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Morphology Meeting Recording

Haematology, Morphology, FRCPath Exams1:06:12

Transcription

Okay, so this is the first case. The screen is visible, right? Uh, yes, but it's slightly blur on the edges. I don't know why. Yes, I don't know, uh, why. Well, it's okay. Concentrate on the central. This is a 62-year-old patient with a high white cell count, and the blood film shows, uh, lymphocytosis. This is the power 10 of the microscope. MH, just an overview at power 10. E, okay. Now we will move to power 50. Let's see some more. Uh, patient has or just the lymph nodes, just the lymph nodes. Sh, I will make it 100. Finally, there is lymphocytosis with small, medium to medium-sized lymphocytes with abundant cytoplasm. However, cytoplasm is showing, uh, projections. Chromatin is quite clumped. Uh, can see nuclear contour is regular. Nucleoli is present in few. Uh, but you just mentioned there is no spleen, any rash, or any autoimmune disease or anything? No, no, just lymph nodes and this. Yeah, RBC morphology is unremarkable. However, I saw few, uh,ocytes there is, uh, cytoplasmic projection, hairlike projections with prominent nuclei. What is this? Is it monocytoid? Okay, I think normal lymphocytosis are present. There is no clefts. There is, uh, no polymorphism in the cells. There are hairy projections. Okay, so now I would ask you to report the blood film. Okay, I, I will repeat whatever I said. It's lymphocytosis, uh, which are small to medium size with abundant cytoplasm in few, and, uh, nuclear chromatin is quite clumped. Nuclear contour is regular. There's, um, few cells still show, I don't know, it's artifact or hairy cell projections. And, uh, RBC morphology is unremarkable, and, uh,ocytes. However, fewocytes were seen. Platelet count seems to be normal. I did not see any spherocytes. So, in conclusion, it's lymphoproliferative disorder. So I would like to go for immunophenotyping or flow cytometry. Okay, so there is lympho, there is lymphocytosis. Is it pleomorphic? No, no. You mentioned there is a possibility of lymphoproliferative disease. H, and you requested for, uh, flow cytometry as well? Yes. All right. So, or patient has fever? Because this one is showing projections, sculping. Oh, Tan has no fever. He is, uh, 62 years old and with lymphadenopathy, generalized lymphadenopathy, no pyrexia, and high white cell count. And white cell count shows lymphocytosis. H, white cell count is 24. Okay, so you requested for flow cytometry. Flow cytometry shows CD2 negative, 3 negative, 4 negative, 19 positive, and 20 positive. What else you want to know? I want to know about CD5. CD5 is positive. Okay, then I want to know about CD23. 23 is negative. Um, then I want to know about, um, SOX11. SOX11 is positive. We did that on a lymph node biopsy. Okay, and for what about Cyclin D1? Cyclin D1 immunohistochemistry is positive. Is positive. So this is mantle cell. Um, but the morphology maybe looks more like, um, um, with abundant cytoplasm. I did not see pleomorphism or I could not appreciate pleomorphism too much. But this flow cytometry goes with mantle cell. Yeah, and the morphology goes with, uh, with, I think monocytoid type or marginal zone type, uh, of mantle cell because there is abundant cytoplasm. Mmm. Uh, mantle cell patients usually have abundant cytoplasm in their lymphocytes. Yes, but again, they, because the cytoplasm is clear, it's not basophilic. No, they have one category of, um, mantle cell lymphoma which has abundant and monocytoid type, type of cells, marginal zone cell lymphoma resembling them. Yes. Now, there are four or categories. Yeah, categories. Yes, because small cell, it resembles CLL. This is not small, small cell mantle cell, and there's no pleomorphism. It is not blastoid type. So maybe rather category. Yes. Mantle cell is very difficult to diagnose on morphology only. You need cytometry for that. Can you appreciate nucleoli in few? In in few of them, there are nucleoli, but not all of them. Yes, not all of them, but few of them have it. I think this one has. See, this one has, and it has abundant, slightly basophilic cytoplasm. What is the, uh, staging modality? How would you stage this patient? Would you like to do CT scan or a PET scan? Um, both are recommended now, but preferable is PET. PET scan is recommended now. Yeah, for the mantle cell, mantle cell staging. Okay, and translocation involved is 11, uh, 14. 11, 14, right? So if this patient is, for example, let's say, stage three and stage four advanced stage, advanced stage disease, but he has no B symptoms. There is no symptomatic like symptoms or organic or there are no cytopenias. What treatment options do you have? There are no cytopenias, but patient is still, uh, has advanced stage on PET CT, indolent disease, asymptomatic disease, but he has stage four or stage three indolent disease. You just wait and watch. Okay, but if this patient has resistant B symptoms and you want to treat this patient, then, then for stage four, I will check patient eligibility if is, uh, transplant eligible at all or the stem cell transplant eligible or not eligible. And, uh, if transplant eligible, then we give, uh, chemo-based therapy, alternating with R-CHOP. MH, and, uh, once the patient is in complete remission or partial remission, we go, uh, we, uh, proceed with autologous transplant and then maintenance Venetoclax for 3 years. And, uh, if patient is not transplanted, protocol. Yeah. And now, because in morphology case, you would not have this much time to write everything. You can just write Nordic protocol. Nordic protocol. Yes. And now, I think Young's trial shows role of Acalabrutinib, yeah, as well with or without transplant. Which trial? You mentioned, um, Young's trial. Right. TRIANGLE trial. Sorry, TRIANGLE trial. TRIANGLE. Yeah, yeah. Young is for autologous stem cell transplant. It is approved, but we have not yet started treating the patient with Acalabrutinib because of the funding issue. Okay, so for a fit patient, you have Nordic protocol or Lima protocol in which you use R-CHOP and you transplant the patient in CR, then maintenance. And what options do you have if the patient is not fit for transplant? If the patient is not fit for transplant, then you have option of BR, R-CHOP, and with BR, we can, but the one which is recommended is R-CHOP. Okay, so if this patient relapses after 2 years, let's say, um, you have given him an R-CHOP protocol, would you offer CAR-T after the relapse? Then I will re-stratify the patient. MH, and I don't remember exactly the stratification, but it depends on K67 more than 30, POD 24, then blastoid morphology, then presence of TP53. We will offer the patient first Acalabrutinib. And if the patient remains in remission with Acalabrutinib, disease becomes stable, we will continue Acalabrutinib. If there is no remission, then we will, and we'll discuss the patient initially with the clinical specialist, MDT, MDT, and clinical specialist. And if the patient does not respond to the treatment of Acalabrutinib, then we will refer the patient for CAR-T therapy. So CAR-T is third line in mantle cell. Yeah, second is, and the patient must have BTK inhibitor, Acalabrutinib, without exposure to Acalabrutinib, you cannot give CAR-T. For a patient in the UK, it is not funded. Mmm. All right. So the second case is a patient who just arrived from Africa to UK. And the GP has you, eosinophilia in the patient. This is power 4. What comes to your mind? If there is eosinophilia, so with the eosinophilia, we can think of parasitic infection, especially with the recent travel history. Mmm. And what else? And drugs and allergy. So in in morphology paper, they may not ask you about the secondary cause of eosinophilia. But if it is a w, like not this exam, the one before us, there was uncinariasis in the malignant, they asked the people, what are the secondary causes of eosinophilia? HUS has given a big table of better to remember five or six from them. So if there is eosinophilia, always start from power 4. There may be a worm in the in the blood. If there's no worm in the powerful, then it will be eosinophilia associated with neoplasm or chronic eosinophilia. This is power 4, and we can see there is a worm inside. Power 10, and in UK, L.L. is quite a lot. And we have, uh, worm blood film from parasite blood film from Nicos after every 3 months. And if it is a, most of them are the, uh, low, low check. Another one, there are quite a lot in this Nas film. But in exam, you have to struggle to find the worm. Most of our people miss the worm in this exam. So what do you think about this one? Is it a sheath or non-sheath? Sheath. Yes, it is a sheath. This is a sheath. B, and this is the head end and this is the tail end. Big 100 power. So have you made any mnemonic to remember the names of the worm? I think you have to revise it. Loa loa. I remember that it extends lower down to the tail. To the tail. Yeah. Yeah. What else was there? I've forgotten your mnemonic. Then there was a Wuchereria bancrofti. B for Wuchereria, and B for bi-nucleated. They have two nuclei in the tip of the tail. And another one was V for Brugia malayi. Brugia malayi tail is empty of, empty their tail does not contain any nuclei. The tail portion is empty of nuclei, while the lower loa extends to the lower end of the tail. So I remember it like this. In the exam, for the exam, do we have to mention Loa? Is it Loa or just it's, no need to mention the species? I think if you mention that, you will get full marks. First of all, they want to know whether it is a sheath or not sheath. Okay, but it is easy to figure out because like this worm has a big sheath hanging around here, so it's easy. And then this, and if you can tell them whether this is Loa loa or Brugia malayi or Wuchereria bancrofti, then you will get full 9 out of 10. Mmm. This is a sheath area. The tail ends here, and all these nuclei are standing to the tail end. If ever I find any Wuchereria or malayi blood film from Nicos, then I will bring it as well. But most of them, I have seen the record of the Nicos for last five years. They mostly send either to Loa loa or Loa loa for malaria. Did you get Loa loa this time? This time it was Loa loa. Mmm. They will ask, report the blood film. What would you say? How to formulate a report for the exam? Yeah, say something. Depending upon the morphology of RBC, there could be anemia or it could be unremarkable. Start with the eosinophilia. Usually they have eosinophilia. So the blood film contains eosinophilia and sheath, sheath worms. Do we have to mention the morphology of these worms as well? Yes, you have to say that, uh, the blood film contains eosinophilia and, and sheath worms. The, uh, worm has nuclei extended to the tail end. Most likely it resembles to Loa loa, which needs to be confirmed by sending the blood sample to the reference lab. So then they, then they usually ask the next question about, uh, investigations. Investigation, we always say send to the reference lab to confirm the diagnosis. And third question is, what are the treatment options? So Loa loa, we usually give them I think Diethylcarbamazine or Bendazole, if I'm not wrong. Diethylcarbamazine and, um, don't try T-worm in the exam. One of the candidates in the mention T-worm. So the next one is a 36-year-old female with headache and agitation. So this is the power 10. Let's go to power 15. Do you have Asma or SA on the line? Dr. I'm, I'm online right now. I think either you or Asma asked for parasite P. Yeah, are you the one living in Halifax? Yes, sir. I'm, I'm in Halifax. I'm not sir. And just you can comment on this blood film. Okay, this patient is from, uh, Northern Africa, and he has headache and agitation. This is the blood film. Uh, in this film here is the, that means some Dr on that on the on the RBCs. Mmm. The, the R formation and the, yeah, the [Music] prominent platelet count. The platelet count is unremarkable. It's, and but the size is like platelet count size is increased. And, uh, what is this? Is there some worm? Look like some, is there any traveling history in this patient? Yes, this patient arrived from Northern Africa yesterday. So is the, is the, um, protozoal parasites? Why they curl up? Show us some straight one. Okay, then I have to start. Yes, because this is curled up, so it gives, uh, impression of, uh, yeah, these are all curled up. The tail is hugging the face. Ah, this one here, here. This one is a bit. It's a, yeah, it's, it's look like a Trypanosoma. Trypanosoma. Is so, it's a nucleus is in the body of the, um, one. Should I describe in more detail? No, they do not expect much description from you. If you have identified that there is Trypanosoma, that is, and there's no need to mention that there is the nucleus and the pointed head and pointed tail. No, but you should know from the geographical distribution whether it is T. cruzi or T. brucei. Because one type of Trypanosoma exists in South America which causes Chagas disease, and another type of Trypanosoma exists in Africa which causes African sleeping sickness. This sleeping sickness has two stages. This one on morphology is cruzi. Right. Brucei is in the, um, no, I'm talking about morphology only. This one is cruzi. Why it is cruzi? Because I just recently received, um, uh, PT proficiency testing, and then they defined that if you have very prominent kinetoplast and small size, that is cruzi. If your kinetoplast is very small, smaller than this, and larger in the size, that is brucei. But he said that the patient is from African like, so and we have to memorize geographically. So cruzi is more common towards the North American, usually in the, um, C for cruzi, C for Chagas disease, which is in South America. American. This, this is NAIKA slide. What was their answer? Cruzi or brucei? Brucei. Very strange. More better. Um, would you move the slide towards those abnormally curled up parasites so that in case parasites, the initially the you should, initially, yeah, this film has a lot of Trypanosoma. Yeah, this is a bit curled. But in the exam, you have to struggle. Remember that because in our exam, our blood smear has only one parasite, one Loa loa, and we have to search for that for 2 minutes. This one with the curled one, you can take this. This is not much. And these two, this is a bit curled as well. Dr. Mara, what difference you have told that in brucei the kinetoplast is small in size? The parasite in cruzi is smaller than the brucei. The whole size of the parasite, and the kinetoplast which is present anteriorly is smaller. It's like a dot. And cruzi has very prominent kinetoplast. This parasite, it has very prominent kinetoplast. That's why I thought in the size because recently I received from CAP, and it was the brucei was bigger with very dot type of kinetoplast. This I reported it as cruzi. This one, and their answer was also cruzi. Okay, I will move this slide. So this is another patient with abdominal discomfort. Went to GP due to abdominal pain, and he took some blood from the patient and sent it to our lab. The BMS called you because he saw some abnormal cells in the blood film. This is power 10. I go to power 50. So this is the first. Then what is the age of the patient? Age is 48. There is lympho, something else. Can you go on higher? Because some cells also were giving impression of eccentric nucleus, nucleus, and are the hairy cells because cytoplasmic projection is all around. Yeah, it's a cytoplasm is quite like adequate and a granular light blue. Can you show some more? Yes, I'll go towards that side because these cells are mostly on the thicker side. This one looks like kidney-shaped nuclei and a nucleus and abundant cytoplasm, more like hairy. [Music] Is, is there any possibility that it could be a T-cell? Not sure. But T-cell? Sorry, I'm not sure. I'm just, uh, GP has very high white cell count. Okay, and and they have basophilic cytoplasm, mature nucleus, and prominent projections bigger than these projections. Okay, see if I can find some more. What is WBC? This looks like typical. What is the WBC count? Three. Is there any spleen in the patient? Any spleen? Yes, he has 22 cm. Very typical of hairy cell leukemia. Classical. So now the question is, report the blood film. How would you report the blood? So basically, it shows, uh, lymphocytes. There is a lymphocyte, uh, prominent, uh, lymphocytosis which are, uh, small to medium size with abundant basophilic cytoplasm showing, uh, circumferential, uh, cytoplasmic projection. A granular nucleus, uh, chromatin is slightly clumped, and there's no nucleolus seen. And, uh, few, uh, cells have had a kidney-shaped nucleus. Um, RBC morphology seems to be unremarkable, and platelet count seems to be slightly decreased. So in presence of splenomegaly, and, uh, low cell count, presence of cells with the circumferential hairy projection, my, uh, suspicion is of hairy cell leukemia, and I will confirm my diagnosis by flow cytometry and B mutation or, um, on immunohistochemistry. I can confirm by TRAP positivity and B proteins. PR is not done here. Remember this, this blood film was from GP. You have to, uh, address something to the GP as well. You mentioned that this patient has, uh, abnormal white cells with hairy projection that you think that can be because of the leukemia. Yeah, you need to confirm that on flow cytometry and invasive investigations like biopsy. Please refer the patient. Refer the patient to hematology, P.Y. clinic urgently for further investigation and [Music] treatment. Then, uh, they may ask you, what is the typical, what flow you expect in this condition? Okay, since it is a classical hairy cell leukemia, I would expect all B-cell markers, CD20, 22, 19 with the positive, CD25, 11c, 123, 103, um, Cyclin D1 can be positive, but not bright expression, and CD200 can be positive. And then, the next question can be that this patient has symptomatic splenomegaly which is affecting his quality of life. Mmm. What are your management options for this? So if it's symptomatic spleen, uh, if the patient has no symptoms, we can wait and watch. In this case, but in this case, the patient has symptomatic splenomegaly, so we will give, and and if I'm your, if I'm your examiner and I ask you that this patient has symptomatic spleen, what is your management option? Do not say that if this patient had no symptoms, then I would not give any treatment. Okay, then we can, I have, because I have already told you that this patient is symptomatic. So we were told that this thing annoys the examiner to not to give statements which are not relevant to the scenario. Examiner has already told you that this patient is symptomatic. So to start from symptomatic. Okay, so in this case, I would go for purine analogues. Cladribine is a drug of choice with or without rituximab. It depends upon the local guidelines or local treatment protocol. Pentostatin is another, that's it. It's enough with, uh, irradiated blood if required. Irradiated blood if required, and prophylaxis along with the chemotherapy. Along. Yes, chemotherapy. The next question can be, how would you monitor the disease, the treatment response? Okay, so the treatment response is, may after 6 months of therapy, and mainly depends upon the clinical symptoms, size of spleen, four to six months. Normally, two to six months. So if this patient relapses, let's say after a year, do you have any options for this patient? Then we can go for, uh, other purine analogue, pentostatin, rituximab. Or if initially he had good response, we can again try cladribine. But since the relapse, he relapsed within a year, so it's better to switch to another purine analogue. I mentioned. If there is a tri-open restaging, I will MDT discussion. Try inhibitors. MO is not used in HCL now because of the problem of capillary leak syndrome. Okay, drop blood pressure significantly. Still, it's not NICE approved. NP22? No, no. It's not yet the same complication we are seeing with, um, anti-CD123 or, uh, BPCDN. Yeah, BPCDN. So the same side effect with that with the capillary leak syndrome. You are saying? Yes. So the patient on OAS for BPCDN, they dropped their albumin and, um, blood pressure point significantly. We have to monitor their albumin, we have to give them albumin, and we have to monitor their blood pressure as well. So this is the last case. This is a 33-year-old patient referred to hematology because of a big mass in the left inguinal area. And the CT scan shows that this is a lymphoid mass. And he has stage four lymphoma. This is a lymphoid mass. There is no other lymphadenopathy, but this is the only big mass in his left inguinal area. The full blood count shows high white cell count, and the blood film is in front of you. Patient has significant constitutional symptoms. This is power 10. Just an overview. At power 50, put some more. Yes, Shaheen, um, you can comment on them on these cells. Yeah, blood film shows, uh, increased white cell count, and these cells are medium size with the basophilic cytoplasm containing vacuolations. Yeah, these are the very basophilic cytoplasm. Yeah, basophilic cytoplasm with vacuolations. Nucleus is, uh, round and open chromatin, while the red cells are showing hypochromic and isocytosis. Same. So what is your impression? Um, I think with abdominal mass and these type of cells, I would think of Burkitt lymphoma. Mmm. So how would you like to report for the exam purpose? Yeah, this slide shows the increased number of abnormal lymphoid cells, and these cells are medium size, uh, with the basophilic cytoplasm and vacuolations. Nucleus is, uh, round and open chromatin, while the red cells are like bit hypochromic and otherwise, U, and platelets reduced. Very bizarre looking. And this is apoptosis or this is multi? Yeah, there are some cells which are dying. A lot of mitotic activity. Is mitotic activity? Yes, because this is high grade. Because it's a high-grade tumor. But its mitotic activity in peripheral blood smear to this extent, I've never seen. Yes, it's unlikely to find these sort of these, uh, disintegrating cells and the mitotic cells in the peripheral blood. This is original [Music] blood, not survived. No, um, sure. Most likely a high-grade lymphoma like Burkitt lymphoma. The patient needs emergent hematology involvement in this patient, and initiation of the treatment. What flow markers do you expect in this condition? But flow markers, um, it is BCL2 negative, BCL6 positive, and B-cell markers. You are telling me, uh, immunohistochemistry. I'm asking for flow markers only. Flow markers, CD5 negative, 10 positive, and 20 as well, positive. Yes, 19 positive, 20 positive, 22. 43 is also, I don't know. I remember always the 43 is positive in in, uh, this. 81 is usually positive in Burkitt. I think it is a marker of, uh, proliferation. Yes, 81. Yes, yes. And 38 as well is a marker of proliferation along with plasma. I think K67, but this is only immunohistochemistry, but it's very high on more than 99. Yes. And the translocations 8:14, 8:2, and 8:22. So how would you manage? We have, you have been given an open question. How would you manage? First is the, uh, TLS prophylaxis and monitoring for the electrolytes, hydration, and then planning for the chemotherapy. Chemotherapy is R-CHOP, M-IAC, but first it's the prophylaxis, TLS, electrolyte monitoring, TLS prophylaxis, and hydration in TLS, monitoring of electrolyte, IV fluids, 3 liters, and UO charting, IV fluids. So such questions can come in long cases as well, like we have a question of plasmolymphocytic dyscrasia in the long question, and APML in the long question as well, and they ask us all about management stuff, like how would you explain prognosis to the patient, what, uh, investigations you would do, and what are the treatment options, follow-up. So when they ask you about management, then management does not mean that you will stop chemotherapy directly. You have to do breaking bad news first. If the patient is under some other team or in the ED, you have to admit under hematology. Breaking bad news, explain the diagnosis, prognosis, and chemotherapy option for the patient because the patient may refuse to have chemotherapy, or his performance status is not well, and he's not fit for aggressive chemotherapy. Assessment of patient performance status for ability. All these things that you do in your practical life in a hospital, you have to mention all of the things in bullet points. And yes, you have to urgently start the treatment. Aggressive, like, uh, prophylaxis, uh, if you're not planning any further biopsy, then steroid to reduce the mass size because if this is a big mass, it may be compressing the artery, veins, or not. And then R-CHOP or, uh, OKE is an alternative regimen. If they are not fit for both of them, then we have a less intensive, a bit hyper-CVAD regimen. If they are not fit for that, then you can give more less intensive therapy. But this Burkitt for response to chemotherapy very quickly. That must usually reduces very quickly. So most people still in exam not because they don't know, but because they do not write the answer in a way they want. You may be knowing a lot, but if you do not write them in a sequence that you usually do in your practical life, they will fail you, and you may have in a lot of examples like that. Oh, so if they ask you how would you manage, you always start with admission. And the patient is not admitted, with breaking bad news, informed consent, explanation of the disease, chemotherapy, radiotherapy if required. Radiotherapy not usually used in Burkitt lymphoma, but for general lymphoma case. And then this is emergency. But other patients who can wait, you discuss in the MDT, and, uh, you know about the patient's performance status and comorbidities as well, and then you plan the chemotherapy. And, okay, you have given the patient chemotherapy, but this patient has to be followed in the community as well. You make a discharge letter, inform the GP, give them a CNS contact number, and follow them up in the clinic as well. Then it completes your full management plan. If it is a 10 marks question in a long case, you will get eight marks. If it is a W question, usually they give you hints, but sometimes they may not give you hints. They only want to listen to you or complete answer. So if you miss some of the points, then they may deduct marks from you. Okay, thank you. Okay.