Transcription
So, this session is interactive and mainly aimed at the FC PA Part Two exam. It will help in daily life as well, but we are aiming at the FC Part exam. So, I would need some volunteers to answer the questions and report the blood films, just as it is asked in the epath exam.
So, this is the first case. A 33-year-old man came to A&E with persistent headache. He was referred by his GP because of the headache, and in the A&E, it was found that his blood pressure is 210 by 130. The full blood count shows hemoglobin of 110, white cell count of 11, platelet count of 210. He is an AK1 with mild raised ALT. The BMS called you because he has seen some abnormal cells in the blood film, and now you are the hematology registrar, and the film is with you. I need a volunteer to comment on this blood film and then report the blood film. Fatima, can I request you?
Yeah, I think I will, um, I will start by, um, checking the power. Um, okay, so I will go to power 10 just to check with this scenario. I will, I will try to, I don't think from this power I'll be able to see platelets, but I will try to identify if there is any apparent thrombocytopenia or RBC fragments. Then I will go in to comment.
Yes, so you have seen here, you have seen here a fragment which is here. Yeah, reticulocyte is here. This patient has a lot of neutrophils, maybe an element of infection. Yes, spleen, it looks high. They are quite a lot in this field only, and fragment, fragment, fragment, quite a lot of fragment here. Yes.
Okay, so you have seen a hemolytic picture here because there are reticulocytes, there are fragments, and you have seen NRBC as well. Yes.
Yeah, yeah. So, what name would you give to this picture?
I will say suggestive of MAHA. MAHA is there. Okay.
Right. So, what is the likely cause of MAHA? Do you have any differential diagnoses in your mind?
Um, when I think, when we speak about MAHA, first I will put TTP, HUS. Okay.
Um, how old is the patient? Sorry, I missed that.
The patient is 33 years old.
Okay. Um, so, yeah, I think TTP, HUS, especially with this renal impairment, I'll consider that on top of my differential. Platelet count is normal though, or looks adequate on this platform.
Mhm. All right. Is there any information in the history that is helping you or not?
The blood pressure of the patient was 210 and 130. Oh, yes. Yes, hypertensive. If she was a female, if she's pregnant or not, then I will consider pregnancy-related causes. Yeah. He is a male. He's a male. Okay. Yeah. So, it could be hypertensive crisis or, yes, malignant hypertension can also lead to MAHA picture as well.
Yes. So, in the exam, you would be asked to report the blood film. How would you report this blood film?
So, I think I will, um, comment. This blood film is showing numerous RBC fragments, more than five fragments per high power field, showing also NRBCs and polychromasia. I will also comment that the platelets are adequate and, um, and white cells showing neutrophils with toxic granulation. So, I will, I will urgently contact the medical team and, so, so you have now completed a segment of the report. The blood film shows RBC fragments, NRBCs, polychromasia with normal platelet count and increased neutrophils with toxic granulation.
Now, the second part is, the blood film is consistent with most likely. Blood film is most likely consistent with MAHA picture or microangiopathic picture.
MAHA picture. So, you have completed two parts now out of three. Now, you will suggest what to do next.
This patient needs further investigation, for example, or need urgent assessment. Yeah. So, I would comment that this patient needs urgent assessment, um, with, with, with full history and examination, and checking kidney functions, taking LFTs and, okay.
Yeah. So, you will mention that the patient needs further investigation to rule out different causes of MAHA, like sepsis. This patient has increased neutrophil count, so the patient would need cultures. You will not mention cultures, anything, but you would say workup to rule out sepsis as a cause of MAHA, hemolytic uremic syndrome, drugs, malignancies, etc.
So, you have mentioned three or four causes of MAHA. So, then your report is complete. Sometimes the blood film is from the GP, then you have to address the GP in your blood film. This patient needs further investigation or referral to hematology, or this is an emergency, needs to be transferred to hematology as soon as possible. So, depending on the scenario, whether the patient is in the hospital or the blood film is from the GP, you have to address accordingly in the exam.
Okay. Now, the second question in the exam would be, what are the differential diagnoses of MAHA or TMA?
Yeah, I think we will go through them again. So, um, TTP, hemolytic uremic syndrome, atypical hemolytic uremic syndrome, hypertensive malignant hypertension, pregnancy-related causes. Yeah, he's a male. Um, okay. Do you have a transplant unit in your hospital?
Yes. Yeah. Yeah. So, which drug is most likely responsible for MAHA picture in a transplant patient?
I think it's Tacrolimus, isn't it?
Yeah. So, Tacrolimus is more. Cyclosporine is also involved in causing MAHA as well. In practice, we see a lot of MAHA picture in transplant patients and in renal patients as well because they use a lot of Cyclosporine and Tacrolimus. And TTP is both, it can be acquired and congenital. Keep in mind this fact. And infections as well. Sepsis, usually a patient in DIC, you would see a lot of fragments in your blood film. And mechanical heart valves, old heart valves which are now dysfunctional, you would see anemia in those patients and fragments. Rest, white cell count will be normal, platelets will be normal, LFT, ALT, everything will be normal. The mechanical hemolysis or from the cardiac valve, you can also see MAHA picture.
Then the last question would be, what is the immediate management of this particular patient?
So, the immediate management, this patient needs to be admitted to the hospital if he's in the community. We need to control his blood pressure because if that's a cause, that means it needs to be dealt with urgently. He may also need escalation of care to ICU or HDU unit for that.
Yes. So, the patient needs specialty involvement, like the renal team, to control his blood pressure urgently. And then repeating of the bloods to see with correcting blood pressure, the blood pressure and the blood tests have improved or not. Then your short case of morphology will be completed. MAHA is a must question in the epath Part Two exam. It will come either in the form of TTP, or in the form of cardiac valve, or in the form of hypertensive emergency or malignant hypertension, but it will come, must. And if you do not see any blood film in the morphology paper, you will see a TTP question in the coagulation paper. Then, because this time we do not have any MAHA blood film in the morphology section, but we have a full question on TTP, so you cannot avoid MAHA for the Part Two exam.
All right. Right. Thank you very much. Thank you.
Okay. Now, the second case. This patient is a 45-year-old female referred to the hematology department because of weight loss, decreased appetite, and abdominal mass on palpation. She is progressively getting anemic as well, and the GP is worried that she may have any hematological malignancy. So, when you examine the patient, she has a large abdominal mass in the left side of the body abdomen, and there are many lymph nodes in the axilla and in the neck area and in the inguinal area. The blood film shows some abnormal cells, and the biomedical scientist is worried that what can this be? The hemoglobin is 110, white cell count is 15, and platelet count is 110. I need a volunteer to comment on this blood film. Anyone want to go on this blood film?
So, yeah, if, um, if we look at this blood film, here we can see evidence of moderate leukocytosis with some, um, um, lymphoplasmacytic, lymphoplasmacytoid lymphocytes. Yeah. So, this is power 10. I will go to power 50, and you can see better. So, yes. So, um, can she, can see here a population of mononuclear cells with irregular nucleus, dense chromatin, and vacuolated cytoplasm. One of them is showing the low shape. Appears, I think, sorry, can you repeat which shape?
The one at around 6 o'clock here, showing the flower shape of appearance. You mean this one? This one. Yeah. I don't know. Irregular nuclear shape. I think I can see that. I will make, show it by you by 100 power. This, this is a bit flowery shape. Yeah. This one is. What about these cells?
So, I will focus it for you. This one. So, yes. So, so this is mononuclear cells with increased NC ratio, dense nuclear chromatin. I don't think I can identify nucleoli here. Cytoplasm, bluish, bluish cytoplasm with some vacuolations. I think I can call it blast.
Okay. Yes. This is a blast. I will show you some more of them. Yeah. Again, this is the flower. We'll go back to 50. About this cell, they're quite large, right? Yeah, they're quite large. Yeah. Increased NC ratio. This one. AC L as well. So, these cells have vacuolations as well. Basophilic cytoplasm, large cell.
So, what do you think are the possibilities here?
Yeah, because of the flowery shape cells, I was thinking about DLBCL, but with the, um, bluish vacuolated cytoplasm. So, what is your differential diagnosis here?
Um, I think about leukemic phase of, or leukemic transformation of lymphoma. Which lymphoma?
Hairy cell, because of the background flowery shape cells. Okay.
So, this patient has no background history, and she presented to you first time with a large abdominal mass and lymphadenopathy everywhere, cervical area, axillary, inguinal area, with B symptoms, and you have seen these large cells, basophilic cytoplasm, and vacuolation.
I think I B should also be on the top of differential because of the vacuolations in the cytoplasm plus blast. Yes. So, if, like many things can cause, um, vacuolation in the, um, lymphoblast on the blood film. You may see vacuolation in Burkitt lymphoma, in ALL, sometimes there are vacuolations as well. And in diffuse large B-cell lymphoma, the Burkitt cells, they are very, very basophilic. They are more basophilic than this cytoplasm, and all of their cells have vacuolation. And the presentation of the patient is usually different. In Burkitt, they have one mass in the body area. They do not give you a disseminated lymphadenopathy. Usually, whenever there is a presentation of Burkitt lymphoma, you will see a mass at a local area, and that's it. This patient has widespread lymphadenopathy. Some of the cells have vacuolation, some do not have vacuolation. Very large cells. You can compare the size with the RBC. Some of them are vacuolated, others are not.
So, you will report the blood film as: "The blood film shows large atypical white cells, most likely lymphoid, with vacuolation in some of the cells. The red cells are okay." Or if you have noticed any NRBC, you can mention NRBC as well. The platelet count is decreased. No platelet count. "The film is most likely consistent with high-grade lymphoma." Because you see this type of large cells and high-grade diseases. The Burkitt lymphoma, DLBCL, only the follicular, mantle cell, marginal zone, they have small to medium lymphocytes. But the Burkitt and the DLBCL, they have large cells. You would say, "Suspected high-grade lymphoma." Or "High-grade lymphoma." This patient needs to be admitted under hematology urgently. We need further investigations like blood flow cytometry in this patient and scans of this patient. CT CAP we usually do to find out the extent of the lymphadenopathy and to stage the patient. After that, a PET scan. So, you cannot make a diagnosis here.
And what is the diagnosis here? But you give your suspicion that this is a high-grade lymphoid disease or lymphoma. You will confirm your diagnosis by requesting further steps, further investigations.
So, what will be the further investigations that you would like to do in this patient to confirm the diagnosis?
So, I think I first mention immunophenotyping, markers, then I'll mention imaging, then I'll mention histological diagnosis, like biopsy from the, yes.
So, first important thing is the flow cytometry. You need to send to the lab to confirm your diagnosis, whether it is high-grade or low-grade. And then the imaging would tell you whether there is any lymph node that you can biopsy or not. If lymph node cannot be biopsied, then it's the bone marrow biopsy. But this patient has a large abdominal mass, so which is easy to biopsy. Um, so you will biopsy. You will mention biopsying of the lymph node.
Okay. The flow cytometry result of this patient is CD5 negative, CD10 positive, CD19 positive, and 20 positive. Do you think this is a large B-cell lymphoma?
Yes, it could be because CD10 positive and the markers positive. CD19, CD20 positive. Right. But if they have given you some other information, like if they say that this patient is MYC positive, TP53 positive on molecular studies, then how would you refine your diagnosis?
If MYC positive, TP53, not quite sure about the TP53. But if MYC positive and Ki-67 is more than 98%, then Burkitt would be the here. I mean to say, whether you will mention double-hit lymphoma or triple-hit DLBCL or not? Because if they have given you MYC, if they have given you BCL2 or TP53, then you have to mention whether this is double-hit or triple-hit DLBCL or large B-cell lymphoma. Right.
This patient is 45-year-old female and stage four disease with a large abdominal mass and persistent B symptoms, decreased appetite. What is the prognostic score that you would use here?
IPI score. IPI score. Okay.
So, for example, IPI score of this patient is three. Do you have any options of treatment for this patient or not?
I think R-CHOP will be the preferred option here. Okay.
Yeah. So, if you mention in the exam that because of high IPI, I will offer the patient R-CHOP trial or six cycles, that is enough because they want to know which chemotherapy you will offer to the patient. The new guideline for DLBCL has algorithms for patients less than 80, more than 80, and stage one or two, stage or high stage, IPI less than two or more than two. Better to memorize them because they can ask about the options of chemotherapy. We have R-CHOP, we have R-EPOCH now, and in young fit patients with no comorbidities and high IPI, you can offer them R-DA-EPOCH or R-ICE as well.
Can you offer them CAR-T if there are refractory in the first year of treatment? And is yes, CAR-T is a second line in DLBCL. In other cases, like in mantle cell, they are third line. But in DLBCL, you can offer them CAR-T if they are refractory or relapse within one year. Do you know the name of the CAR-T cells that we use in DLBCL?
Axicabtagene ciloleucel. Right. And the last question, do you know any new treatment for DLBCL as a third line? You may be using GBRM in your hospital or LBRM in your hospital. Epcoritamab is also approved now for DLBCL.
So, I asked more than usual questions in this scenario because DLBCL is a hot topic in WWA. If they asked you regarding DLBCL, they will give you a scenario. Go through the flow cytometry investigation to confirm the diagnosis, double-hit and triple-hit lymphoma, IPI score, they will tell you that this is the LDH, this is the age of the patient, and this is the stage of the disease. What is the likely IPI of the patient? And then pre-treatment tests. Patient can send this patient is 45. Pregnancy test as well. And then choice of first-line therapy in this patient. What if this patient relapses? What are the second-line options? Do you have CAR-T or auto-transplant? And what is the third-line option in the patient? Now we have many bispecifics and long-acting, and the GBRM and the bispecific side effects, the CRS. They can ask you about this as well. So, DLBCL is a favorite question for WWA.
When it comes to the diagnosis, just to clarify that point, I don't need to say specific diagnosis, do I? Is it just to say just of high-grade? In the blood film, you cannot diagnose knows that this is Burkitt lymphoma or this is DLBCL or this is CL or mantle cell, etc. You always need supportive diagnosis that we do in our routine practice. When we see such blood film, we send the blood to HMDS as soon as possible and get the provisional flow within an hour to see which side we are heading. Whether this is high-grade lymphoma. If yes, it is a Burkitt or it is a DLBCL. This is routine practice that we do in our hospitals. We cannot diagnose anything on the blood film. You always need flow cytometry, cytogenetics, and this stuff to confirm your diagnosis. Yeah. Even for CL, you need flow cytometry to differentiate it from mantle cell because mantle cell lymphoma has five different variants. It can be a small cell variant, it can be a marginal type of mantle cell, it can be pleomorphic, it can be a blastic mantle cell which presents like ALL. Yes. Right. So, always you have to see, you have to say in your paper, the morphology paper, that "most likely consistent with this diagnosis, but you need certain tests to confirm the diagnosis," and you will mention flow cytometry, bone marrow biopsy with cytogenetics and molecular studies, or lymph node biopsy if amenable to biopsy on imaging.
Now, the touch case. Yeah. So, this is the trephine of a 50-year-old patient who has persistent low back pain and abdominal discomfort. The blood film shows pancytopenic picture. Because of pancytopenia, you did the bone marrow biopsy for this patient, and this is the Giemsa stain with power 4. I need someone to comment on this.
Okay. Yes, I can. Yes. So, this is the power 4. I can go here and there slowly, and then I will move to power 10. And this is the Giemsa stain. Okay. Okay. I will go to power 10 for [Music]. Right. Do you have any thoughts about that?
Well, as far as on low power, I can comment on the trephine biopsy. I can see three to four interocular areas, and while these are slightly thickened. Sorry, which area is thickened?
Trephine biopsy. But bone marrow is, I am seeing that.
Can you have my? Sorry, I cannot hear you clearly.
Okay. This is now, yes, somewhat better. This is the particular area. This is the power 50. The in-between spaces, the cells are somewhat normal, but near the particular area, they are having a distinct structure. Yes, it's altered background structure. So, slightly. These are like FB blasts and clipper-shaped cells, but I cannot see or focus the individual cells. It should be very difficult to focus on individual cells in trephine because they are very small. These cells are few cells having the eccentric nucleus with slightly pinkish cytoplasm. I think these are plasmacytoid cells which are prominent.
So, you have low back pain, you have pancytopenia, organomegaly, and you have a Giemsa stain trephine in the exam. Few lymphoid cells are also present here. These cells, these are the diagnostic cells. The spindle-shaped cells. These are spindle, slipper-like cells, and maybe non-optic cells or so. Spindle-shaped cells is the feature of mast cells. And the characteristic feature on the trephine is particular fibrosis, and they are best seen on Giemsa stain. So, you can see the body is fine, but the particular area is all like fibrotic. This is the feature of systemic mastocytosis. Okay. So, remember this point. If you see very particular fibrosis, think about monocytes. And the monocytes are spindle-shaped cells which are very well pictured here on high power. Okay. Yes.
So, now, how would you report this trephine?
Adequate length trephine biopsy, and slightly thickened bony trabeculae and cellular for the age. Slightly higher cellular for it, and I can see the altered background fibrosis as the fibrosis is prominent in the particular areas, and these spindle cells are also there. Spindle cells are also prominent in the particular areas, and slightly trage hyperplasia is active and trabeculae are also thickened. Yes, most likely consistent with consistent with any infiltration of mast cells. Monocytosis. Most likely consistent with monocytosis.
But you have a criteria to diagnose systemic mastocytosis. Do you know the major and minor criteria of systemic mastocytosis?
On biopsy, I think I'm not remembering. I haven't remembered, but maybe more than 30% mast cells in biopsy is a major criterion. I don't remember.
So, in the major criterion, you need an aggregate of more than 15 mast cells in the marrow or in any other organ in which you are suspecting mastocytosis. And for minor criteria, you need more than 25% spindle-shaped mast cells. Number one, number two is the KIT mutation, D816V. Number three is certain flow cytometry markers like CD25 and CD30. And the last one is serum tryptase is more than 20 nanograms per ml. So, you need one major or one minor criterion to diagnose systemic mastocytosis, or three minor criteria to diagnose it as systemic mastocytosis.
Yeah. So, you need to do flow cytometry on this patient. You need to send serum level on this patient, and molecular would be done on this biopsy for KIT mutation to find out if this is systemic mastocytosis or not. So, particular fibrosis, Giemsa stain, because Giemsa stain is the best thing to find out mast cells, bony lesions or bony pain of the patient, pancytopenia, these are all the hints that are given to you in the exam to diagnose systemic mastocytosis.
How do you treat systemic mastocytosis?
By means of supportive treatment and chemotherapy. Targeted therapy. Do you do you know any chemotherapy drug? It depends upon the molecular abnormalities. Midostaurin can be used. KIT, what TKI inhibitors? What on the molecular abnormality? What under cause? So, you can use KIT inhibitor. TKI can be used. But if there is KIT inhibitor and PDGFRA mutation as well, is there, then we have a new medication these days, Everolimus, which is a bit new in systemic mastocytosis.
AB. Yes, sorry. Are you saying Abrocitinib can be used?
In systemic mastocytosis? Everolimus. Yes. This is a new drug. Everolimus. And there are many trials going on in systemic mastocytosis. So, if asked in WWA, you should remember their name and the name for good.
One of the drug is called Bizuclast. It is under trial. And another one is Elagolix. Still in trial. But Everolimus has been approved, and we are using it in our patients.
Right. The second last case. So, this is a 33-year-old female referred from a district general hospital to you with a suspicion of leukemia. The full blood count shows hemoglobin of 131, platelet count of 150, and white cell count of 420. This is the blood film. I need a volunteer to comment on the blood film. Anyone?
Saalam Alaikum. Yeah. So, this is the power 10. Yes, of the of the patient, and you can see it is full of cells, right? I will go to power 50. I think this picture has all the cells that you need to know for the diagnosis. So, there is marked neutrophilia, like myeloid proliferation with all the stages, like promyelocytes and myelocytes. And there is this, this one is the basophil as well, with the neutrophil. And this one on the right. Yeah, this one. So, so there are different stages of myeloid maturation, like promyelocytes and myelocytes and neutrophils. There's a lot of neutrophils, more than other. So, so in this age and this lady, with with basophilia, it's it's a peripheral. I think it is it's the peripheral film. Yeah. So, it looks like a CML. Uh, but it could be in the differential with the CML, with the neutrophilia, but but it could be, but my initial provisional should be the CML for that patient. Chronic Myeloid Leukemia. The blasts are 21%. So, it could be in the blast phase.
[Music] Then. So, you cannot say that this is CML straight away on the blood film. Okay. Uh, you need blast percentage. You need BCR-ABL translocation. And then, okay, you can comment whether this is CML or CML in the blast phase. Okay. Because in Pakistan, when we used to do the morphology, normally go for the peripheral film for the CML patient, and just, yeah, there's the myeloid hypoplasia and the age favors that, and there's basophilia as well. So, not very advanced techniques, but our provisional could be with the CML for that. Yes.
So, most likely consistent with chronic myeloid leukemia. But you need, yeah, for the test to exclude blast phase or AML. Because, yeah, if a CML patient with blast more than 20% is AML according to WHO 2022.
Okay. All right. Is there any other category where a 20% blast cutoff is required to diagnose it as AML?
I think there are three, except the three, like core binding factor leukemias and in translocation 16;16 and inversion 16, except that, all need the 20% according to the new WHO classification. They doesn't require the 20% criteria for that. All, yeah, sorry. MDS, if MDS converts to acute myeloid leukemia, then requires more than 20% plus CML will also require more than 20% blast. No, in acute myeloid leukemia, all categories, if you have the specific mutations over there, 8;21 and translocation 16;16, I think these these doesn't need the 20%. I think if I'm not wrong, and I'm not seeing the reverse. WHO 2022 has mentioned two categories: AML with defining genetic mutation and AML defined by differentiation. So, all these mutations come in defining category where there is PML-RARA, RUNX1, BCR-ABL1, KMT2A, NPM, etc. If any of these mutations are present, they are called as AML without looking at the blast count, except BCR-ABL and CBF. CBF needs more than 20% blast to call it as AML. Yes. So, there are two defining mutations in AML which need to be to have more than 20% blast to consider it as AML. So, in that case, here, if the BCR-ABL1 positive, then we should need 20% criteria for that to diagnose to label it as AML. Yes. If this person has 8% blast in reality, but if she had 21% blast, then I would treat it as AML. Okay. Okay. I got you. Thank you.
Okay. All right. So, now [Music]. Um, you have done the BCR-ABL1 for this patient, which is positive. Blasts are 8%. And this patient is diagnosed as chronic myeloid leukemia in chronic phase, not in blast phase. Chronic phase. Yeah. Yes.
Okay. So, how would you explain to the patient that you have chronic myeloid leukemia and CP, and how would you explain the management with in that patient?
I will explain that it's a leukemia of blood. And although my clinical is not that much good in reference of some like counseling or just to tell the patient about the diagnosis, but I will, I will tell him about his proper diagnosis and, uh, and we will start from the, um, nip. And for that, the TKI is, I will offer the TKI for that. And, uh, I will tell him about, tell her about the response that we will check for that patient in a year, at three months, six months, and 12 months for that patient. And I will explain about that it will be the treatment for for a year, and we will check the response, and then for at least, we will continue this patient until the patient is not going into complete remission for that. And, uh, we will go for the monitoring of that patient on the basis of molecular and the cytogenetics. And then I will go for the drug details and its side effects for that patient. So, I will start that there could be different side effects of the TKIs, major grade, minor grade, late effects of all the disease, the drugs.
Explaining diagnosis and prognosis to a patient was a question this time in FC exam. The patient had a diagnosis of APML, and we were asked to mention prognosis, treatment options, complications of the treatment, and diagnosis to the patient. It was in the morphology paper, right?
Okay. You can expect any question in the exam. And these things we do routinely in our daily life. Whenever we have a diagnosis, we ask our staff, the CNS with us, or what staff to come with us, and we carry with ourselves the leaflet of the disease and the possible treatment options with us and ask the patient that we have the results of your disease. Do you want us to explain it to you now, or you need some family member to be present in the room or not?
Okay. So, is there any guidelines for that? Because, um, we are basically from the diagnostic part, and we really don't know about all these counseling, and because we don't have interaction with the patient, so is there protocols or any guidelines for that?
You, no. If you are appearing in FC Part Two exam, you are appearing, you are becoming a consultant. And once you become a consultant, ST6 or ST7 registrar, or act as a consultant here, and the expectation is quite a lot from the registrar ST6, ST7. When you have a diagnosis like this, you need to explain to the patient what is the next step you would like to do, what are the treatment options, whether the patient is fit for the treatment or not. All this has to be done by you. No one else would do that for you.
So, in terms of this patient, patient is 33 years old. Pregnancy consideration is very much important. And then prognostic score, you have to apply here. The ELTS or SoCal score. SoCal score is old now, but we apply ELTS score, which includes blast percentage, age, spleen, and one more, to find out whether the patient is high risk or low risk. Then you have explained to the patient that diagnoses that you have the leukemia of the white blood cell, but it is in mild to moderate stage and not in aggressive state. So, you do not need intensive chemotherapy at the moment. You are fit for the tablet form of therapy to control your cell count. But we need to do some investigations on you to find out whether you are fit for chemotherapy or not. The first step is the pregnancy test, because she is a young female. Because if she is pregnant, you have to be careful with TKIs, and you have the option of interferon. Okay. Then, second thing is that you want to do the bone marrow biopsy on the patient to find out whether this patient has major chromosomal abnormalities or not. Do you know major chromosomal abnormalities? Yeah, other than the, these are like other abnormalities like trisomy 8, or trisomy 9;19, or is there any other complex karyotype? Yes, extra Ph and chromosome 17. Yes, extra chromosome. Because the presence of these major chromosomal abnormalities means poor prognosis. Yeah. And then patient examination for any edema, any lung abnormalities, like effusion, infection, cardiomyopathies by echo, ECG, chest X-ray, baseline HbA1c, which is called Q risk scoring. You have to do as a baseline in this patient. Okay. And then, and then if the patient, if this patient has high ELTS or SoCal score, or if this patient wishes to have kids in the future, and wants a rapid molecular response to achieve, then you can start from second-generation TKI, Dasatinib, not from first-generation Imatinib, because there are few indications of second-generation TKI where you can start them as a first line. If the ELTS score is high, if the patient is young, fit, and wishes to have pregnancies in the future, the female patient, and if you want to bring the patient quickly into remission in case your transplant team is thinking about transplanting due to the presence of major chromosomal abnormalities, then you can offer them second-generation Dasatinib. Yes. Then there are three or four TKIs that you can use first line. You should remember their contraindications and side effects. Do, Dasatinib desaturates the person by causing effusion. Nilotinib has contraindication of neurovascular symptoms, stroke, and cardiovascular. Imatinib has the least side effects and contraindications. And remember these stuff in the exam. CML has appeared twice in the WWA in Aro. The last epath exam and the one before that had a CML question in a young lady, and they asked us about differential diagnosis, prognostic scores, pre-treatment testing, first-line drugs, second-line drugs, third-line drugs, and treatment-free remission TFR as well. Yeah. So, these are the favorite questions of the exam. It's been always complicated to decide for what should be for the patient as the first line, second line, and the third line. It's all dependent on the contraindications and the side effects and the patient suitability for that drug. Yes. And the ELTS score. If it is a high-risk ELTS score, then you start from second generation. If it is a low-risk ELTS score, then you consider first line as Imatinib is the best one. Because there was a very confusing table, I think in the ELN, for for the suitability for the first line and the second line drug, and there were lots of side effects and the contraindications, and they decided for which drug. It's been always confusing for me to decide for any patient to go for which drug exactly for that patient. So, the BSH says goes according to the ELTS scoring and patient condition, patient condition, and their comorbidities. Yes. But if someone has a past history of cardiomyopathy, you cannot give them nilotinib. If someone has a past history of stroke, then you cannot give them nilotinib.
The last question. Dr. Rama, I have a question. You said they also asked you about the differential diagnosis. So, my first question is, when you report this case, you will write that there is a myeloid hyperplasia, hyperplasia, and you find findings are consistent. Will you say your findings are consistent with chronic myeloid leukemia and you want to confirm it with either with FISH or BCR-ABL? Yes. So, you would say, "Consistent with most likely CML, but I would like to confirm it with further testing, flow cytometry, PCR, because if the blast percentage is more than 20%, then this is AML. If even on peripheral film, you think that the blast percentage is not more than 20% and they are less than that, still you will go for the flow cytometry." Yes, for confirmation, you have to do that. But you do not have this much time in the exam to count the blast percentage.
Can I add one thing here?
Yes, go ahead, please.
Yeah, according to the new WHO guideline, if there is less percentage of blast, even they are less than 20% of blast in case of CML, and the peripheral blood picture is suggestive of the chronic myeloid leukemia, and you have the less than 20% blast, and these blasts on flow cytometry are bona fide lymphoblasts, then whatever the blast percentage it is, it is treated like it is an acute lymphoblastic leukemia. What are you saying about this?
CML is now excluded. And yes, we have only chronic and blast phase. But one which you are talking about treating as ALL, never heard about that. Because accelerated phase has been excluded in the new guideline, and now this chronic phase with disease progression. So, whenever there is less, more than 10% blast, and you are seeing in the blood film, and you have the suspicious of CML, and these blasts are consistent with lymphoblasts, then whatever the percentage of blast you are having, the most strongly suspicious of lymphoblastic leukemia, so you can label it as a blast crisis of lymphoblastic phase. So, I don't know. I just read about it. And so, I have confusion about it.
The blast crisis or AML, almost the same thing. You give them intensive chemotherapy. Yes. You give them intensive chemotherapy. If you see the CML guidelines of the BSH, they have mentioned algorithm for myeloid blast crisis only, blast crisis, and both of them have been treated with intensive chemotherapy as the acute leukemia. No, I'm not talking about the treatment options or flowchart. I am talking about the diagnosis. So, you mentioned you treated as ALL. How? Like ALL has separate flow cytometry markers and genetic mutations, and CML has separate flow cytometry markers, and one is myeloid, one is lymphoid. You can send me the question, I will go through it and then I will answer accordingly.
Kindly tell the differential diagnosis of CML. So, it can be, this one, what is called, leukemoid reaction. It can be a leukemoid reaction. It can be an AML. It can be a CML. It can be a CNL as well. So, you give three or four differentials, that is fine. But that depends. CNL, but it will depend on the age of the patient. We can't say CNL in a young patient. And when we, that's why it is one of the differential, and you will exclude it on this basis that there is myeloid peak in this film. Alternative count is high, but they are not mature. And in leukemoid reaction, although the white cell count is high, but there should be no basophil in the reaction. So, you will exclude it like this. All right. Okay.
So, the last question. We have 8 minutes. So, this is a 45-year-old patient with refractory psoriasis, not responding to antiallergics, topical creams, and steroids. Anyone? The last case. Can you hear me?
Yes, yes, we are hearing you. Yes. So, take the last case and then we will wind up. This patient has a refractory psoriasis. He is 45 years old, and his psoriasis is not responding to any medication. He has applied a lot of steroid cream, antiallergics, a lot of medication he has used, but no relief. Any comments on these cells?
So, we can see a population of mononuclear cells, small to medium size, with increased NC ratio, and some of them have indented nuclei.
Okay. The nucleus is mature or immature looking? Like mature nucleus also. But but is nucleus also. One to two nucleoli, I think. This one might look like the mirror appearance. Okay. So, this one has a hammer appearance. What about the nucleus? The nucleus is slightly open chromatin with prominent nucleoli in that one. I might be wrong, but they seem mature to me. Let me show you a few more. What about this cell? It's a large size cell with irregular nuclear contour, low NC ratio. Mhm. And the nuclear chromatin is right.
The history and these cells, any thoughts? I'm for this. What about this cell? Again, it's a large size cell. Actually, even in the chromatin, there are areas of euchromatin and heterochromatin, that some lighter and some darker areas. Actually, they are not the nuclei, they are the nuclear pattern of these atypical lymphocytes. I might be wrong, but I think. Do you think these nucleus are cerebriform? I want to make them, but I'm not convinced. The patient history and these nucleus shapes because their nucleus is different than other cells that we have seen so far, small ones. If this one is looking like a cerebriform, lower one. Me, both look like a cerebriform, and this one as well. They have a lot of folds in the nucleus. The top one. See this fold? And this one, or this, or these are scissoring cells. And what about this one, Dr. M?
What I have seen, I had seen a case of cerebriform T-cell lymphoma. There were some like fetus-shaped nucleus. I mean, they have prominent cleaving in the nucleus. But you are right, one to two cells. I had suspicion when I was seeing, but I was not convinced. They are called cerebriform. So, cerebriform has a lot of lines in the nucleus. So, these cells have a lot of lines in the nucleus as well. And this one is just like a brain shape with a brain stem as well. So, this one has a lot of cerebriform lines. The top one. So, these are the scissoring cells, which will come in the exam, and they will ask you about the flow cytometry. This is a typical scissoring cell with cleaving, with lines, large nucleus, mature cell, and folded, just like the cerebellum of the cerebellum of the brain. So, refractory psoriasis plus these cells make a diagnosis of Sezary syndrome.
Right. So, how would we report it?
Okay. So, the blood film shows multiple atypical lymphocytes with mature nucleus having a lot of cleavage in the form of cerebriform. The red cells and platelet count look normal. The blood film is consistent with most likely Sezary syndrome, but we need to confirm this on flow cytometry. So, if this patient has any lymphadenopathy, which is less likely, you can send biopsy from the lymph node. But usually, it is the skin biopsy that tells us whether there is Sezary syndrome infiltration or not.
So, do we get go then? Yes. Very rare cases in which there is infiltration of various organs. As far as literature is saying, yes, the Sezary syndrome, when it infiltrates different organs, then it becomes Sezary syndrome. That's why this is the name. Otherwise, I think if it only involves the skin, it is called mycosis fungoides. It cannot be wrong. It is a peripheral T-cell lymphoma, but when it involves other organs, then it becomes syndrome.
Can we write in our report that our findings are consistent with T-cell lymphoma? Will it give us some points or will deduct our points?
How can you say this is a T-cell lymphoma when you don't have the flow cytometry with you? Because just because of the history, because of the presence of psoriasis, it came to mind that it's some T-lymphoproliferative disorder. I was trying to make it cerebriform, but I was not convinced that what I didn't say. But still, it was in my mind, it could be cerebriform. It's related to some T-cell lineage. So, in the exam, you were not sure. So, what would be your safe reporting in that case, or you just go for your intuition?
I would not say it is a B-cell lymphoma or T-cell lymphoma because I need flow cytometry markers for that to surely say that this is B-cell or T-cell. I would say this is, if I'm not sure that this is unknown Hodgkin lymphoma, but I need further investigation to confirm the lineage and the type of lymphoma. But if they have given you a refractory psoriasis, so I think their expectation will be more that you have seen a lot of such cases in your practice and you will be able to narrow your diagnosis to peripheral T-cell lymphoma, or peripheral T-cell lymphoma like Sezary syndrome, because these are the ones which involve the skin. Mhm. Okay. I'm not sure about anaplastic T-cell lymphoma whether it involves the skin or not, or the other one which involves the skin is mycosis fungoides. But mycosis fungoides is usually diagnosed on skin biopsy, but it is very, very rare to give you presentation like this because we have seen the blood films of mycosis fungoides, and they are completely empty. They don't have any significant cells in the peripheral blood. But these cells are quite significant, mature, cerebriform with right. So, you can narrow your diagnosis. And also, you cannot give any differential diagnosis on the blood film, and this is not an expectation from you. Even PhD consultant professors cannot make a diagnosis on blood film. They always need supportive investigations to confirm any diagnosis. We have recently a blood film which we were thinking as a registrar that this can be NPM1 AML because the cells were just looking like AML. Our consultant says that no, this looks like CL. The patient has splenomegaly, but when the report came from the HMDS, it was a DLBCL. So, you cannot be sure on the blood film. You cannot say that this is the diagnosis. You have to request for supportive investigations. So, that's why I'm saying, can we go straight to cerebriform just by looking? That's why we say "most likely consistent with." I'm not saying this is consistent with Sezary. I'm saying "most likely consistent with Sezary syndrome, but I need further investigation to confirm this, which is flow cytometry."
Okay. And how far they go for this investigation for this case? This case does not come in the WWA. It is a short case. Always it has appeared multiple times where they ask regarding report the blood film, what is the expected flow cytometry, and what is the management of Sezary syndrome?
So, what is the management?
So, the Sezary syndrome management is quite wide. You give immunosuppressive therapy, steroids. If refractory, then we use photopheresis for these patients. And if not responding to photopheresis, then there are some special chemotherapy drugs. And I forget the name, but there is one drug for that, including interferon as well, which is not licensed here. It is FDA approved, but on compassionate basis, we use it here. Starting from B, but I forget the name.
Okay. Thank you.
Okay. So, that's it for today. And see you next week.
Sorry, one more thing. There is no any specific immuno marker for it. But there are two, three, there are CD7 and CD8 negative, and CD25 negative. But there is no specific immuno marker which is present in cerebriform. It's like that. Yes, there is no specific marker for them. They should be having T-cell markers and CD8 negative. Thank you. And the morphology will help you in diagnosis. It's okay. Then see you next week. Thank you. Thank you very much. Thank you.