Lymphomas Flashcards
Hodgkin Lymphoma (20%):
- Usually involves B Cells
- Is associated with presence of _____________ (found in HL only)
- Usually derived from B lymphocytes, classically considered crippled germinal center B cells, meaning they have not undergone hypermutation to express their antibody
- Usually superficial (________/ _______) +/- mediastinal, w stepwise predictable anatomic spread to adjacent nodes
Reed-Sternberg Cells;
cervical / supraclavicular
What are high grade B cell lymphoma i,e aggressive lymohoma (grows v quickly, die within months without treatment. Can be cured)
- DLBCL: 37% of all NHL
- Burkitt’s Lymphoma
- Mantle Cell Lymphoma
What are low grades B call lymphoma i,e indolent lymohoma (grow v slowly, may live for years without treatment. Cannot be cured, can only be controlled)
- Follicular lymphoma – 29% of all NHL
- Small lymphocytic B cell lymphoma (Lymphocytic variant of CLL)
- Lymphoplasmacytic Lymphoma
- Marginal Zone Lymphoma
What are the investigations for lymphoma?
Examination of peripheral blood
Lymph node biopsy (excision, core) 🡪 FNAC less useful for diagnosis and lymphoid malignancies won’t normally seed into skin
BM aspirate
- Cytology
- Cytogenetics/FISH -> e.g. in Burkitt’s lymphoma (8q-14q+ translocation)
- Flow cytometry analysis
- Microbiology
Trephine (core of bone sample)
- H&E stain
- Reticulin stain
- Immunohistochemistry stain
- Molecular study
Imaging (CT thorax/ abdomen/ pelvis)
Imaging (PET/CT scan)
What are the principles of management for lymphoma?
Chemotherapy
Radiation
Immunotherapy
- Monoclonal antibodies
- Cellular therapy (allogenic stem cells transplant)
- Immunostimulants
- Chimeric antigen receptor
Targeted therapy
- Pathogenic molecules e.g BCR-Abl (imatinib)
- Signaling pathway
What is the Ann Arbor staging of HL and NHL?
Stage I: Affects one group of LN. Stage I often will not have outward symptoms.
Stage II: >1 group of LN (or Lymphatic Organ) confined to 1 side of the diaphragm
Stage III: Involves LN or Lymphoid Organs on both sides of the diaphragm
Stage IV: Involves extra-lymphatic organs –> liver, BM, nodular involvement of lungs
Modifiers:
- A: Absence of B Symptoms
- B: Presence of B Symptoms (Mnemonic: Wednesday Night Fevers)
- B Symptoms indicate poor prognosis 🡪 requires combination therapy asap
[Hodgkin Lymphoma]
Reed Sternberg cells are neoplastic B cells. They are CD20- and thus do not respond to __________. They have multi-lobed nuclei with ____________, forming a distinct owl-eye appearance. They secrete various cytokines, which may produce ______________ which are not usually present in non-Hodgkin Lymphoma.
Reed Sternberg cells do not form the bulk of the tumour mass. Most of the tumour mass is formed of other reactive immune cells which have been recruited to the tumour site by the various cytokines secreted.
rituximab;
prominent nucleoli;
constitutional B symptoms like fever, chills, night sweats
[Hodgkin Lymphoma: Classical HL]
Nodular sclerosing (most common)
- Commonly arises in ____________
- Characterized by a ___________ that is enlarged and demonstrates ____________ that divide the immune cells
- Inspection of the immune cells reveals Reed-Sternberg cells found in lake-like spaces. These are called __________.
- Associated with ______
Lymphocyte-rich
- Best prognosis but can transform into _________
- No association with EBV
- Normally presents as isolated lymphadenopathy
Lymphocyte depleted
- Poorest prognosis
Mixed cellularity
- Eosinophilia often seen as eosinophils recruited via IL-5.
Lymphocyte Predominant
young adult females;
cervical or mediastinal lymph node;
bands of sclerosis;
lacunar cells;
EBV
high grade B cell lymphoma
[Hodgkin Lymphoma]
What are the clinical features of Hodgkin Lymphoma?
Clinical Features of HL
- Lymph node enlargement is the most common presenting feature, usually affecting the neck (cervical / supraclavicular) and the mediastinum.
- Lymphadenopathy is painless, non-tender, rubbery
- B symptoms – Night sweat, fever, weight loss and pruritus may also occur 🡪 indicative of worse prognosis
- Alcohol-induced pain in the affected lymph nodes is thought to be virtually diagnostic of Hodgkin’s lymphoma.
- May have pruritis
Clinical Features of Classical HL
- Young
- Associated with EBV
- Histology: Reed Sternberg Cells, Hodgkin Cells, Inflammatory Cell infiltrate w Eosinophils
[Hodgkin Lymphoma]
What are the investigations performed for Hodgkin Lymphoma?
FBC – neutrophilia (mild), eosinophilia
ESR – raised
LDH – raised (commonly)
LFTs
Bone marrow (may show some infiltration)
CT for staging: Ann-Arbor’s Classification
- Stage 1: one group of LN only
- Stage 2: more than one group of LN, but confined to one side of diaphragm
- Stage 3: LN on both sides of diaphragm affected
- Stage 4: extra-nodal involvement (BM/liver)
[NON-HODGKIN LYMPHOMA]
Non-Hodgkin lymphomas can be divided into B cell lymphomas and T cell lymphomas. The non-Hodgkin B cell lymphomas can be classified based on cell size into those with small, intermediate and large B cells.
Small B cell lymphomas tend to be the most _______. They are thus the least aggressive and tend to grow in patterns somewhat (but not exactly) resembling normal architecture.
- __________ produce many hyperplastic follicles that are found both in the cortex as well as outside the cortex.
- ____________ tend to expand the mantle zone.
- ____________ expand the marginal zone, which is only rarely present in normal lymph nodes.
- ____________ is also a small B cell lymphoma that can arise from CLL.
The main intermediate-sized B cell lymphoma is _____________, associated with EBV infection.
The main large B cell lymphoma is ___________, which is the most undifferentiated, does not produce any specific growth pattern resembling normal histology and is the most aggressive. It is also the most common non-Hodgkin Lymphoma.
Most of the lymphomas present simply as a ________________.
T cell lymphomas include Adult T cell leukaemia/lymphoma, enteropathy associated T cell lymphoma, cutaneous T cell lymphoma and anaplastic large cell lymphoma. T cell lymphomas have in common the tendency to ___________________.
differentiated;
Follicular lymphomas ;
Mantle cell lymphomas;
Marginal zone lymphomas;
Small lymphoblastic lymphoma;
Burkitt Lymphoma;
Diffuse Large B-cell Lymphoma
painless enlarged nodal mass or extranodal mass
migrate to the skin and cause a type IV hypersensitivity and rash
[FOLLICULAR LYMPHOMA]
It presents with ____________ usually in late adulthood
It is driven by a ______ translocation in which
the _________ on chromosome 18 is translocated with the ____________ gene on chromosome 14.
- This results in massive overexpression of BCL-2.
- BCL-2 is an anti-apoptotic protein.
- The one place in which BCL-2 should not be upregulated is in the follicle, as the death of B cells is a normal part of B cell selection in affinity maturation.
- BCL-2 upregulation leads to defective apoptosis.
painless lymphadenopathy;
t(14;18);
BCL-2 gene;
Immunoglobulin Heavy Chain
[MANTLE CELL LYMPHOMA]
Mantle cell lymphoma involves a neoplastic proliferation of B cells expanding the mantle zone.
It also presents usually in late adulthood with painless lymphadenopathy.
It is driven by a _______ translocation which results in translocation of the cyclin D1 gene to the immunoglobulin heavy chain locus, resulting in overexpression of cyclin D1.
Cyclin D1 drives the cell cycle and promotes _________ in the cell cycle.
t(11;14);
G1/S transition
[MARGINAL ZONE LYMPHOMA]
Marginal zone lymphoma involves a neoplastic proliferation of B cells expanding the marginal zone.
The marginal zone is usually associated with ____________ cells; thus, marginal zone lymphoma is highly associated with conditions of chronic inflammation.
This includes:
- ____________ and ____________
- ___________, which causes gastric MALT-oma, a type of marginal zone lymphoma. Importantly, this gastric MALT-oma can regress with treatment of the infection.
post-germinal B;
Hashimoto thyroiditis;
Sjogren syndrome;
H. pylori gastritis
[BURKITT LYMPHOMA]
Burkitt Lymphoma is a neoplastic proliferation of intermediate-sized B cells. It is found in three main forms, all of which involve a _______ translocation of the c-myc gene to the immunoglobulin heavy chain locus.
(1) Endemic form: associated with EBV infection in _________
(2) Sporadic form: tends to occur in developed countries.
(3) Immunodeficient form: tends to occur in AIDS patients, possibly due to EBV reactivation.
The presentation of the African and sporadic forms differs:
- The African form is associated with an ________________
- The sporadic form is associated with an ______________
Histologically, Burkitt Lymphoma is characterized by a _______________.
- The background of the “sky” is formed by intermediate sized B cells.
- The stars are formed by prominent tingible body macrophages. Unlike in follicular lymphoma, there is prominent proliferation due to oncogene activation, but there is no inhibition of apoptosis.
t(8;14);
Central Africa;
extranodal mass of the face or jaw;
extranodal mass of the abdomen
starry-sky appeareance
