Transcription
Morning all. Can you hear me? Yes. Yes, sir. Okay. Right. So, let's start the first case. Uh, this is a 56-year-old man who presented with B symptoms, weight loss, uh, night sweats, and lymphadenopathy. CT scan shows a big mass in the inguinal region. The patient has bone marrow involvement as well. There is anemia and high white cell count with slight thrombocytopenia. And this is the blood. This is power 10. A general overview. Now I will go to power 50. All right. Any thoughts up until now? For example, I am the lab scientist. Yes, I have seen this blood film and I have referred this blood film to you because you are the clinical hematologist. I am thinking as a lab scientist that this is a reactive lymphocytosis because I don't know about the patient history. I'm working in the lab. I have just seen the blood film and after seeing this blood film, I'm thinking this may be reactive lymphocytosis, but still I would like to take your opinion because some of the lymphocytes have uh vacuolation. Now, now you are the clinical hematologist and I would ask you to report this um blood film. Anyone be quick. It is a sunny Sunday. I have to go to the mosque as well. Okay. The first one on the list is Saha Ali. Hi. Can you please report this blood? I think, yeah, I can see there is a uh medium to large mononuclear cells, lymphocytes with abundant cytoplasm, mature clump chromatin with multiple nucleoli. Mhm. I thought it might be prolymphocyte. There is some with vacuolation. I think this is a monocyte. A pro-monocyte. Probably maybe one person at a time. Yes. This is another cell for you. Yeah, I mean, to be honest, I got the impression that uh it's prolymphocyte, but yeah, it might be pro-mono. There is no cytoplasmic granules. Sorry, what is the history? I didn't join early. This is a 56-year-old man with B symptoms. Yeah. CT scan shows lymphadenopathy above and below the diaphragm. He has a big mass in the left inguinal area. Yeah. That has been biopsied as well. But he has bone marrow involvement. His hemoglobin was low. Yeah. White cell count was high. So we made a blood film for this patient. And this is the blood film of the patient. Yeah. Yeah. I mean, so it's a mainly uh, it's it's look like for me it's mainly lymphocytosis with some. It is lymphocytosis, but what do you think? Uh, what is your impression? High-grade, high-grade lymphoma. Why do you think this is high-grade lymphoma? Because there is some vacuolation and there is some nucleoli in the uh, some also the cytoplasm here. This one looks less mature with some nucleoli. So I thought this is likely high-grade B-cell lymphoma. High-grade lymphoma. Okay. All right. So you have noticed lymphocytosis and uh some abnormal void cells with multiple nuclei and prominent nuclei. Your impression is high-grade B-cell lymphoma. What test would you suggest for this patient? Uh, brief flow cytometry and uh, already the lymph node biopsy was done. Is taking scan PET. Mhm. To look for the high avid lymph, high avid lymph nodes more targeted for biopsy. Okay. This patient is uh CD5 negative, 19 positive, 20 positive, 10 positive, 23 negative, 43 negative, 200 negative. Yeah, I think this is uh suggestive of MCL from CD5 positive and 23, 43 negative. CD5 negative, 10 positive, 19 positive, 20 positive, 23 negative, 200 negative. All right. Yeah, CD10 positive, it's likely uh germline B-cell lymphoma. I grade. I will ask for the uh immunohistochemistry. Three BCL2 and BCL6 positive. BCL2 double hit lymphoma. Double hit high-grade lymphoma. These lymphoma rarely appear in the blood, but sometimes when they involve the bone marrow, then you can and you can see their features in the in the peripheral blood film as well. This is a high-grade lymphoma, B-cell lymphoma, DLBCL, which we diagnosed on the referral blood film and the biopsy report came later and it shows DLBCL. The patient is still inpatient and he is under treatment. What treatment would you suggest for this 56-year-old patient having no background morbidities? All right. Yeah. I mean, if he's a fit patient and apparently he had the he had two and above, he's taking four diseases and uh likely he will be fit for R-CHOP. Which score will you calculate before deciding R-CHOP? You will calculate some score for this patient to decide uh whether he will be fit for R-CHOP or R-DA-EPOCH or uh R-EPOCH. IPSS. He will be entitled for R-EPOCH if he's IPSS score two or more. IPSS. IPSS is for myelo. Myelodysplastic syndrome. I can't remember. It's IPI. IPI score. If IPI score is two or more, then then this patient is okay for. Or we thought about R-DA-EPOCH or R-ICE as well because he's a young patient, 56-year-old, no comorbidities, previously fit. But then the MDT decided to go ahead with R-CHOP because physically he looked a bit frail. So that's why. All right. Yeah. These DLBCL lymphocytes are quite big. You can see multiple nuclei. They can have vacuolation sometimes as well, but they are different from Burkitt lymphoma because Burkitt lymphoma cells are very deeply basophilic. The cytoplasm is very deeply basophilic and they have vacuolation as well. Right. You're going for part two in autumn, right? H, yeah. Okay. So you give this patient uh R-CHOP and he relapses within um within 12 months. What are your second-line options? Uh, I mean, if he relapses within the 12 months, option is for bispecific and also CAR-T. Anything before bispecific? You mentioned or or or autograft or autograft. Okay. Within 12 months, we prefer CAR-T if the patient is fit for that. And after 12 months, we usually look for uh autograft or bispecific. Third line or bispecifics. Do you know bispecifics? Which drugs are available currently for DLBCL? Uh, Epcoritamab and Glofitamab. Anything else? These two are currently used and Tafasitamab is in in trial at the moment. So these will be the questions from you in your short questions. Report the blood film. What flow cytometry do you expect or what immunohistochemistry do you expect? What are the options for first-line treatment? What to suggest if the patient relapses? Or they may ask you just name the options of medication in first line, second line or third line. If it has to appear in the long case, it will be follicular lymphoma blood film first and then they will give you another scenario that after 5 years, this patient presented to you again, he has lymphopathy again, and this is the blood film. What do you think it will be? Transformation from follicular to DLBCL. And they will be asking questions related to that. You need to write this question. You can have practice of answering these things in 9 minutes. You may have heard from your colleagues who appeared in the exam yesterday, what difficulty they faced. So I'm sure you will act according to that. Okay. This is the second case. This patient is uh 50-year-old, feeling um weakness and cold symptoms for 4 weeks. Presented to emergency department with world finding difficulty. CT scan shows intracerebral hemorrhage. The peripheral blood count shows hemoglobin of 110, white cell count of 30, platelet count of 55. And this is the blood. This is power 10. Now I will go to power 50. All right. So this is power 50. Okay. So, any thought about this blood? Dr. Aisha Shahid is the second one on the list. Uh, Assalamualaikum. Um, um, the RBCs show uh normocytic, normochromic predominantly uh uh morphology with few teardrop cells and the platelets seem to be uh markedly reduced, um, or reduced, not markedly reduced. And in the WBC shows a predominant population of large uh cells with scant cytoplasm and large nucleus and nuclei are not prominent. You say nuclei are not prominent. I will show four nuclei. Uh, okay. Yes, they are. I I couldn't appreciate. Sorry. Right. The cyto, the nucleus is quite basophilic. I think this is pinkish nucleus, not this. Okay, sir. Right. That's it. Um, should I give an opinion on this? I think So you should give some opinion because this patient is dying in the ED because he has intracerebral hemorrhage. You are the clinical hematologist. You have seen the blood film. I think you should give some opinion to this patient. From here, she will get the opinion. Um, I have two differentials. Mhm. One is acute leukemia. Can I can I get the cytochemistry of uh this? I would like to see whether they respond to Sudan Black or not. This is the blood film. Patient just arrived an hour ago to the to the uh emergency department. We have done full blood count for this patient and we have made this blood film. The blood will go to diagnostic service HMDS and it will take uh few more hours for the flow cytometry. Okay. What do you think about this blood film? I would report it as acute leukemia or leukemic spell of uh lymphoma. My differential, main differential is uh acute leukemia. And since there are there are no mature cells present and I would like to see if it's Sudan positive or not. So why you want to do Sudan for this patient? I am uh trying to confirm its myeloid lineage. We don't do Sudan for myeloid lineage here. Why not to do MO? Okay. Do MO. We can do MO. Okay. But now this patient is in the ED with hemorrhage and flow cytometry or immunohistochemistry is the second step. First, you have to report this film because you have to go back to the ED to inform the people or they will call you. You have seen the blood film, your clinical hematologist. Why this patient's platelet count is low and why this patient has anemia and high white cell count? You have to tell doctor something. So go ahead. Because of bone marrow infiltration. Mhm. Okay. So your differential is this is uh leukemia. Yes. Why this patient has hemorrhage? Might be having sepsis. No. Patient is afebrile. Okay. Uh, then the platelet count maybe low. Platelet count is one. And second, um, he might be having a deranged PT, PTT. I don't know about the liver whether it is involved or not because of low PT, PTT because liver. Um, what is this? Does this give you any hint or not? No, I I don't want to make guesses. Maybe I'm not aware. I can learn something new. I am not catching the thing which you might. Yes. Right. We will discuss then. Anyone of you has a guess which type of AML is this before telling you any flow cytometry or any immunohistochemistry? I think the last cell it was lobed. It was not lobed. The two cells were sticking together like this. Yeah. Any guess which type of AML is this? Might be hypogranular APL. No. No. Okay. When you said about bleeding, I did think of that. But the thing is that the cells do not match the promyelocyte morphology at all. Um, yes, I agree with you. Or anything like that. No, that's why I didn't. Somebody said cupping. Yeah. Okay. You can say these uh depressions in a nuclear material. This one. These are called fish mouth or cup shape like. Yeah. Yes. So these AMLs are very easy to pick. Which one is this one? They are the NPM1 mutated AMLs. All right. Yeah. Okay. And you can see the nuclear material is very pinkish, which is a feature of myeloid cells. If they if they were bluish, then you may think about that they may be lymphoid in nature. This is just morphological differences. This patient has um NPM1 mutated AML admitted last week with hemorrhage because the platelet counts were low and the PT, PTT was abnormal because these myeloid blasts they absorb the fibrinogen and they cause acquired fibrinogen deficiency leading to bleed in the patient. So these are the two mechanisms of bleeding in NPM1 mutated AML. And the patient died unfortunately on day three because the bleed extended in the brain. And do you know they are CD34 negative or CD34 positive AML? CD34 negative. Yes, they are one of the three CD34 negative AML. And on the WHO 2022 uh category or standard risk. And in fit patients, we give them uh intensive chemotherapy. And once they are in remission, we monitor them. If they have intermediate or worse category, then fit patients, we give them intensive chemotherapy, FLAG-IDA, and then transplant. So this is NPM1 unmutated AML. In reporting, when you report the blood film, comment about the abnormality first. This patient has uh prominent blasts in the in the blood film. Talk about blast thrombocytopenia and then come to red blood cells. Give your opinion and then um give your suggestion that this patient would need original flow cytometry and followed by bone marrow biopsy. But at the moment, the patient cannot have bone marrow biopsy because he has a big hemorrhage. He's not fit for that. They would ask you in the exam about reporting. They would ask you about the WHO category. They would ask you about um most likely treatment for this patient. With hemorrhage, you cannot treat with intensive chemotherapy. You have to involve first uh neurosurgical team in that. Or they may say that this patient is 80 years old. Okay. And ask you about the option of chemotherapy. And obviously, you cannot give FLAG-IDA or DA to an 80-year-old. You have to think about low-intensity chemotherapy for them. Any question? Can you just point again to the morphological feature that is um pointing to the NPM1 mutation? Okay. So let's find Some dust. Let's fix that. These depressions, this one, you will see other blasts as well. These depressions are either called fish mouth or cup shape. Let's see somewhere. And another blast. This depression or this depression, they are called fish mouth or cup shape. This one. This depression again, cup shaped or fish mouth. So these are the features of um NPM1 mutated. Oh, this one is better. This depression, this one, this is either fish mouth or cup. This is more like a cup shape and this is a fish mouth. Is that okay? Perfect. Thank you. This type of AML is quite common. You will see once someone. Yes. This is a 50-year-old man presented to emergency department with worsening fatigue, shortness of breath and uh pallor. His um full blood count shows hemoglobin of 67, white cell count of four, and platelet count of 300. This is power 10. The first question in this case would be list the abnormalities that that you see in this patient in this slide. What's well, sites, thrombocytopenia, anemia? Let's go to length. List the abnormalities. It has six marks. So list them. What do you see? So third on the list is Nahid. Nahid, what do you see? Uh, yes, Dr. Ramar. I can see dual population of red blood cells. Uh, one very small, more like spherocytes, and others are uh large. So when I see such kind of cells, like two types of population, the first thing that comes in my mind is might be the patient uh has transfused. Or so I will give the history of transfusion in the patient. The question is list the abnormalities in the blood. Yes, there are prominent spherocytes that I can see uh in this uh slide. Okay, number one is spherocytes. Number two, number two, maybe some macrocytes as well. Number two is macrocytes. Number three, the um lymph, the cells, the WBCs, they are also um I think some abnormality in the WBC. I can see with the blebs on the uh blebbing of cytoplasm. Might be This is a reactive lymphocyte. Okay. Reactive lymphocytes. Number three. What is number four? Maybe some sorry, there are schistocytes here. Schistocytes. I can't appreciate a very prominent this one. This one. Yes. One. Yes. This bivalve cell. It is um these are not proper helmet cells. So cells can have different types. Yes. When schistocytes, it will cover all. Okay. There's another schistocyte on your left side as well. What about the neutrophil? Um, I think they are hyper segmented a bit. And granulated as well. Hypergranulation. Yes. Yes. Activated lymphocytes are prominent. Activated lymphocytes. So you have commented on RBC line. You commented on the white cell line. What about the platelet? Platelets seem normal to me. This is a finding as well. You have to mention that platelet morphology and number are normal. Okay. So now the question is um what is your impression? There are some rouleaux formation here as well on this side. You have to mention that this one, this one. So what is your impression in for this induction? Some uh immune hemolytic anemia. So how did you find that this is immune hemolytic anemia? I will do uh DAT of the patient, direct antiglobulin test, and I will do other uh hemolytic screen like LDH, bilirubin, haptoglobin. Yeah. So you will say this is hemolytic anemia. On the basis of that, I will uh determine whether it is hemolytic anemia or it is uh hereditary spherocytosis. That is another DD for spherocytes because the rouleaux formation here. Yes, here I can see a few of the cells. Uh, but rouleaux formation is not that prominent. However, I will confirm it by DAT. If it is DAT positive, then it is immune type. And if it's negative, yes, this is um DAT positive or IgG positive. Okay. So, this is warm autoimmune hemolytic anemia. What is the immediate intervention in this patient? Uh, steroids. We give to these patients. Steroids. What you are appearing in consult? So tell the uh tell us what type of steroid you will give. Liquid form? No, I will give or what what steroid you will give to this patient? Uh, Prednisolone oral. I will give. I am I am from ED. I am from. You are clinical hematologist. You said Prednisolone. What I would say? Okay, what is the dose? What is the formulation? It's 1 mg per kg, but you like maximum 80 mg per day we can give to the patient. Um, depending upon. We can start from the lower dose, 40 mg per day, and then we can increase the dose up to 80 mg per kg. There is no such indication to start from uh 40 mg per kg. Cap is 80 mg. Okay. Okay. If the patient is more than 80 m, 80 kg, then cap is 80. If the patient is less than 80 kg, then according to his weight, he may be 60 kg, then give 60 kg, uh, 60 mg per day. Okay. Steroid, then what else? Then we will see the response of the patient to steroids and will determine accordingly what to do next. So this is not a reply from a consultant level exam candidate. You give this patient steroid. What else? If I'm an ED doctor, this patient is hemorrhaging. I call you. What should I give this patient? You will only see steroid. You will kill this patient with gastric ulcer. Yes, I will give uh the patient PPI as well for gastric protection. And if the patient um and folic acid. Yes, folic acid we can give because the patient is uh constantly hemolyzing. We need supplements of folic acid as well. U so, steroids, folic acid, and uh PPIs. But but that that is all that is coming in my mind at this time. And if the patient is unstable, then we will and if the patient is bleeding, then urgent management. Management in a hemolyzing patient is IVIG, which can immediately like, um, reduce the level of combat the IgG in the patient. IGG mediated hemolysis in this patient. That's it. This patient's hemoglobin was 67 and he was very symptomatic as well. Yes. Okay. You need to arrange blood transfusion for this patient. Yes. Steroid is the right option. But in acute cases, we usually give them methylprednisolone. Okay. 500 mg IV OD for 3 days along with IVIG because this is an acute episode. Steroid takes time to show its effect. IVIG takes 12 to 24 hours to show its effect. Plus PPIs to prevent stomach complications. Plus vitamin D because this patient would need long-term steroids. Okay. Is the first line and VTE prophylaxis. You have to do because hemolyzing patients are at risk of developing thrombosis. Yes, this patient would need um VT prophylaxis as well. You you have to give him steroid card as well because you are giving him steroid for IVIG and blood transfusion. You have to take consent from. This will complete your answer in exam. If you only mention steroid, they will say kindly come again in the exam. Okay. Okay. Thank you. They may ask you, okay, DAT is positive. What do you mean by hemolytic anemia? What are the causes of DAT positive warm autoimmune hemolytic anemia? This is a nine-mark question. You have reported the you have listed the abnormalities in the blood film for which was for five marks. Um, then for another three marks, you have mentioned the urgent intervention. The last two months, we are asking you what are the causes of DAT positive autoimmune um infections and primary and secondary. What are the secondary? You say infection. What else? Drug-induced. And um and in the disorder, disorder and autoimmune diseases. Autoimmune diseases and multiple myeloma. Okay. What else? Transfusion reactions. Transfusion reaction and post-BMT. Okay. So there are four major causes of secondary autoimmune hemolytic anemia: cancers. It can be solid organ or hematological cancers. Infections, all types of EBV, CMV, hepatitis, mycobacteria, malaria, leishmania, they can lead to secondary autoimmune. Then autoimmune and then post-transplant. And the main is the last question and last slide. Right. This is a 56-year-old man um presented to the hematology clinic because he has pancytopenia. He was referred by the GP to you because of pancytopenia. Let's see his blood film and see what details. This is power 10. Now I'll go to power. This is a defect. Okay. Any thoughts about this blood? This patient was referred by the GP for pancytopenia. I'm on a thick side of the slide for a reason. What do you, anyone, any comments? I think this is a lymphoproliferative disorder. Uh, most likely hairy cell. I can see hairy projections. You need to report the blood. Normocytic, normochromic RBCs, WBC. Then again, I would say comment on abnormality first. You have seen, sir, what's the age of the patient, sir? 56. Uh, WBC shows uh large uh lymphoid cells with abundant cytoplasm and cyto, prominent cytoplasmic projections. Uh, nucleus is uh condensed, condensed uh nucleus and abundance having abundant cytoplasm with cytoplasmic projections. Platelets uh are reduced on film. All right. What else? So rouleaux formation also said. No, this is I'm on the thick side. I'm on a thick side, that's why there are rouleaux formation. Okay, sir. In pancytopenia patient, you have to see the thick side always. Okay, sir. Thank you. Okay. [Music] Report the blood. Be quick. Someone has to report the blood quickly, please. Iman Ibrahim, you're next. If you want to report this, then please God. Oman. Ravia. Ravia Hussein. Yes, I can see. Yeah, you have to report. I can see hypochromic cells and I saw one teardrop in the previous. The previous, there is microcytes also. Mhm. Okay. Yes. Here I can see some teardrops. Yes. So you need to report it because you are sitting in the exam. You need to report this blood cell. I can find another cell and then we will stop there. This is spin cells are very few. You are lucky you got very interesting cells. Yeah. Now report this blood film. Yes. I can see some hypochromic cells, uh hypochromic RBCs and low platelets. Okay. Uh abnormal uh uh lymphoid cells, abnormal WBCs with projections, cytoplasmic projections. Mhm. Enlarged nuclei. [Music] Um, I can't see others. So the main features are hypochromic RBCs with low platelets and abnormal WBCs. Teardrops as well. Uh, teardrops in this film, I can't report, but I saw one before this. Yes, sir. I see, I see. I saw one teardrop occasionally in the previous uh sections. All right. What is your impression? Um, I I I think it is a hairy cell leukemia. Your impression should be lymphoproliferative disorder. Yes. Yes. Most probably leukemia. You you do not give diagnosis on a blood film. You say probably. So what you would do next? Uh, I will send uh sample for most likely uh tomorrow for uh immunophenotyping. You will send a sample for flow cytometry and you will request bone marrow biopsy on this patient. Yes, sir. There is usually dry tap in hairy cell leukemia. That's why we will go for bone marrow biopsy. Yes. Yes, it is not not it is not that dry to that you will not get anything. Bone marrow biopsy contains two steps: aspirate plus trephine. There are features in the trephine. Mostly in hairy cell leukemia, you will see product appearance of the cells in the trephine. Okay, sir. Thank you. So the blood film shows pancytopenia. There are multiple um abnormal lymphocytes with cytoplasmic projections, normocytic, normochromic anemia with multiple teardrop cells and genuine thrombocytopenia. Impression is likely lymphoproliferative disorder. We need to do flow cytometry in this patient and request bone marrow biopsy. What is the expected flow? There will be massive also in hairy cell leukemia. Yes. Yes. But not always. This patient, the spleen was not that enlarged. It was just 7 cm, not massive. In some patients, it is up to 17, 18, 19, 20 cm. But in that patient, no, because I think we picked it up early. That's why. Okay, sir. But because if this patient has massive spleen, we would have seen target cells and Howell-Jolly bodies as well. But this film does not contain target cells or Howell-Jolly bodies. Why to see the thick side in a pancytopenia patient? Because one of the um reason of pancytopenia is hairy cell leukemia, and you would see hairy cells mostly on on the thick side. That's why go for thick side when they give you a blood film or pancytopenia opinion. Okay. So do not forget to see the thick side. Maybe the hairy cells are present on the thick side. You have seen in this blood film, um, there are no cells on on the thin side. All the hairy cells are on the thick side. What is the expected uh immunophenotype? Uh, it is CD19 positive, CD20, 22, 11c, 25 and 103 and 123 also, sir. One, 123, 103 and 123. Yeah. Which of them is positive? Which of them is negative? So 103 will be positive. Mhm. What about 11c, sir? 11c will also be present. Yeah. Positive. 25 positive. Positive. 103. And no CD CD25 negative. Usually negative. No, it's positive in hairy cell. CD5 negative. 25. 25 not said. 200 will be negative, I think so. Here is a leukemia panel include four markers: 11c, 25, 3, and 123. Okay, sir. What is the treatment? Treatment options? Purine. Yes. To this patient is the treatment. Will you treat this patient at all or no? Will you treat this patient or not? Yes. Uh, he is symptomatic. If he's symptomatic, then we need to. Yes. He has thrombocytopenia and he may bleed and he may get infection because of neutropenia. So he will need treatment. Okay. Dr. Can, one question. When we see these uh villous projections, why are we thinking only hairy cell leukemia? Why are we not seeing the differential diagnosis of uh splenic marginal zone lymphoma and other variants? We should say differential or we should say only lymphoproliferative disease. And mostly when you say when you say lymphoproliferative disorder, it covers all. Hairy cell leukemia, it's a variant which is not existing now, and marginal zone lymphoma as well. And in marginal zone lymphoma, you will see a lot of rouleaux formation. There will be no there will be no pancytopenia in marginal zone lymphoma, and their cells are a bit different. They especially the splenic marginal zone lymphoma, they have polarized projections and more uh basophilic cytoplasm. And here is a leukemia variant. You have leukocytosis, not pancytopenia, not leukopenia. And their cells are large with very prominent nuclei. In the hairy cell leukemia variant, which is now called splenic lymphoma leukemia with prominent cytoplasmic projections, SLLPN. And in hairy cell leukemia, you have monocytopenia. In um in the SLLPN variant or variant cell, hairy cell leukemia, you will see monocytes over there as well. And what will be findings for T-PLL? It also has these projections. In T-PLL, the blood film is full of full of the um small mature lymphocytes with Mickey Mouse ears. You have seen Mickey Mouse ears? Yes. Yes. So there is difference between Mickey Mouse ears and hairy. These are hairy. And the hair is cell, sorry, the T-PLL, they have round ears, a lot of cytoplasmic projections, or they and their nuclear material is very mature. They are small cells. You will rarely see any nuclei in those cells. And they are quite high in number as well. Sometime they will say white cell count is 100, white cell count is 60, 80, while in hairy cell leukemia, it is cytopenic. In T-PLL, it is cytosis. Okay. And are we call as cytoplasmic blebs or blebs projections? T-PLL is blebs. Blebs. Okay. Okay. Yes. And the marginal zone variant and hairy cell leukemia, they are cytoplasmic projections. Projections. Okay. Okay. Thank you. If no other question, then we will.