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Other Types – Lymphoma

by Paul Moss, PhD
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    00:01 cycles and indeed this is curative in the majority of patients these days. In contrast, the classic low-grade lymphoma is this disorder of follicular lymphoma. The molecular biology of follicular lymphoma is fascinating. This tumor carries a specific translocation the t(14:18) translocation and that involves the gene bcl-2. I do not know if you know but bcl-2 is one of the most important genes within an oncology and it regulates apoptosis, it stops the B cell from dying. The name itself comes from B-cell lymphoma #2. This disorder is often seen in older patients and they can be very slowly progressive. CT scans again are critical in showing the extent of disease, but treatment may only be given if the disorder was causing clinical problems because this is something that is very difficult to eradicate.

    01:00 For those who do this treatment, we have a number of options probably the first line may be this combination therapy of R-bendamustine or R-CVP and as we learnt on the previous site, the R refers to the antibody against CD20. So again that regimen of an antibody with some form of chemotherapy. Let me talk about the third major subtype of non-Hodgkin lymphoma, mantle cell lymphomas. The mantle zone is an area of B cells around germinal centers and follicles of B-cells. It is a less common lymphoma, but here we see a particular protein called cyclin D1, which is overexpressed because of a characteristic translocation in this disorder. This can be quite a challenging disease to treat, but combination chemotherapy can be affected and what is interesting is that the tablet, which blocks BTK, the Bruton's tyrosine kinase molecule is proving very effective in this disorder, similar to the chronic lymphocytic leukaemia, but BTK is also finding a very important role.

    02:26 Another very interesting subtype of non-Hodgkin lymphoma is lymphoblastic lymphoma. This tends to occur within lymph node and bone marrow and that gene MYD88 is mutated in the great majority of cases very useful for making the diagnosis and also helping us to understand the pathogenesis of this challenging disease. What is interesting about lymphoplasmacytic lymphomas is they often make an IgM paraprotein. That is an antibody, but they make it very high levels and of course it is a clonal antibody. For this reason, this disorder used to be known as Waldenstrom macroglobulinemia and indeed it is often used for that term still to this day. Now, The problem with the IgM paraprotein is that it can cause a number of clinical problems. IgM is a very big antibody and that makes the blood quite viscous difficult for the heart to pump around the body. On the right, you will see some retinal hemorrhages and the patient who have a high IgM level within that blood and the treatment of this disorder again is within combination chemotherapy and CD20 specific antibodies. Sometimes in the early stage of the disease, we actually have to take plasma of patients with lymphoplasmacytic lymphomas to lose some of those IgM antibodies to give the patient some relief before the chemotherapy starts to work. Burkitt lymphoma again is a remarkable subset of lymphoma with some unique features. It is a highly aggressive lymphoma. It proliferates very aggressively and if you look at this biopsy of this tissue may be 90 percent or more cells may be trying to divide. It is characterized by over-expression of myc often through that specific translocation of t(8:14) and on the right you will see a map of Africa.

    04:46 Now we have used that because Burkitt lymphoma is often seen in children who live in Africa particularly in malarial regions and here it is triggered by EBV infection. So we have two infectious complications, EBV and malaria coming together causing genetic damage and leading to Burkitt lymphoma. Elsewhere across the world, we do see Burkitt lymphoma.

    05:13 We call those sporadic cases and sometimes EBV is involved in these cases as well.

    05:21 Burkitt lymphoma is also more common in people carry HIV infection. The Burkitt lymphoma is an aggressive disease. It needs urgent treatment, but intensive chemotherapy now is allowing us to cure most patients with Burkitt lymphoma and is one of the great success stories of chemotherapy within lymphoma. I said earlier on that 15 percent of non-Hodgkin lymphoma are all T-cell origin. These are less common and some more what more difficult to treat, but I have just chosen to pick up four these subtypes and I explained a few things about these now. On the top left, cutaneous T-cell lymphoma. This is a disorder in which the malignant T-cells . . . to the skin and cause a range of clinical problems in the skin. This includes mycosis fungoides and Sezary syndrome. This is a difficult disorder to treat and some therapy is needed to be skin directed or can be given as intravenous chemotherapy. On the top right is a group of disorders called peripheral T-cell lymphomas, which presents similarly to diffuse large B-cell lymphomas and highly difficult to treat and cure. On the bottom left are anaplastic lymphomas. These are interesting because they tend to express ALK protein and there is a drug that can inhibit that protein and be used in these disorders and finally in the bottom right a rare subset of disease called adult T-cell leukaemia/lymphoma. This is seen in people from Japan or areas of the Caribbean and is particularly important and interesting because this is driven by infection by retrovirus called HTLV-1 and those in the past world in which virus is quite common.

    07:28 So In summary, we have learned in this lecture that Hodgkin lymphoma defined by the Reed-Sternberg cell is now highly treatable and the therapy really aims to minimize damage to the patient from intensive chemotherapy. We can use PET scans that help us to approach that.

    07:52 As you have seen, there are many subtypes of non-Hodgkin lymphoma defined by histology and increasingly by the genetics and in the lecture, we have looked at most of the major subtypes of non-Hodgkin lymphoma and thus I hope I have given an impression to you treatments are improving in most areas although unfortunately only a minority of cases remain curable at the current time.

    08:18 I hope you find this as a useful lecture.


    About the Lecture

    The lecture Other Types – Lymphoma by Paul Moss, PhD is from the course Hematology: Advanced.


    Included Quiz Questions

    1. Hodgkin Lymphoma
    2. Follicular Lymphoma
    3. Mantle cell Lymphoma
    4. Lymphoplasmacytic Lymphoma
    5. Burkitt Lymphoma
    1. Overexpression of BCL-2
    2. Decreased expression of BCL-2
    3. Overexpression of BCL-6
    4. Decreased expression of BCL-6
    5. Overexpression of BCL-4
    1. R bendamustine
    2. CHOP regimen
    3. MOPP regimen
    4. ABVP regimen
    5. BEACHOPP regimen
    1. Over expression of cyclin D1
    2. Decreased expression of cyclin D1
    3. Overexpression of BCL-2
    4. Overexpression of BCL-6
    5. Overexpression of Myc
    1. IgM
    2. IgD
    3. IgE
    4. IgG
    5. IgA
    1. HIV patients
    2. Low socioeconomic
    3. Coal miners
    4. Industrial workers
    5. Healthcare professionals
    1. aaaa
    2. Cutaneous T cell lymphoma
    3. Peripheral T cell lymphoma
    4. Anaplasitc lymphoma
    5. Adult T cell lymphoma
    1. Abnormal thrombosis
    2. Vasculitis

    Author of lecture Other Types – Lymphoma

     Paul Moss, PhD

    Paul Moss, PhD


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