haematological malignancies

Question 1

myeloid neoplasms

Answer 1

Acute Myeliod Leukaemia AML.
Chronic Myeloid Leukaemia CML.

Myeloproliferative Neoplasms (MPN)
Essential Thrombocythaemia (ET)
Polycythaemia Rubra Vera (PV)
Myelofibrosis (MF)
Idiopathic Hypereosinophilic Syndrome (IHES)
Systemic Mastocytosis (SM).
Myelodysplastic syndromes MDS

Question 2

lymphoid neoplasms

Answer 2

Acute Lymphoblastic Leukaemia (ALL)

Chronic Lymphocytic Leukaemia ( CLL)

Plasma Cell Disorders eg Myeloma

Non Hodgkins Lymphomas eg
Hodgkins Disease
Diffuse Large B NHL (DLCL)
Follicular Lymphoma (FL)
Mantle Cell Lymphoma (MCL)
Marginal Zone Lymphoma (MZL)
Burkitts Lymphoma (BL)

T cell lymphomas

Question 3

acute leukaemia’s

Answer 3

leukaemia= malignancy of the bone marrow.
very rapid growth. may fill marrow before spilling out into blood.
High WBC not always present.
present with bone marrow failure: anaemia, thrombocytopenia, neutropenia

Question 4

Acute Myeliod Leukaemia AML

Answer 4

3.5 per 100.000 per year
M > F
Oldest > youngest
Median age 67

Question 5

Acute Lymphoblastic Leukaemia (ALL)

Answer 5

Commonest malignancy of children
Peak incidence age 4 –5 years
May present with cytopenias or chest masses
90% can be brought into Remission with induction chemotherapy
85% cured
Higher relapse rates in older children and boys (Testes and CNS are ‘sanctuary sites’)

Question 6

common symptoms of leukemia

Answer 6

fatigue, weight loss, fever, infections, weakness, tenderness or pain in joints, swollen lymph nodes, spleen/liver enlargement, night sweats, easy bleeding and bruising, purplish patches or spots

Question 7

treatment (principles)

Answer 7

delay in treatment makes infective complications worse. commence chemotherapy immediately on diagnosis.
AML= strong iv chemotherapy in short sharp bursts.
ALL= mix of strong chemotherapy and persisting milder tablets to prevent relapse.
Allogenic stem cell transplant.
CAR-T

Question 8

Chronic Myeloid Leukaemia CML.

Answer 8

present with high white cells but not usually bone marrow failure.
High WBC ( +/- leukostasis )
Splenomegaly
Priapism.
Due to t(9:22) = Philadelphia chromosome
Gene fusion produces BCR-ABL fusion protein
Treatment now involves specific inhibition of this tumour cell specific enzyme by the drug IMATINIB

Question 9

Myeloproliferative Neoplasms (MPN)

Answer 9

• present with an excess of mature cells in the blood
• Present with an excess of mature cells in the blood

Polycythaemia Rubra Vera (PV) = excess red cells
Essential Thrombocythaemia (ET)= excess platelets
Both PRV/ET may progress to myelofibrosis or acute leukaemia
Myelofibrosis (MF) = excess bone marrow scarring due to abnormal megakaryocyte activity – leading to bone marrow failure

may cause stroke or heart attack due to abnormal clotting

Question 10

Myelodysplastic syndromes MDS

Answer 10

disordered maturation of blood cells in bone marrow.
any or all cell lines may be affected.
east to diagnose if a chromosomal abnormality is detected or if disorganisation of marrow is severe

Question 11

Chronic Lymphocytic Leukaemia ( CLL)

Answer 11

Relatively common ( 3000 cases/year in UK )
Increases with age
Majority of patients die of unrelated conditions
Treatment is only required for troublesome symptoms, bulk disease or marrow failure
Reproductive rate of most CLL is less than ordinary blood cells, but defective apoptosis means they don’t die normally
Usually presents incidentally on a routine FBC for other reasons, but may present with lymphadenopathy

Question 12

non Hodgkin lymphoma

Answer 12

Grouping of a variety of different disease entities all showing tumour growth of lymphoid cells
30% occur outside lymph nodes
More common in the elderly
Some may be related to viruses eg EBV, HTLV, HHV8, HIV
Some ?related to chemical exposure
Some ?related to sunlight exposure
B symptoms or lymphadenopathy are the usual clue to lymphoma

Question 13

Hodgkin lymphoma

Answer 13

Strictly a subtype of the Non Hodgkins Lymphomas
Related to EBV (epstien-Barr virus) infection
2 age peaks – teens/early twenties and elderly
Age peaks may be related to where the EBV has integrated in the lymphocyte DNA – closer or further away from proto-oncogenes
Presents with B symptoms + contiguous nodal spread
The bulk of the tumour in HD are ‘normal’ white cells reacting to the presence of tumour cells

Question 14

lymphoma

Answer 14

a group of blood cancers that develop from lymphocytes. lymphocytes change and grow out of control

Question 15

diagnosis of lymphomas

Answer 15

History of weight loss, fevers, night sweats
Scan or examination suggests lymphadenopathy
Biopsy is vital – no biopsy = no diagnosis
PET/CT used to stage tumour extent and response to therapy

Question 16

immunosecretory disorders

Answer 16

Myeloma
Asymptomatic myeloma
MGUS (Monoclonal Gammopathy of Uncertain Significance)
Localised plasmacytoma
Waldenstroms Macroglobulinaemia
Cold HaemAgglutinin Disease (CHAD)
Amyloidosis

Question 17

antibodies

Answer 17

IgD is expressed by newly mature B lymphocytes
IgM clears pathogens from circulation
IgG clears pathogens from tissue fluid
IgA prevents pathogens invading mucosal surfaces
IgE protects against parasites

Question 18

paraprotein

Answer 18

Normal plasma proteins can be analysed by electrophoresis

Normal antibodies occur as a polyclonal smear on EP

Paraprotein = monoclonal antibody, causing a spike in the normal globulin pattern

Urine paraprotein = isolated light chains = Bence-Jones protein

Question 19

myeloma

Answer 19

2 out of 3 conditions must be met

1. Plasma cells in marrow >10%
2. Detectable paraprotein in blood or urine
3. Lytic lesions on MRI

Question 20

diagnosis in haematological malignancies

Answer 20

Blood test
BM biopsy (morphology, Flow Citometry, Cytogenetics, Molecular)
CT, PET
MRI

Tissue biopsy