Intro to Haematological Malignancies Flashcards
Who does haematological malignancies affect?
All age groups, even children
Which gender of adult gets haematological malignancies more?
M > F
Pathology of haematological malignancies
Multi step process
Acquired genetic alterations to a long lived cell
Proliferative/survival advantage to that mutated cell (have to have a proliferative/survival advantage over the other cells to give it a malignant phenotype)
This produces a malignant clone
The malignant clone grows to dominate the tissue (e.g. bone marrow or lymph nodes)
Drivers of haematopoiesis
Multipotential haematopoietic stem cells
Features of multipotential haematopoietic stem cells
Can self renew
multipotential i.e. can produce all types of cells
Definition of haematopoiesis
Refers to the commitment and differentiation processes that lead to the formation of all blood cells from haematopoietic stem cells
Myeloid lineage of malignancies are called what?
Myeloid malignancies
Types of cells of myeloid malignancies
Red cells
Platelets
Granulocytes
Monocytes
Lymphoid lineage of malignancies are called what?
Lymphoid malignancies
Types of cells of lymphoid malignancies
B cells
T cells
What is the commonest malignancy of childhood?
Acute lymphoblastic leukaemia
Pathology of development of AML (acute myeloid leukaemia)
Genetic mutation in the stem cells
Early accumulate of myeloid progenitor cells which keep proliferating without maturing or differentiating -> bone marrow cells -> AML
so the bone marrow is stuffed with useless cells
No N cells in the blood
Pathology of the development of ALL (acute lymphoblastic leukaemia)
Genetic mutation in the stem cells
Ongoing proliferation at a slightly higher rate and an increase in differentiation
Accumulation of more N cells (red cells, neutrophils etc) in the blood
ALL
How do mature lymphoid malignancies (e.g. Hodgkin / non Hodgkin lymphoma) come about?
Mutations occur in a later place e.g. bone marrow, lymph node after already having ALL
Most likely occur in the germinal cell of the lymph node
Different mutations in the same stem cell compartment lead to what?
Different phenotypes
AML can lead to what?
Myeloproliferative disorders
What is the difference between leukaemia and lymphoma?
The distribution of the disease
Bone marrow malignancy is described as what?
Leukaemia
Lymphoma is found in what?
Lymph tissue or
Solid organs
Commonest form of leukaemia is what?
Chronic lymphocytic leukaemia
Features of chronic lymphocytic leukaemia
Perfectly well
Elderly usually
Features of Burkitt’s lymphoma / leukaemia
Most aggressive
commonly presents with lumps
Can affect young adults / children
Can be both lymphoma and leukaemia as it can present with both
Acute leukaemias
Acute lymphoblastic leukaemia (ALL)
Acute myeloid leukaemia (AML)
Chronic leukaemia s
Chronic myeloid leukaemias (CML)
Chronic lymphoid leukaemia (CLL)
The malignant lymphomas
Non-Hodgkin Lymphoma (NHL) Hodgkin Lymphoma (HL)
What does MDS stand for?
Myelodysplastic syndromes
Acute vs chronic leukaemia name is related to what?
The pace of the disease
Pathology of acute leukaemia
Leukaemic cells do not differentiate
Bone marrow failure over a short period of time
Rapidly fatal if untreated
- being well to very unwell to dead within weeks
Is acute leukaemia potentially curable?
Yes
Clinical features of acute leukaemia
Bone marrow failure - anaemia - thrombocytopenic bleeding (purpura and mucosal membrane bleeding) - infection because of neutropenia (predominately bacterial and fungal) as cant make puss so infections spread easier Bleeding - Petechial - GI - eye
What is the triad of symptoms of bone marrow failure?
Anaemia
Thrombocytopenic bleeding (mucosal, purpura)
Infection (because of neutropenia)
Pathology of chronic leukaemia
Leukaemic cells retain ability to differentiate
Proliferation without bone marrow failure
Very white blood
Survival of chronic leukaemia
Survival for a few years
Quite well for a long time
Is chronic leukaemia potentially curable?
Yes, with modern therapy
Bone marrow (aplasia) can fail for a number of reasons…..
Malignancies
other conditions
chemotherapy
Structure of a lymph node
Inner medulla Outer cortex Follicles dotted in lymph node - germinal centre (B cells mature here) - mantle zone (around germinal centre) - marginal zone (around mantle zone)
Where do B cells mature in the lymph node after coming from the bone marrow?
Germinal centre
Lymphomas commonly develop in what cells?
Mutations of the cells when in the germinal centre
Presentation of lymphoma
Nodal disease - lymphadenopathy Extra-nodal disease Systemic symptoms - fever - B symptom - drenching sweats - B symptom - loss of weight (10% of weight) - B symptom - pruritic - fatigue
What are the B symptoms?
Fever
drenching sweats
Loss of weight
What do people with B symptoms indicate?
A less favourable prognosis and may need more treatment
Nodal disease HL vs NHL
HL = > 90% present with nodal disease NHL = approx. 60% present with purely nodal disease
If lymphadenopathy is localised and painful - what does this indicate?
Bacterial infection in draining site
If lymphadenopathy is localised and painless, what does this indicate?
Rare infections, catch scratch fever, TB
Metastatic carcinoma from draining site - HARD
Lymphoma - RUBBERY
reactive, no cause identified
If lymphadenopathy is generalised and painful/tender, what does this indicate?
Viral infections EBV CMV Hepatitis HIV
If lymphadenopathy is generalised and painless, what does this indicate?
Lymphoma Leukaemia Connective tissue diseases, sarcoidosis Reactive, no cause identified Drugs
What about a lymph node indicates a metastatic carcinoma from a draining site?
HARD
What about a lymph node indicates lymphoma?
RUBBERY
What is multiple myeloma?
Malignancy of the plasma cells in the bone marrow
What does multiple myeloma produce?
An abnormal immunoglobulin/antibody into the blood
Presentation of multiple myeloma
Bone pain
Lytic lesions (destruction of skeleton by activation of osteoclasts - NOT sclerotic)
Anaemia
- renal failure
- anaemia of chronic disease
Recurrent infections
Renal failure (an immunoglobulin blocking the renal tubule)
Amyloidosis (deposition of chains in other tissues e.g. kidneys)
Bleeding tendency
Hyper viscosity syndrome (malignant cells producing huge amounts of paraproteins)
Causes of thrombocytosis
infections post surgery / trauma malignancy iron deficiency inflammation - IBD / RA primary myeloproliferative disorder
Presentation of myelofibrosis
Splenomegaly (can be massive) Cytopenia symptoms Spleen symptoms Weight loss Extreme tiredness Leukoerythroblastic blood film, teardrop red cells Marrow fibrosis - reticulin stain
Mutations common in myelofibrosis
JAK2
CALR
MPL
What happens in myelofibrosis?
The bone marrow is replaced by fibrous (scar) tissue
Possible causes of lymphocytosis
Viral infection (e.g. EBV, HIV) other infections e.g. TB, syphilis Vasculitis Acute lymphoblastic leukaemia Chronic lymphocytic leukaemia Lymphoma
Treatment of neutropenia (if risk factors)
Filgrastim (as brings up neutrophil count more quickly in those at high risk)
What is filgrastim?
Granulocyte colony stimulating factor
Examples of patients at high risk for febrile neutropenia
Elderly
Specific malignancies (e.g. NHL, ALL)
Previous neutropenic episodes
Those receiving combination chemo and radio
What is checked before each round of chemo and why?
Neutrophil levels
As if neutropenia, increased risk of developing an infection or neutropenic sepsis
