Hodgkin Lymphoma – Lymphoma

by Paul Moss, PhD

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    00:03 Hello, Welcome to this lecture on the important topic of lymphoma. In this lecture, you will learn a number of important points. In lymphoma, the malignant lymphoid cells accumulate in the lymphoid tissue rather than blood. There are two broad sub-types of lymphoma - Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is diagnosed by the presence of the Reed-Sternberg cells whereas non-Hodgkin's lymphomas are an extremely heterogeneous group of disorders. Lymphoma is a disorder of malignant lymphoid cells, but in lymphoma these cells accumulate in lymphoid tissue whereas in leukemia they are mainly in the bone marrow and blood.

    00:54 If you look at the slide on the right, you will see that this patient has a very large lymphoid node mass in the neck. The incidence of lymphoma is the increasing, particularly non-Hodgkin lymphoma. We really do not know the epidemiology behind this trend.

    01:13 The treatments of lymphoma depend on the accurate diagnosis of the disease subtype and during this lecture, we will spend time working out how to make the correct diagnosis.

    01:27 Let us start with Hodgkin lymphoma. This disorder was described by Thomas Hodgkin in 1832.

    01:35 He worked at . . . Guy's Hospital in London and on the right this very beautiful drawing shows the original description of Hodgkin lymphoma from that time and it actually shows one of the major features of Hodgkin lymphoma, which tends to spread down the lymphatic system, in this case from the neck into the axillary lymph nodes. The most common presentation of Hodgkin lymphoma is within large lymph nodes usually in the neck and as I said from the picture, it tends to spread through the lymphatic system rather than through other tissues. There may be additional symptoms, which are important in staging Hodgkin lymphoma.

    02:23 These are fatigue, weight loss, and fever. The diagnosis of Hodgkin lymphoma as with all these diseases depends on the history, examination and investigations. The history should focus on the time course of the swelling of the lymph nodes, which may indicate any other systemic symptoms as well. EBV infection is implicated as a course of many cases of Hodgkin lymphoma. This is seen because there is evidence of EBV infection in many of the tumor cases and also interestingly when some people get that first EBV infection, they can get glandular fever or infectious mononucleosis nor that always clears up. Many years later they do carry a high risk of developing Hodgkin lymphoma.

    03:22 Examination of the patient should be of the major lymph node groups, the neck, under the arms and in the abdomen and groin. Blood tests may show anemia and very often patient will have a CT or an MRI scan to look for evidence of disease. On the right, you can see a chest x-ray showing mediastinal lymphadenopathy. But to make the diagnosis, you need to get some lymph node tissue and that biopsy is critical for looking for the Reed-Sternberg cell. This is the characteristic feature of Hodgkin lymphoma, the Reed-Sternberg cell.

    04:07 It is an unusual cell in histology, which is large generally, has a bilobed nucleus and has very prominent nucleoli. You can see some of the cells on that specimen, which have a white cytoplasmic halo and a very prominent nucleolus. The Redd-Sternberg cell is derived from a B-cell and it expresses markers such as CD15 and CD30 and pathologists used these stains to make the diagnosis of Hodgkin lymphoma. Pathologists also categorize Hodgkin lymphoma into four major types, nodular sclerosing, mixed cellularity, lymphocyte depleted and lymphocyte predominant and this will affect the prognosis of the patient in some cases.

    05:06 Now when a patient is diagnosed with non-Hodgkin lymphoma, it is very important to stage the disease and essentially what we are doing here is seeing how far the disease has progressed because that will indicate the type of treatment that we need to give. Hodgkin lymphoma is staged from I-IV. Let us look at these in more detail. In stage I disease, there is swelling of a lymph node in one region perhaps in the neck as shown in this picture.

    05:43 In stage II, there is involvement of two lymph node groups but on the same side of the diaphragm as you will see in the picture there in which case we have lymph node swelling and mediastinal swelling. Stage III disease shows disease above and below the diaphragm whereas stage IV is disseminated disease and involves abnormal lymphoid tissues perhaps the spleen or the bone marrow. In addition, we also have to stage the disorder on whether the patients have systemic symptoms such as fevers or weight loss. A indicates the absence of these whereas B indicates that these are present and that represents a more challenging disease to treat.

    06:38 So a patient may be categorized as stage IIA or IIIB for example.

    06:48 The treatment of Hodgkin lymphoma depends on the use of chemotherapy and radiotherapy in various degrees of combination. The standard chemotherapy regimen for many years has been that ABVD regimen (Adriamycin, bleomycin, vinblastine and dacarbazine) and this is a very effective treatment for Hodgkin lymphoma. Now one of the big questions, when you are thinking about treatment of Hodgkin lymphoma, is the amount of chemotherapy and perhaps radiotherapy, which you might want to give to the patient and doctors are moving towards trying to minimize the amount of treatment that is given so as to maintain the high cure rate while it is limiting the side effects of chemotherapy and radiotherapy. Here I have shown some examples of regimens that you might consider the different stages of the disease.

    07:50 So stage IA is very early disease, limited to one area and with no systemic symptoms and here relatively short courses of chemotherapy or chemotherapy with small amounts of radiotherapy may be used. For stage IB or II, you might want to give 4 to 6 courses of ABVD every month and may be only given radiotherapy to very large lymph node groups whereas some more advanced disease, you may wish to give a lot many more courses, 6-8 courses of ABVD and with radiotherapy to lymph nodes that we made at the end of treatment.

    08:30 People are always to trying to improve and advance treatment and in some cases you have slightly different chemotherapy regimen and there is an example there of one that is used for some more intensive chemotherapy called BEACOPP, which incorporates some additional chemotherapy agents. Now, The PET scan, the positron emission tomography scan is highly important in the treatment of Hodgkin lymphoma. The PET scan involves the injection of fluorodeoxyglucose, which is an analog of glucose. It is taken up tumor cells and his case Hodgkin lymphoma cells and then admits gamma rays. These are detected by an external scanner and they can be combined with the CT scan. It is a PET/CT scan. You can see that on the right.

    09:28 The PET scans are very useful for indicating areas of the active tumor. They can be useful for guiding the need for further treatment and also for distinguishing between tumor and scar tissue. That is particularly important in Hodgkin lymphoma because lymph nodes can remain large even after treatment when there is no active disease and the other way where the PET scans are quite interesting is that they may be used to guide and potentially limit the amount of treatment that are given to individual patients, so to titrate the therapy against the response. The outcome for patients with Hodgkin lymphoma is very good. Unfortunately relapse can occur and this tends to be treated by different courses of chemotherapy, the stem cell transplant perhaps using stem cells from the patient themselves called an autologous transplant or an allogeneic transplant from another person, antibodies to block PD-L1 are emerging as a very effective immune therapy for Hodgkin lymphoma and may actually come to be used in first-line therapy in future years and antibody is again CD30, which we have learned earlier on as expressed on the Redd-Sternberg cells are also proving effective. If you put all of this together, we can see that overall survival is excellent for patients with Hodgkin lymphoma and there are over 85 percent of patients can achieve a long-term cure. But a major concern with therapy in Hodgkin Lymphoma is to avoid the complications of the treatment itself. This can be seen as secondary malignancies many years later or cardiac toxicity from the chemotherapy and radiotherapy and that is driven and moved to limit the chemo and radiotherapy to the just minimum needed for disease control. Now let us move to the other major subtitle

    About the Lecture

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

    Included Quiz Questions

    1. It expresses CD35+
    2. It is a ‘crippled’ B cell
    3. It has very prominent nucleoli
    4. It defines the diagnosis of Hodgkin lymphoma
    5. It expresses CD15
    1. Stage A means that systemic features are present.
    2. Swelling of lymph nodes in only one region is stage I.
    3. Stage III refers to disease above and below the diaphragm.
    4. Systemic features include fever or weight loss.
    5. Involvement of the spleen or bone marrow would define stage IV.

    Author of lecture Hodgkin Lymphoma – Lymphoma

     Paul Moss, PhD

    Paul Moss, PhD

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