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62 Cards in this Set
- Front
- Back
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Lymphomas
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- Heterogeneous group of disorders
- Many (over 40) types of lymphoma due to multiple stages of normal lymphocyte development (at which cell have genetic abnormality) - Genetic abnormalities result in uncontrolled proliferation of neoplastic lymphocytes at a particular developmental stage |
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Primary Lymphoid Tissues
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- Bone marrow
- Thymus |
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Secondary Lymphoid Tissues
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- Lymph nodes
- Spleen - Tonsils - Clusters of lymphoid tissue in the GI and pulmonary tracts |
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Normal B cells development occurs in..
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the bone marrow before the cells enter the peripheral blood circulation and migrate to secondary lymphoid tissues
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Lymph Node Cortex Contents
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- Primary follicles
- Secondary follicles |
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Lymph Node Paracortex Contents
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T cells
- Antigen presenting dendritic cells - High endothelial venules |
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Lymph Node Medulla Contents
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- Plasma cells
- Medullary sinuses |
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Lymph Node Sinuses Contents
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Macrophages, histiocytes that capture antigen and process it
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Primary follicles
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Naïve (cells that have not come into contact with an antigen) B cells
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Secondary follicles
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- B cells that are proliferating after encountering an antigen
- Naïve B cells in secondary follicles get pushed to periphery and form the mantle zone - Have germinal centers |
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germinal centers
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- Dark zone: centroblasts (spread out nucleus because of cell division)
- Light zone: centrocytes (denser nucleus b/c maturing and differentiating) - Tingible body macrophages: destroy B cells with “wrong” antibodies |
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Cortex of the Thymus
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- Thymic epithelial cells interact with lymphocytes (when they arrive) to help them differentiate
- Physical and chemical interactions - Undergo rapid proliferation (look like lymphoblasts originally) and move in toward medulla |
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Medulla of the Thymus
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- Final development of T cells occurs here
- Look like resting lymphocytes - Only 5% of the cells in the cortex make it this far |
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Why do only 5% of T cells make it through to the medulla from the cortex?
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Positive and Negative Selection
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Positive Selection
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- Thymic epithelial cell has an MHC (major histocompatibility complex) molecule on its surface
- TEC presents a peptide produced from processing an antigen - Thymocyte recognizes the MHC protein (self) and the antigenic peptide (nonself) via the T cell receptor - Signal for spontaneous apoptosis is turned off b/c it can differentiate self from nonself |
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Negative Selection
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- Uses central tolerance and peripheral tolerance to induce apoptosis and anergy, respectively, when the thymocyte has a high affinity for the self MHC molecule and the antigen presented
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Central tolerance
(T cell selection) |
Part of Negative Selection
- Any thymocyte that has a high affinity for the self MHC molecule and a peptide found on the antigen presenting cells in the thymus gets apoptosis induced |
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Peripheral tolerance
(T cell selection) |
Part of Negative Selection
- Many tissue specific antigens are not present in the thymus - Similar mechanism that occurs outside the thymus, except: - Cells do not undergo apoptosis, but anergy (unresponsiveness) |
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Why is positive/negative selection helpful?
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- Fewer autoimmune problems
- Molecular mimicry may play a role (when autoimmune problems occur) |
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If T cell receptor is produced from alpha and beta genes
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then T cells primarily stay in thymus
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If T cell receptor is produced from gamma and delta genes
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then T cells primarmily migrate to various places in the body, such as the epithelium of the GI tract (to help with mucosal defenses)
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Lymphomas can be broken into many groups...
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- B cells or T cells
- Aggressiveness - Location of derivation - Hodgkin vs. Non-Hodgkin Lymphoma |
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How do we split up Non-Hodgkin Lymphomas?
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- Highly aggressive
- Aggressive - Low Grade * use this grouping scheme because it is the same categorization as their treatment |
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Which cancers are commonly seen on the lymphoma-leukemia spectrum?
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Burkitt’s Lymphoma/Leukemia
Pre-B cell ALL/Lymphoma Pre-T cell ALL/Lymphoma CLL/SLL |
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Which cancer has relative heterogeneity in terms of grade?
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Mantle cell lymphoma
(it is classified as both aggressive and low grade) |
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Follicular Lymphoma
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- Most common low grade non-Hodgkin lymphoma (22% of new NHL dx)
- Incidence increases with age (Median age 60-70 y/os) |
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Follicular Lymphoma
Histologically |
- Lymph nodes are FILLED WITH FOLLICLES
- "small cleaved cells" = buzz word - B cell lineage |
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What does flow cytometry detect in Follicular Lymphoma?
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CD20+
CD10+ Bcl-2+ CD5- |
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What is the relationship between grade and centroblasts in follicular lymphoma?
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The higher the grade (the more aggressive), the more central blasts there are
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What are the follicular lymphoma cells?
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(obviously B cells)
- centrocytes (small cleaved cells) - centroblasts (larger cells that divide more) |
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Grade IIIa in follicular lymphoma
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- centrocytes present
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Grade IIIb in follicular lymphoma
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- solid sheets of centroblasts
- Acts more like intermediate grade lymphomas |
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Grade II
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6-15 centroblasts/hpf
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Grade I
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0-5 centroblasts/hpf
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In follicular lymphoma what changes occur in lymph nodes?
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Overall lymph node architecture is recognizable but…
- Mantle zone is lost - Follicles start to merge together - Polarization of germinal center is lost - Paracortex is lost |
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Approximarely 85% of patient with follicular lymphoma have what genetics?
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t(14;18)
- up to 30% of DLBCL pts will also have this translocation |
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What is on chromosome 14?
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igH locus (heavy chain)
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What is on chromosome 18?
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bcl-2 locus
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What is the treatment for follicular tymphoma?
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- Not curable, but is very treatable, (ie: responsive to chemotherapy to remove symptoms)
- No definite standard of care - Treatments may range from watchful waiting to stem cell transplantation |
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What are the adverse prognostic factors in the Follicular Lymphoma International Prognostic Index?
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1. Age > 60 years
2. Ann Arbor Stage III-IV 3. Hb < 12 g/dl 4. Number of nodal areas >4 5. LDH > upper limit of normal |
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What indicates your risk group in the FLIPI?
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number of the five factors that you have
- low risk = 0-1 factors - intermediate risk = 2 factors - high risk >= 3 factors |
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Diffuse Large B Cell Lymphoma
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Example of aggressive lymphoma
- Most common of the intermediate grade lymphomas (~30% of all new NHL dx) |
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DLBCL cell markers
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CD19 +
CD 20 + .: B cell lineage |
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DLBCL histology
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cells are larger than a normal B lymphocyte
- normal architecture is usually effaced (thinned out until gone) |
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DLBCL and cytogenetics
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there are no standard cytogenetics for Diffuse Large Cell B Lymphoma
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DLBCL and treatment
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- Chemo responsive
Standard treatment is R-CHOP: R: rituximab (Rituxan) C: cyclophosphamide (Cytoxan) H: Hydroxy-doxorubicin (doxorubicin) O: Oncovin (vincristine) P: Prednisone |
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DLBCL Revised International Prognostic Index (R-IPI)
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- Little Risk = Very good response to chemo = 0 factors
- Medium Risk = Good response to chemo = 1, 2 factors - High Risk = Poor response to chemo = 3, 4, 5 factors |
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Adverse Prognostic Factors in DLBCL
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1. Age > 60 yo
2. ECOG > 2 (pt can do daily functions) 3. LDH > upper limit of normal 4. >1 extranodal site 5. Stage III/IV disease |
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Burkitt's Lymphoma
Doubling time |
doubling time = 24-48 hours
- one of the fastest growing tumors - pretty much every cell is undergoing division |
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Ki-67
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- stain used to determine how fast the lymphocytes are growing (brown = positive stain)
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Burkitt's Lymphoma
Types |
1. African: affects jaw or facial bone
2. “American”, or endemic: affects lymph nodes in abdomen, GI tract 3. Immunodeficiency-associated |
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Burkitt's Lymphoma and EBV
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- first known virus to be involved in the pathogenesis of cancer in humans
- EBV infection is only correlated with African type Burkitt's Lymphoma |
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Do children with sickle cell trait get burkitt's lymphoma?
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Sickle cell trait patient are protected from both Burkitt's lymphoma and malaria
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Where do the tumor cells in African Burkitt's Lymphoma originate?
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Tumor cells originate from a SINGLE EBV INFECTED B CELL
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Epidemiology of African Burkitt's Lymphoma
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-Usually 4-7 y/os
- Male : female ratio = 2:1 - Incidence is 50 times higher than in US Burkitt's Lymphoma - Involves bones of the jaw and other facial bones; kidneys, GI tract, other extranodal sites - EBV is almost always found - Children with sickle cell trait were mostly free of both malaria and Burkitt’s lymphoma - Found in tropical Africa except at high altitudes or relatively cool climates |
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Sporadic Burkitt’s Lymphoma
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(a.k.a. endemic/American)
- Usually what we see in the US - Occurs worldwide regardless of climate - Accounts for 1-2% of lymphomas in adults and up to 40% of lymphomas in children - Involves the abdomen, ovaries, kidneys, omentum, Waldeyer’s ring, and other extranodal sites - 15-30% of cases will be EBV(+) |
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AIDS-defining malignancies
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- Burkitt's Lymphoma (EBV)
- Kaposi’s sarcoma (HHV8) - Systemic NHL, primary effusion lymphoma, CNS lymphoma ... this is when fluid collects in the wrong places (effusions, acites) - Cervical cancer (HPV) |
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Immunodeficiency-Associated Burkitt’s Lymphoma
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- Primarily occurs in patients affected with HIV
- Also seen in allograft recipients, congenital immunodeficiency states - Accounts for 30-40% of all of NHL in HIV (+) patients |
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Burkitt's Lymphoma
Dx |
Dx with tissue sample
- buzz word = starry sky pattern (small stars=vaculoes, bigger stars = macrophages) - ~100% Ki-67 staining (all dividing) Flow cytometry is CD20+, CD10+, CD5- |
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Cytogenetic Abnormalities in Burkitt's Lymphoma...
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- always involve chromosome 8 and the c-myc gene:
- t(8;14): Ig heavy chain gene on chr 14 - t(2;8): Kappa light chain gene on chr 2 - t(8;22): Lambda light chain gene on chr 22 |
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Burkitt's Lymphoma Treatment
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- Tx must begin immediately
- it is an 8 month treatment - CNS is prophylaxed interthecally with chemo - Monitor for spontaneous tumor lysis syndrome (high risk patients) |
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What are the sanctuary sites for Burkitt's Lymphoma?
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CNS
Testicles |
