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  2. 2. DEFINITION It is a defined as lymphoma is a cancer of . lymph node lymphoma is a type of cancer that begins in immune system cells called lymphocytes .production of one or more abnormal cells in one or more of the lymph nodes.
  3. 3. Abnormal lymphocytes collect in one or more lymph node or in lymph tissues such as spleen ,tonsils and eventually they from mass of cells called tumor. Cancer that forms in the germ-fighting lymphatic system is called lymphoma. Lymphoma: A tumor of the lymphoid tissue. The major types of lymphoma are Hodgkin's disease and non-Hodgkin's lymphoma
  4. 4. IMMUNE SYSTEM PROBLEM •This may be because their immune system is weakened by another medical condition, such as: •being on drugs to prevent rejection of an organ or bone marrow transplant (immunosuppressive drugs) – lymphomas that develop in this situation are sometimes called post-transplant lymph proliferative disorders
  5. 5. INFECTION •Infections •Certain lymphomas are linked to particular infections. A few viruses cause lymphomas directly – the virus lives in the lymphoma cells and makes them grow and divide. Other viruses and bacteria cause lymphomas indirectly – the infection stimulates the immune system chronically (over a long time), which makes lymphoma more likely to develop.
  6. 6. Con……. •Epstein–Barr virus •human T-lymphotropic virus 1 human herpes virus hepatitis C virus Helicobacter pylori, Chlamydia psittaci,
  7. 7. ABNORMAL B CELL •B cells develop large abnormal cells ,these abnormal cancerous cells are called Reed-sternberg cells . Instend of undergoing the normal cell cycle of life and death, •Reed-sternberg cells don't die and they continue to produce abnormal B cells in a malignant process . These cells also attract other normal immune cells that cause the tumor ..
  8. 8. •Previous cancer treatments •Chemotherapy and radiotherapy treatment given for a previous cancer can increase the risk of someone developing lymphoma. This is thought to be due to damage caused by these treatments to genes of the lymphocytes
  9. 9. •Older age •Many lymphomas, like other cancers, are more common in older people. This is because as time goes on more changes happen in the genes and the body is less able to repair these.
  10. 10. •Lifestyle •Smoking Many cancers are caused by smoking but there is much less evidence that it leads to lymphoma. Smokers may have a slightly increased risk of follicular lymphoma
  11. 11. Lymphoma Main types: 1) Hodgkin lymphoma 2) Non Hodgkin lymphoma # B-cell lymphoma # T-cell lymphoma
  12. 12. •B lymphocytes (B cells): B cells make proteins called antibodies to help protect the body from germs (bacteria and viruses). •T lymphocytes (T cells): There are several types of T cells. Some T cells destroy germs or abnormal cells in the body. Other T cells help boost or slow the activity of other immune system cells.
  13. 13. HODGKIN LYMPHOMA •Lymphoma is the most common blood cancer. The two main forms of lymphoma are Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Lymphoma occurs when cells of the immune system called lymphocytes, a type of white blood cell, grow and multiply uncontrollably. Cancerous lymphocytes can travel to many parts of the body, including the lymph nodes, spleen, bone marrow, blood, or other organs, and form a mass called a tumor. The body has two main types of lymphocytes that can develop into lymphomas: B-lymphocytes (B-cells and T-lymphocytes (T-cells). •.
  14. 14. Hodgkin lymphoma progresses it compromises body's ability to fight infection .common beginning Lymph nodes located in upper part of body ….
  15. 15. TYPES OF H L •Nodular Sclerosis HL is the most common subtype of HL, accounting for 60 to 80 percent of all HL cases. In nodular sclerosis CHL, the involved lymph nodes contain RS cells (Reed/Sternberg ) mixed with normal white blood cells. The lymph nodes often contain a lot of scar tissue, which is where the name nodular sclerosis (scarring) originates.
  16. 16. Epstein-Barr virus infection: Having been infected with EBV might lead to mutation(s) in the B-lymphocytes, causing the abnormal Reed- Sternberg cells to develop •HIV infection and AIDS: This subtype is more commonly associated with HIV infection MIXED CELLLULARTY HODGKIN DISEASE
  17. 17. Lymphocyte-Depletion •. Involvement of lymph node by HIV- associated classic Hodgkin lymphoma of the lymphocyte depletion subtype. Large Hodgkin Reed-Sternberg (HRS) cells with multiple nuclei and prominent nucleoli are present. HRS cells express the typical phenotype with intense staining
  18. 18. The Revised European American Lymphoma Classification (REAL) I. Precursor B-cell neoplasm: # Precursor B-lymphoblastic leukemia/lymphoma II. Mature (peripheral) B-cell neoplasms # B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma # Lymphoma of mucosa-associated lymphoid tissue type (MALT) # Follicular lymphoma # Mantle cell lymphoma # Diffuse large cell B-cell lymphoma # Burkett's lymphoma
  19. 19. The Revised European American Lymphoma Classification (REAL) I. Precursor T cell neoplasm: # Precursor T-lymphoblastic lymphoma/leukemia II. Mature (peripheral) T cell and NK-cell neoplasms # Adult T cell lymphoma/leukemia (HTLV1+) # Mycosis fungoides/Sézary's syndrome # Peripheral T cell lymphoma, not otherwise characterized # Anaplastic large cell lymphoma, T/null cell, primary systemic type T-Cell and Natural Killer Cell Neoplasms
  20. 20. Hodgkin lymphoma 1) Nodular lymphocyte predominance Hodgkin's lymphoma 2) Classical Hodgkin's lymphoma Nodular sclerosis Hodgkin's lymphoma Lymphocyte-rich classical Hodgkin's lymphoma Mixed cellularity Hodgkin's lymphoma Lymphocyte depletion Hodgkin's lymphoma
  21. 21. Epidemiology
  22. 22. Hodgkin lymphoma  Definition: A neoplastic transformation of lymphocytes particularly in lymph nodes. Characterized by: 1) the presence of Reed-Sternberg cells on histology 2) spreading in an orderly fashion to contagious lymph nodes ( For example, Hodgkin lymphoma that starts in the cervical lymph nodes may spread first to the supraclavicular nodes then to the axillary nodes )
  23. 23. Red-Sternberg cells # Cells with mirror image nuclei and prominent, eosinophilic, inclusion- like nuclei.
  24. 24. Etiology Hodgkin disease has bimodal age distribution-- one peak in the 20s and 60s. Doctors seldom know why one person develops Hodgkin lymphoma and another does not. But research shows that certain risk factors increase the chance that a person will develop this disease. Having one or more risk factors does not mean that a person will develop Hodgkin lymphoma. Most people who have risk factors never develop cancer.
  25. 25. Risk factors 1) Certain viruses: Epstein-Barr virus (EBV) Human immunodeficiency virus (HIV) 2) Weakened immune system: inherited condition  certain drugs used after an organ transplant 3) Age: Hodgkin lymphoma is most common among teens and adults aged 15 to 35 years and adults aged 55 years and older. 4) Family history: Family members, especially brothers and sisters, of a person with Hodgkin lymphoma or other lymphomas may have an increased chance of developing this disease.
  26. 26. Clinical presentation  Enlarged, painless, rubbery, non- erythematous, nontender lymph nodes are the hallmark of the disease.  May become painful after drinking alcohol  Patients may develop ‘’B’’ symptoms which are: # Drenching night sweats. # 10% weight loss # Fever  25% have ''B'' symptoms  Although pruritus is common in the disease it is not one of the ‘’B’’ symptoms.  Cervical, supraclavicular and axillary lymphadenopathy are the most common initial signs of the disease.
  27. 27. Clinical presentation Extralymphatic sites may be involved such as: # Spleen # Liver # Bone marrow # Lung # CNS Extralymphatic involvement is more common with non- hodgkin lymphoma.
  28. 28. Clinical presentation Emergency presentation: Infections SVC obstruction ( facial edema, increased JVP and Dyspnea)
  29. 29. Staging The doctor considers the following to determine the stage of Hodgkin lymphoma: The number of lymph nodes affected. Whether these lymph nodes are on one or both sides of the diaphragm. Whether the disease has spread to the bone marrow, spleen, liver, or lung. Each stage is divided into A or B symptoms according to the presence of systemic symptoms.
  30. 30. Staging
  31. 31. Diagnosis An excisional lymph node biopsy is the essential first step in diagnosis. A biopsy is the only sure way to diagnose Hodgkin lymphoma. The biopsy can be: 1) Excisional biopsy 2) Incisional biopsy 3) Fine needle aspiration usually cannot remove a large enough sample for the pathologist to diagnose Hodgkin lymphoma. After that the most important step is to determine the extent of the disease because the stage will determine the nature of the therapy, that is, radiation vs. chemotherapy
  32. 32. Investigations used for staging  Chest x-ray : X-ray pictures may show swollen lymph nodes or other signs of disease in the chest .  CT: Chest, abdomen and pelvis ( CT is sensitive enough to detect any abnormal nodes)  MRI  PET scan  LP for CSF cytology if any CNS signs  Lymphangiography and laparotomy are no longer used for staging.  A bone marrow biopsy is used when : 1) B symptoms 2) Stage3 or 4
  33. 33. Abnormal lab tests ( don’t alter the stage of the disease) CBC: anemia and high WBC ( Eosinophilia is common) LDH: high ( poor prognostic factor) ESR: high ( poor prognostic factor) LFTs: help determine the need for liver biopsy
  34. 34. After lymphoma is diagnosed, a variety of tests may be carried out to look for specific features characteristic of different types of lymphoma. These include: 1) Immunophenotyping 2) Flow cytometry 3) FISH testing. The classification of lymphoma can affect treatment and prognosis. Classification systems generally classify lymphoma according to: 1) Whether or not it is a Hodgkin lymphoma. 2) Whether the cell that is replicating is a T cell or B cell. 3) The site that the cell arises from.
  35. 35. Histology Hodgkin has several histological subtypes. Lymphocyte-predominant has the Best prognosis. Lymphocyte-depleted has the Worst prognosis.
  36. 36. Treatment Therapy is entirely based on the stage. Localized disease ( stage IA and IIA ) is managed predominantly with radiation. All patients with evidence of ‘’B’’ symptoms as well as stage III and IV are managed with chemotherapy. The most effective combination chemotherapeutic regimen for Hodgkin lymphoma is ABVD ( adriamycin, bleomycin, vinblastin and dacarbazine).
  37. 37. Treatment  ABVD is superior to MOP (meclorethamine, vincristin(oncovin) , prednisolone and procarbazine) because ABVD has fewer side effects such as: 1) Permanent sterility 2) Secondary cancer formation 3) Aplastic anemia 4) Peripheral neuropathy
  38. 38. International Prognostic Index The International Prognostic Index (IPI) was first developed to help doctors determine the prognosis for people with fast- growing lymphomas. The index depends on 5 factors: 1) The patient’s age 2) The stage of the lymphoma 3) Whether or not the lymphoma is in organs outside the lymph system 4) Performance status (PS) – how well a person can complete normal daily activities 5) The blood (serum) level of (LDH)
  39. 39. Follicular Lymphoma International Prognostic Index The IPI is useful for most lymphomas, but it’s not as helpful for follicular lymphomas, which tend to be slower growing.
  40. 40. Non-Hodgkin lymphoma (NHL) Definition: The neoplastic transformation of either B or T cell lineages of lymphatic cells. NHL causes the accumulation of neoplastic cells in both the lymph nodes as well as more often diffusely in extralymphatic organs and the bloodstream. Absent reed-Sternberg cells.
  41. 41. Risk factors INFECTIONS: Human immunodeficiency virus (HIV)  Epstein-Barr virus (EBV): linked to Burkitt lymphoma. Helicobacter pylori: Extranodal tissues generating lymphoma include MALT ( Mucosa associated lymphoid tissue) Human T-cell leukemia/lymphoma virus( HTLV-1) Hepatitis C virus Age: Most people with non-Hodgkin lymphoma are older than 60.
  42. 42. Clinical Presentation Clinical presentation is the same as for Hodgkin lymphoma. The difference is that Hodgkin is localized to cervical and supraclavicular nodes 80%-90% of the time. Whereas NHL is localized 10-20% of the time. CNS involvement is more common with NHL. HIV positive patients often have CNS involvement.
  43. 43. Staging and diagnosis Staging and Diagnosis are the same as for Hodgkin lymphoma. Differences: Bone marrow biopsy is more central in the initial staging of NHL Because the presence of bone marrow involvement means the patient has stage IV disaese and therefore needs combination chemotherapy, further invasive testing such as laparotomy is not required.
  44. 44. Grades NHL divided into Low or high grade A high grade lymphoma has cells which look quite different from normal cells. They tend to grow fast (aggressive).usually look follicular. Incurable. Wider dissemination at presentation. Low grade lymphomas have cells which look much like normal cells and multiply slowly(indolent).usually look diffuse. Long term treatment maybe achievable.
  45. 45. Low-grade lymphomas Many low-grade lymphomas remain indolent for many years. Treatment of the non-symptomatic patient is often Avoided.  In this case watchful waiting is often the initial course of action. This is carried out because the harms and risks of treatment outweigh the benefits. If a low-grade lymphoma is becoming symptomatic, radiotherapy or chemotherapy are the treatments of choice. They don’t cure the lymphoma, they can alleviate the symptoms. Patients with these types of lymphoma can live near-normal lifespans, but the disease is Incurable.
  46. 46. High-grade lymphomas Treatment of the aggressive, forms of lymphoma can result in a cure in the majority of cases. However, the prognosis for patients with a poor response to therapy is worse. Treatment for these types of lymphoma typically consists of aggressive chemotherapy, including the CHOP or R- CHOP regimen.
  47. 47. Treatment Same principles of treating Hodgkin Lymphoma. The initial chemotherapeutic regimen is CHOP  ( cyclophosmamide, hydroxy-adriamycine, oncovin and prednisolone). CNS lymphoma is often treated with radiation in addition to CHOP. Relapses can be controlled with BM transplantation. Some pts express CD-20 antigen in greater amount. In this case, monoclonal antibody Rituximab should be used. Rituximab is an anti-CD20 antibody that has limited toxicity and add survival benefit to the use of CHOP.