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The superficial cortex is predominantly a ____-cell zone; the deep cortex is more of a ____- cell zone. ________ cells are more prominent in the medulla.
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What is the presence of enlarged lymph nodes referred to as?
Lymphadenopathy
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Non-Hodgkin Lymphomas are neoplastic, clonal proliferations of lymphocytes. These may be nodal, extranodal, or both. Which is more common?
They may also be B-cell or T-cell derived. Which is more common in the US?
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Do Non-Hodgkin Lymphomas tend to be disseminated (systemic) or localized at diagnosis?
Disseminated
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Lymphomas are tumors of what?
Lymphocytes
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Non-Hodgkin Lymphomas tend to be diseases predominantly of what age group?
Older -- 60s and 70s
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Most cases of Non-Hodgkin Lymphomas have no obvious predisposing factor, but what are some possible predisposing factors?
- Genetic Predispostion
- Chemical Exposure
- Ionizing Radiation
- Immunosuppression
- Viral Infections
- Chronic Antigenic Stimulation
- Autoimmune Diseases
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The immunoglobulin heavy chain gene (IgH) is located on the long arm of chromosome ____; this locus is probably the single most common locus involved in chromosome translocations in B-cell Non-Hodgkin Lymphomas.
14 (14q)
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In Non-Hodgkin Lymphomas, recurrent cytogenetic alterations are common. These are usually _________ translocations. There are specific alterations associated with specific lymphoma types, and these usually involve ______________ and either ____________ genes (B-cells) or _______________ genes (T-cells).
- Reciprocal
- Proto-Oncogenes
- Immunoglobulin Genes
- T-cell Receptor Genes
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Lymphocytes are the only cells in the body where -- as a part of normal development -- the DNA gets cut up and stitched back together. This occurs in the immunoglobulin (Ig) genes in B-cells and the T-cell receptor (TCR) genes in T-cells. Rearrangement may occur between these two genes and what? What does this predispose to?
- Proto-oncogenes
- Genetic Accidents
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What are the cytogenetics associated with Burkitt Lymphomas? __________ is associated with cell proliferation; it is overexpressed in Burkitt Lymphomas.
- t(8;14)
- c-MYC/Immunoglobulin Heavy Chain Gene (IgH)
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What are the cytogenetics associated with Follicular Lymphomas? The ________ protein confers resistance to apoptosis; follicular lymphomas don't grow because the cells proliferate quickly, but grow slowly; the cells just don't die.
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What are the cytogenetics associated with Mantle Cell Lymphoma? The _________ protein is associated with cell proliferation, but it doesn't drivge rapid proliferation; just slower but relentless.
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What is the most common clinical presentation of Non-Hodgkin Lymphoma? What are some other symptoms?
- Enlarged Lymph Nodes: most common
- Tumor in Extranodal Sites -- GI tract, skin, brain, other organs
- Systemic Symptoms -- fever, night sweats, weight loss
- Hematologic Disease -- lymphocytosis, leukopenia, anemia, thrombocytopenia
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What does the WHO classification system attempt to do?
Identify distinct entities, based when possible on cell of origin
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What is an important difference between the WHO classification system and the Working Formualtion (older classification system)?
The WHO does not divide NHL into broad prognostic groups
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What are the three main categories of the WHO Classification System? What types of tumors does this include?
- B-cell (including plasma cell)
- T-cell
- Hodgkin Lymphomas
- Includes all tumors derived from lymphocytes: both lymphocytic lymphomas and lymphocytic leukemias
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Under the WHO Classification System, B-cell and T-cell neoplasms are divided into what two types?
- Immature (precursors): acute lymphoblastic leukemias and lymphoblastic lymphomas
- Mature (peripheral): most NHL, chronic lymphocytic leukemias, plasma cell neoplasms
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What is the difference between lymphomas and leukemias?
- Lymphoma: no bone marrow involvement
- Leukemia: bone marrow involvement
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In general, __________ architecture and _______ cell size indicate more aggressive clinical behavior.
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What are the two architectural types involved in Non-Hodgkin Lymphomas? Which is linked to more aggressive behavior?
- Follicular & Diffuse
- Diffuse
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When looking at NHL types by histological grade, which type makes up about half of lymphomas? Which type constitutes about a quarter? And which type is rare?
- Intermediate Grade Lymphomas
- Low Grade Lymphomas
- True High Grade Lymphomas
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What is the single most common type of non-Hodgkin lymphoma in the US?
Diffuse Large B-Cell Lymphomas (DLBCL)
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Are Diffuse Large B-Cell Lymphomas typically indolent or aggressive? A significant number of patients are curable with with treatment?
- Aggressive
- Combination Chemotherapy
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What are the two major molecular subtypes of Diffuse Large B-Cell Lymphomas (DLBCLs)? What is the prognosis with each?
- Germinal Center B-Cell: better prognosis
- Activated (non-germinal center) B-Cell: more aggressive; worse prognosis
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Identify the lymphoma type seen below:
Diffuse Large B-Cell Lymphoma (DLBCL)
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What is the second most common Non-Hodgkin Lymphoma in the US?
Follicular Lymphoma
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Are Follicular Lymphomas typically indolent or aggressive?
Indolent
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Most Follicular Lymphomas aren't rapidly proliferative. Why/how do they grow?
Because the cells aren't dying like they should due to the anti-apoptotic gene (BCL2)
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Follicular lymphomas are divided into three grades. What are the grades based on? Which is more aggressive, grade 1 or grade 3?
- Based on the number of large cells in the neoplastic follicles (grade 1 has fewest, grade 3 the most)
- Grade 3
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What is the most common extranodal lymphoma in the US? Where are most of these located? Are they typically indolent or aggressive?
- Extranodal Marginal Zone (MALT) Lymphomas
- GI Tract
- Indolent
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Unlike other low-grade lymphomas, what type tend to be localized on diagnosis and are potentially curable if they are localized?
Extranodal Marginal Zone (MALT) Lymphomas
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Which type of lymphoma responds to antibiotics and often doesn't require chemo?
Gastric MALT Lymphomas
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Gastric MALT Lymphomas are often associated with what type of bacteria, and may even regress after eradication of this bacteria?
H. pylori
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Small Lymphoctyic Lymphoma (SLL) is essentially identical to B-cell chronic lymphocytic leukemia (B-CLL). What distinguishes the two?
Presence or absence of lymphocytosis
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Identify the Lymphoma below:
Small Lymphocytic Lymphoma
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What is possibly the worst of all lymphomas? This type has a relatively short survival (median 3-5 years), and is incurable with conventional therapy.
Mantle Cell Lymphoma
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What lymphoma has the fastest doubling time of any neoplasm? This is a very high grade NHL. It is strongly associated with EBV and has malaria as a co-factor (therefore is common in Africa).
Burkitt Lymphoma
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Identify the lymphoma type below:
- Burkitt Lymphoma
- "Starry Sky" Pattern
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What type of lymphomas are highly heterogenous in all respects, tend to be aggressive clinically (often advanced stage, systemic symptoms common, extranodal disease frequent), and has a bad overall prognosis? There are several variants of these.
T-Cell Lymphomas
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What is the most common T-cell Lymphoma? What is very important at diagnosis for T-cell lymphomas?
- Peripheral T-cell lymphoma, unspecified (PTCL)
- Clinical presentation -- sites of involvement, presence of systemic symptoms
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What does the Ann Arbor Staging System Measure?
Anatomic spread of disease
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What drug, known as an anti-CD20 antibody (CD20 = B-cell antigen), is often used in combination with chemo to treat Non-Hodgkin Lymphomas? This drug is also commonly used in low grade B-cell lymphomas.
Rituxan (Rituximab)
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What is the common treatment for Aggressive NHLs?
Combination of chemo used (CHOP plus Rituximab)
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In NHL, serum LDH tends to correlate with tumor bulk and aggressiveness: the bulkier and/or more aggressive the disease, the ___________ the LDH is going to be. However, this is not specific for lymphomas.
Higher
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There is a marked increase in NHL risk in what patient subset? These are nearly always aggressive or high-grade types. B-cell >> T-cell. Incidence increases with decreasing _____ count.
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What type of lymphoma is relatively common in HIV patients, but is very rare in non-immunocompromised patients?
Primary CNS Lymphoma (lymphoma involving the CNS with no evidence of lymphoma elsewhere)
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What is another disorder, very similar to HIV-related lymphomas, that is liekly due to these patients being in an immunocompromised state? These are often high stage, extranodal sites; have aggressive histologic types, B-cell >> T-cell; EBV involved in pathogenesis (all similar to HIV-related).
Post-Transplant Lymphoproliferative Disorders (PTLD)
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What is the most common cause of reactive lymphadenopathy (common in children, less so in adults) (part of differential for enlarged lymph nodes)?
Infections
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What are the two main options for pathologic diagnosis of Lymphoma?
- Fine Needle Aspirate Cytology (FNA)
- Excisional Biopsy
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Fine Needle Aspirate Cytology can often be used to make a definitive diagnosis of NHL when combined with what other test?
Flow Cytometry
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What group of lymphomas have a long median survival, but are incurable with conventional therapy?
Indolent
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What group of lymphomas are potentially curable with chemotherapy, but have a shorter survival if not cured?
Aggressive
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