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Lymphoma DR: Gehan Mohamed Learning objectives • • • • important types of lymphoma Clinical presentation Diagnosis Staging ALL CLL Lymphomas Myeloma naïve B-lymphocytes Lymphoid progenitor AML Hematopoietic stem cell Myeloid progenitor Plasma cells T-lymphocytes Myeloproliferative disorders Neutrophils Eosinophils Basophils Monocytes Platelets Red cells Normal structure of reactive lymph node Microscopic picture of reactive lymphoid follicles lymphoma • Definition : malignant neoplasm of lymphoid origin, typically causing solid tissue mass usually in form of lymphadenopathy but may be presented as extra nodal mass as in brain or intestine. Epidemiology of lymphomas • 5th most frequently diagnosed cancer in both sexes • males > females Causes of lymphoma • Genetic alterations causing mutations in chromosomes. • Infection specially with viruses as Human T- cell leukemia Lymphoma virus , Epestein Bar virus. • Immunosuppression Pathogenesis of lymphoma • There is monoclonal expansions of lymphocytic cells at certain developmental stages either of the : (1)immature type which arise from lymphoblast . (2) the mature type which arise from lymphocyte. WHO classification of lymphoid neoplasms • B cell neoplasm. • T cell neoplasm. • Hodgkin lymphoma. B-CELL NEOPLASMS (A)Precursor B cell Iymphoblastic leukemia/ Iymphoma (B)Peripheral B-Cell Neoplasms • B-cell chronic Iymphocytic leukemia/small Iymphocytic Iymphoma . • lymphoplasmacytic lymphoma • Mantle cell Iymphoma: • Follicular Iymphoma • Marginal Zone B-cell Lymphoma of mucosa-associated Iymphoid tissue (MALT) type • Hairy cell leukemia • Burkitt Iymphoma T-CELL NEOPLASMS (A)Precursor T cell lymphoblastic leukemia/lymphoma . (B)Peripheral T-cell and NK-cell neoplasms • Aggressive NK cell leukemia • Nasal and nasal-type NK/T cell Iymphoma. • Mycosis fungoides . • Angio-immunoblastic T-cell Iymphoma. • Adult T-cell leukemia/lymphoma (HTLV1+). • anaplastic large cell Iymphoma (ALCL) . Lymphoma are classified according to the presence or absence of Reed sternberg cell (R.S)into: • (1) Hodgkin lymphoma which have R.S cell. • (2) Non Hodgkin lymphoma which have no R.S cell. Reed-Sternberg cell Risk factors for NHL • • • • immunosuppression or immunodeficiency family history of lymphoma infectious agents ionizing radiation Sites for non Hodgkin lymphoma • A- Nodal lymphoma start in the lymph nodes. • B-extra nodal lymphoma: - intestine - Central nervous system - Skin - Brain - testis - spleen - ovary Clinical manifestations • Variable • severity: range from asymptomatic to extremely ill. • Systemic manifestations • weight loss, anorexia. • Local manifestations • lymphadenopathy, splenomegaly most common • any tissue potentially can be infiltrated Diagnosis of lymphoma • A- gross examination • B- microscopic examination: requires an adequate biopsy before treatment is initiated So we do : - Haematoxylin and eosin stained sections. - immunohistochemical stained sections using tumor markers. Gross picture for intestinal lymphoma Microscopic picture of Non Hodgkin lymphoma • Lost normal histologic architecture of the lymph nodes. • Diffuse infiltration of the lymph node by monoclonal type of malignant lymphocytes. • Immunohistochemical staining can help in the diagnosis as: - T cell lymphoma are +ve for CD3. - B cell Lymphoma are +ve for CD20 Microscopic picture of reactive lymphoid follicles Non Hodgkin Lymphoma (H&E) Both c&d show little inflammatory cell infiltrate in the intestinal mucosa associating intestinal inflammation Intestinal lymphoma Immuno-histochemical diagnosis for NHL using CD20 for B cell lymphoma Hodgkin lymphoma Thomas Hodgkin (1798-1866) Classical Hodgkin Lymphoma Epidemiology • less frequent than non-Hodgkin lymphoma • overall M>F • peak incidence in 3rd decade Associated (etiological?) factors • Epestein Bar Virus infection. • May associate Human Immunodeficiency Virus infection. • possible genetic predisposition. Hodgkin lymphoma • cell of origin: B-lymphocyte present in germinal centre can change to Reed-Sternberg cells (or RS variants) which is the malignant cells but the other surrounding white blood cells in the affected lymph node are reactive cells ( polyclonal) not neoplastic cells. Hodgkin lymphoma Reed-Sternberg cell A possible model of pathogenesis transforming event(s) EBV? loss of apoptosis cytokines germinal centre B cell RS cell inflammatory response Microscopic picture of Hodgkin lymphoma • Lost normal histologic architecture of the lymph nodes. • The only malignant cells is the classic Reed sternberg cell or one of its variants. • But the surrounding cells for the RS cells are reactive and not malignant. • Immunohistochemical staining can help in the diagnosis as: - R.S cell is +ve for CD15, CD30. HODGKIN LYMPHOMA (Hodgkin's Disease) are further subclassified into : (A)Nodular lymphocyte predominance Hodgkin Iymphoma. (B) Classical Hodgkin Iymphoma which include: • Nodular sclerosis . • Classical Hodgkin lymphoma, lymphocyte-rich. • lymphocyte depleted. • Mixed cellularity type. RS cell and variants classic RS cell lacunar cell (mixed cellularity Hodgkin lymphoma) (nodular sclerosis Hodgkin lymphoma) popcorn cell (lymphocyte Predominance Hodgkin lymphoma) Clinical manifestations: • lymphadenopathy • extranodal sites relatively uncommon except in advanced disease Staging of lymphoma to identify the degree of spread of Hodgkin lymphoma Stage I Stage II Stage III Stage IV A: absence of B symptoms B: fever, night sweats, weight loss complications of lymphoma • bone marrow failure due to infiltration. • CNS infiltration • compression of structures (e.g spinal cord, ureters)