Haematological Malignancies 3: lymphoma and myeloma Flashcards
How is lymphoma different to infection?
Tenderness in lymph nodes indicates infection.
What are malignant lymphomas?
Replacement of normal lymphoid tissue by abnormal cells
What are the main types of lymphoma?
Non-hodgkin lymphoma (many sub-types)
Hodgkin lymphoma
What is the difference between leukaemias and lymphomas?
Leukaemias involve the bone marrow and the blood.
Tissue sites are affected by lymphomas.
There is some overlap; CLL starts in the bone marrow and spreads to lymphoid tissues making it look identical.
How is NonHodgkin’s Lymphoma classified?
B vs T cell (WHO)
Cells: morphology and immunology and stage of normal lymphoid cell maturation.
Grade: low vs high (aggressive)
What virus can cause NHL to develop?
Ebstein Barr virus
What bacterial infection can cause NHL?
Helicobacter Pylori
What is a possible reason for the rising incidence of NHL?
The aging population (because NHL correlates with age)
What are the clinical features of NHL?
Enlarged lymph nodes.
Hepato-splenomegaly
Systemic symptoms (Fever, night sweats, weight loss) [cytokine release by cells of lymphoma]
Lymphadenopathy
Interference with normal organ function
Bone marrow failure
How is NHL diagnosed?
Pathology of tissue involved:
Pattern
Cell size: small, large
Cell differentiation: well or poorly defined
Cell phenotype: B / T cells
Genetics: karyotyping and FISH
How is NHL staged?
Extent of disease (radiological imaging to look for spread to other tissue from the source)
Imaging: CT or PET scan of neck, chest, abdomen, and pelvis
BM sample
Lumbar puncture (CSF indicates potential spread to brain)
What is follicular lymphoma?
A low grade B cell NHL which has is caused by a t(14,18) translocation.
What is Burkitt lymphoma?
A NHL lymphoma commonly caused by Ebsteinn Barr Virus which is endemic to Africa and is quite aggressive.
What is diffuse large B cell lymphoma?
A type of NHL that is increasing in number and is quite aggressive
How common is follicular lymphoma?
2nd most common type of NHL
How does follicular lymphoma look at diagnosis?
Usually widely disseminated at diagnosis
How is follicular lymphoma diagnosed?
CD20, CD10, and BCL2 positive on flow cytometry.
What is the 5-year survival rate of follicular lymphoma?
70 - 80%
What is follicular lymphoma growth like?
It can be slow growth and then transform to an aggressive NHL
How is follicular lymphoma treated?
Watch and wait if indolent
Options:
Radiotherapy
Chemotherapy (CHOP regimen)
Antibody-based therapy: anti-CD20 (rituximab)
Combination therapy with antibody + chemotherapy
Transplant options
What indicates treatment of NHL?
Constitutional symptoms such as painful lymph nodes.
Anatomical obstruction or organ dysfunction
Cytopenias
What pattern is typical of follicular lymphoma trephine?
Follicular pattern
Predominantly small cells
What translocation is typical of follicular lymphoma?
t(14;18)(q32,q21)
What protein expression is up-regulated by follicular lymphoma?
Up-regulates expression of anti-apoptotic protein Bcl-2
What is Burkitt lymphoma?
A Non-Hodgkin lymphoma derived from Germinal center of lymphatic tissue
What causes Burkitt lymphoma?
In African populations it is commonly associated with EBV whereas in adults it is not.
What changes are characteristic of Burkitt’s lymphoma?
Swollen face and enlarged lymph nodes
In adults it commonly affects the eyes.
It grows very fast
What gene is activated in Burkitt’s lymphoma?
there is a translocation on chromosome 14 where the immunoglobulin heavy chain sits. As a result the oncogene MYC-IGH is activated on chromosome 8 due to the translocation causing the MYC-IGH gene to be continuously expressed resulting in cells constantly being in mitosis stage.
What characteristic blood slides are seen in people with Burkitt’s lymphoma?
Monotonous B cell infiltrate which looks like a highly vacuoled (fat filled) starry-sky pattern
What is the treatment for Burkitt’s lymphoma?
Aggressive chemotherapy which can completely cure the disease
How common is diffuse large B cell lymphoma?
The most common lymphoma which is 30% of all NHLs
Who gets large B cell lymphoma most commonly?
Adult elderly people
How does large B cell lymphoma present?
Rapidly enlarging masses
What is going wrong during diffuse large B cell lymphoma?
diffuse infiltration by large cells (B cells)
Diverse histology with high proliferation rate
How is diffuse large B cell lymphoma treated?
Combination chemotherapy (eg CHOP)
What is the rate of effectiveness of combination chemotherapy in treating diffuse large B cell lymphoma?
60 - 70% complete remission rate and approximately 30% curable.
What factors are highly influential on prognosis for NHL? (not assessed)
International prognostic index
Clinical features used include:
Age <60 vs >60
Performance status
LDH: lactate dehydrogenase is elevated in people with lymphoma
Disease stage:
Extra-nodal involvement:
(not assessed) 1 point for each bad feature
What is hodgkin’s lymphoma/
Reed-Sternberg cell: minor cell component found in appropriate microscopic cellular background. (pathognomonic of this disease)
Bimodal age incidence: Young adults and after age 50
What does pathognomonic mean?
Characteristic of the disease
What are the clinical features of Hodgkin’s lymphoma?
Painless, non-tender, rubbery lymph nodes. (more common in cervical than axillary lymph nodes)
Dyspnoea (when mediastinum is involved)
Splenomegaly (rare)
Constitutional symptoms (B cell symptoms) fever, pruritis and weight loss.
What tests are commonly done for Hodgkin’s lymphoma diagnosis?
Immunophenotyping: Reed-Sternberg cells express CD15 and CD30.
Clinical staging: CT, MRI, PET
How is hodgkin’s lymphoma staged?
In 1 location (usually cervical region) is stage I
In 2 locations but both above or below diaphragm ios stage II
Above and below the diaphragm is stage III
If the liver or the bone marrow is involved it is considered stage IV
The higher the stage the more treatment required and the less likely for illness to be completely cured.
How is hodgkin’s lymphoma treated?
Chemotherapy and radiotherapy to site of disease.
What percentage of people with hogkin’s lymphoma are completely cured?
80 - 90% especially stage I and II
What is the danger associated with hogkin lymphoma treatment?
It can result in other forms of leukemia and lymphoma (lung and breast cancers common which is dose - response related)
Damage to bone marrow resulting in acute myeloid leukaemia
What is multiple myeloma caused by?
Disease of end stage B cells
Homogeneous immunoglobulin are produced from a single clone (paraproteins)
What is the prognosis like of Hodgkin’s lymphoma?
It is a curable malignancy
Cure rate is approximately 80%
Prognosis based on staging and bulk of disease
Infections: Reduced cell-mediated immunity
Relapsed disease: difficult to treat so it has a more poor prognosis especially if it results in secondary malignancies in lungs and breast
What immunoglobins are most common in multiple myeloma?
IgG (but it isn’t always IgG it can be others)
What are the clinical features of multiple myeloma?
Free light chains can be seen known as Bence Jones proteins which are small enough to be cleared by kidneys.
IgG antibodies present in large quanitities in the blood.
Lytic bone lesions which cause pathological fractures and renal failure is also common
Clinical problems from organ infiltration by neoplastic plasma cells and this is common in bone marrow (for obvious reasons)
Production of excess immunoglobulin
calcium loss and bone wasting
Recurrent infections are common
What is the common demographic associated with multiple myeloma?
People that are >60 years of age
What happens to haemoglobin in people with multiple myelomas?
It drops
What happens to Mean Cell Volume in people with multiple myeloma?
it is elevated
What happens to white blood cells in multiple myelomas?
Decreased
What happens to platelet count in people with multiple myelomas?
They decrease dramatically
What does the bone marrow look like in multiple myeloma?
Bone marrow is filled with activated B cells
What x-rays are performed in people with multiple myelomas?
Head and neck x-rays; damage to bone is common in these people
What is the result of lytic lesions?
The bone can be broken as a result of small amount of trauma
What kidney problem is associated with multiple myeloma?
Large amount of protein cleared in the urine.
Lambda light chains (Bence Jones protein) are toxic to renal epithelium
Amyloid deposits in the glomeruli
Hypercalcemia
What is the median survival of multiple myeloma?
5 years.
Very low survival rate
How do people die from multiple myeloma?
Kidney failure
Haemorrhage
Infections
