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Lymphoma
Dr Asheesh Mehta Internal Medicine Specialist December 06, 2018
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Lymphoma is a type of cancer affecting lymphocytes which are important cells of the immune system. Lymphocytes in the lymphatic system are primarily involved in lymphoma, the lymphatic system forming a critical part of the immune system. The lymphatic system consists of a network of channels carrying a fluid called lymph from the limbs and other organs towards the heart. The channels join to form lymphatic ducts which drain into one of the larger veins in the chest. Lymphoid tissue consisting of lymphocytes and other immune cells along with connective tissue is located along the lymph channels. Aggregations of lymphoid tissue form lymph nodes and these are scattered in many parts of the body including the neck, the inguinal region in the groin area, the armpit, in the abdomen and chest. The tonsils in our throat and adenoids located behind the nasal passages are also lymph nodes. Lymphocytes serve important immune functions with the two main types of lymphocytes being the B and the T lymphocytes. B lymphocytes produce immunologically active proteins that are called antibodies in response to foreign particles which are termed antigens. T lymphocytes on the other hand have the capability to attack antigens directly. They also modulate the activity and functions of the immune system. Both B and T lymphocytes have different sub-types. Lymphocytes are also present in blood in large numbers, being one of the types of white blood cells.

Cancer affecting lymphocytes in the lymphatic system is termed lymphoma. Cancer of lymphocytes in blood behaves somewhat differently and is termed lymphoid leukaemia of which also there are different types. In lymphoid leukaemias blood and bone marrow are primarily involved while in lymphomas the primary involvement is of lymphoid tissues including lymph nodes and spleen. Cancer refers to unregulated division of abnormal cells and in lymphoma too this is the case. The large number of abnormal cells results in formation of a mass in the affected lymph node or other organ such as the spleen. Cancerous lymphocytes usually spread to other lymph nodes via lymph channels. However, spread is not restricted to the lymphatic system and other organs too become sites of lymphoma deposits. Lymphoma spread to organs other than lymph nodes are termed extranodal deposits. There are many different types of lymphoma with one type given the name of Hodgkin’s lymphoma (HL) and all the other types coming under the group heading of non-Hodgkin’s lymphoma (NHL). Clinical presentation of all types of lymphomas is fairly similar with almost identical symptoms and signs making differentiation of HL from NHL on clinical grounds alone almost impossible. The differentiation is on the basis of microscopic findings of a biopsy specimen. This readily determines the type of lymphoma. Hodgkin’s lymphoma arises from an abnormal B lymphocyte line of cells while NHL may arise from either an abnormal B or T cell line. Even in HL, five different types are described depending on specific findings at microscopy. Regarding NHL the characteristics vary quite a bit among different types and about 30 sub-types have been identified. It is important to identify the type and sub-type of a lymphoma since the treatment and prognosis of HL and NHL and also of the various sub-types varies quite a bit.  Lymphoma is one of the commoner types of cancer and usually finds itself in the top 10 adult cancers in most countries while in children it is usually amongst the top 5 cancers. NHL is much commoner than Hodgkin’s. While lymphomas occur at all ages, HL has two peaks of increased frequency – one from about 15 years of age till the middle of the fourth decade and the other peak in people older than 55 years of age. NHL is commoner in older people.

Cancer affecting lymphocytes in the lymphatic system is termed lymphoma. Cancer of lymphocytes in blood behaves somewhat differently and is termed lymphoid leukaemia of which also there are different types
Although a number of factors have been associated with an increased risk of lymphoma development, the exact cause is not determinable in most cases. In common with many cancers, increasing age is one such risk factor especially in the case of NHL. Another important risk factor is the increased incidence of lymphoma in people with certain types of infections. Epstein Barr virus (EBV) causes a relatively common infection called infectious mononucleosis. The virus may persist in the body and its presence is believed to contribute to development of lymphoma in a few individuals. However, lymphoma does not develop in the majority of individuals harbouring this virus. Chronic iInfection with hepatitis B virus or hepatitis C virus is also found to increase the incidence of lymphoma development. These viruses are responsible for hepatitis B and hepatitis C respectively and much more commonly they are associated with the development of liver cancer. H.pylori is a bacterium colonizing the upper part of the gastrointestinal tract and responsible for most cases of ulcers in the stomach and duodenum. Many different diseases including increased incidence of stomach cancer, ischaemic heart disease and lymphoma have been attributed to this bacterium at some time or the other. Lymphoma is also much commoner in people with compromised immunity. The poor immunity allows diseased cells to survive. A leading cause of lowered immunity is HIV infection. Use of drugs to suppress immunity, commonly used after organ transplant is another very important cause. Lowered immunity is also a characteristic of a number of other inherited as well as acquired diseases. Exposure to noxious chemicals is another important cause of lymphoma. Various industrial chemicals, pesticides, insecticides, etc have been implicated. Radiation exposure as may occur during a nuclear accident or during radiotherapy cancer is another well known cause.

Symptoms are fairly similar in most types of lymphoma. Enlargement of lymph nodes is evident as swellings most usually detectable in the neck, armpit and groin areas. It needs to be remembered that lymphoma is only one of the quite long list of causes in which lymph node enlargement occurs. In lymphoma the nodes are usually painless. The spleen which is located in the left upper abdomen may also enlarge and this may sometimes be painful. Deeply situated lymph nodes as in the chest and abdomen are also enlarged and may cause symptoms by compressing surrounding structures. Systemic symptoms occur in a proportion of patients and include prolonged fever with or without chills, night sweats, weight loss, poor appetite, unexplained itching, unusual fatigue, etc. Most of these symptoms also occur in a number of infections and hence while the diagnosis of lymphoma may be suspected from these findings further tests are needed for confirmation of diagnosis.

The definitive test for diagnosis is microscopic examination of tissue obtained at biopsy. Needle biopsy is less traumatic and more easily carried out but interpretation is more difficult and also false negative is more frequent. Surgical biopsy of enlarged lymph nodes, if readily accessible, is a good method of obtaining adequate tissue. When only lymph nodes in the chest or abdomen are enlarged a biopsy is carried out by inserting an endoscope through a small incision. Bone marrow biopsy can also be carried out on out-patient basis and is also often quite helpful. Various imaging techniques such as ultrasound, x-ray, CT scan, etc also detect enlarged lymph nodes or involvement of other organs. Blood tests are also required. On the basis of the various tests grading and staging of the lymphoma are done. Grading refers to how well the lymphoma cells retain characteristics of the original cells. Poorly differentiated cells are denoted by a higher grading and suggest a more aggressive lymphoma. Staging gives an idea of the degree of spread of the lymphoma, higher staging meaning greater spread and poorer prognosis.

Various types of treatment modalities are available to treat lymphoma. The conventional ones are radiotherapy and chemotherapy. Very often both are given in combination. Both are associated with significant toxicity which can be ameliorated to a significant degree by using judicious doses and by giving other medicines to reduce side effects such as nausea. Chemotherapy is usually given as combination of multiple drugs and in cycles with drug-free periods in between cycles. Different drug protocols are advised for different types of lymphomas and even for the same type of lymphoma the protocol may vary depending on factors such as the age of the patient, the type and sub-type of lymphoma, the stage and grade of the cancer, etc. Differing drug protocols may also be adopted by different treatment centres. Also, depending on the introduction of new medicines as well as changing responses to therapy, newer protocols are recommended from time to time. A third option is immunotherapy usually in the form of monoclonal antibody or cytokines. These are less frequently used but have shown excellent results in selected patients.

Compared to most other cancers, lymphoma has a much better prognosis. In general HL responds better to treatment than NHL. The 5 year survival rates for HL are above 80% and 90% in adults and children respectively while for NHL this is above 60% and above 85% for adults and children respectively.
 

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