Malignancy Flashcards
Where do precursor cells come from?
progenitor cells that come from stem cells
What cells can self-renew?
stem cells
What is differentiation? When does it occur?
committing to a lineage
- when a multi-potent progenitor becomes either a myeloid or lymphoid progenitor
Describe a bone marrow sinusoid
discontinuous capillary increases permeability
How do blood cells pass through the sinusoid?
sinusoid dilates to increase blood flow and blood cells can pass through fenestrations
Which type of marrow is haemopoietically active?
red
What hormone regulates megakaryocytes and therefore, platelet production?
thrombopoietin
How can we investigate non-lymphoid cells?
blood count
cell indices
morphology on blood film
How can we investigate precursor cells?
bone marow aspiration
- immunophenotyping for lymphoid cells
Where do B cells mature?
bone marrow
Where do T cells mature?
thymus
Where do blood vessels enter and exit a lymph node?
hilum
Where does the thoracic duct carry lymph to?
left venous angle
Where does the right lymphatic duct drain lymph into?
right venous angle
Where do the venous angles drain into?
the internal jugular veins
What can cause regional lymphadenopathy?
- infection (CMV, EBV, HIV
What can cause generalised lymphadenopathy?
systemic inflammatory process or widespread malignancy (lymphoma/leukaemia)
Where is the spleen located?
ULQ of abdomen
What are the parts of the spleen parenchyma?
red pulp
white pulp
What is the red pulp made up of?
red pulp is “red” due to the presence of large numbers of erythrocytes in blood vessels called sinuses
+ splenic cords (reticular cells and fibres)
+ macrophages
What is the white pulp made up of?
lymphatic tissue cords containing B cells and T cells
+ branch of splenic artery (central artery)
+ nodules (made of B cells)
What do lymphocytes gather around the central artery to form?
PALS - peri arterial lymphatic sheath
made up of T cells
Symptoms of splenomegaly
dragging sensation in LUQ
discomfort with eating
pain (if infarction)
What is hypersplenism?
splenomegaly + decrease in blood component + cytopenia corrected by splenectomy
Causes of hyposplenism
splenectomy
coeliac disease
sickle cell disease
sarcoidosis
What characterises malignant haemopoiesis?
increase in abnormal, dysfunctional cells
loss of normal activity
What causes malignant haemopoiesis?
somatic mutations in regulatory genes (driver genes that confer growth advantage)
Features of histologically aggressive disease
large cells with high nuclear-cytoplasmic ratio, prominent nucleoli, rapid proliferation
What is a myeloma?
cancer of plasma cells
How can symptoms arise in myeloma?
plasma cells produce monoclonal antibodies called paraprotein that clog the kidneys and bone marrow
What is a lymphoma?
a cancer of mature lymphocytes in lymphoid tissue
What is acute leukaemia?
cancer of immature (blast) cells in the bone marrow
can be myeloid or lymphoid
How can acute leukaemia present?
failure of normal bone marrow function
- increased white cells
- anaemia
- thrombocytopenia
What is the most common childhood cancer?
acute lymphoid leukaemia
What is chronic leukaemia?
cancer affecting mature cells in the bone marrow
can be myeloid or lymphoid
What are myeloproliferative disorders?
cancer affecting bone marrow cells that produce rbc, platelets or fibroblasts
Give examples of myeloproliferative disorders
polycythaemia rubra vera
essential thrombocythaemia
myelofibrosis
chronic myeloid leukaemia
What is myelodysplasia?
pre-cancerous disease of the bone marrow which may cause abnormal/inadequate blood cell production
What is involved in a chronic lymphocytic leukaemia
blood and lymph nodes
Does pancytopenia always indicate bone marrow failure?
no can also be due to increased destruction
What is pancytopenia?
anaemia + neutropenia + thrombocytopenia
What is affected in bone marrow failure?
reduced production due to inherited syndromes or acquired causes
How do inherited syndromes result in bone marrow failure?
defect in DNA repair or ribosomes
Give an example of an inherited syndrome that results in bone marrow failure
Fanconi’s anaemia
How does fanconi’s anaemia present?
- short stature
- cafe au lait spots
- hypogenitilia
- endocrinopathies
- bone marrow failure
- acute myeloid leukaemia
Primary acquired causes of bone marrow failue
idiopathic aplastic anaemia
myelodysplastic syndromes
acute leukaemia
Secondary acquired causes of bone marrow failure
drug-induced aplasia vitamin B12/folate deficiency infections (viral, mycobacterial) metastatic cancers storage disorders
What is the bone marrow like on examination in myelodysplastic syndrome?
hypercellular
What is the bone marrow like on examination in aplastic anaemia?
hypocellular
What can myelodysplastic syndrome become?
Acute myeloid leukaemia
Causes of increased destruction resulting in pancytopenia
hypersplenism
- congestion in portal hypertension, congestive cardiac failure
- systemic disease eg rheumatoid
- haematolgical disease eg splenic lymphoma
Features of pancytopenia
anaemia –> fatigue, SOB, CV compromise
neutropenia –> infections
thrombocytopenia –> bleeding (purpura, petechiae, visceral bleeds)
How can you treat congenital bone marrow failure?
transplant
How can you treat idiopathic aplastic anaemia?
immunosuppression
What test allows us to detect abnormal immunoglobulins?
serum electrophoresis
Name some causes of paraproteinaemia
MGUS
myeloma
amyloidosis
In a normal individual, what percentage of the bone marrow will be plasma cells?
under 5%
In an individual with myeloma, what percentage of the bone marrow is plasma cells?
over 10%
What else is produced in myeloma other than an excess of plasma cells?
immunoglobulins and free light chains
What immunoglobulins are produced in myeloma?
most commonly IgG
then IgA
Give some direct tumour cell effects in myeloma
bone lesions
hypercalcaemia
bone pain
marrow failure
Give some paraprotein mediated effects of myeloma
renal failure
immunosuppression
hyperviscosity
amyloid
How does hypercalcaemia present?
moans (tiredness, depression)
bones
stones (kidney)
abdominal groans
How do light chains cause renal impairment
- Free light chains are filtered through the glomerulus then kidneys reabsorb these small proteins in the proximal tubules
- If proximal tubules are overwhelmed/damaged then light chains pass into loop of Henle
- Combine with Tamm-Horsfall proteins to produce insoluble casts that block the nephron
- Cast nephropathy causes renal failure
What are MGUS proteins?
monocloncal gammopathy of undetermined significance
- paraproteins present but no end organ damage
- 1% progress to myeloma per year
Which gene mutation is associated with polycythaemia rubra vera?
JAK2
In what condition, are Bence-Jones proteins seen in the urine?
myeloma
Which targeted therapy is successful in chronic myeloid leukaemia?
tyrosine kinase inhibitors eg imatinib
Give an example of a monoclonal antibody
rituximab
What is the action of rituximab?
it binds to CD20 on B cells to treat Non-Hodgkin’s lymphoma
Which gene is only present in CML? Why?
BCR-ABL due to presence of philadelphia chromosome
Features of CML
- Asymptomatic
- Splenomegaly
- Hypermetabolic symptoms
- Gout
Common features of myeloproliferative disorders
- Asymptomatic
- Increased cellular turnover (gout, fatigue, weight loss, sweats)
- Splenomegaly
- Marrow failure (fibrosis or leukaemic transformation)
- Thrombosis
What is polycythaemia rubra vera ?
a myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets.
Features of PRV?
headache
fatigue
itch after hot bath
Treat PRV
venesect to <0.45
aspirin
hydroxycarbamide
What is essential thrombocytosis?
Megakaryocyte proliferation results in an overproduction of platelets which have abnormal function causing bleeding and thrombosis
What is myelofibrosis?
a myeloproliferative disorder
thought to be caused by hyperplasia of abnormal megakaryocytes
the resultant release of platelet derived growth factor is thought to stimulate fibroblasts
haematopoiesis develops in the liver and spleen
Features of idiopathic myelofibrosis
o Marrow failure o Bone marrow fibrosis o Extramedullary haematopoiesis o Leucoerythroblastic film appearances (See erythroblasts and myelocytes) o Teardrop RBCs
What can chronic lymphocytic leukaemia transform in to?
non-Hodgkin’s lymphoma
unexplained petechiae and hepatosplenomegaly in a young person
leukaemia
What translocation is seen in the philadelphia chromosome?
t(9;22)(q34;q11
What are the b symptoms of hodgkin’s disease? What do they mean?
weight loss > 10% in last 6 months
fever > 38ºC
night sweats
- indicate poor prognosis
What are smudge cells on blood film characteristic of?
CLL
How does CML present?
anaemia
splenomegaly
weight loss
an increase in granulocytes at different stages of maturation +/- thrombocytosis
Unexplained cytopenia + lymphadenopathy
? HIV
Which type of lymphoma is associated with HIV?
Non-Hodgkin’s lymphoma
Which type of lymphoma is associated with EBV?
Burkitt’s lymphoma
What does starry-sky appearance on lymph node bioppsy indicate?
Burkitt’s lymphoma
When is IgM paraproteinaemia seen?
waldenstrom’s macroglobulinaemia
An 18 year old student presents with an 8 week history of an enlarging lump in his neck and night sweats. On examination, he has a 4x5cm nodal mass in the right anterior triangle of his neck and right axillary lymphadenopathy.
What is the diagnosis and how is it diagnosed?
Hodgkin’s lymphoma
lymph node biopsy
Marked lymphocytosis would suggest what?
CLL
How do you prevent tumour lysis syndrome?
IV allopurinol
A raised ESR and osteoporosis indicate what?
multiple myeloma
What is a disorder of
a) plasma cells?
b) clonal B cells?
a) myeloma
c) CLL
