Haem - Myeloma, Lymphoma, DIC Flashcards
Myeloma - what is it?
Haematological malignancy that arises due to plasma cell proliferation
Cancer of the plasma cells - type of B lymphocyte that produce antibodies
Myeloma - what is multiple myeloma?
Is when the myeloma affects multiple areas of the body
Myeloma - pathophysiology?
- Plasma cells are B cells (B lymphocytes) of the immune system that have become activated to produce a certain antibody
- Called B cells because they are found in the bone marrow
- Myeloma is a cancer of a specific type of plasma cell where there is a genetic mutation causing it to rapidly and uncontrollably multiply
- These plasma cells produce one type of antibody, and antibodies are also called immunoglobulins
- They are complex molecules made up of two heavy chains and two light chains arranged in a Y shape
- Help the immune system recognise and fight infections by targeting specific proteins on the pathogen
- They come in 5 main types: A, G, M, D and E
- When you measure immunoglobulins in a patient with myeloma, one of those types will be significantly abundant
- More than 50% of the time this is immunoglobulin type G (IgG)
- This single type of antibody that is produced by all the identical cancerous plasma cells can be called a monoclonal paraprotein
- This means a single type of abnormal protein
The “Bence Jones protein” that can be found in the urine of many patients with myeloma is actually a part (subunit) of the antibody called the light chains
Myeloma - what is the median age at presentation?
70 years old
Myeloma - what are the clinical features?
CRABBI
Calcium (elevated) - due to increased osteoclast activity
Renal failure - due to light chain deposition within renal tubules
Anaemia (normocytic, normochromic) - bone marrow crowding suppresses erythropoiesis
Bone pain/lesions - bone marrow infiltration by plasma cells
Bleeding - bone marrow crowding also results in thrombocytopenia, so increased risk of bleeding/bruising
Infection - reduction in the production of normal immunoglobulins results in increased susceptibility to infection
Myeloma - what area does bone pain commonly present at?
Presents as back pain commonly
Myeloma - what are the blood results on investigation?
Bloods:
FBC - show anaemia and thrombocytopenia (because of A and B in CRABBI)
U&E - raised urea and creatinine (because of renal failure)
Raised calcium
Myeloma - what are the other investigations you can do, and what are their results?
- Serum or urine protein electrophoresis: raised concentrations of monoclonal IgA/IgG proteins will be present in the serum
- In the urine, they are known as Bence Jones proteins
- Bone marrow aspiration and trephine biopsy: confirms the diagnosis if the number of plasma cells is significantly raised
- Whole-body MRI (or CT if MRI is not suitable) is used to survey the skeleton for bone lesions
Myeloma - what is a common XRAY finding?
‘Rain-drop’ skull
Numerous randomly placed dark spots seen on X-ray which occur due to bone lysis
‘Raindrops keep falling on MYeloma head’ - way to remember finding
Myeloma - what three factors is symptomatic multiple myeloma defined at diagnosis by?
Symptomatic multiple myeloma is defined at diagnosis by the presence of the following three factors:
- Monoclonal plasma cells in the bone marrow >10%
- Monoclonal protein within the serum or the urine (as determined by electrophoresis)
- Evidence of end-organ damage e.g. hypercalcaemia, elevated creatinine, anaemia or lytic bone lesions/fractures
Myeloma - management?
No Cure
Initial treatment:
- If suitable for autologous stem cell transplant (ASCT) - Bortezomib + Dexamethasone
- If UNsuitable for ASCT - Thalidomide + an Alkylating agent + Dexamethasone
Myeloma - what do you give if the patient relapses after initial treatment?
Bortezomib monotherapy
Myeloma - what are the complications and how do you manage them?
- Pain: treat with analgesia (using the WHO analgesic ladder)
- Pathological fracture: Zoledronic acid is given to prevent and manage osteoporosis and fragility fractures
- Infection: patients receive annual influenza vaccinations, may also receive Immunoglobulin replacement therapy
Lymphoma - what is it?
- Lymphomas are a group of cancers that affect the lymphocytes inside the lymphatic system
- These cancerous cells proliferate within the lymph nodes
- Cause lymph nodes to become abnormally large (lymphadenopathy)
Lymphoma - what are the definitions of Hodgkin’s lymphoma and non-Hodgkin’s lymphoma?
Hodgkin’s lymphoma is a specific disease
Non-Hodgkins lymphoma encompasses all the other lymphomas
Hodgkin’s Lymphoma - what is it caused by?
Caused by the proliferation of lymphocytes
Hodgkin’s Lymphoma - what is the age distribution?
Bimodal age distribution
20 years old
75 years old
Hodgkin’s Lymphoma - what are the risk factors?
HIV
Family History
EBV
Autoimmune conditions like sarcoidosis or RA
Hodgkin’s Lymphoma - what is the presentation?
Key presenting symptom - lymphadenopathy
These lymph nodes are characteristically non-tender and feel rubbery
Some patients will feel pain in lymph nodes when they drink alcohol
Hodgkin’s Lymphoma - what are the B symptoms?
Systemic symptoms of lymphoma:
Weight loss
Night sweats
Fever
Hodgkin’s Lymphoma - what are other symptoms patients might experience?
SoB
Fatigue
Cough
Itching
Recurrent infections
Hodgkin’s Lymphoma - what is a blood test you can do and what is it’s finding?
- Lactate Dehydrogenase (LDH) - RAISED, but not specific
Hodgkin’s Lymphoma - what is the key diagnostic test and key finding?
Lymph Node Biopsy
Reed-Sternburg cells, look like an owl on histology
Hodgkin’s Lymphoma - what system do you use to stage?
Ann Arbor Staging
Hodgkin’s Lymphoma - what are the stages of Ann-Arbor?
- Stage 1: Confined to one region of lymph nodes
- Stage 2: In more than one region but on the same side of the diaphragm (either above or below)
- Stage 3: Affects lymph nodes both above and below the diaphragm
- Stage 4: Spread beyond lymph nodes, such as to the lungs or liver
Each stage may be subdivided into A or B
A = no systemic symptoms other than pruritus
B = weight loss > 10% in last 6 months, fever > 38c, night sweats (poor prognosis), or just presence of B symptoms
Hodgkin’s Lymphoma - management?
Aim to cure with: Chemotherapy and radiotherapy
Hodgkin’s Lymphoma - what are the potential side effects of chemo and radiotherapy?
Chemotherapy creates a risk of leukaemia and infertility
Radiotherapy creates a risk of cancer, damage to tissues and hypothyroidism
Non-Hodgkin’s Lymphoma - what is it?
Non-Hodgkins lymphoma is a group of lymphomas
Non-Hodgkin’s Lymphoma - what cells does it affect?
B or T cells
Non-Hodgkin’s Lymphoma - what are three examples?
Burkitt lymphoma - associated with EBV, malaria, HIV
MALT lymphoma - affects the mucosa-associated lymphoid tissue, usually around the stomach, associated with H. pylori infection
Diffuse large B cell lymphoma - often presents as a rapidly growing painless mass in patients over 65 years
Non-Hodgkin’s Lymphoma - what are some risk factors?
HIV
Epstein-Barr Virus
Family history
Autoimmune disorders - SLE, Sjogren’s
H. pylori (MALT lymphoma)
Hepatitis B or C infection
Exposure to pesticides and a specific chemical called trichloroethylene used in several industrial processes
Non-Hodgkin’s Lymphoma - what is the clinical presentation?
Very similar to Hodgkin’s Lymphoma - only way to differentiate is by lymph node biopsy
- Painless lymphadenopathy (non-tender, rubbery, asymmetrical)
- Constitutional/B symptoms (fever, weight loss, night sweats, lethargy)
- Above similar to HL
- Extranodal Disease - gastric (dyspepsia, dysphagia, weight loss, abdominal pain), bone marrow (pancytopenia, bone pain), lungs, skin, central nervous system (nerve palsies)
Non-Hodgkin’s Lymphoma - how do you differentiate between HL and NHL?
only way to differentiate is by lymph node biopsy
Non-Hodgkin’s Lymphoma - while biopsy is occurring, what aspects of the clinical presentation can help point towards Hodgkin’s lymphoma or non-Hodgkin’s lymphoma?
- Lymphadenopathy in Hodgkin’s lymphoma can experience alcohol-induced pain in the node
- ‘B’ symptoms typically occur earlier in Hodgkin’s lymphoma and later in non-Hodgkin’s lymphoma
- Extra-nodal disease is much more common in non-Hodgkin’s lymphoma than in Hodgkin’s lymphoma
Non-Hodgkin’s Lymphoma - what investigations can you do?
- Excisional node biopsy is the diagnostic investigation of choice - certain subtypes have classical appearance, Burkitt’s lymphoma, ‘starry sky’ appearance
- CT chest, abdomen and pelvis - assess staging
- FBC and blood film - normocytic anaemia and can help rule out other haematological malignancy such as leukaemia
- ESR - useful as a prognostic indicator
- LDH - a marker of cell turnover, useful as a prognostic indicator
Non-Hodgkin’s Lymphoma - what is the staging system and stages?
Ann Arbor system
Same as Hodgkin’s Lymphoma
Non-Hodgkin’s Lymphoma - management?
Management dependent on specific sub-type of non-Hodgkin’s lymphoma and will typically take the form of watchful waiting, chemotherapy or radiotherapy
All patients will receive flu/pneumococcal vaccines
Patients with neutropenia may require antibiotic prophylaxis
DIC - what is it?
It is the inappropriate activation of the clotting cascade, resulting in thrombus formation and depletion of clotting factors and platelets
DIC - what are the causes?
Sepsis
Burns
Trauma
Malignancy
Severe obstetric complications
DIC - what is a typical blood picture?
- ↓ platelets, due to them all being used up in thromboses
- ↓ fibrinogen, due to them all being used up in thromboses
- ↑ PT & APTT, due to decreased platelets and fibrinogen, so can’t clot as quickly
- ↑ fibrinogen degradation products, fibrinogen, broken down to make fibrin for clots, and then fibrin broken down through fibrinolysis, to make sure clot isn’t too big that it doesn’t need to be
- Schistocytes due to microangiopathic haemolytic anaemia, way to think about it is that the microclots that from in the blood veseels due to DIC, shred the RBCs as they pass by, leads to schistocytes
DIC - how does it present?
Patients present with excess bleeding e.g. epistaxis, gingival bleeding, haematuria, bleeding from cannula sites
Patients may also present with fever, confusion, or coma
Physical signs include petechiae, confusion, and hypotension
DIC - what leukaemia is associated with DIC?
Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia that is associated with DIC
DIC - what is FDP?
fibrin degradation products
