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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.
What is the presence of enlarged lymph nodes referred to as?
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?
Do Non-Hodgkin Lymphomas tend to be disseminated (systemic) or localized at diagnosis?
Lymphomas are tumors of what?
Non-Hodgkin Lymphomas tend to be diseases predominantly of what age group?
Older -- 60s and 70s
Most cases of Non-Hodgkin Lymphomas have no obvious predisposing factor, but what are some possible predisposing factors?
- Genetic Predispostion
- Chemical Exposure
- Ionizing Radiation
- Viral Infections
- Chronic Antigenic Stimulation
- Autoimmune Diseases
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.
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).
- Immunoglobulin Genes
- T-cell Receptor Genes
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?
- Genetic Accidents
What are the cytogenetics associated with Burkitt Lymphomas? __________ is associated with cell proliferation; it is overexpressed in Burkitt Lymphomas.
- c-MYC/Immunoglobulin Heavy Chain Gene (IgH)
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.
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.
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
What does the WHO classification system attempt to do?
Identify distinct entities, based when possible on cell of origin
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
What are the three main categories of the WHO Classification System? What types of tumors does this include?
- B-cell (including plasma cell)
- Hodgkin Lymphomas
- Includes all tumors derived from lymphocytes: both lymphocytic lymphomas and lymphocytic leukemias
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
What is the difference between lymphomas and leukemias?
- Lymphoma: no bone marrow involvement
- Leukemia: bone marrow involvement
In general, __________ architecture and _______ cell size indicate more aggressive clinical behavior.
What are the two architectural types involved in Non-Hodgkin Lymphomas? Which is linked to more aggressive behavior?
- Follicular & Diffuse
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
What is the single most common type of non-Hodgkin lymphoma in the US?
Diffuse Large B-Cell Lymphomas (DLBCL)
Are Diffuse Large B-Cell Lymphomas typically indolent or aggressive? A significant number of patients are curable with with treatment?
- Combination Chemotherapy
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
Identify the lymphoma type seen below:
Diffuse Large B-Cell Lymphoma (DLBCL)
What is the second most common Non-Hodgkin Lymphoma in the US?
Are Follicular Lymphomas typically indolent or aggressive?
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)
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
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
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
Which type of lymphoma responds to antibiotics and often doesn't require chemo?
Gastric MALT Lymphomas
Gastric MALT Lymphomas are often associated with what type of bacteria, and may even regress after eradication of this bacteria?
Small Lymphoctyic Lymphoma (SLL) is essentially identical to B-cell chronic lymphocytic leukemia (B-CLL). What distinguishes the two?
Presence or absence of lymphocytosis
Identify the Lymphoma below:
Small Lymphocytic Lymphoma
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
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).
Identify the lymphoma type below:
- Burkitt Lymphoma
- "Starry Sky" Pattern
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.
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
What does the Ann Arbor Staging System Measure?
Anatomic spread of disease
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.
What is the common treatment for Aggressive NHLs?
Combination of chemo used (CHOP plus Rituximab)
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.
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.
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)
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)
What is the most common cause of reactive lymphadenopathy (common in children, less so in adults) (part of differential for enlarged lymph nodes)?
What are the two main options for pathologic diagnosis of Lymphoma?
- Fine Needle Aspirate Cytology (FNA)
- Excisional Biopsy
Fine Needle Aspirate Cytology can often be used to make a definitive diagnosis of NHL when combined with what other test?
What group of lymphomas have a long median survival, but are incurable with conventional therapy?
What group of lymphomas are potentially curable with chemotherapy, but have a shorter survival if not cured?