CP7-11 myeloma and lymphoma Flashcards
What is a myeloma?
An incurable malignant disorder of clonal plasma cells
What is the epidemiology of myeloma?
60-70 per million in UK
Median age at presentation = 70
Higher incidence in Afro-Caribbeans compared with Caucasians
What is myeloma preceded by in all patients?
Asymptomatic MGUS
What change in the immune system is known as myeloma?
Terminally differentiated type of B cells (plasma cells)
Why are immunoglobulins affected by myelomas?
As immunoglobulins are produced by plasma cells which are the affected B-cells in myeloma
What are the different types of heavy chains that an immunoglobulin can have?
IgG
IgM
IgA
IgD
IgE
What are the different type of light chains that an immunoglobulin can have?
Kappa or lambda
What is protein electrophoresis?
Lab technique whereby serum is placed in gel and exposed to an electric current
Which proteins are separated in protein electrophoresis?
Serum albumin
Alpha-1 globulins
Alpha-2 globulins
Beta globulins
Gamma globulins
What on a protein electrophoresis may suggest myeloma?
An M-spike showing excess production of a certain protein
What is immunofixation? When is it performed?
Procedure performed when an M-spike seen on protein electrophoresis which enables detection and identification of monoclonal immunoglobins. A positive result involved a complex being precipitated.
What spectrum is myeloma on?
Plasma cell dyscrasis aka paraproteinaemias
When is myeloma diagnosed?
When a patient has clonal BM plasma cells >/=10% or a biopsy proven bony or extramedullary plasmacytoma AND one or more of the CRAB features or MDEs
What are the CRAB features?
C- hyperCalCaemia
R - Renal insufficiency
A - Anaemia
B - Bone lesions
What are the MDEs?
Myeloma defining events
- >/=60% clinal plasma cells on bone marrow biopsy
- SFLC ratio >100mg/L provided the absolute level of the involved LC is >100mg/L
- >1 focal lesion on MRI measuring >5mm
What is the epidemiology of kidney problems in myeloma patients?
20-25% have renal insufficiency upon diagnosis
50% have renal insufficiency at some point during disease course
50% will have persistent renal impairment despite therapy
2-12% will require renal replacement therapy
What external factors associated with myeloma can cause kidney problems?
renal vein thrombosis
bisophonates
hypercalcaemia
ACEi
dehydration
NSAIDs
CT contrast
hyperviscosity
type 1 cryglobulinaemia
What are the clinical symptoms of myeloma?
confusion
poor appetite
nausea
constipation
thirst
chest infections
breathlessness
bone pains
pathological fractures
polyuria or oliguria/anuria
peripheral oedema
What are acute complications of myeloma?
Hyperviscosity (especially when IgA and IgM is affected by myeloma) usually affecting eye and brain
Hypercalcaemia
Sepsis
AKI
Spinal cord compression
What are acute complications of myeloma?
Hyperviscosity (especially when IgA and IgM is affected by myeloma) usually affecting eye and brain
Hypercalcaemia
Sepsis
AKI
Spinal cord compression
What does rouleaux levels on a blood test tell you?
that red blood cells are stacking up as they are sticking together due to raised immunoglobulins
What blood investigations are done into myeloma?
bloods including:
- FBC to look at: Hb, WBC, platelets and blood film
- U&Es
- Calcium
- C-reactive protein
- Immunoglobulin levels
- protein electrophoresis
- light chain analysis ( f no paraprotein present in protein electrophoresis but still clinical suspicion of myeloma)
What imaging investigations are done for suspected myeloma?
skeletal survey
whole body CT or MRI
PET scan - although not all myelomas appear on PET
How is myeloma treated?
Steroids
Treat associated AKI quickly as medical emergency
What treatments for myeloma are being developed?
individualised therapies
monoclonal antibody therapies
targeted therapies
maintenance therapies
What is the epidemiology of MGUS by age?
increases as you age
affects M>W
What is the risk of MGUS progressing to myeloma?
1% per year
majority will eventually progress
What is AL amyloidosis?
amyloid light chain amyloidosis - where light chain fragments misfold and self aggregate to form beta-pleated fibrils which get deposited into organs.
What are some clinical features of AL amyloidosis?
nephrotic range proteinuria (mainly albumin)
cardiac and liver damage (30% of patients)
peripheral neuropathy (10% of patients)
End stage renal failure (40% of patients)
What is a lymphoma?
Malignant proliferation of B or T cell lymphocytes which predominantly affects lymph nodes and may affect bone marrow and other organs in later stages
How are B-cell lymphomas classified?
According to presence of absence of Reed-Sternberg cells
What lymphoma is characterised by the presence of Reed-Sternberg cells?
Hodgkin’s lymphoma
What lymphomas are characterised by absence of Reed-Sternberg cells
T-cell lymphomas
Non-Hodgkin’s lymphoma
What are the two types of non-Hodgkin lymphoma?
aggressive and indolent
How does aggressive non-Hodgkin lymphoma present?
rapid onset lymphadenopathy
night sweats
weight loss
How does indolent non-Hodgkin lymphoma present?
insidious onset lymphadenopathy
systemically well
How does Hodgkin lymphoma present?
lymphadenopathy
night sweats
weight loss
fatigue
uncommon for basement membrane involvement
What are examples of aggressive non-Hodgkin lymphoma tumours?
DLBCL
Burkitt lymphoma
What are examples of indolent non-Hodgkin lymphoma?
follicular lymphoma
marginal zone lymphoma
What is important to ask in a history of a patient presenting with a neck lump?
nature of lump - size, rate of change, tenderness, skin changes, history of trauma
if noticed lumps anywhere else
if Hx of weight loss or night sweats
if Hx of breathlessness, haemoptysis or cough
PMHx
SHx
FHx
What investigations are done for a suspected lymphoma?
Bloods
- FBC
- U&Es
- LFTs
- Ca
- LDH
- immunoglobulins and protein electrophoresis
Imaging
- chest X-ray
- CT neck, chest, abdo, pelvis
- +/- PET scan
- ultrasound scan of neck lump
Biopsy
- Fine needle aspirate and/or core biopsy
- bone marrow biopsy depending on results of other tests
What is follicular lymphoma?
A indolent non-Hodgkin lymphoma characterised by a slowly enlarging lymph nodes
What % of non-Hodgkin lymphoma is a follicular lymphoma?
15%
What is survival of follicular lymphoma like?
Median survival = 8-10 years
What can be used to determine prognosis in follicular lymphoma?
Follicular international prognostic index (FLIPI)
What categories are used in FLIPI?
Age >=60
Ann Arbor stage III or IV
LDH above normal upon diagnosis
Hb <120g/L
Presence of more than 4 nodal sites of disease
What is the incidence of hodgkin lymphoma?
2.7/100,000 people in Uk
How do Hodgkin Reed-Sternberg cells affect the body?
They fail to express surface immunoglobulins and evade apoptosis by activating NFkB, incorporate EBV and latent membrane proteins like LMP1 and LMP2
How does patients with Hodgkin lymphoma present?
Hx of breathlessness, night sweats, feeling itchy, fever, unexplained weight loss, fatigue, lymphadenopathy
How is Hodgkin lymphoma treated?
chemotherapy
radiotherapy
What is used to determine the doses/number of courses of treatment a patient receives for Hodgkin lymphoma?
the stage of the lymphoma
What is the prognosis of Hodgkin lymphoma?
good - 86% 5 year survival rate
What are leukaemias characterised by?
If acute or chronic
If myeloid or lymphoid
What is chronic lymphocytic leukaemia?
a malignant disorder of mature B-cells
What is the epidemiology of chronic lymphocytic leukaemia?
1% of all cancers in the UK
How may a patient with chronic lymphocytic leukaemia present?
ranges from asymptomatic to extreme:
asymptomatically - incidental finding
to
widespread lymphadenopathy, splenomegaly, bone marrow failure and systemic symptoms
What system is used to stage chronic lymphocytic leukaemia?
Binet system
Do genetics play a part in development of chronic lymphocytic leukaemia?
Yes - there is an impact of adverse cytogenetics including 17p deletion
What are some complications of chronic lymphocytic leukaemia?
Recurrent infections secondary to reduced immunoglobulin production
Autoimmune phenomenon including:
- ITP
- haemolytic anaemia
- pure red cell aplasia
- autoimmune neutropenia
Richter’s transformation into an acute cancer
What is an example of an acute cancer developed from chronic lymphocytic leukaemia by Richter’s transformation?
Diffuse large b-cell lymphoma
What symptoms suggest transformation of chronic lymphocytic leukaemia into a high grade lymphoma?
Sudden deterioration of symptoms +/- rapid enlarging of CLL affected lymph node group
