Lymphoma - PDF

LYMPHOMA NUR NAJMI MOHAMAD ANUAR  that develop from Blood cancer ↑ ms. Lymphocyte (B , cells) T, NK · Uncontrol...

LYMPHOMA NUR NAJMI MOHAMAD ANUAR  that develop from Blood cancer ↑ ms. Lymphocyte (B , cells) T, NK · Uncontrolled proliferation malignancy a systemic - nodes Presence ofRe of lymph a > enlargement - sympto Course Outline Hodgkin Lymphoma-classificationNodularSclerosis, Rye Lymphuyle Predominant HL / - Non-Hodgkin Lymphoma subtypes Lymphocyte Deplete H - DEFINITION &I cell with , EBV HL Burkitt Behavour : T cell NHL Indolent TYPES OF LYMPHOMA : Slow-growing ↑ 1 HIV Lyme oma Aggressive fast-growing : risk of NHL : pyloriInfection- H - Immunodeficiency gastric MALT : Lymphoma. ETIOLOGY # - node ↑ > - lymph - - 3 HISTORY… Thomas Hodgkin (August 17, 1798 - April 5, 1866) Founder for Hodgkin’s disease (lymphoma). Later lymphoma were further studied Hodgkin Lymphoma (15%) Non-Hodgkin Lymphoma (85%) 4  Diagnosis Haematological findings ◦ CBC/FBC > NBL - ◦ Bone marrow biopsy Biochemical Findings Cytogenetics & Immunophenotyping (more ? culartechniques more advanced MOLECULAR TECHNIQUE  T B CD MARKERS (B and T cell) > - important diagnosis  - B Cell * try to find out CD Markers meaning CD MARKERS WORKUP FOR LYMPHOMA  Cytogenetics - see what's wrong with the chromosomes Burkit Lymphoma t(8;14)(q24;q32) Technique: karyotyping, FISH  Chromosome Translocation Chromosome translocation  Immunophenotyping Cluster Differentiation (CD) marker Cell surface molecule Each unique molecule is assigned a different number designation Unique of each type of lymphomas Techniques: ◦ Flow cytometry ◦ Immunohistochemistry Flow cytometry  a LYMPH NODE pri ↳ issue that Hodgkin Lymphoma HODGKIN’S LYMPHOMA - Malignant lymphoma 1 - Epstein-Barr virus (EBV) - Presence of Reed-Sternberg cells in the 2 the affected lymphoid tissues (B cell) - Affect early adulthood and elderly (all 3 ages) 16 HODGKIN’S LYMPHOMA CLINICAL FEATURES ◦ Painless, firm and discrete enlargement of superficial lymph nodes ◦ Splenomegaly, ◦ Fever, night sweats, loss of weight, weakness 17  HODGKIN’S LYMPHOMA HODGKIN’S LYMPHOMA Enlargement of the superficial LN : Cervical nodes Axillary nodes Inguinal nodes Abdominal nodes Chest nodes 18 Reed-Stenberg Cell Large lymphoid cell with biloped nucleus, abundant cytoplasm, eosinophilic Large transformed lymphocytes B origin owl-eye appearance a pale staining acidophilic cytoplasm one or two large nuclei showi ng clumping of chromatin deeply acidophilic neucleoli frequently shows a  RS-cell (arrow) also known as Hodgkin cell darker apoptotic RS-cell also knows as “mummified” variant of RS- cells (arrowhead) among a background of inflammatory cells consisting of histiocytes (curved arrows), small lymphocytes, and plasma cells. HODGKIN’S LYMPHOMA STAGIN- CLINICALLY Ann Arbor staging- Asimpo A Stage I Based on the number and the site of the lymph nodes involved- eg : = Stage I , 10 Criteria for staging is the same for both Hodgkin’s and Non Hodgkin’s lymphoma symptom 21 HODGKIN’S LYMPHOMA Histological classification ◦ Based on relative proportions of Reed-Sternberg cells, lymphocytes, and area of fibrosis ◦ 4 subtypes- Rye classification ◦ Can determine prognosis and therapeutic options Types / Criteria Lymphocyte Mixed Cellularity Lymphocyte Nodular Sclerosing Predominant Depleted Prevalence 5% 30% 5% 60% Age Young Middle Old Young Female Positive Reed Sternberg Reed Sternberg Low Moderate High Cells with the presence Cells of Collagen band Position Cervical and Cervical, chest and Abdominal node Cervical and chest nodes Inguinal nodes abdominal nodes Cure Rate/Prognosis 90% 75% 45% 85% 22  HODGKIN’S LYMPHOMA Haematological findings: ◦ Normochromic,normocytic anemia ◦ Leucocytosis and neutrophilia ↑ WBC ◦ Platelet count is normal in early stage and reduced in later stages ◦ Bone marrow involvement in late stage Biochemical findings: ◦ ESR and CRP raised (monitoring disease progress) ◦ Elevated transaminases level indicate liver involvement ◦ LDH raised 23 Hodgkin Lymphoma HODGKIN’S LYMPHOMA ↳ most prominent type of Lymphoma Nodular Classical CD45, CD20 RS cell (2 lobes lymphoid cell) Popcorn cell –CD30+, CD15+, usually negative CD20, CD45 –weak or absent crippled germinal center B cells, meaning they have not undergone hyper mutation to express their antibody Hodgkin Cell  HODGKIN’S LYMPHOMA TREATMENT : ◦ Radiotherapy ◦ Chemotherapy ◦ Stem cell transplantation 25 HODGKIN’S LYMPHOMA NON HODGKIN’S LYMPHOMA Malignant lymphoma without the Reed-Sternberg cells 5 times more common than Hodgkin’s lymphoma Most commonly in children 27 ETIOLOGY : Multifactorial Viral infection : EBV, HTLV-1 Mutation of genes : c-myc, Bcl-2, ↳ abromalities in these gane 28 NON HODGKIN’S LYMPHOMA CLINICAL FEATURES : ◦Superficial lymphadenopathy ◦Fever, night sweats and loss of weight ◦Anemia,neutropenia ◦Hepatomegaly,splenomegaly 29 NON HODGKIN’S LYMPHOMA Staging of the disease is the same as in Hodgkin’s lymphoma 30 NON HODGKIN’S LYMPHOMA HISTOLOGICAL CLASSIFICATION A number of classification have been used over the years ◦ Rappaport classification ◦ Kiel classification ◦ Lukes-Collins classification ◦ Working formulation classification ◦ Revised American European Lymphoma (REAL) & ◦ WHO most common 31  Key points in NHL Classification Prognosis Good Bad Proliferative Low High Capacity Cell’s Presence of Absence of cleaved morphology Cleaved cells cells Cell’s size Small (matured Large (immature) cells) ① cleareda Cell’s Follicle Diffuse distribution 32 NON HODGKIN’S LYMPHOMA REAL/WHO CLASSIFICATION ◦ Includes histological appearance, immunophenotypic and genetic features proginator◦◦ 2Precursor & main subtypes: B- or T-cell lymphomas chromosome ◦ Peripheral B- or T-cell lymphomas ↓ Twatred gene form 33 NON HODGKIN’S LYMPHOMA NON HODGKIN’S LYMPHOMA B CELL (85%) T CELL (15%) PRECURSOR B-CELL NEOPLASM PRECURSOR T-CELL NEOPLASM - Precursor B-lymphoma -Precursor T-lymphoma MATURE (peripheral) B-CELL MATURE (peripheral) T-CELL NEOPLASM NEOPLASM -B cell chronic lymphoma -Adult T cell lymphoma -Lymphoplasmacytic lymphoma -Marginal zone B-cell lymphoma Extranodal marginal zone B-cell Extranodal T-cell lymphoma lymphoma Anaplastic large cell lymphoma Mantle cell lymphoma Peripheral T-cell lymphoma Follicular lymphoma Angioimmunoblastic T-cell Nodal marginal zone B-cell lymphoma lymphoma Anaplastic large cell lymphoma Diffuse large B-cell lymphoma Burkitt’s lymphoma 34 Non-Hodgkin – B cell neoplasm important &: Non-Hodgkin – T/NK cell neoplasm  Non-Hodgkin Lymphoma Most common NHL - Germinal centre, B cell Follicular Pan B cell follicle - CD19, CD20, CD10, BCL-6, contrast with reactive follicle, neoplastic cell Lymphoma express BCL-2, so decreases sensitivity to apoptotic - Death lead to cancer T(14;18)(q32;q21), BCL-2 lymphadenopathy  Pre-germinal centre cell in primary follicle or mantle region Pan B cell (cd19, 20, cd5) CD19, CD5, (CD22+, cd23-, BCL-1(cyclin-D1)) Mantle Cell – contrast with CLL Lymphoma T(11;14)(q13;q32)  regulation of BCL-1 gene Lymphadenopathy, BM and tumour cell infiltration Angular nuclei -under microscope  Nodal, extranodal and splenic Mucosal associated lymphoid tissue Arise from pre-existing inflm or autoimmune disorder like stomach - and thyroid Marginal -mucosal layer Common gastric malt from H.Pylori zone Lead to accumulation of reactive lymphoid lymphoma tissue (MALT) Splenomegaly CD20, CD19, - BCell Absent CD5, CD10 T(11;18)(q21;q21) – apoptosis-inhibitor gene API2 and MLT gene  Germinal centre (more favor) or peripheral B Diffuse Large cell B-cell Larger cell than normal lymphoma Cd20, 19, 5, 10, bcl-6, cd30, cd 138 Of raised serum LDH – bad prog  Omitosis DLBCL shows an immunoblastic morphology with large cells containing moderate to abundant amphophilic cytoplasm and generally single prominent nucleoli (arrowhead). Compare the size of an immunoblast with that of a small lymphocyte (long arrow). A mitosis is also shown (arrow).  Endemic and sporadic Basophilic vacuolated cytoplasm Germinal centre origin, Cd19, Cd20, Cd10, BCL-6, BCl- 2 negative Jaw bone mass –endemic 4-7yrs Burkitt Starry sky appearance –histiocyte phagocyte apoptotic debris –show highly proliferative Lymphoma Abdominal mass Highly proliferative In African – prevalance at malaria area EBV infection womentO T(8;14), 2;8, 8;22…C-MYC oncogene overexpressed Massive lymphadenopathy jaw, usually children Starry sky - distinct presence of histiocytes with phagocytosis of nuclear debris (arrow). The cellular debris is accumulated as a result of rapid rate of apoptosis in tumor cells. Note that starry-sky pattern may also be seen in patients with lymphoblastic lymphoma * * * zone Marginal Lymphoma * (Diffuse Large B-cell Lymphoma) *  NON HODGKIN’S LYMPHOMA HAEMATOLOGICAL FINDINGS: ◦ Normochromic,normocytic anaemia ◦ Neutropenia, thrombocytopenia BIOCHEMISTRY FINDINGS: ◦ Raised LDH – prognostic factor ◦ Elevated transaminases indicating liver involvement T CELL B CELL ACTIVATION LEUCOCYTE MARKERS COMMON ANTIGEN CD2 CD19 CD23 CD45 CD3 CD20 CD25 CD5 CD22 CD30 CD7 CD24 T Cell Rare B subsets cell CD4 45 CD8 CD5 NON HODGKIN’S LYMPHOMA TREATMENT : ◦ CHEMOTHERAPY ◦ RADIOTHERAPY ◦ STEM CELL TRANSPLANTATION 46 47 Self study.. 1. Hodgkin Lymphoma 2. Follicular Lymphoma Low grade 3. Mantle Cell Lymphoma 4. Marginal zone lymphoma (MALT) 5. Diffuse Large B-cell lymphoma High grade 6. Burkitt Lymphoma 7. Multiple myeloma (plasma cell neoplasm)