Transcription
All right, so today we will discuss five cases again, um, in the form of FC part exam style. I'm sure you all know the cases and diagnosis, but FC part exam needs, uh, something else. Uh, people have paired the, uh, art exam by five marks and one mark. So, uh, it is not only important to know the diagnosis, it's important to answer other questions in the exam as well. Moreover, the part two exam is the first week of October, and anyone amongst you going for that exam, I wish you good luck.
So, this is the first case. This is a GP blood sample, uh, referred to a T hospital for annual review. The full blood count is abnormal. Hemoglobin is 110, white cell count is 92, and platelet count is 150. Now, the film first goes to a biomedical scientist. If anyone from the lab wants to comment on the blood film, sir? The peripheral film, uh, of the patient is showing leukocytosis.
Okay, so this is power 10. I will make it power 50 for you to, to be more clear, and then you can comment on that. Right, on the papers made, the abnormal population is of increased number of mononuclear, abnormal mononuclear cells with moderate, um, uh, which are moderate, medium to large in size with high NC ratio, chromatin, um, uh, finally open chromatin and nucleoli apparent in most of the abnormal cells. And cells are also present, few smudge cells. They are multiple. What about the red cell and the platelet? So, red cells are showing, uh, rouleaux formation, and platelets, uh, that's why no normal cells. Platelets appear normal.
Okay, so what is your impression? Acute leukemia. Okay. Uh, you are a hematologist, or you are the, you know, sir, I'm a lab, lab hematologist. Lab, you have seen the blood film, you have, you have noted leukocytosis with a lot of lymphocytes with clear, with clear cytoplasm, few smudge cells, normocytic RBC, and normal platelets, and you think that this is acute leukemia. All right, okay. And you refer the film to a clinical hematologist because you think this is acute leukemia. Right? Yes. Now, I want a clinical hematologist to report this film for the purpose of FC B exam, please. Six marks for reporting this blood film in the exam. Each short case carries 10 marks. Six marks are for the reporting of blood. Anyone from the clinical hematologist site to report this blood film? Come on, guys. Anyone reported here? You will be fine in the exam, even if it is wrong here, okay? There is no clinical hematologist today with us. Who wants to report the blood film?
So, the blood film shows leukocytosis. There are multiple smudge cells or smear cells. These are the smudged cells which have burst during the smear preparation. This one and this one. The abnormal leukocytes show high nuclear to chromatin ratio, dense, pale chromatin. Few of the lymphocytes show nucleoli which are prolymphocytes. The red blood cells are normocytic, normochromic. Few of the cells show teardrop appearance here, and the platelets are normal here. So, my impression for this case is that, uh, this is most likely a lymphoproliferative disorder, and it needs a flow to be sent to HMDs for, uh, diagnosis. So, small lymphocytes, they are almost the size of RBC, a little bit bigger than RBC, with few smudge cells and some prolymphocytes. Patient is completely normal. This is a general sample from the, uh, annual review sample from the patient.
So, what are the possibilities here? CLL, prolymphocytic leukemia. Okay. So, you think that this is CLL. Okay. What could be the expected flow cytometry for CLL here? The CD5 positive, CD, uh, 2 positive, uh, 11C positive, uh, um, CD5 positive, surface immunoglobulin IGD positive, positive. I'm just taking between 23 and 25. It's 23, 25 is a marker here. Positive CD23. Yes, sir. Okay. Right, sir. CD5 positive, CD23 positive, positive, uh, surface immunoglobulin positive. Surface immunoglobulin is weak here. So, two of the malignancies, you can say CLL and mantle cell, they are CD5 positive and 10 negative. Both of them are CD20 positive because they are B, uh, and CLL is 23 positive, 43 positive, and 200 positive. As previously, we used to use the Moud score, which includes a panel of CLL called CD23, FMC7, surface immunoglobulin, in CD79b and CD5. But nowadays, we do not use Moud score anymore.
All right, so you have got the flow cytometry for CLL. What are the, uh, prognostic mutations in N? Which one is bad? Which one is, um, worse or standard? Hypermutation is good. What about IGVH? Zap-70, IGHV is good, sir. Zap-70 and CD38 are bad. What about Notch? Notch 1, that's good. SF3 is good. Notch 1 is bad. BC3 is bad, and SFB 31 is a bad mutation in the, uh, CLL. If you have deletion 13Q, it is a good. That is good. Yes. 17p is bad. TP53 or 17p is bad. Yeah, they will ask you what are the, uh, prognostic cytogenetics in CLL. You need to mention, uh, IGHV, Notch 1, SF3B1, BC3, and deletion 13.
This patient is completely asymptomatic with the white cell count of 92. Would you treat this patient? Anyone? Would you treat this patient for CLL? His white cell count is 92, but he is not symptomatic. He's good. Good morning. Mornings. Yes, morning. Yeah. So, um, depends on the, uh, like clinical situation of the patient. How old is he? Um, so we don't depend on the CLL on the lymphocytes, like, for example, symptomatic spleen, symptomatic lymphadenopathy, doubling time of lymphocyte count, what else? I mean, other features we need other features to decide upon treatment, not, not only the lymphocytic details. This patient is asymptomatic, and this is an annual, uh, blood review sample from a GP. We show white cell count of 92. Patient is asymptomatic, and he is 50 years old. Okay. Uh, then I would, I would say, so what is the hemoglobin and platelet count? Platelet count is 150, and hemoglobin count is 110. I would just observe this patient. Right. This is correct.
So, um, in the exam, they can ask you that whether you would treat this patient or not, um, or they can ask you in part one exam, which is day after tomorrow, what are the indications for treatment of CLL. A CLL question came. So, again, I would say reporting is not only necessary to report the blood film. The report should be done according to the exam style. Report carries six marks, but you need other questions as well to, uh, answer it, and then you will pass the exam. People have failed the exam by point. One by point zero five or one mark, uh, in EP 2 exam as well, right? And, uh, the Eath exam contains simple cases. They are not like they will not give you histology or anything like that. The daily life simple cases that you see.
Now, the second case is about again, a 50-year-old man. The patient has rheumatoid arthritis and is under the treatment of a rheumatologist. He has some blood tests done today which were sent by the rheumatologist, and the white cell count is slightly high, that is 11. Platelet count is normal, and white cell, red cell, the hemoglobin is normal as well. But because of some abnormal cells, the lab is a bit worried. This is power 10. Anyone from the lab first want to say anything about R? There, oh, maybe not. Yeah, so what did you say? Can you please repeat? Is Ru over there? Oh, okay. I will make it to 50 to make it more clear. E, okay. The count. Sorry, can, can you please repeat? What's the neutrophil count? Neutrophil count is two. Okay. Um, so we've seen lymphocytes, neutrophils, and one monocyte so far. MH, okay. I want you to report it. No more cic, no more chromic. I think there is some red cell anisocytosis. Some cells are large, some are small, and this one is an elliptocyte. This is a fragment here, and this looks like a spherocyte. So, maybe because the patient is under rheumatology and he may be using heart, not heart, the deod therapy for the rheumatoid arthritis, so it has an effect because it leads to folate deficiency. It can lead to those effects. Is it polychromatic or, uh, just color problem? Polychromasia? No, maybe a bit of color issue. I should make it more bright. You, what is the CRP like? The CRP is 80. Sorry. Process then, right? There is thrombocytosis, I think, and some giant platelets. Yes, because the patient has rheumatoid arthritis, so a reactive thrombocytosis is expected. What is this? Um, it's not clear. I need to focus. H, is it clear now? Yeah, artifact to start with. These are lymphocytes, aren't they? Aren't they? Yes, they are. I agree with that. What, what is the cytoplasmic like? I, I don't know. Is it stippling? Is it, I don't know what's called actually in morphology, but there's abnormal, abnormal cytoplasm in one of them. And what about this one? The cytoplasm is faint, I mean, pale. Okay. What about this one? Is it like hair projections? It's not very clear actually. No, like stippling or inclusion bodies in the cytoplasm of the lymphocytes. Is that right? Yeah. So, what, what are these inclusion bodies? Let me check. Any lymphocytes we call them granular lymphocytic, uh, what we call it, uh, so I have given you a hint in the beginning that this patient has an autoimmune disease which is rheumatoid arthritis, and all the autoimmune diseases are associated with large granular cells. Mhm. Your mind should directly click towards large granular lymphoma if there is a hint of any autoimmune disease in the scenario, because you have only nine minutes in the exam, and those nine minutes pass very quickly. These are all dysplastic. This one here. Yeah, this plastic. Yeah, this one has quite a lot of granules. Any other large one? Right. So, this is the, uh, blood film of large granular lymphoma, uh, in association with rheumatoid arthritis in the background. In this particular loop. Do you know anything about large granular lymphoma? How would you treat large granular lymphoma? Is it, is it a form of chronic B lymphomas or low, low grade B lymphomas? T-cell. T-cell. Okay. It can be T-cell or it can be NK cell as well. So, uh, depending on the flow cytometry that you get. First of all, what is the mutation associated with LGL? STAT5B, STAT3, or STAT5B? And what is the first-line treatment for LGL if indicated? It depends on the cause. We can give methotrexate or cyclophosphamide, I guess. Yes. If there are cytopenias, then it means this is the indication for treatment. You can give them cyclosporine or methotrexate along with GCSF as well. This patient doesn't have neutropenia, but usually LGL in advanced cases comes with neutropenia. So, for the exam purpose, if you see any scenario with any autoimmune disease, especially rheumatoid arthritis, think about LGL first in your mind, and it can be T-cell or it can be NK-cell depending on the flow cytometry. So, if you have rheumatology world in in your hospital, keep an eye on the patients. See their blood films. They may have LGL for sure, but they are referred to hematology only if they have persistent cytopenias. Then the rheumatologist would ask you for advice. Should we give cyclosporine? Should we give methotrexate or cyclophosphamide or no? All right, right.
Now, this is the third case. Which one question for me is the down? All right. So, this is again a 50-year-old patient who presented to A&E with worsening fatigue and shortness of breath. He had noticed some epistaxis as well. The full blood count of the patient, uh, shows white cell count of 110, hemoglobin of 90, and platelet count of 90. As 12. This is the power 10 blood film of the patient, and the biomedical scientist from our lab colleagues, they think that this is a chronic myeloid leukemia type picture. Yes, sir. I see many P of in F. Sorry, don't seem to see. I can't see many he around. Yeah, so I will make it to power 50 to make it more clear. This was the comment of me. I'm, let's say I'm a biomedical scientist, and I have commented like that, and then I said, uh, refer this blood film to a clinical hematologist for a second opinion. So, this is blast, aren't they? Report the blood film. We go back to our 10 focus. All right. So, this is the situation. Blast. Okay. Which type of blast are they? So, they appear to be myeloblasts. Okay. So, this one is granular. They appear to be myeloblast, but this one is clear. This blast is clear. This is granular. This one is clear. Clear as well. Some of them are clear, some of them are granular. So, they may be of mixed, mixed phenotype. Why would you say mixed phenotype? Um, now, this is power 100. You can see them. This is granular, sir. Is it necessary for myeloid blast? All the blast must have the granules? They are apparently same in size, and they, the nucleus, chromatin condensation is same. No, the opening of the chromatin is same. Yes, because they are all blast, but some of them are granular, some of them are not. Does it matter? Yes, sir. They might belong to two different lineages. They might be mixed lympho and myeloid blast. How, how, what are the requirement to call it as a, as a biotypic or multilineage leukemia? I think it's to score from each, minimum of two lineages. So, this case is this C blast, Philadelphia CML in blast phase. And most of them are myeloid blast. Initially, the blast don't have granules. With the passage of time, they develop granules when, uh, at promyelocyte stage and so on. So, um, but we haven't seen any eosinophil and basophil here, right? There is no basophil here. There is no eosinophil here, right? There are some mature neutrophils. A lot of blast, and some of the blast are clear, some of the blast have, uh, eosinophil. Can I see MML? Chronic myeloid leukemia? No, sorry, sir. No, chronic myeloid leukemia should have a lot of. Yes, sir. The blast percentage is quite high. Yeah. So, we have seen multiple cases in the recent few months like this. We were thinking whether this is myeloid or this is lymphoid, but it turned out to be a mixed lineage. I haven't heard about any mixed lineage case in the exam yet, but they can appear because of the increased number of candidates in the F part two exam. They are more focusing on blood films. Blood films can be from AML as well this time. So, yeah, so some of the cells, they are very clear, their cytoplasm is very clear. Some of them have a lot of granules, so they are mixed phenotype acute leukemia. The WHO 2022 have mentioned a criteria to call anyone mixed phenotype. So, you would say that this patient has leukocytosis with multiple blast in the blood film. Some of the blast are granular, some of the cells have a clear cytoplasm. The most likely, the red cells and have normal morphology. Platelets are decreased in number. No platelet count. This is most likely consistent with acute leukemia. Need urgent flow and further investigation like bone marrow biopsy for confirmation of diagnosis. So, on the basis of flow, you can only say that this is, um, um, AML. So, this is WHO 2022 diagnosis of AML. And they have mentioned what you need from myeloid lineage, from T lineage, and from B lineage. If myeloid is positive, then it is myeloid. From the monocytic side, you need at least two of these following. Or if myeloid is negative, then you need two myeloid markers at least to be present in AML. If it is a T lineage, you need to have a strong cytoplasmic CD3 or surface CD3. Or if it is a B lineage, you need a CD19 with at least one of the following these among these three. Or if CD19 is weak, you need two of the following, 29, 22, and 0. They would ask you what is the, report the blood film for six marks. What is the diagnostic flow marker for AML? Again, two marks. And then they can ask you about the treatment option. Whether you will treat this patient or not. It depends on patient age, Charleston comorbidity index, patient wishes, and MDT decision, whether fit for transplant or not. AML is rare, but recently we have three or four cases like that, and looks like their frequency is increasing. All right.
So, the fourth case is a young boy who was brought to A&E with headache and confusion. And when they did the CT scan, the patient has a large intracranial bleed. And when they did the blood test, the blood film is like that. Inside the whole blood film is like that. So, it will be difficult to find a thinnest portion in this film. So, you can imagine his white cell count is more than 800. This is power 10, and this is power 50. Okay. This is power 50. The patient came with intracranial hemorrhage to the ED, and his white cell count is 800 plus. First, report the blood. What do you see in the blood film? There are M1. Is it? Sorry. This is what? Acute leukemia. Lymphoblastic leukemia. Okay. But how would you report that for the exam purpose? So, the peripheral film of the, uh, patient is showing marked leukocytosis. The abnormal cells are, uh, small to medium in size with high nucleo to, uh, cytoplasmic ratio, open chromatin, and few of them are showing, uh, elongation of the cytoplasm on one side. Many of them having conspicuous nuclei. Inconspicuous and few have conspicuous nuclei. Just say prominent nuclei. In the cytoplasm. I cannot say it any. Okay. So, leukocytosis with high NC ratio having multiple or many of the cells shows prominent nuclei. Will start cytoplasmic projections. You forget red cells and platelets again. Thrombocytopenia. Is it there? Thrombocytopenia. And red cells are, there is no normal lymphocyte to compare with that. But in that patient, the hemoglobin was on the lower side. It was 10.5. All right. So, the impression is acute leukemia. Need blood to be sent urgently to HMDs for flow, and then a bone marrow biopsy once the patient is stable. Because this patient is with intracranial hemorrhage. Why the patient blood leukocytosis? Leukocytosis affects the, uh, white cells have eaten all the onean factor from this patient, plus thrombocytopenia. What would you do to, uh, decrease this white cell count? We can do leukapheresis. Yes, I think it's contraindicated if the patient is bleeding. Patient has intracranial hemorrhage. So, we have to leukapheresis for this patient because if you give hydroxycarbamide, it would take many days to decrease the count, plus patient has at high risk of tumor lysis as well. His kidney will fail because the count is very high. So, we did leukapheresis two days in a row, and his white count came to double-digit figure. Right. Again, what are the, uh, standard and poorest factors in all the age, gender, lymphocyte doubling time is for CLL. It's not for. So, age below one year and more, uh, in adults, it is with bad prognosis. Female and male, male has the bad prognosis. What else? Many factors that white blood cells more than 100. Yes. Uh, response to treatment. I mean, yes. Philadelphia chromosome if positive, then it is a bad risk. Whereas 11q23 or T(L) is a good one. Which one? Can you repeat, sir? Tell AML. 11q23, I guess. T(L). T(L) 12;21. Yes. 12;21. That is it. It is now called ETV-RUNX1. Right, sir. ETV-RUNX1. That's a good one. Hyperdiploidy is a good risk factor as well. But, uh, the common things are the age, white cell count at presentation, and delayed response to the initial chemotherapy. Philadelphia chromosome presence, and the karyotype. If it is 11q or 4;11, or if it is a complex karyotype or hypodiploidy, usually they are considered as poor factors.
Now, this patient is young, he is just 22 years old. Do you have anything in mind to offer to this patient in terms of chemotherapy? Intravenous method, exit. What I mean in terms of chemotherapy, do you have any, uh, chemotherapy in mind? Any protocol in mind to offer to this 22-year-old patient who is pH negative B-ALL? Yes, we have two protocols here in UK now. You can give him, you call for UK call 19 because he is pH negative, Philadelphia chromosome negative, and you can also discuss in the MDT regarding allogeneic transplant as well. For a young patient, we have two trials. Depends on the pH, uh, chromosome, Philadelphia chromosome, whether positive or negative. If he was Philadelphia chromosome positive, then I would have given him, you call 14, because you can give you call 14 to those patients who have pH positive and low AL. And in pH positive, you cannot give allogeneic transplant. They will not ask you about these protocols in the exam, but you should have an idea when to give you call 14, when to give you call 19, when to give you call 60, or allogeneic transplant. Like in E part 2, they can ask you in the management of ALL or AML. So, you are dealing with them in your routine life, daily. So, they expect you that you should know the name of the protocol and indication of the protocol at least. They will not ask you what drugs are present in you call 14 and what are the doses and when to give which drug, but they can ask you about the side effect of the drugs. Like, these drugs, you call for, has asparaginase. So, what are the risks associated with asparaginase? Pancreatitis, toxicity, low antithrombin, low fibrinogen, and lots. The important thing is reporting the blood film. Report the blood film. Whatever you see in the film, mention the dominant component first. Do not skip any cell line. Write your impression and then suggest further testing. Then it will complete your report. Again, I would say, do not take anything easy for the part two exam. Many people have lost part two on 0.5 marks or one mark, and this is very heartbreaking. This is not difficult if you practice daily because you are seeing blood films in your hospital daily. So, report them according to the exam style, you will, you will not fail.
Right, the last case. This is power 10. So, this is again a 50-year-old patient admitted to ICU with sepsis, and he has some blood tests done today, and the white cell count is 50. Anyone from the lab to comment on this? Neutrophil. Okay. So, count like, make it to 50. 50. Sepsis. No, no, I mean, I will make the film 50, not the platelet count. Oh, sorry. Platelet count is 400. Oh, okay, sir. There is neutrophilic leukocytosis having toxic granulation. Yes. Along with that, the white, the red cells, they are also showing like, uh, microcytic hypochromic picture. There are few teardrop cells. Platelets seem adequate. I think so. What's the platelet count? Platelets. This seems adequate, sir. And I can only appreciate the toxic granulation in the neutrophils. Band forms as well. Yeah, yeah. Life shifts. Again, I would request you to report it for the, uh, example. Report this blood film.
So, the peripheral film of the patient, uh, is showing leukocytosis with predominant population of neutrophils. Many of them having the, uh, band shape, that shows the, uh, immature form in the, uh, band form. 4% till 4% it is normal. In any case, then and predominant population is of neutrophils showing the, uh, toxic granulation, and few of them having the re-granulation. The red blood cells are, uh, normochromic, uh, normocytic, and microcytic hypochromic. And the, the platelets are normal. Fades are also seen. This is a bit thicker side, that's why there is some rouleaux formation. So, the film shows leukocytosis. There are multiple, uh, neutrophils with toxic granulations, and there are multiple band forms as well. The platelet count looks normal. There are no platelet clumps, and the white cell, the red cell shows two very rare schistocytes and some teardrop formation as well. The film is consistent with, uh, neutrophilic leukocytosis. This patient needs, uh, investigation for the cause of neutrophilic leukocytosis, which can be sepsis, solid organ malignancy, etc.
So, now the exam question is that, difference between neutrophilic leukocytosis or leukemoid reaction versus CML versus chronic neutrophilic leukemia. How would you differentiate among the three? First of all, the history of the patient. In, uh, case of sepsis, it will be a short history. In case of chronic neutrophilic leukemia and CML, there will be a long history of more than, uh, four to six weeks and associated symptoms that were, that, uh, were examined by the, uh, the physician. In case of sepsis, neutrophilic leukocytosis, the lab score will be high. In case of CML, it will be low. I don't know about CNL. The count of the, we don't do lab scoring anymore for. Okay. CML. Right. So, why this is not CML? Just tell me on the basis of blood film. Why this is not CML? The findings of the blood film are, and why this is not CNL? Sir, it is not CML because you cannot appreciate all the left shift up to the level of the blast. You can only appreciate neutrophils which are like more than 90% present in this film. Along with that, we can also see toxic granulation, that is also a sign of like neutrophilic leukocytosis. In CML, you can't appreciate toxic granulation. So, you have mentioned that this is not CML because there is no eosinophilia, no basophilia, no metamyelocytes. Are the CML features? Okay, I agree with that. Why this is not a chronic neutrophilic leukemia? Granules and band forms, maybe. What else? The chronic neutrophilic leukemia has a specific diagnostic criteria in WHO 2022. The persistence of neutrophilia. So, the diagnostic criteria for CNL in WHO 2022 says that there should be leukocytosis, and the leukocytosis should be more than 25. It should contain 80% or more than 80% of neutrophils, and with less than 10% circulating precursor, mature neutrophils, 80% or more than 80% mature neutrophilia, less than 10% band forms, and the white cell count should be about 25. So, they can ask you this question as well because it was a question in the L Eath exam. And what mutation is associated with chronic neutrophilic leukemia? CSF3R. CSF3. CSF. This can be a part one MCQ question as well.
All right, so again, I would stress on the exam because the part, part exam one is on Tuesday, and part two is on the first week of October. This exam is not only about the knowledge, it is about knowledge plus exam skills, both. You may be knowing a lot of things, more than me, but if you don't know how to put that in the exam, you will fail the exam. Exam need for the part two per exam need reporting the blood film and plus answering other questions as well, and each short question is of 10 marks, and you need to pass them at least four to get a passing question. Right. So, on the next Sunday, there will be no morphology class. It will be a last-minute advice for Epath for two candidates, and after that Sunday, we will have a class of how to prepare for part two, and then we will resume our morphology sessions again. Any question? No. Okay. Thank you. Thank you very much. Please subscribe to the channel and thank you very much. Have a nice Sunday. Take care. Bye-bye. Thank you. Thank you. You're talking. Did.