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Morphology Online Session: DLBCL, LGL, CMML, MCL, CLL and AML(Myelomonocytic)

Haematology, Morphology and FRCPath Exams1:13:52

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 leucocytosis. The white cell count is 17. The hemoglobin abducted terms are normal. So this is the power 10. 50. Any come in on anyone. What are these cells and and how the blood >> LG >> How did you identify? >> Um the lymphocytes are little bit larger and with clear cytoplasm and some having a few granules. Mhm. >> How would you determine the tonality 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 leucocytosis with absolute lymphocytosis. Lymphocytes are a large lymphocytes with abundant cytoplasm with granules. uh I haven't seen any blast 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 flowcytometry 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 kidneys. Your impression is that this is uh lymphoproliferative disorder and then you have suggested that you do flowcytometry in this patient to confirm the clonality of this case. Okay. So this turn out to be LGL the uh clonality is positive. >> Mhm. uh how would you approach the treatment in this patient? >> Uh immunosuppression is the main stay 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 do methine >> yes what is the nutrition involved in this case >> stat five 305 They will always ask what are the associated conditions uh with this. You have to mention the autoimmune disease especially the motto of orophagia sometime as well. They are associated with degree and Now this is the 90 year old patient who presented to A&E and a bit unwell. His hemoglobin is 100 1 the white cell count is 62 and the plate count is 98. This is the power 10. Now I will go to forward 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 blast has granules. Some of the blast look like monocytes promonocyte like these ones. >> So it will favor more leukemia than >> you can't tell whether without flow. >> Okay. So you will how will you will report it? This blood film contains cells and sorry blood contain multiple blast. >> So monomorphic cells medium medium to uh medium size increase 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 you will 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 first of course and to see how the patient is he's doing is he's hiding 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 granu some of them has 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 steroid 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 all it comes out to be AML on flow. Sometime we think that this is AML it comes out to be ALL on the floor. 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 low 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 performance patients performance status and comorbidities. Yes, because um when I discussed this with my uh registrars, everyone start saying uh we will give him fludarabine, we will give him DA or we will um find out what is his cytogenetics categorize him intermediate, standard or worse category. So yes, he has AML but he is 90 year old. He is not fit for DA 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 age comorbidities and then answer in the in 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 uh given there. Yes. If if this patient was uh 40 year old then I would have uh decided whether I should give DA or either this patient cytogenetics were 69 uh worse category uh but because of his age and comorbidities we didn't give him anything we just validate him and he died This is another case. He is 52 year old and presented with confusion. The family member says that he had night sweats since 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 come in 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 RBC's this microcytic hypochromic uh polychromasia is there band cells can be seen and RBC's count is less atypical lymphocytes and see 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 cell. 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 RBC's 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 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 cell in front of >> Yeah. Hello. >> Yes. Mayo. Yeah. So, so these are mononucleated cells with increased nucleocytoplasmic 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. follicular 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 PLNL >> 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 rituximab 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 nikas slide as well. Uh it is rare to see high-grade lymphoma in in blood but when it involve 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 present 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 adequate with platelet satellitism around the atypical lymphocytes and RBCs are and isopoikilocytosis. >> Uh so uh these findings are suggested for lymphoproliferative disorder uh 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 leuko satellitism >> leuko satellitism um I mentioned it I think I 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 lately 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 for 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 um 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 is most is um mantle because of it's medium uh 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 follicular type because follicular type is like cleaved in it and CLL is very small like lymphocy so it's morphology is more likely to mantle cell >> okay so you will always say that this is lymphoproliferative disorder uh low If they give you any 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 even sorry skyen blastoid and market variants. It has different variants in the new 2024 guideline. 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 clues 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 sometime we think that this film is ALL it comes out to be AML. Sometime 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. Sure. >> But then treatment >> and then PML RARA stain 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. is another patient. Something has happened to the camera. So this is another 60-year-old man who referred to hematology because of leucocytosis. This is power 10. Yes, from far is like leucocytosis, 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 cell? >> 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 population is very small lymphocytes and slightly big like prolymphocyte 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 cell on that. >> There were smudge cells >> uh very um 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 red cell are very slow. And what do we expect in this patient? Is he transformation? >> Transformation to. >> So it looks like he was a CLL transforming into diffuse large B cell lymphoma. >> How do you >> say that this patient is transforming to diffuse large B cell lymphoma >> 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 T-cell DLBCL or large B cell 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 sometime 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 test 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 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 a normal hemoglobin he has normal platelet count he has no B symptoms he has no megaly 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 DLBCL he would have B symptoms he would have lymphadenopathy everywhere in the body cervical axillary groinopathy 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 CLL. If they are more than 15% we say that this patient has CLL with prolymphocytic progression. If these cells are more than 55 cells then we say that this patient has transformed into another category which is called SLL-LPL screening lymphoma leukemia with prominent endocular 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 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 make a diagnosis by seeing this. This patient has mature lymphocytosis lot of smudge cells. This is most likely 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 patient presented us with B symptoms. He had a lymph node biopsy and 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 because 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 H&DS 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 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 leucocytosis token total leucocytosis with the left shift up to myelocytes. There is marked also. >> Some YouTubers show these plastic features. Why this RB uh to some 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 is a CMML is 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 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? And because of monocytes um prominent monocytes with dysplastic features and if monocytes is more than one then and with dysplastic features is more than 10%. Then we can consider the CMML and of course is the left shift myeloproliferative I said myeloproliferative type because of his WBC count is seems more than 13 >> one or two >> um um we will do the blast count if it is it's peripheral blood less than five it seems less than 5% so I will say M1 type but if it is 5 to 19 and then we can go for this M CMML 2 so I hardly see any blast here one maybe so it seems CMML one okay yes this is was this is my projective type of CML and category one there. We don't have CML zero now because it it has been removed by WHO 2022. >> All right. What prognostic score do we use in CM? >> Uh CPSS score molecular CPSS. CPS has score 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 the hydroxycarbamide for leucocytosis and of course he has splenomegaly also and um hypomethylating agent like azacitidine and if fit we will see if the patient is fit we can consider the 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 for 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 apology 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 nephroy leucocytosis. So take care everyone.