Transcription
Hello everyone. Can you hear me?
>> Yeah, we can hear you clearly. [Music] So this is the first case. So a 60-year-old man who was referred by his GP due to leukocytosis. The white cell count is 17. The hemoglobin and other terms are normal. So this is the power 10. 50. Any comment on anyone? What are these cells and and how the blood?
>> LG.
>> How did you identify?
>> Um, the lymphocytes are a little bit larger and with clear cytoplasm and some having a few granules. Mhm.
>> How would you determine the clonality in sex?
>> These are receptor arrangements. Just and is there any association of these?
>> It's usually associated with autoimmune diseases.
>> All right. So, how will you report this blood center?
>> Uh uh, if I go by cell line by cell line. So uh red cells, most of the red cells are normochromic, normocytic. Uh platelets adequate in number and morphology. White cells uh, leukocytosis with absolute lymphocytosis. Lymphocytes are large lymphocytes with abundant cytoplasm with granules. uh I haven't seen any blasts and uh altogether if I conclude this um, the lymphocytosis is could be due to a chronic lymphocytic lymphoma like a chronic lymphoproliferative disease. Uh I would suggest further investigations including flow cytometry um and genetic rearrangements of T-cell receptors and uh to look for underlying autoimmune disease.
>> You mentioned this is leukemia like CLL.
>> Sorry, not CLL, chronic lymphoproliferative disorder. Mhm. Okay. So the lymphocyte count is high. So when you are reporting it, uh comment on the lymphocyte count first.
>> Mhm.
>> Yeah.
>> And then come to the normal cell lines or the other cell line like RBC and the platelets. Your impression is that this is uh lymphoproliferative disorder and then you have suggested that you do flow cytometry in this patient to confirm the clonality of this case. Okay. So this turned out to be LGL, the uh clonality is positive.
>> Mhm. Uh, how would you approach the treatment in this patient?
>> Uh, immunosuppression is the mainstay of treatment for these patients. So we can consider about um, MTX or cyclosporine. Patient hemoglobin is normal, is normal, white cell count is just 17. Still you will give him cycl.
>> No, first of all, we want to see whether there are treatment indications. If patient does not have any underlying autoimmune diseases which is troublesome at the moment, I think I would continue to monitor the patient.
>> If the patient is asymptomatic and there are no certain opinions, then then usually you just monitor him. uh if the patient is symptomatic or with cytopenias, yes, then you have immunosuppression.
>> Mhm.
>> As the uh treatment of low.
>> Methotrexate.
>> Yes. What is the mutation involved in this case?
>> STAT5, 305. They will always ask what are the associated conditions uh with this. You have to mention the autoimmune disease, especially the rheumatoid arthritis, sometimes as well. They are associated with degree.
Now, this is a 90-year-old patient who presented to A&E and a bit unwell. His hemoglobin is 101, the white cell count is 62, and the platelet count is 98. This is the power 10. Now I will go to power 15. Any comments on this 90-year-old patient? Anyone who and photo. Russia, can you tell us what's going on here? Yes. Ha. Your hand is up.
>> Sorry. Yes.
>> Yeah. Uh, actually I'm I'm I'm not sure about the finding because uh I see um immature monocytes but uh I cannot appreciate them like promonocytes. Uh the patient has also thrombocytopenia. Uh I I see a leukoplastic picture, left shift, and uh I have noticed the single nucleated RBC. So I cannot preach you the definition of these are.
>> Sorry, mon.
>> You have to tell me. Okay. Can I comment?
>> Yes.
>> So, um, you want me to report the film?
>> Yeah.
>> So, the red cells, um, I think they look unremarkable. Um, I don't know whether this is focuses or not, the one in the middle, but the overall picture looks unremarkable. Platelets, there is true thrombocytopenia. White cells, there is.
>> On the affected line first, please.
>> Yeah. Okay. White cells, there is monomorphic cells with with increased nuclear cytoplasmic ratio. There is cytoplasmic vacuolations, um, slightly open chromatin, and there is granulation. So there is our blast for differential, I need a flow. It could be the patient is anemic, he's 90 something with thrombocytopenia. It could be um, dendritic cells, could be, could they are medium to large size, could be diffuse large, could be a differential of a blast with vacuolation, could be Burkitt, could be ALL.
>> But these blasts have some of them have granules.
>> Yeah. As you granulation. Yeah.
>> So, can it be lymphoma then? If there are granules?
>> It's it's usually myeloid in origin if there is there is granulation.
>> Yeah. So some of the blasts have granules. Some of the blasts look like monocytes, promonocytic like these ones.
>> So it will favor more leukemia than.
>> You can't tell whether without flow.
>> Okay. So you will, how will you report it? This blood film contains cells and sorry, blood contains multiple blasts.
>> So monomorphic cells, medium, medium to uh, medium size, increased nuclear cytoplasmic ratio, cytoplasmic vacuolations with granulations.
>> Mhm.
>> Need urgently to be, need urgent urgent flow to be sent for analysis. Okay. And what else will you advise?
>> So the patient is anemic, 101, I think, and plate is 91. He needs to be admitted uh under hematology care and then need assessment, any bleeding, any fever, of course, and to see how the patient is he's doing, is he's having hemodynamically stable, anything.
>> Okay.
>> And then treat accordingly.
>> Right. So this is myelomonocytic leukemia. All right. Uh, you can see multiple blasts. Some of them have granules, some of them have uh, some of them are promonocytic. Uh, they have a lot of vacuolation with bluish cytoplasm. This is then red cells. They are not okay. They have hypochromia. There are scyes. There are teardrop cells. There are some schistocytes as well. So you have to comment on all everything that is present in the cell line because the examiner when they are marking your morphology paper, they will have all the comments mentioned on the key. If you have not mentioned schistocytes or teardrop in your answer, they will deduct marks from you. Yes, this patient is thrombocytopenic as well. You have to mention that your impression is acute leukemia. This is enough to differentiate whether this is this is leukemia or biphenotypic. It will be on the flow. Most of the time we think that this is AML, it comes out to be AML on flow. Sometimes we think that this is AML, it comes out to be ALL on the flow. So saying this is acute leukemia is enough. Then yes, we have to do, we have to send urgent peripheral blood to uh for flow cytometry to admit under hematology and assessment and uh to discuss bone marrow biopsy with the patient. Okay. So he has acute myeloid acute myelomonocytic leukemia on the flow and bone marrow. What next? What is the next step?
>> Stratification.
>> How you do that?
>> So you send various cytogenetics and molecular markers. But of course, this patient is 90 years old. So whether or not there is uh, whether he's even fit for treatment and evaluation of patient's performance status and comorbidities. Yes, because um, when I discussed this with my uh registrars, everyone starts saying, uh, we will give him fludarabine, we will give him IDAR, we will um, find out what his cytogenetics, categorize him intermediate, standard or worse category. Yes, he has AML, but he is 90 years old. He is not fit for IDAR or fludarabine or even not fit for when at 90 age with with multiple comorbidities, I will palliative him. This is important as well to look at the patient's age, comorbidities, and then answer in the exam that yes, whatever you say will be correct, but it will not fit this particular patient which is in your exam scenario. So always tailor your answer according to the scenario given there. Yes, if if this patient was uh 40 years old, then I would have uh decided whether I should give IDAR or either this patient's cytogenetics were 69, worse category, but because of his age and comorbidities, we didn't give him anything. We just palliated him, and he died.
This is another case. He is 52 years old and presented with confusion. The family member says that he had night sweats since a week. He has lost weight and he has a visible lump in the axilla and in the neck area. So this is power 10 of this patient. Now we will go to power. It's going to find the correct cells for you that you can comment from there. And this another I can make. We go back to 50 and see some more cells. It's the same.
>> So, can I tell?
>> Yes. So first of all for RBCs, this microcytic hypochromic, polychromasia is there. Band cells can be seen and RBC count is less. Atypical lymphocytes and trying to maximize the cells for because these are the abnormal cells that we are seeing here. Nucleated RBC.
>> This one. This one is not obviously. This is bigger than. Go on, continue with your report. The immature uh red white blood cells can be seen. Band cells.
>> Mhm.
>> So compare the size of this this cell with these cells. This is not an obvious. This is something else. So I will make it 100. This one. Then you can continue your.
>> Yes. Now go on.
>> Um, microcytic hypochromic polychromasia is there in RBCs. RBC count is less and uh, we can see um, immature lymphocytes and band cells.
>> Mhm. So chromatin, there is open chromatin can be seen.
>> Mhm. Then size is uh, greater than the normal. So what do you think this patient has? Confusion? He has night sweats, weight loss, lump in the uh, neck and in the axilla. Um, this is the blood film. What do you think?
>> Probably we can go for lymphoma if we consider it with the symptoms.
>> Yes. Lymphoma. What type of lymphoma do you?
>> Say? Sorry, I can't hear you. What type of lymphoma do you think this patient has?
>> Looking at these cells? Anyone else? Find some another cell phone. This is power 100 of this set. Is there? What do you think? Sorry, it's lymphoma.
>> Lymphoma.
>> Yes, this is this is lymphoma because the patient has B symptoms. But I I want a report and I want to know what type of lymphoma is this. This is a low-grade lymphoma, high-grade lymphoma. And this is the example of cells in front of.
>> Yeah. Hello.
>> Yes. Mayo. Yeah. So, so these are mononucleated cells with increased nucleiocytoplasmic ratio with some having more than three to four nuclei. This looks like um, I will say aggressive lymphoma and my thinking with this one will be maybe a blastoid mantle.
>> Um, anyone else has a different opinion about this? So it can be low grade because band cells can be seen.
>> Which low grade? What do you what is any low?
>> These cells have cleaved nucleus. Maybe follicular lymphoma. Informational cells are very small to the size of RBC or more a little bit bigger than this.
>> Amir, does he have any skin lesion?
>> Any skin lesion?
>> Skin lesion?
>> No. Let's describe this lymphocyte. What do you think the color of cytoplasm is? Basophilic.
>> It's basophilic. Basophilic cytoplasm, large cell with nuclei. This one has one prominent nucleus and looks like this one as well. Um, so there are two differentials for such.
>> Uh, PNL.
>> Either either it can be large B cells or it can be Burkitt. Burkitt has a blue cytoplasm like this or it contains a lot of or it can be large B cell lymphoma. This patient has confusion. This patient has B symptoms. And this patient has large um atypical lymphocytes with multiple nuclei.
>> So large B cell lymphoma.
>> Yeah, this is large B cell lymphoma. Patient is currently inpatient with us receiving chemotherapy, R-CHOP, because his disease is mainly in the CNS and um, he has a systemic disease as well as CNS disease. So please see the blood film for Burkitt lymphoma and large B cell lymphoma. It must be present in your lab and it must be present in the Nicas slide as well. Uh, it is rare to see high-grade lymphoma in in blood, but when it involves the bone marrow, it can appear in the blood as well. Mhm. Burkitt lymphoma can uh, cells can appear in the blood. Diffuse large B cell lymphoma can appear in the blood as well. They are cells are very basophilic like these ones. The Burkitt lymphoma cells uh, they have uh, they have a lot of vacuolation and the Burkitt lymphoma usually presents with localized mass, either a mass on the jaw, either a mass in the groin area, or in the abdominal, anyway, but a single mass. And diffuse large B cell lymphoma has a lot of lymphadenopathy everywhere in the body. Okay. So this is this was diffuse, not Burkitt.
Another case which was referred to us by a GP because a patient was down were high on routine blood test. This is the power 10. Just to show you slide over. Now we will go to 450. From what you have seen multiple cells, what do you think is going on here? Yes. Go on.
>> Asalamikum sir.
>> Uh, can I speak? Can I tell you?
>> Yeah.
>> Um, yeah. It's a platelet satellitism is going on here around the atypical lymphocytes.
>> Mhm.
>> These these lymphocytes are small to medium in size, high NC ratio with clumped chromatin and um not prominent nuclei. um platelet seems um adequate with platelet satellitism around the atypical lymphocytes and RBCs are and isocytosis.
>> Uh, so uh, these findings are suggestive for lymphoproliferative disorder, most likely mantle cell lymphoma.
>> What is this? Uh, because this set.
>> This one. This may be debris.
>> This much. This is another. Did you mention this in your report? And when this slide was discussed in the part two group, I think no one commented on the platelet satellitism.
>> Platelet satellitism. Um, I mentioned it. I think I have written this. Yes. Whatever you see in the blood film, you have to mention. You have seen smudge cells, you have to mention that you have seen platelet satellitism, you have to mention.
>> Or we see here, they have a lot of different shapes and topology.
>> These are this trop microcyte. Yeah, on every everything. So you think this is mantle cell lymphoma? Why you?
>> It is for proliferative uh disorder um um but we have to investigate further for immunophenotyping, lymph node biopsy, and FISH analysis. uh the more um uh most likely is mantle. I'm saying because satellitism is most looking around the um um mantle cell lymphoma uh it is associated with mantle cell lymphoma.
>> It can happen in any lymphoma.
>> Is there any specific reason? Is there any specific reason? Mantle because.
>> Yeah, because of specific reason.
>> Is there any specific reason mantle lymphoma would lead to platelet satellitism? I don't know about that reason. Satellitism is basically because of EDTA clumping actually. But here in the morphology, it's most is um mantle because of it's medium, it's not too much small cells, it's medium size cells and uh and there is um of course high NC ratio, but it's not CLL type, it's not the uh follicular type because follicular type is like cleaved nucleus and CLL is very small like uh lymphocy. So it's morphology is more likely to mantle cell.
>> Okay. So you will always say that this is lymphoproliferative disorder, low grade. If they give you any clues, then you can distinguish whether this is um CLL or mantle cell because if you see the new guidelines of mantle cell lymphoma, mantle cell has many different types and one of the type is small cell variant as well. I think if I am not wrong, it has blastoid variant, small cell variant, I think the vegetative variant or marginal variant, something like that, but they have described the guideline have described five different types. So it can be ready.
>> Yes.
>> So they say it is a classic phenotype and blastoid small cell variant, blastoid variant, marginal variant, something like that. It has different variants in the new 2024 guidelines. So you always rely on the clues. Um, yes, these are medium size cells. They are not large. They are not small. And this is a classic phenotype of the mantle cell where the nuclear material is a bit square shaped. That's how I identify the um classic mantle cell of the blood, but it's it's difficult to actually identify what type it is. If if you have a clue, then yes, you can identify. So what flow cytometry do you expect in this patient?
>> Sorry, Dr. Amir, could you please repeat what is the characteristic morphology of mic?
>> The mantle cell has different subtypes, morphological subtypes. It can be small cell variant. It can be marginal zone variant. It can be classic phenotype. It can be blastoid variant as well. The classic phenotype which I recognize is you can see these nuclear material, nucleus, they have a square shape, but whenever I see them under the microscope, I do not say that this is mantle cell lymphoma. I always ask for the clues to confirm that because mantle cell lymphoma is very dodgy lymphoma under the microscope. And and you never make any diagnosis on the blood film. You always uh look at the flow. As I mentioned in the first case, sorry, in the second case, that sometimes we think that this film is ALL, it comes out to be AML. Sometimes we think that this film is AML, it comes out to be ALL on flow. So you never make diagnosis on based on the blood film. Blood film, you always need something else to confirm your diagnosis. But it does not mean that that if you have seen bilobed cells, um, you wait for the diagnosis. If you have seen basophilic cells, you have to give.
>> But then treatment.
>> And then PML-RARA takes only 1 hour in in our hospital. It tells us whether this patient has positive PML-RARA stain or negative PML stain, and we take it from there. Okay. So whatever you see in the blood film, it is uh, you have to write that in your paper. Some people in the YouTube commented that this is mantle. This is not mantle.
This is another patient. Something has happened to the camera. So this is another 60-year-old man who was referred to hematology because of leukocytosis. This is power 10. Yes, from far it's like leukocytosis, lymphocytosis, and so many smudge cells. So it's maybe leading to CLL, but we will see closer.
And now this is power. Do you think these cells are different from the previous slide cells?
>> Yes. Oh.
>> So um, that cells are um, like um, these are small cells also, small lymphocytes and slightly big also, like prominent nuclei. uh, but that cells are medium in size and all cells are mononuclear type, means monotonous population, not small and big like same population, and that cells are um, high NC ratio. Here the two populations are very small lymphocytes and slightly big like prolymph type with prominent nuclei and with cytoplasm also, and the other one is not like that. So that's the difference for me, I think. And there is here is too many smudge cells and there is no smudge cells on that.
>> There were smudge cells.
>> Uh, very um, very few. Right. Here is too many.
>> Yeah. So smudge does not always mean that it will be CLL. They can be present in follicular. They can be present in mantle. These are just burst out uh, lymphocytes during preparation. They can be present anywhere. But these cells, these cells are very mature looking, small, smaller than the previous cells. Their nuclear material is more mature than the previous cells. And yes, they have another population of cells as well, which are called prolymphocytes. And even some of them have the size of the red cell as well. This nucleus and this uh, red cell are very slow. And what do we expect in this patient? Is he transforming?
>> Transformation to.
>> So it looks like he was a CLL transforming into diffuse large.
>> How do you.
>> Say that this patient is transforming to diffuse large.
>> Or or Burkitt? I'm not sure.
>> No, CLL does not transform into Burkitt. Never. It has never happened before that CLL goes into Burkitt. Yes, it can go into Richter transformation or Richter transformation, which is DLBCL, Diffuse Large B Cell Lymphoma, or large B cell lymphoma. But these cells are not diffuse large B cell lymphoma. Like diffuse large B cell lymphoma or large B cell lymphoma cells are very big cells and they have typical morphology which we have seen in the Case number three. There are large cells with deeply basophilic cytoplasm and sometimes contain one or two vacuoles and multiple.
>> So what history or what blood? We didn't get any of his blood. You just only say that his white cells is high.
>> Yes. So here in UK, we have annual blood tests with the GP and those blood results are then processed in the hospitals. If the white cell count or any parameter of the full blood count is abnormal, a blood film is made. So this patient has routine blood standard GP and then when the GP saw that this white cell count is high, then he referred the patient to us. His white cell count looks like to be 80 or 90 like that, but he is asymptomatic. He has normal hemoglobin, he has normal platelets, he has no B symptoms, he has no megalia. He just needs. If he had B symptoms or cytopenias, then yes, we would have discussed treatment with him. And if he was transforming to uh, DLBCL, he would have B symptoms, he would have lymphadenopathy everywhere in the body, cervical, axillary, groin lymphadenopathy. So that's why it's less likely that he is converting to DLBCL. These cells, these are prolymphocytes, very prominent. These are prolymphocytes, which is a part of the uh, CLL. If they are more than 15%, we say that this patient has CLL with prolymphocytic progression. If these cells are more than 55%, then we say that this patient has transformed into another category which is called SLL-PL, Splenic Lymphoma Leukemia with Prominent Endothelial according to WHO 2022 criteria, which we follow here in.
>> Will we have in the exam just a blood film to report or would we need a flow in order to know that the suspected diagnosis?
>> They will only tell you that this patient has uh, blood test done at GP and the GP has referred the patient to you with lymphocytosis. Please comment on the blood film or report the blood film. So you will report this blood film and then the next question will be, what is the expected flow cytometry in this patient? So I assume you would have made a diagnosis by seeing this. This patient has mature lymphocytosis, lot of smudge cells. This is most likely um, chronic lymphocytic leukemia. So you will write the flow cytometry, expected flow cytometry for the patient. Then they will ask you, what um, what are the treatment options for this patient? Then you will say, if symptomatic, then another column, non-symptomatic. If symptomatic, then you would see the TP53 status of the patient, comorbidities, and performance status and decide whether you want to give continuous therapy or fixed duration therapy. And if the patient is asymptomatic, then he needs monitoring. In some of the cases, they may give you flow cytometry as well. This uh, the patient presented us with B symptoms. He had a lymph node biopsy and uh, the flow markers are here. He has a blood film done as well because of cytopenia. Please comment on the blood film. What is the diagnosis? Because they have given you the clues and then they will ask you, what is the treatment for this patient? Cuz it is a 10-mark question. Four to five marks are for the reporting, and another two to three marks for the other two questions. The total mark for a short case is 10, and you have 9 minutes to see the blood film and to write the answers for each slide. Thank you.
It can be aspirate, it can be trephine, and less likely that they will give you lymph node biopsy or CSF or pleural fluid. I haven't heard about that that they have given such thing in exam. This is the last. And if you are working in UK or if you are not working in UK and you are going for the exam, ask your hemato-pathologist consultants or HDS or HODS consultants here in UK to arrange exam-related slides for you. In UK, you receive the NIA slides as well. They have a lot of findings, especially the slides of September, which was CDA in the blood film. You must see them. These things appear in the exam as well.
So this is the last case. Again, a 70-year-old patient um presented to ED because of healing. And this is the blood. This is power 10. Oh. So, what do you think is going on here? Has been.
>> There.
>> Sorry.
>> Is there any basophilia in the CBC?
>> I have no CBC in hand. I have only blood film with me. Patient has marked leukocytosis, total leukocytosis with a left shift up to myelocytes. There is marked also.
>> Some YouTubers show these plastic features. Why this uh RB uh to some um anisocytosis, some macrocytes, some normocytes. Platelets are decreased. There is thrombocytopenia. Does he have infection?
>> No.
>> No infection. So, most likely uh uh MPN picture of MPN.
>> Mhm. Hold on. So I will ask for BCR-ABL and.
>> Translocation is negative.
>> Can I add please?
>> Mhm. For me, it's a CMML, myeloproliferative type subtype uh, because his WBC count is very high, elderly age, and splenomegaly, so many monocytes with dysplastic features and so most likely CMML. We'll go for further uh, bone marrow and phenotyping, then cytogenetics, basically cytogenetic abnormalities and molecular for confirmation.
>> Why do you think it is?
>> Sorry.
>> Why do you think this is CMML?
>> Because of monocytes um, prominent monocytes with dysplastic features and uh, if monocytes is more than uh, one, then and with dysplastic features is more than 10%, then we can consider the uh, CMML. And of course, it's a left shift, myeloproliferative. I said myeloproliferative type because of his WBC count is seems more than 13.
>> One or two.
>> Um, uh, we will uh, do the blast count. If it is, it's peripheral blood less than 5%, it seems less than 5%. So I will say M1 type. But if it is 5 to 19, then we can go for this M uh, CMML 2. So I hardly see any blast here, one maybe. So it seems CMML 1. Okay. Yes, this is was this is myeloproliferative type of CML and category one there. We don't have CML zero now because it has been removed by WHO 2022.
>> All right. What prognostic score do we use in CMML?
>> Uh, CPSS score. Uh, something molecular. CPSS. CPS has small. What treatment can they give this gentleman? So I will see first the counts. If need the supportive care of um, any blood products or erythropoietin or something, then of course, this is myeloproliferative, so we can start hydroxycarbamide for leukocytosis and of course, he has splenomegaly also and um, hypomethylating agent like azacitidine. And if uh, if fit, we will see if the patient is fit, we can consider allogeneic stem cell transplant or any clinical trials.
>> Yes, his count is very high. You can reduce the count with hydroxycarbamide and asetidine is nicer to patients. So if the MD agrees, then you can give asetidine as well. But the important thing is to look for transplant. If patient is fit and agrees and donor, will transplant after controlling the.
Last case. We will have a pathology session next month again because it's now only one summer. The other Sundays are for two sessions. So somebody has.
>> Put something in the chat. Atypical lymphocytes, square shape. Can chronic inflammation lead to this? Chronic inflammation would not lead to this much of cells. They are very, very high count. The cell count in the CMML patients were 180. So it's unlikely that infection would lead to this much of uh, uh, myeloid leukocytosis. So take care everyone.