Introduction to Lymphoma

Introduction to Lymphoma September 15, 2006 Dr. Carolyn Faught Ottawa Hospital Objectives 1. 2. 3. 4. 5. To outline the elements of blood, bone marrow and the lymphatic system Describe the epidemiology of lymphoma How to diagnose lymphoma Classification of lymphoma Staging/prognostic factors Bone Marrow     Spongy tissue where development of all types of blood cells takes place Occupies central cavity of bone All bones have active marrow at birth Adulthood - vertebrae, hip, shoulders, ribs, breast and skull contain marrow Bone Marrow Aspiration/Biopsy Normal Bone Marrow Biopsy Blood Cell and Lymphocyte Development STEM CELLS Multipotential myeloid cells Differentiate & mature into 6 Types of blood cells Multipotential lymphocytic cells Differentiate & mature into 3 Types of lymphocytes red cells basophils neutrophils monocytes eosinophils platelets T lymphocytes B lymphocytes Natural Killer Cells What is the Lymphatic System?     Made up of organs, such as the tonsils, spleen, liver, bone marrow and a network of lymphatic vessels that connect glands, called lymph nodes Lymph nodes located throughout the body Lymph nodes filter foreign particles out of the lymphatic fluid Contain B and T lymphocytes Lymphatic System Lymph nodes act as a filter to remove bacteria, viruses, and foreign particles  Most people will have had “swollen glands” at some time as a response to infection  Lymphocytes      Most lymphocytes are in lymph nodes, spleen, bone marrow and lymphatic vessels 20% of white blood cells in blood are lymphocytes T cells, B cells, natural killer cells B cells produce antibodies that help fight infectious agents T cells help B cells produce antibodies and they fight viruses How Cancer Develops      Normal cells are programmed to multiply, die when they’re old Signals to multiply and die are controlled by specific genes Mutations can occur in these genes If enough mutations occur in genes controlling growth or cell death a cell begins to multiply uncontrollably The cell has then become cancerous or “malignant” Features common to cancer cells 1. Growth in the absence of “go” signals 2. Growth despite “stop” signals 3. Locally invasive growth and metastases to distant sites What is Lymphoma    Lymphomas are cancers that begin by the “malignant transformation” of a lymphocyte in the lymphatic system Many lymphomas are known to be due to specific genetic mutations Follicular lymphoma due to overexpression of BCL-2 (gene that blocks programmed cell death) Risk Factors for Adult NHL          Being older, male Autoimmune disease HIV/AIDS Other viruses (EBV, HTLV-1) Helicobacter pylori infection (in stomach) Long term use of immunosuppressant drugs Pesticides Past treatment for Hodgkin’s lymphoma or with radiation Other unknown environmental factors ? incidence mortality Symptoms of Lymphoma        Painless swelling in the lymph nodes Fever Drenching night sweats Unexplained weight loss Fatigue Itchy skin Organ specific symptoms How To Classify NHL  WHO (World Health Organization) classification – over 30 types, a big list! Based on the grade or “aggressiveness”  Divided into Hodgkin’s lymphoma and NHL  NHL divided into B and T cell  WHO Classification of Lymphoma  Table 2. Diagnostic Designations of the LymphomasI. Types and Frequency of Non-Hodgkin Lymphomas A) B-Cell Lymphomas (>85%) Diffuse Large B-Cell Lymphomas (31%) Follicular Lymphoma (22%) Mucosa-Associated Lymphatic Tissue (MALT) Lymphoma (7.5%) Small Lymphocytic Lymphoma-Chronic Lymphocytic Leukemia (7%) Mantle Cell Lymphoma (6%) Mediastinal (Thymic) Large B-Cell Lymphoma (2.4%) Lymphoplasmacytic Lymphoma-Waldenstrom Macroglobulinemia (<2%) Nodal Marginal Zone B-Cell Lymphoma (<2%) Splenic Marginal Zone Lymphoma (<1%) Extranodal Marginal Zone B-Cell Lymphoma (<1%) Intravascular Large B-Cell Lymphoma (<1%) Primary Effusion Lymphoma (<1%) Burkitt Lymphoma-Burkitt Leukemia (2.5%) Lymphomatoid Granulomatosis (<1%)                  B) T and NK Cell Lymphomas (~12%) Extranodal T or NK-Lymphoma Cutaneous T-Cell Lymphoma (Sézary Syndrome and Mycosis Fungoides) Anaplastic Large Cell Lymphoma Angioimmunoblastic T-Cell Lymphoma    C) Immunodeficiency-Associated Lymphoproliferative Disorders Grades of Lymphoma (NHL)  Low Grade (slow growing, incurable)  Follicular, small lymphocytic, Waldenstrom’s  Intermediate Grade (rapid growing, potentially curable)  Diffuse large B cell, mantle cell, anaplastic large (T cell) NHL  High Grade (fastest growing, potentially curable)  Burkitt’s lymphoma, lymphoblastic lymphoma Hodgkin’s Lymphoma   Nodular lymphocyte predominant Classical Hodgkin’s     Nodular sclerosis Mixed cellularity Lymphocyte rich Lymphocyte depleted * The stage is more important than the type for prognosis The Diagnostic Process  Mandatory lymph node biopsy  Excisional biopsy  Core biopsy  Needle aspiration/biopsy Blood tests (complete blood count, LDH, liver and kidney function) Staging procedures Lymph node biopsy – Follicular NHL Lymphoma Involving Bone Marrow Staging Process    CXR CT scans Bone marrow aspiration/biopsy     PET scan Gallium scan MRI Lumbar puncture Staging of Lymphoma  Staging classifies tumours into categories based on where the tumour is present Ann Arbour system Useful in determining specific treatments, prognosis   Ann Arbour Staging     Stage I – limited to one group of lymph nodes or a single area of organ involvement Stage II – two or more groups of lymph nodes on the same side of the diaphragm Stage III – lymph nodes on both sides of the diaphragm Stage IV – widespread disease outside the lymph nodes Staging of Lymphoma Prognosis   Many factors involved Some important variables         Sub-type of lymphoma Age Stage Extra-nodal disease LDH Performance status (how sick you are) Hemoglobin level Number of lymph node sites