Transcription
Hey everyone, this is Medicosis Perfection Alice. Let's continue in our series of lectures on hematology and oncology. Today's topic is myelodysplasia, or MDS, myelodysplastic syndrome. Your bone marrow is sad, this plastic, useless. But don't forget, bone marrow in MDS is hypercellular, full of dysplastic cells. And since the bone marrow is useless, you will have pancytopenia. So here in MDS, hypercellular marrow with pancytopenia. This is different from aplastic anemia because aplastic anemia had pancytopenia with hypocellular marrow; huge difference. As I've told you before, MDS is an intermediate gateway between normal state and acute myelogenous leukemia. It can progress towards acute leukemia. The whole purpose of treatment is to prevent the progression of MDS into leukemia. You know from pathology the dysplasia is precancerous, and in hematology, myelodysplasia is preleukemic, especially AML. Yep, this makes sense.
If you recall from my previous video on sideroblastic anemia, sideroblastic anemia was a defect in protoporphyrin synthesis. If there is no protoporphyrin, there is no heme. When there is no heme, there is no hemoglobin, and this is anemia. Okay. Causes of sideroblastic anemia included congenital, acquired, reversible, or acquired clonal, such as MDS, which is today's topic. Hello. The summary of your myeloid stem cell disorders: As you know, your bone marrow has myeloid lineage and lymphoid lineage. The myeloid stem cells in disorders include AML, MDS, and CML. Remember, MDS can progress towards leukemia. Dysplasia—the name has the answer. What does dysplasia mean? Synthesis or growth; dysplasia—difficulty of growth, abnormality of growth. Myelo generally it means the bone marrow; specifically, it means the myeloid lineage of the bone marrow. So here we have myelodysplasia—problems of maturation in the bone marrow, especially the myeloid lineage. Don't confuse myeloproliferative disorders and myelodysplastic syndrome. Both are myeloid, that's true, but still they are different. Myeloproliferative disorder: there is no pancytopenia, but in MDS, there is pancytopenia. And myeloproliferative, there is adequate maturation, and in MDS, inadequate maturation. This pleasure—MDS is commoner in males than females, around 50 to 80 years of age, so the median age is 60 or more. Okay, this is an old stem cell disorder with ineffective hematopoiesis. True. Dysplasia, defects in maturity. Why? It's a dysplasia of all cell lines of the myeloid lineage; that's why you will have pancytopenia, because all cell lines are involved. MCV will be high. Again, I told you, when cells mature, they decrease in size. When you have problems in maturation, you are stuck with the big cells; the MCV will be high. MDS is an acquired clonal disorder; could be caused by de novo mutation or environmental exposure, such as to benzene, chemotherapy, or radiation. Dysplasia and cytopenia are evident. By cytopenia, we mean pancytopenia. Anemia will lead to fatigue; thrombocytopenia will lead to bleeding; and leukopenia will lead to infections. MDS has a risk of transformation to AML in 30% of cases. This makes sense because dysplasia is precancerous.
A famous slide of hematopoiesis: This is the myeloid lineage. MDS effects all of this; you end up with anemia, leukopenia, thrombocytopenia. Classification of MDS: refractory anemia, refractory anemia with ring sideroblasts, refractory anemia with excess blasts, and refractory anemia with excess blasts in transformation. These are the four subtypes of MDS. Refractory anemia is the slowest subtype to progress to AML; refractory anemia with excess blasts in transformation is the fastest subtype to be transformed to AML. As you know, myeloid cells: RBCs, white blood cells, monocytes. And here the lymphoid—MDS only effects the myeloid.
Doctor, now I have MDS, is it really bad? This is the question of prognosticators. So, favorable prognostic factors are the 5q deletion, 20q deletion. 5q deletion is commoner in females. You'll have a female with thrombocytosis and good prognosis. Okay, this is cool. Unfavorable prognosticators: increased percentages of blasts. As you know, acute leukemia by definition has blasts greater than 20%. In MDS, you have blasts, but they are less than 20%. If the amount of blasts increases, it means you're going in the direction of acute leukemia, and this is bad. That's why increased percentage of blasts is a bad prognosticator. Also, increased number of cytopenias like anemia, thrombocytopenia, leukopenia—the more the cytopenias, the worse the prognosis. Increased age, of course. Cytogenetic abnormalities with chromosome 7.
To diagnose MDS: CBC, peripheral smear, and the bone marrow biopsy. On CBC, you will get pancytopenia with high MCV because immature cells are larger; low retic count because your bone marrow is a loser; it cannot respond. Peripheral smear: you will get pseudo Pelger-Huët anomaly. Okay, so normally your neutrophil is like this—okay, segmented nucleus. In pseudo Pelger-Huët, it's like this—okay, the neutrophil has a bilobed nucleus; two nuclear materials connected with a thin filament of chromatin. They can also be seen after chemotherapy. Basophilic stippling of the red blood cells—again, it's associated with sideroblastic anemia, which is due to lead poisoning. Again, in lead poisoning, you had basically stippling of the red blood cells. Large agranular platelets—large because they are immature; agranular because your bone marrow is such a loser; cannot produce normal platelets, because normal platelets have granules, and platelet without granules is like a car without tires; it's useless. Ring sideroblasts—again, sideroblastic anemia; don't forget, ring sideroblasts are nucleated and they have iron around the nucleus. Dimorphic red blood cells because some of them are macrocytic, some of them are microcytic. Okay, together we call them dimorphic red blood cells. When you have macrocytic and microcytic in the same blood smear, the RDW will be high. I've made a video on red cell distribution width, so make sure to check it out. Bone marrow biopsy: you will find blasts less than 20%. If blasts were more than 20%, this is acute leukemia. What type of blast? The myeloid blasts. Hypercellular marrow. This is different from aplastic anemia because aplastic anemia had hypocellular marrow. You have dysplasia in MDS; that's why we call it myelodysplasia. Leukoerythroblasticosis can be found in leukoerythroblastosis. You have immature white blood cells and immature red blood cells; like being crazy and stupid.
Differential diagnosis of MDS: B12 or folate deficiency. Why? All of them can lead to a macrocytic anemia; however, MDS is the only one that can lead to dysplasia. Aplastic anemia. Why? Aplastic anemia as well as MDS can lead to pancytopenia, but only MDS will have a hypercellular marrow. Myelofibrosis. Why? Myelofibrosis and MDS can cause nucleated red blood cells to be found as well as low retic count. What's the difference? In MDS, there is no proliferation; in MDS, there is no JAK mutation; no proliferation, no JAK mutation. This is so musical. Are you ready for this vignette? Let's get started.
69-year-old male coming for follow-up complaining of being "tired all the time" and "cannot walk as much as I used to." On physical exam, you discover that the conjunctiva are pale. Lab and CBC: you got white blood cells of 1.4 x 10 to the ninth power; this is like saying 1400 in a microliter. Platelet count 103—this is low. Hemoglobin 9.1—this is low. Hematocrit 35%—this is low. This is called pancytopenia. The MCV is high, so we have pancytopenia with high MCV. Peripheral smear shows large red blood cells which are immature, nucleated red blood cells which are immature, giant platelets which are immature, but there are no blasts. Okay, I don't care about blasts in the peripheral smear, but I care about blasts on the bone marrow biopsy. Bone marrow biopsy: there is hypercellular marrow with inadequate maturation. Okay, could be dysplasia. 11% blast—this is not acute leukemia yet; this is probably MDS. This is the correct answer. Why is that? You have an elderly patient; you have pancytopenia; you have high MCV; you have 11% blasts, less than 20%; you have inadequate maturation and hypercellular marrow. All of this points to MDS. Why not CLL? Because CLL can occur in the elderly; CLL can have anemia and thrombocytopenia; however, in CLL, this is leukemia; white blood cells will never be low. Hello, it's leukemia.
Next question: The patient is at risk of developing AML, B-cell ALL, CML, or CLL. And the answer is AML. MDS can progress into AML because dysplasia is precancerous. Thank you so much for watching. If you like this video, I would like to support the channel; go to patreon.com/medicosis. Also, you will get access to my videos before anybody else; you can ask me questions; you can request new videos to be done. If you'd like to test your knowledge on medical topics, go to my playlist called Medicosis Vignettes for more cases so that you can see if you can answer these questions. Or that's it for today; see in the next video. Have to manage myelodysplastic syndrome. Until next time, be safe, stay happy, and study hard.