Transcription
Hello, can you hear me?
Yes, Amir. We will start our session. Other people join later.
So, this is the first case. This is a 5-year-old boy who was admitted to the hospital because of severe bruising on the body and feeling unwell. You can see at power 10 that's, uh, it's very low. He has very low hemoglobin. And then we will move to our 50. You see some white cells. All right. So, this is a 5-year-old boy with severe bruising. And on full blood count, the hemoglobin is 60, platelet count is 70, and white cell count is 9. And this is the blood film. So, what do you suspect in this patient? Anyway, yeah, I would like to exclude acute leukemia. Sorry, what, um, I would like to exclude acute leukemia. How? Why do you think this is acute leukemia? Report the blood film. Right. Um, looking at, um, red cells, there is marked reduced, uh, red cells. You can say, say that again, sorry. You can say marked anemia. Yeah, marked anemia. Yeah. Um, also reduced platelets. In terms of the white cells, it looks like, um, there is, um, I think it's abnormal lymphocytes. Yes, because, um, it looks like a medium to large cell, mononuclear cell with very minimal cytoplasm. Mhm. Compacted chromatin. Sorry, I missed the slide. Okay. Um, yeah, I think it's open chromatin. Open chromatin. Yeah, this one. It's more open. Yeah. There is some with cytoplasmic vacuolation as well. And I think seen hand mirror shape. One. Yeah. Yeah. It's so most of the cells has scanty cytoplasm. Yeah. And some of them has vacuoles as well. Yes. The white, do I've got small vacuoles here? So, what do you think is the lineage of this patient? Is it myeloid or lymphoid? It's likely lymphoid. Yeah, likely lymphoid. So, the cytoplasm is very scanty. Yeah. There is a lot of open chromatin and cells are nearly medium size. Some of them has vacuoles as well. This most like, this one has also one vacuole on the top. Most likely this is B. Yeah. But in the report, you will say, um, this is most likely acute leukemia. This patient would need a peripheral blood and bone marrow biopsy to confirm the type of leukemia, whether it is B or T or rare myeloid leukemia. Because on the morphology, it is not very certain always to make an exact diagnosis. You may be thinking of acute lymphoid leukemia, lymphoblastic leukemia, but the flow will be of myeloid leukemia or sometimes it is B. Yeah. So, you always, you always give, uh, the, you always say the likely diagnosis is acute leukemia. We need urgent peripheral blood and bone marrow biopsy to confirm the diagnosis and type. Yeah. So, in these cells, the typical hand mirror shape was not present. And most of the cells are small to medium size with minimal cytoplasm. So, we were suspecting that this is B type ALL. And the flow showed that this is B. Previously, we had seen one case in the session which has typical hand mirror shape and it was a T type. So, in terms of cytogenetics, this one has nice, uh, translocation. Um, in terms of the cytogenetics. Yeah. What are the poor risk? What are the cytogenetics? Um, yeah, it's a translocation 11;19 translocation. Standard poor risk. I think yes. Poor risk. Philadelphia. Mhm. Yeah. Medium risk. 9;22. Yeah. So, high age is a poor risk. If the white cell count in this patient is more than 30, because this is ALL, it is a poor risk. 9;22 is a poor risk. 11;19 is a poor risk. Hypodiploidy is a poor risk. Or if the patient has complex karyotype, it is a poor risk. And if you have 12;21 translocation or hyperdiploidy, then it will be referred to as standard risk cytogenetics. Yeah. And what protocol you would use to treat this baby? To this child? Yeah. Um, UK ALL 14, UK ALL 14 is for a bit of the adults. All right. UK ALL 2011 is the one which is for pediatric. Okay. UK ALL 11. Did you say yes? UK ALL 11 is used by the pediatric people for treating this. So, when you are reporting it, do not say that this is exactly ALL because we never diagnose any, uh, condition on morphology. We always give our impression that this is the likely impression, acute leukemia or lymphoblastic leukemia, but we need to confirm this on peripheral blood and bone marrow biopsy in this patient. Sure. Yeah. If you are working in a pediatric setup or if you are working in DGH, you will see these cases a lot. Excuse me, Dr. Amir. MH, I have a little question about it. That what is the difference between UK ALL 11 and UK ALL 19? There are five protocols for ALL to treat. Mhm. UK ALL 11, 14, 19, 60, and all together. It depends their inclusion and exclusion criteria depends on the age and the, uh, Ph positivity, the BCR-ABL positivity. M. So, for the children, we use 2011 protocol. And then, uh, we have UK ALL 60. And the name itself says that it is for the older age, uh, population. The UK ALL 16. Then we have UK ALL 14. If the age of the patient is between 25 and less than 65, then you can use UK ALL 14. But if someone is BCR-ABL positive, you can start UK ALL 14 from age 19 to 65. M. Then we have UK ALL 19. The UK ALL 19 starts from age 1 to 24. But if they, if they are Ph positive or sorry, the BCR-ABL positive, you cannot use UK ALL 19. Okay. UK ALL 60 is mentioned for about, um, 60-year-old patient. And then the other one is ALL together. ALL together in UK is for a patient age between 0 to, uh, 29. But in other rest of the world, they use UK ALL 60 between 0 to 45 years of age. Okay. Yes. And again, exclusion criteria is there should be no BCR-ABL in this patient and not a relapse condition. Sorry, UK ALL 60 for 0 to 45. UK ALL 60 is about 60, 60. And for older, for older population, it is UK ALL 60. Okay. For younger population, it is UK ALL 14 or ALL together. But this, but we need to check the Ph positivity. If there is BCR-ABL positive, I cannot offer them ALL together. Okay. So, there are five protocols in the UK for the UK ALL. And what about UK ALL 12? Is it for transplant? The CT1 is the ALL together, which ends up in the, like, ALL together. When you start ALL together, the aim is to do chemotherapy for them. And the other one has UK ALL 14 and UK ALL 19. If the patient comes into remission and then they relapse, then you can think about stem cell transplantation. Chemotherapy alone is a third-line treatment. In UK ALL 12, we have not used it. It's UK ALL 2011. Okay. Thank you.
This is the second case. It's about a 36-year-old lady who was admitted again with anemia and fatigue. She has, uh, laryngitis 5 days ago. And then, um, on blood test, she has severe anemia. Hemoglobin is 70. Platelet count is normal. And white count, white cell count is 12. This is the power 10. And make it to power 15. E. Okay. So, you have seen few cells in this patient. Anyone would like to comment on it? Anyone? So, the abnormal population, uh, include, um, low number of white blood cells that are, uh, apparently, uh, immature looking like blasts. They have a moderate size with moderate amount of cytoplasm and nucleus. Uh, it has foldings. M. And indentations. There are few, uh, NRBCs also seen. These, uh, are making the wing-like appearance or the figure of eight. Okay. So, what do you think is going on here? So, most probably, this is a case of acute leukemia. M. Uh, most probably myeloid acute myeloid leukemia. Okay. Why do you think this is acute myeloid? Uh, because of the appearance of the blasts. They are moderate to large size of blasts. And they have the fine, uh, open chromatin, moderate amount of cytoplasm. They have the folded nuclei, making a figure of eight or wing-like appearance. And I'm going to say it may be a case of, what do you call this? Uh, please, um, let me check another one. If it is minute. Okay. So, I would like you to arrange your report while I'm searching for another cell like this. How would you report that for the exam purpose? You are in FC2 exam and they are asking you to report this blood film. Right, sir. I'm just looking for an ideal cell. You can start your report. So, is this a bone? Is this a peripheral smear? The peripheral smear of the patient is showing anemia, thrombocytopenia, and decreased lymphocyte count. The prominent population is of blast cells. They are moderate to large size blast with high NC ratio, open, dispersed chromatin, few having a moderate amount of cytoplasm, prominent nucleoli. And there are few NRBCs. It's decreased. Are normal? Okay. So, what is your impression? Your impression is acute leukemia. What to do next? Peripheral blood and bone marrow aspirate. Examination. Interim. By. So, I was thinking asking you about these different depressions in the nuclear foldings. These are called fish mouth depressions. Okay. Okay. These are right, sir. These are seen in myeloid leukemias with NPM1 mutation and FLT3 mutation, mostly. Yes. But in the report, you will not write, not say that this is NPM1 like mutation, unless you have done the, uh, H procedure in this patient. Okay. This is acute, acute myeloid leukemia confirmed on the bone marrow biopsy. She is 36 years old. What treatment would you offer to this patient? She has no other background history. Sir, I can't comment on medication because I'm from basic lab hematology. So, any clinical hematologist with us who can comment? What regimen would you offer to this patient? If she's only NPM1 mutated, I will give DA and my L. And if it's positive, I will go for DA and my distractor. Okay. Okay. She is now in remission. Then she's not on remission after the second cycle. She has come into remission. Would you transplant her? Usually, NPM1, we will not transplant. But if it's IDH mutated, we transplant in first line. But if there is NPM1 positivity after the, uh, second cycle, then she is eligible for transplant. Yeah. If NPM1 second. So, those patients who have favorable cytogenetics according to WHO 2022, once they are in remission, we do not transplant them. If they have intermediate risk category or worse risk category according to WHO 2022, we would transplant this patient after chemotherapy. Do not forget to do a pregnancy test in a young female, because it will change your management. Yeah. And do you know what cytogenetic panel I should send in a new AML? According to WHO 2022? So, 2022 AML guideline says that we should at least send four types of tests on a bone marrow of suspected AML. One is karyotyping, which will tell you translocation. Second one is FISH or PCR for inversion 16, 8;21, and KMT2A. Third one is molecular testing for FLT3, IDH1, IDH2, and NPM1. And fourth one is NGS panel, which will include a whole lot of molecular mutations like ASXL1, RUNX1, U2AF1, TP53. So, these are the minimum genetic tests that you would do on the bone marrow of a suspected AML patient. It will tell you whether the patient is of high risk category or intermediate risk or worse risk. NPM1 is quite common. You may not find these cup-shaped or fish mouth shapes in all NPM1 patients because NPM1 has multiple types. I think three or four different types of NPM1 mutations are there. It is a type 1 which has fish mouth appearance. Right.
So, the third patient is an 87-year-old female. Dr., sorry for the interruption. Can we send PML-RAR alpha by FISH on the patient if we have suspicion from morphology in the first panel immediately? Can we add this? So, the karyotyping will tell you if there is any translocation of APL. But if you are suspecting APL, then you will act very urgently in this patient. Those tertiary hospitals here in the UK who have HMDs or HMDs type department, they will do the PML-RAR stain within one hour, within one hour if it is a working time, 9 to 6. Okay. Otherwise, the rest of the PCR usually takes a few hours to come back. But the morphology should be very promising to you that this is an APL patient. Then in such a case, we do not delay. We start treatment within the first few hours. Okay. Thank you.
Now, this is an 87-year-old female. It progresses. New white cell count is 10 and platelet count is 300. This is the power 10 overview. Renal function is normal. Liver function is normal. In the previous slide, there were some red cell agglutination as well. Do not forget to comment on that because the patient has a recent laryngitis. The infection-induced agglutination can be there as well. Do not miss any findings in your. So, this is power 50. And the patient is anemic. 87-year-old. What do you see in this blood film? The red cells are showing anisocytosis and poikilocytosis. In poikilocytes, are these called the irregularly contracted red blood cells? On this one, this one, this one, this one. Okay. These are just schistocytes. This line is an artifact. So, think more. So, what do you think is going on in this patient? There is a prominent commented RBC and macrocytosis. As I can see, a few macrocytes RBCs. And yes, platelets are reduced on the smear analyzer. What, what is the count of platelet count? 300. Okay. And the, uh, in WBC, neutrophils, I can appreciate the neutrophils. Neutrophils are preserved. M. And, so, there is, what is your impression? What's going on in this blood? There is, is there is platelet count or normal? But schistocytes are present on the peripheral smear with anemia. M. This can be, I can't say that this is a MAHA because platelet count is normal. Only macrocytes and fragmented RBCs are present. Microangiopathic hemolytic anemia. Okay. So, anemia is there. If there is, if there is thrombocytopenia, then call it maybe suspected TTP or HUS. There is anemia going on. This is 87-year-old lady. Oh, 87. Okay. Yeah. Why this patient would have hemolysis at this age? We should take the history for any malignancy in this patient. Malignancy. So, you're going to secondary TTP again? But this patient's platelet count is normal. Organ functions are normal. MCV is certainly high. 98. Any drug-induced drug history? No. He's not taking any drug. I would like to exclude the basics like henic deficiency, severe folate deficiency here. Neutrophils, you have seen they are not hyposegmented. He has no liver disease. He is not alcoholic to have such macrocytosis. MDS? Why you think this is MDS? I mean, these features of ineffective erythropoiesis maybe. And at I would, I would expect MDS if she had normal henics. We have not seen any leukoblastic picture here. No NRBC, no schistocytes, no hyposegmented neutrophils. DCT positive or negative? Negative. Somebody asked that we would take history. What, what history you want to take from the patient? History of cardiac disease. She has any valve replacement? You didn't mention that. She's not on drugs. What replacement can lead to any metallic valve replacement give you intravascular hemolysis? So, from older population, if they are coming with isolated anemia, you would exclude iron deficiency anemia first to find out if there is any bowel cancer or not. But her MCV was not low. Her MCV was on the higher side. There were schistocytes. There is no microcytosis in the blood film. It means something else is going on. She is not hypertensive to have malignant hypertension and MAHA. Pregnancy is out of the picture. She is not on drugs to have oxidative hemolysis. She does not have any infection to have infection-induced hemolysis. She had a valve replacement in 1970. And now she is 87. She is s. She has a valve metallic valve for 17 years, which is now dysfunctional and it has led to mechanical hemolysis. But do remember the differentials of hemolysis. Isolated hemolysis in the exam. They may give you a hint or they may not give you a hint. They may ask you that this is the blood film. Right. The differential diagnosis of this blood film according to the age. So, do not write pregnancy for them. Or they can tell you that this patient has valve replacement many years ago. Now she's completely well, but since 2 months is progressively anemic. Lids are normal. Renal functions are normal. Liver functions are normal. She's not alcoholic, not on any medications, no infection, no new drug. What can be the, uh, well, mechanical. The next question is a 60-year-old. What, what was the impression for the last case? Mechanical valve-induced hemolysis. Sorry, is it? Yeah. Schistocytes are high. I think the schistocytes were normal, isn't it? Sorry, the schistocytes were high. Many schistocytes, polychromia. Yeah. Okay. So, such cases in the exam are not for diagnosis. Such cases in the exam will be for reporting the blood film and write your differential diagnosis. Dr. Amir, sorry for this question. I have read somewhere that in even in autoimmune hemolytic anemia, we can have some schistocytes along with spherocytes. Can we comment like that in the exam if they ask? Yes. Or be a blender? Yes, because I mentioned to you that they will ask you such blood films for differentials. You can write autoimmune hemolytic anemia if DAT is positive. But one of the candidates asked whether the DAT was negative or positive. I mentioned that it is negative. So, if you are writing the differentials of hemolysis, you will see that my differentials are malignant hypertension, drug-induced, infection-induced, autoimmune hemolysis, if DAT is positive, or mechanical valve-related hemolysis or Buns. But do not write stuff regarding pregnancy. He is 87 years old. Thank you.
So, this patient is 60 years old to present to ED because of abdominal pain. CT scan of the abdomen shows a large abdominal mass. On examination, he has some nodes and supraclavicular nodes as well. The full blood count: hemoglobin 110, white cell count 15, and platelet count 150. This is the blood film at power 10. Sorry, I mean, what is the blood count again for the patient? 110 is the hemoglobin, 16 is the white cell, and 150 is the platelet. All right. The patient has, um, so, lymphadenopathy and abdominal pain. I will make it 50 now. These are all evaluations to make it big for all. All right. So, what do you think that this patient can have? Patient has lymphadenopathy and this is the blood film. So, we need to rule out infection and malignancy. Okay. So, these are two extremes. Yeah. With this vacuolated white cell, I would like to exclude high-grade lymphoma. Which high-grade lymphoma? You are suspecting the disappearance. I would like to exclude Burkitt lymphoma. Why Burkitt lymphoma came to your mind? Presentation-wise and the morphology. It's very vacuolated. The cytoplasm of the first case today that we have done was also vacuolated. Yeah, compared to this one, it was much less. But of course, it's, um, I will need like further tests to confirm my impression in terms of FLT3 and this diagnosis. Basically, it's, I would need like, um, imaging again, if not biopsy. I think the deeply basophilic cytoplasm as well, very vacuolated and very vacuolated. Yeah. It's medium-sized cell with, um, round nuclei, compacted chromatin. The first one that we saw, it was a bit open chromatin and there was minimal vacuolation in the first case. This is, it is there is moderate cytoplasm, very basophilic. This is not that much basophilic. The B cells are deeply basophilic. This can be the large B cell lymphoma. And differential. Why do you think it is large B cell? Because these are the, uh, intermediate to large-sized atypical lymphoid cells which are showing vacuolation involving the side of the nucleus. And along with history that the patient presented with the abdominal mass and lymphadenopathy. So, this is, uh, B-cell lymphoma. And Lymphoma. So, what is the presentation of B-cell lymphoma? B-cell lymphoma usually presents with disseminated lymphoma. No, no. I'm not saying about B-cell lymphoma. I'm saying about high-grade lymphoma like DLBCL, diffuse large B-cell lymphoma, because the patient's age is 60 years old and these are not so much basophilic. So, it is my differential. In general, B-cell lymphoma would present as a single node, single location. It is not disseminated. And these cells are not that much basophilic. Next, we will see B for differentiation. The DLBCL has lymphoma stage 4 everywhere in the body and usually one big mass that you would biopsy and know the diagnosis. These are large cells. They are basophilic. Yes, I agree. But they are not deeply basophilic. Deeply basophilic is just like this one. This nucleus is very, very basophilic. And yes, there are a lot of vacuolation. DLBCL is one of the differential of vacuolated lymphoma. You can see vacuolation in ALL, you can see vacuolation in DLBCL and Burkitt lymphoma. These are the few causes with vacuolation. So, when we did the flow cytometry for this patient after biopsying the abdominal mass, it was CD5 negative and CD10 positive, BCL2 positive, BCL6 positive. What is the likely diagnosis then? Double hit. Double hit lymphoma. It is double hit DLBCL lymphoma or high grade. This patient's age is 60 and, uh, raised LDL 1200. He is completely independent and no other comorbidities. And multiple nodal sites were involved. His IPI score was high. It was two. It was three. What should we offer him as a first line? If he has high IPI score and fit, based regimens are not first line in UK. If they have IPI, these lymphoma, the high-grade lymphoma, um, they rarely come to the blood. Most of the time, they will appear in the lymph node only. But if they involve the bone marrow, you will see findings in the blood as well. So, this is a young child, 30-year-old patient. Dr., what was the treatment of patient? Previous case, you said that. Yeah. So, if someone is age between 18 and 60, M, and his IPI score or DLBCL is high, like two or above, then we give them R-CHOP or six cycles. Okay. Once six cycles are done, then the MDT would decide to give this patient any radiotherapy for the residual lymphadenopathy or not. Some patients, lymph nodes will regress with this regimen, but sometimes, some patients, lymph nodes will remain over there, like in a small size, but remain over there. Then the MDT decides regarding radiotherapy, whether to give these patients radiotherapy or not. If the IPI score is between 0 to 1, then it is usually R-CHOP. But for high IPI, the recommended regimen now is R-CHOP. Okay. And all the, in all these patients, you will do CNS IPI scoring to find out whether he is eligible for CNS prophylaxis or not. Okay. Okay.
Yeah. So, this is the aspirate of a 30-year-old patient who has laryngeal-pharyngeal mass, HIV positive, and cytopenias as well. That's why we did biopsy for this patient as well. This is power 10. We will go to power 50 to find out the features of these cells. Did find out some good cells with vacuolation. These are the cells at power 50. And now let's see at power 100 to differentiate the vacuolation. So, first, we will mention this aspirate is particulate. Yes. Sample with reduced dry lineage because we did not see any megakaryocytes and infiltrated with population like blast, 90%. Yeah. Going to adjust the light to. Yeah. And given he has HIV positive, I will put in my mind lymphomas. But in the background, I will stop here. Yes. Kids usually get this disease. And then need not to be HIV positive. They get this disease in their jaw when they have big masses under the jaw. And we biopsy it and we see such morphology in them. So, it could be Burkitt. Yes. This is Burkitt. Just to differentiate it from the previous case which has vacuolation. Yeah. These vacuolations are large and the cytoplasm is very basophilic. This is called deeply, deeply basophilic cytoplasm. The color of the cytoplasm and the nucleus is almost the same. The vacuolation is large. This is just to differentiate it from the ALL vacuolation and blast and DLBCL vacuolation and blast. And if they have given you any molecular information, they would tell you that Ki-67 is 100%. While in DLBCL, Ki-67 is high, but not 100%. And usually, the Burkitt, they are related to a single area, not disseminated in the body. You would not have seen any Burkitt lymphoma case which was diagnosed from a biopsy from the axillary lymph node. They are always either in the inguinal or in the tummy or a mass hanging from the jaw. And this man with this involvement degree of the bone marrow, it will be Burkitt leukemia lymphoma. So, if you biopsy this patient and run immunohistochemistry, it will tell you that this patient is CD5 negative, CD10 positive, and the Ki-67 is 100%. When you see that this Ki-67 is 100%, the only thing that should click your mind is Burkitt. And upon karyotyping, you will see t(8;14) translocation. Make RGH translocation. This is the commonest translocation in the Burkitt's, but you can also see t(2;8) and t(8;22) translocations as well in the Burkitt. So, what about the terminology of Burkitt leukemia variant? When do we use it? When there is peripheral blast? I think no. We haven't seen any. If anyone else has seen, they can come in. But in my practice, we haven't seen any Burkitt leukemia variant. Burkitt leukemia. Just we will say Burkitt leukemia in case if the bone marrow involvement is like this and the blast is outside in the peripheral. So, it is Burkitt lymphoma. But reaches a degree of involvement of the bone marrow and peripheral blast as well. So, just the term Burkitt leukemia, that means it is Burkitt lymphoma-rich peripheral blood. Because usually lymphoma is assigned to the lymph nodes only. But stage 4 Burkitt lymphoma that involves the bone marrow. And then if we found the peripheral blast, we will say leukemia. Yeah. Okay. So, what regimens do we have for Burkitt lymphoma in UK? R-CHOP. Myeloma. And we don't have any NHS guideline for Burkitt lymphoma. But you can follow the MSSG algorithms for it. It is very helpful.
This was the. I have a question. According to the WHO now classification has been changed. So, should we label or should we investigate for the EBV positivity and negativity? Because we check virology in all of them. Because if there is HIV positivity, then we have to contact the ID department to add the IV treatment. As previously, it was classified under the immunodeficiency Burkitt lymphoma. But now, according to the new WHO, it is either EBV positive or EBV negative. It will not change the regimen, but we have to add the treatment according to the virus positive. Because if EBV viraemia is very high and the concentration of EBV is more than 10,000, and sometimes we add rituximab or any other treatment, like for the EBV. In pediatric, we are using COPADAM, my V, and then R-CHOP. It is not applicable in adults as well. No, we haven't seen stuff in the. Do we use radiotherapy in Burkitt? No, just the chemo and auto-transplant. Sometimes, auto-transplant is also very less because these people's response rate to the chemotherapy is very, very good. You will not see any Burkitt lymphoma patient in your lymphoma unit for auto-transplantation. There is the response rate is very, very. Yeah. Okay. Um, I think it's 10:15 here. We can stop and enjoy your. Thank you so much. Bye. Thank you.