Transcription
Hello everyone, can you hear me? Yes, sir. This is the first case. So, this is a 30-year-old female who presented to the emergency department with bruising on the body, especially on the arm, chest, and thigh area. The full blood count shows hemoglobin of 120, white cell count of 21, and platelet count of 98. This is the power 10. Texture and the lab hematologist. So, the peripheral smear of this patient of 36 years of age is showing a leukocytosis on power of 10. Okay, then let's go to 50. Admit your colleague who are in the waiting area, please.
So, this is now power 50, and let's go through it. What do you see? E. All right. What do you think is going on here? So, the prominent population is of abnormal mononuclear cells, which are large in size and they have heterogeneous morphology. Few of them have large or round nucleus with abundant cytoplasm, and few of them have indentation. Few of them have foldings. Few are myelocytes with abundant granules inside. Mhm. What are your suspicions? For me, this is a case of acute myeloid leukemia, and I'm confused between promyelocytes. And it may be. Made it power 100. These cells have the large, large in size with the indented nuclei, abundant cytoplasm with granules. So, these for me are abnormal promyelocytes. Promyelocytes. Okay, then what is your next next step for the testing of the patient, especially for coagulation profile, immunophenotyping? If this is a peripheral smear, then a bone marrow examination as well. Bone marrow examination for what, sir? For the involvement of bone marrow. You will do bone marrow, and bone marrow will be reported in a few days. When a patient... No, sir. Initially, the coagulation profile and immunophenotyping on the peripheral smear, on peripheral blood sample. What do you want to look in the coagulation profile and immunophenotype of this? I want to associate the coagulation profile in prolonged PT and aPTT, and the level of the D-dimers to associate with the findings of the morphology of this peripheral smear, which I am suspecting as acute promyelocytic leukemia. Because this is an emergency. If it is acute promyelocytic leukemia, if this is an emergency, you would do a FISH. FISH for PML. This is this is 12:00 here, and HMDs or HS is closed. If you ask about management, Dr. R, I can go for ATRA. I'm not asking about management. I'm asking about the next step. If you are suspecting this is APML, I would not wait for FISH because it may be a Christmas holiday, and HS or HMDs is closed for a few days. And if you say bone marrow biopsy, bone marrow biopsy will be reported in seven days. If you are thinking this is APML, then you have to stop this. These are all kidney bean shaped cells in this patient, and he is bruising as well. Platelet count is very low. How will you report this blood film for the exam? Clinical hematologist. Going for exam. So, the peripheral smear of this patient is showing an increased number of abnormal white blood cells that are large in size with the round to oval in shape nucleus, having indentation or kidney bean shaped nucleus, abundant cytoplasm, many of them having abundant granules inside, and there is thrombocytopenia. Have you seen Auer rods in any of them? I'm trying to figure them out, but up till now, I have not seen any. Complete your blood film report. You have described the cells. What is your impression and what is your suggestion? Yes, sir. The findings of the peripheral smear are suggestive of acute leukemia, most probably acute promyelocytic leukemia. And I will further advise for the coagulation profile that will include prothrombin time, activated partial thromboplastin time, and D-dimers, and immunophenotyping for further confirmation of the findings. And meanwhile, I will inform the clinical hematologist and the treating physician about these patient findings to start the therapy for acute promyelocytic leukemia. Okay. This patient needs urine. PML stain. PML stain, if your HS is open, will give you results in one hour. And FISH will give you results in six hours. PCR will give you results in 48 hours. What category of APML is this? Higher risk or low risk? What were the counts? WBC and the platelet count. 21 is the count for white cells. Okay, so it's high risk because it's more than 10. Okay. And what treatment options do you have for this patient? For high risk, we have to go with ATRA plus chemotherapy. ATRA and chemotherapy involving idarubicin. Would you like to do any test before going for ATRA and idarubicin in this patient? Echo? Anything else? Pregnancy test. Pregnancy test has already been done. Cytogenetics and... So, I mentioned to you and to part one people as well, whenever you see a young female in the scenario or in the exam, always do a pregnancy test. You would start ATRA and idarubicin for this patient, and later on, the examiner will say this patient is 20 weeks pregnant. And then... So, always do a pregnancy test. It is a very important. It may harm you as well in the exam if you do not mention it in a young female because it changes your management. And when you suspect this is APML, always act urgently. Do not go here and there. You have seen Auer rods, you have seen very granulated cells. This is likely APML. Inform the patient and your consultant on call and discuss starting ATRA in the patient. And in this patient, because the white count is very high, we will start an order. It will be seen after consent.
In this... This is a 50-year-old man presented to the emergency department with progressive weakness and fatigue. His hemoglobin is 80, platelet count is 130, and WBC is 17. This is power 10. Yes. Any lab hematologist? Lab scientist. So, the peripheral smear of this patient is showing anisocytosis in red cells. The predominant population among the white blood cells are lymphocytes on power of 10. Okay, let's go to power 50. E. Yeah. Any comments? Yeah. It, it, it looks like there is anisocytosis with polychromia. Some large RBCs are seen, like they're probably reticulocytes. And I can also see a fair number of mature small lymphocytes. Till now, I cannot see any other leukocytes, and platelet counts are markedly diminished. So, are you a lab scientist or are you a clinical hematologist? No, I'm a clinical hematologist. Are you preparing for part two? Yeah. Okay. So, report this blood film for the exam. RBC: marked anisocytosis with polychromia and stippling. WBCs: relative lymphocytosis, small mature. Platelet count: markedly reduced. What about the red cells? RBCs as well. You have commented on the blood cells. What is your impression and what is your suggestion? Then your blood report will be complete. Yeah. The impression is a possibility of chronic lymphoproliferative disorder with autoimmune hemolytic anemia. And what will you suggest? I will suggest to do a flow cytometry for chronic lymphoproliferative disorder panel and DCTP, reticulocyte count, and hemolytic markers, hemolytic screen. If you mention that there is hemolytic anemia secondary to LPD, so you will do flow cytometry and hemolytic screen for this patient as well to rule out this is immune or non-immune hemolytic anemia. Yes, the blood film reporting was correct. What treatment would you give to this patient? If a patient has a chronic lymphoproliferative disorder like CLL and if the hemolytic screen shows presence of autoantibodies, that means the patient has autoimmune hemolytic anemia. We will have to get other relevant information regarding bulky disease or presence of these symptoms or presence of any organ compromise to the lymphoid organs to see if the patient needs chemotherapy. Those factors are absent, then I will start the patient with glucocorticoids. Rather, start with me at one. Okay, so you are starting this patient on steroids because the patient has autoimmune hemolytic anemia plus anything else you would add along with the steroid? At this point of time, I will not start the patient on any treatment if other factors are absent. If the patient doesn't want, there is no lymphadenopathy, there is no symptoms, only he has hemolytic anemia, he has few cells from the blood. Yeah, I will only start glucocorticoids and monitor the response to glucocorticoids. If the patient doesn't respond to glucocorticoids, then... Whenever you start steroid in a patient, I always mention that you will give this patient bone protection and gastric protection as well. This patient is having hemolysis, so you will give this patient folic acid as well. And if the patient does not respond to steroids, then the guideline says then you will think about the chemo therapy. If you are given rituximab, rituximab is a component of the chemotherapy. And most of the regimens. So, one of the indications of chemo treatment would be autoimmune hemolytic anemia not responding to standard therapy. Standard therapy is steroid. But most of the patients in practice, they will respond to steroid. Yeah. Thank you. Right. So, you are planning to start this patient on chemo treatment because the patient is not responding to steroid, or he has a massive spleen or massive lymphadenopathy that is compromising the muscular structure or nerve structure. He is a 50-year-old fit person and no other comorbidities. What are the regimens that you have for the treatment of CLL? For the treatment of CLL, our regimens, if we have to start treatment, we have to first assess whether the patient has TP53 mutations. We will run FISH for TP53 as well as mutation analysis for IGHV gene rearrangement. If TP53 mutation is present, then the frontline therapy will include BTK inhibitors with or without rituximab. I can use venetoclax plus rituximab, or I can also use single agent ibrutinib. If TP53 is absent and IGHV is unmutated, then we can use... we may or may not use BTK inhibitors. We can also use chemotherapy, and also we can use BTK inhibitors. However, if the IGHV is also mutated and absent, then the ideal regimen of choice will be FCR, which gives an operational cure for many patients. And if FCR is intolerable, then we will opt for... The total duration of cycles will be six cycles followed by end of treatment. So, as per the new guidelines and new advancements in CLL in UK, the treatment for TP53 and non-TP53 is almost the same. We are not using FCR anymore. It is abolished in UK because of the requirement of irradiated blood and risk of secondary cancer, especially skin cancer. We have fixed duration. When Ibrutinib or Venetoclax, the patient cannot take this, then we have less intensive regimens. The chemo or... as a... FCR is no more. CLL is one of the diseases which is very, very rapidly evolving in terms of treatment. The BS guidelines are I think from BS 2022, but even after 2022, there are a lot of advancements. Okay. FCR is okay. It is still present in the guideline, but in practice, we do not use it anymore because of the risk of laboratory-induced hemolysis requiring irradiated blood and being associated with secondary risks of cancers. But if you do mention it in the exam, they will not deduct any marks. They may ask you an extra question. Is there any risk associated with FCR? When you have to mention this, just one question regarding Venetoclax plus Rituximab, is it the frontline? I mean, is it recommended for frontline? Okay. When... When Ibrutinib, they are now in the frontline therapy. Someone was asking. Yes. Yeah. Basically, I have a question. It means in CLL, currently we are not differentiating the patients in two categories, TP53 mutation is present or not. We have to differentiate to find out the prognosis. If TP53 is mutated, it has bad prognosis. Yeah. Means I mean asking about the treatment regime. When to collect... When to collect Rituximab or Venetoclax, Venetoclax, and Ibrutinib. All the treatment options will be the same in both categories. Yes. But some people, they would tolerate intensive regimens. The Venetoclax-based regimens are intensive regimens. But there may be people who have underlying comorbidities, they may not tolerate Venetoclax or Ibrutinib. So, for them, you have to give them less intensive regimens and oral regimens, which are just like in AML, who those who are fit, we give them intensive chemotherapy, FLAG-IDA, or for those who are not fit, we give them less intensive therapy like... The same goes with CLL. Answer. Okay. Thank you.
So, this is a 60-year-old patient with pancytopenia and splenomegaly. Do you have any differential in your mind? If the scenario says pancytopenia and splenomegaly? Yes, it may be... Okay. When is... Yeah. Here, leukemia, myelofibrosis, infiltration of the marrow by secondaries. Right. So, this is power 40. In the exam, you will first see whether the specimen of the tissue is okay or crushed or not. And it will also give you an overview whether the infiltration is very trabecular, nodular, diffuse, or if there is any fibrosis. Fibrosis is peritrabecular or diffuse type. You are seeing this. This is the trabecular piece. It is very thick. You have seen that. Now, let's go to... So, are these trabecular thickenings because of some disease or these are some error in taking the sample? You have to tell me. Is the picture clear? Yes, it's clear. The patient has pancytopenia and splenomegaly because the pancytopenia was persistent, the team decided to do a bone marrow biopsy for this patient, and this is the marrow histology of the patient. So, this is an adequate length defined biopsy sample of a 60-year-old patient. Hypercellular for age, and our architecture is... eas... because of the diffuse infiltration of abnormal mononuclear cells having central nucleus with clearing of the cytoplasm, appearing as a "fried egg" appearance. It can... I can't associate this with my impression of disease. What do you think now? Sorry, she, we cannot hear you. Still, we cannot hear you. We cannot hear you. There's a lot of noise. Very... So, which one is... So, what features are telling you that this is a... Nuclear... Everywhere around the around the... So, this is a cell, and this whole area is a white. This one. This area is one. This area is all cleared. This is the feature of here in the histology, and they are called "fried egg" appearance. Fried egg. So, this is a typical histology you will get either a Hairy cell or a Fox L1, which is quite common in the exam. This is the appearance of Hairy cell leukemia. Go to your HMDs and lab and ask them that we need a histology or Hairy cell, and they will give you. Once you see them by yourself, you will never forget. But you should see things by your own eyes, not online, not on the websites. You see them by yourself. I don't have the histology of Gaucher disease. Gaucher disease people usually mix the Gaucher disease with... The Hairy cell leukemia. Gaucher disease is an inherited disease. It happens in the pediatric population. They have also cytopenia and splenomegaly as well, and they have bony deformities. While Hairy cell leukemia will happen in the elderly population. You will not see Hairy cell leukemia in a 10-year-old child. But if the scenario says a 10-year-old child with pancytopenia and splenomegaly, bony deformity, and your mind should think about Gaucher disease. Um, asking your lab if they have a sample for Gaucher disease or not. The appearance is almost similar, but this defined has Hairy cells everywhere, and in that Gaucher, they will have localized appearance of cells like this with distance and in between the marrow will be normal. So, see the Gaucher disease histology or aspirate before your exam. If you are attending V course or part two, he has one Gaucher disease as like because it is very rare, so it may not be present everywhere. Okay. What is the... So, why the trabeculae thicken in this case? Because here is here is a leukemia, usually associated with fibrosing. The trabeculae get thick, and all fibrosis-related disease, if you have a myelofibrosis, if you have a systemic monocytosis, or if you have a Hairy cell, you will find thick because of the extra fibrosis. Right, sir. Thank you. What is the typical Hairy cell leukemia marker? CD11c, CD25, and CD103. Mutation. And BRAF mutation. In the variant, there is no variant. Okay. Okay. Yes, that has been included in Splenic Lymphoma with prominent... Yes, sir. Do you know where else the BRAF mutation is present? Systemic monocytosis. They have de... Anyone living near Chester or in Chester? So, they can be found in colonic and lung adenocarcinoma as well. I just found on the internet. I think Adam Chester, the Chester disease of mutation. That's why I asked. Anyone living in Chester or near Chester? Chester is a city. There is a big zoo, and we go there. Other... Okay. This is a blood film of a one-day-old infant. What are the features in this blood film? This is power 10. I will make it... May be normal for the newborn. So, the question is, what are the features in this? Stippled RBCs are on the... And RBCs there. Sorry. Micro RBCs are there. They are maybe normal for the newborn. Macrocytosis. What else? What is this? This one? Spherocytes. So, you will have one question, either yes, mostly in short cases in the part two exam, where they will not ask you any diagnosis or differential diagnosis. They will ask you to enumerate the features in the blood film. So, then you have to pick up all the features. This patient like, like one, two, three, NRBC, macrocytes, packed red cells, Howell-Jolly bodies, spherocytes. If you see any other abnormality, then you have to mention all of them. So, you will have one slide like this, which will be not for diagnostic purpose or differential diagnosis. They will only ask you, what are the features in this good film? Or then the next questions will be, does this patient need any treatment? Or what is the expected mutation? What next test would you do? ET. Or they can ask you, why this patient has Howell-Jolly bodies? Why there are NRBCs in this patient's blood? So, then you have to explain that. In... So, do you see blood film of a newborn? Because most of the people say that this is leukoblastic or bone marrow is stressed because of severe infection or sepsis or severe hemolysis is going on. This is wrong. This blood picture is okay enough for a one-day-old child. If this picture is not present, and I will be worried whether this patient has any bone marrow failure or because of the NTK antibodies or something else. And is it normal that Howell-Jolly bodies are present in the newborn? Because of hyp... Their organs are not developed. Their organs are not developed fully. So, everything is low in the newborn. If it is coagulation factors, if it is spleen, they are all low in the newborn. It takes some time to reach the maximum function. This was just a newborn blood film to show it to you that it can come in the exam. It has appeared before, just for the enumeration of the features in the blood.
Now, as the last case, this case is a bit of interesting one. If you can pick that up, it is increasingly common in practice and may appear in the exam. And so, this is an aspirate of a 35-year-old lady who has macrocytic anemia and recurrent elbow joint inflammation. Because of the persistent macrocytic anemia with normal B12, we decided to do a marrow on her. This is the aspirate. These are the particles, and these are the cellular trails. So, first of all, what are the different causes of macrocytic anemia when B12 is normal? In anemia, there are certain causes that are macrocytic, non-megaloblastic, that will include the physiological findings in the female that is pregnant and in a newborn. In the other causes are hypothyroidism, alcoholism, and aplastic anemia, MDS. MDS, even hemolysis causes a high MCV. Hypothyroidism, some medications as well. Hydroxyurea, ic, my people have... So, this is the aspirate of the patient, and make it to power 50 to see if you can see anything distinguishing. There are giant... M... cells. I can appreciate on the MH, and it is active. And sorry, can you say again? I could not hear you. Myeloid is active, and there is a giant myelocyte. Present with all stages of maturation. All, all of maturation. You mentioned and joint metamyelocyte? No, I'm saying that myeloid is active with all stages of maturation, and there is also joint myelocyte and metamyelocyte can be appreciated. But what are... Question... Looking like myeloid, but maybe... I cannot appreciate the granules. Approaching this cell has some granules. This cell has no granules. It looks like myeloid. These are the myeloid cells. Majority of the cells are myeloid cells. I cannot hear you clearly. Okay. I am... The cells. Which cells are this? This cell is a precursor. Okay. This is a precursor, which is... That is a plasma cell. It has a lot of granules. Maybe it is clear. If it is... If you are thinking that this is a plasma cell, then there should be a lot of plasma cells. Plasma cells should cover more than 10% or more than 6%. But they are very few. One of the... Somebody mentioned that erythroid precursors are there. Okay. Blasts are there. Blasts are there. Yeah. See where else. This one. I can put some more. Why this patient has recurrent elbow swelling? Swelling? H? What kind of swelling? You are seeing this patient has recurrent elbow swelling. This is power 100 to show you the structure of these cells. Fortunately, it cannot be clear more than this. The basophilic like marginal cytoplasm with the high NC ratio, like looks like erythrocyte precursor. More likely. So, you have identified that there are erythroid precursors and there are some myeloid series as well, which is correct. They are all granulated. There is a large precursor with vacuoles. Vacuoles. And this is myeloid with multiple vacuoles here. If an erythroid precursor has been and myeloid series cells have vacuoles, and the patient has recurrent joint inflammation, is it VEXAS syndrome? It is VEXAS syndrome. And what mutation should I expect in VEXAS syndrome? UBA1 mutation. UBA1. This patient has UBA1 mutation. And the aspirate feature is that you will see myeloid precursors and erythroid precursors with vacuolation, and the patient will have recurrent inflammation in any joint. It has not yet appeared in the exam, but it's a hot topic these days. Be ready for that. They can ask you in the exam as a part of MDS, or they can give you an aspirate like that with vacuoles in the erythroid precursor and in myeloid precursor, and the history is giving you some hint as well, elbow joint inflammation or knee joint inflammation, because the feature of VEXAS syndrome, VEXAS syndrome is autoinflammation, mostly it is joint inflammation. What's the reason for the raised MCV for that patient? You said that these patients come with the raised MCV because of the bone failure secondary to MDS. It is a type of MDS. That's why... That's why the MDS. That's where the MCV is. They can give you as a short case. It depends on the number of candidates. If the number of candidates are less, so they can give you aspirates and paraffin in the short cases as well. If the number of candidates are more, then usually they cannot bring more aspirates and paraffin from a single patient. They cannot make 150 slides or 100, 30 aspirates because then the quality will go down. If you see the nasal blood for the parasites, they will have a lot of worms and ring forms. But when you appear in the exam, they will have only one BM in the slide or one ring form in the or malarial parasite. You have to search for it because it's very difficult to distribute equally all the... Is it find out the fuses in the slide? Like it's not that much in this slide. F areas is a bit difficult to find out because most of the time we could find the Leishmania and the other one, but it's really hard for me to pick the fuses. Which, which one? Fuses. Yeah. So, first thing is that you need to find out a worm. Second thing is that you need to find out whether it is sheathed or unsheathed. If you have found out this is a worm and it is sheathed or unsheathed, you have reached the diagnosis. And that's it. If you name it, this is B, or this is Leishmania, or if this is the third one, Bankrofti, that is okay as well. They will give you 10 out of 10. But if you mention that this is a worm and sheathed worm or unsheathed worm, and this is correct, you will get nine out of 10 marks. Yeah. But in UK, Leishmania is quite common. Every three months, you will see a nasal blood film of a parasite with either malaria or Leishmania. So, to prepare for these worms to come, one parasite will come in the exam. It can be... It can be Trypanosoma as well. Trypanosoma has appeared previously, and Leishmania in the aspirate. You said that is associated with MDS. Just want to have a look on the megakaryocytes if you could scroll on that slide for the... What happened? Can you repeat please? I just want to have a look on the megakaryocytes in the previous slide if you could. It's possible because you said it's been associated with the MDS, so there could be some finding related to the MDS in the megakaryocytes as well. Maybe in... What megakaryocyte? Mega. Okay. Let's see if I can find any megakaryocyte for you. But looks like there is no megakaryocyte. Now it is all filled with these cells. No, there is no megakaryocyte. Only this one I have found. This is the only megakaryocyte in this whole slide. A bit distorted one. It has three nuclei. Can it be confused with the large B-cell lymphoma? If there is no history with that patient, because there you also find vacuolation and not that much basophilic cytoplasm. Cell. Enlarged B-cell lymphoma. You will find vacuolation, but it will be in the lymphoid cell, in the erythroid cell, but there is the blue cytoplasm as well in the... Not it's not in the lymphoid. Because we make a differential diagnosis with Burkitt. And you say that the Burkitt there is a deeply basophilic cytoplasm. So, last time we have seen Burkitt lymphoma, if you remember, it. The Burkitt lymphoma cells, they are very, very basophilic. Their cytoplasm is just like this one. Like this cell has an appearance of dark blue here. Cytoplasm is just like that, and a lot of vacuolation here. DLBCL has large cell lymphoid cell, not myeloid or erythroid cell, and they will have vacuolation over there. Also cells have also vacuolation in the blood film or in the aspirate, but they are lymphoid looking cells. They are not myeloid or erythroid like cells. And the history will also tell you that this patient has lymphadenopathy. 40-year-old patient with lymphadenopathy and pancytopenia. Now you have done bone marrow biopsy, and what is the likely diagnosis? They will not say that this patient has microcytic resistant macrocytic anemia or joint inflammation itself. So, history is important in the making. Okay. So, I think this is...