essays on session, except for those Saturdays and Sundays we are on call and cannot discuss. And we share MCQs in the part one group as well. That will be your MC practice as well. Okay. If you had listened to the part one session last week, it has more information. If you are in a part one group, hopefully you will be ready for the exam. Don't worry about it. Okay. Okay. Thank you. Nothing else. Then we will close the session now. And if you guys can donate to maintain my site holding fee, I would be thankful. I will share the link. Have a nice Sunday. Take care. Bye-bye. Thank you very much. Thank you. Thank you. Appreciate it. You.