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MBChB Phase 3 > Week 3: Haematology > Flashcards

Week 3: Haematology Flashcards

1
Q

What is haemopoiesis?

A

The process of blood cell formation

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2
Q

What are the different sites of haemopoiesis throughout life?

A 
FOETUS:
0-2 months = yolk sac
2-7 months = liver, spleen
5-9 months = bone marrow 
INFANT = all bone marrow 
ADULT = red bone marrow (vertebrae, ribs, sternum, femur)
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3
Q

What are the characteristics of haemopoietic stem sells?

A 
Self renew,
unspecialised, 
ability to differentiate, 
rare, 
quiescent
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4
Q

Where are haemopoietic stem cells found?

A

Red bone marrow
Peripheral blood after treatment with G-CSF
Umbilical cord blood

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5
Q

What is symmetrical and asymmetrical division?

A 
Symmetrical = contraction of stem cell number/ expansion of stem cell number 
Asymmetrical = maintenance of stem cell numbers
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6
Q

What is the stroma?

A

The bone marrow microenvironment that supports the developing haemopoietic cell
Rich environment for growth and development of stem cells

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7
Q

What are some stromal cells?

A 
macrophages
fibroblasts 
endothelial cells 
fat cells 
reticulum cells
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8
Q

What is leukaemogenesis?

A

A multi step process
Neoplastic cell is HSC or early myeloid/lymphoid cell
Dysregulation of cell growth and differentiation
Proliferation of leukaemic clone with differentiation blocked at early stage

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9
Q

What is a CLONAL stem cell disorder?

A

Haematological malignancy arising from a single ancestral cell

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10
Q

What is the evidence of a clonal stem cell disorder?

A
  1. Carry unique rearrangement of immunoglobulin or TcR gene
  2. In leukaemia clonal proliferation carries an active maternal or paternal X chromosome
  3. Acquired cytogenetic/molecular change arising during development of a malignancy [eg philadelphia translocation in CML]
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11
Q

Define myeloproliferative disorders

A

Clonal disorders of haemopoiesis leading to increased numbers of one or more mature blood progeny

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12
Q

What mutations are myeloproliferative disorders associated with?

A

JAK2V617F and calreticulin

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13
Q

What is essential thrombocytosis?

A

High platelets (>600x10^9)

Features:
Thrombotic complication
Haemorrhagic complications
Splenomegaly

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14
Q

How is high risk essential thrombocytosis managed?

A

1st line = hydroxycarbamide + aspirin

2nd line = anagrelide + aspirin

IFNa - useful in management during pregnancy
JAK2 inhibitors

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15
Q

What are JAK2 mutations?

A

JAK 2 mutations result in continuous activation of JAK receptor regardless of ligand binding

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16
Q

What are JAK 2 inhibitors?

A

Eg ruxolitinib
Inhibits JAK1/2
Side effect = thrombocytopaenia

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17
Q

Define myelodysplastic syndromes

A

Characterised by dysplasia dn ineffective haemopoiesis in >1 of the myeloid series.
Characterised by progressive bone marrow failure

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18
Q

What are the clinical features of MDS?

A

predominantly affects elderly

Majority present with fatigue due to anaemia

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19
Q

How is MDS managed?

A

Supportive care - blood and platelet transfusion
Growth factors: EPO + granulocyte colony stimulating factor (G-CSF)
Immunosuppression
Low dose chemotherapy (eg hydroxycarbamide)
Demethylating agent
Intensive chemo
Allogeneic stem cell transplantation

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20
Q

What is Fanconi Anaemia?

A

Aplastic anaemia
Bone marrow failure
Autosomal recessive

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21
Q

What are the characteristics of Fanconi anaemia?

A 
Somatic abnormalities
Bone Marrow Failure 
Short Telomeres
Malignancy 
Chromosome Instability
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22
Q

What are some abnormalities in Fanconi Anaemia?

A

microphthalmia
GU/GI malformation
Mental retardation
Hearing loss

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23
Q

How is Fanconi anaemia treated?

A

Gold standard = allogeneic stem cell transplant
Other options: supportive care, corticosteroids, androgens
Lifetime surveillance for secondary tumours

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24
Q

Name the main types of stem cell transplant and define them

A

Autologous: use patients own blood stem cells
Allogeneic: stem cells come from donor

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25
Q

What are the different types of donors?

A 
Syngeneic: between identical twins 
Allogeneic: HLA identical 
Haplotype identical: half matched family member 
Volunteer unrelated
Umbilical cord blood
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26
Q

Explain autologous stem cell transplants

A

Indications: relapsed Hodgkins disease, non Hodgkins Lymphoma, myeloma
Almost all use mobilised peripehral blood stem cells harvested by apheresis
Patients receive G-CSF to make stem cells leave bone marrow to be collected from blood

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27
Q

Explain allogeneic stem cell transplants

A

Can use peripheral blood stem cells, bone marrow or umbilical cord blood
Indications: acute/chronic leukaemias, relapsed lymphoma, aplastic anaemia, hereditary disorders
In malignant disease it has the benefit of graft vs leukaemia effect (at the expense of graft vs host disease)

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28
Q

Explain volunteer unrelated donor transplants

A

70% chance of finding a VUD
Increased risk of GvHD compared to family donor
Majority are caucasian

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29
Q

What are some recent advances in stem cell transplants?

A

Non-myeloablative SCT: low dose, less toxic, prove immunosuppression
Cord blood transplant
Donor lymphocyte infusion after SCT: prevents or treates relapse after SCT

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30
Q

Explain umbilical cord blood transplants

A

Blood collected from umbilical cord and placenta
Cells are tissue types and frozen in liquid nitrogen in cord blook banks
Advantage: more rapidly available than VUD, less rigorous matching to patient as immune system naive
Disadvantage: small amount (often need double cord transplant), slower angraftment, can’t have DLI if relapsed

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31
Q

Explain graft versus host disease

A

Occurs in patients with allogeneic transplant
Donor’s immune system recognises hosts body as foreign and starts to attack it
Manifestation: rash, jaundice, diarrhoea
Types: acute (1st 100 days), chronic (after first 100 days)
Treated with immunosuppressants

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32
Q

Explain graft versus leukaemia

A

Cels which cause GvHD also attack leukaemia cells

Doesn’t occur in autologous transplant as there’s no GvHD

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33
Q

What are the problems with a stem cell transplant?

A 
Limited donor availability
Risk of mortality 
GvHD
Immunosuppression 
Infertility 
Risk of cataracts/osteoporosis
Hypothyroidism 
Relapse
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34
Q

What does normal red cell production involve?

A

EPO, genes, iron, B12, folate, minerals, functioning bone marrow

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35
Q

What is the difference between anaemia and polycythaemia?

A 
Anaemia = not enough red cell production
Polycythaemia = too much red cell production
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36
Q

What is the main function of red blood cells?

A

Gas transfer: CO2 removal, O2 delivery from lungs to tissues

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37
Q

What is haemoglobin made from?

A

4 globin chains (2a, 2B), 4 haem groups (1/globin chain)

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38
Q

Explain Hb binding with oxygen

A

Hb can reversibly bind to oxygen without undergoing oxidation or reduction

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39
Q

How is iron transported in plasma?

A

Transferrin

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40
Q

What is transferrin?

A 
Used in plasma iron transport 
Glycoprotein 
Synthesised in hepatocytes 
2 iron binding domains 
Delivers iron to all tissues, erythroblasts, hepatocytes, muscle
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41
Q

How is iron stored in macrophages?

A

As derritin

Serum ferritin is in proportion with RES iron. The problem is that serum ferritin is an acute phase protein

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42
Q

How is iron absorbed from the intestine?

A

Fe2+ (haem iron) diffuses into enterocyte, Fe3+ (non haem iron) is transported into the enterocyte by DMT1
Fe2+ is transported out of the enterocyte by hepcidin

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43
Q

How are effete red blood cells removed from the blood?

A

By macrophages of the reticuloendothelial system

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44
Q

How is RES iron stored?

A

as ferritin/haemosiderin

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45
Q

How is Tf-iron taken up?

A

via Tf receptors on erythroblasts, hepatocytes etc

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46
Q

How is iron metabolism regulated?

A

Hepcidin is most important in regulating iron metabolism.
It reduces levels of iron in plasma
Hepcidin binds ferroportin and degrades it (- reduces iron absorption and decreases iron release from RES)
Synthesised in liver

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47
Q

What is IDA?

A

Commonest anaemia where there aren’t enough healthy RBCs.

Microcytic Hypochromic

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48
Q

What could microcytic hypochromic RBCs mean?

A

IDA (not enough haem)
Thalassaemia (not enough globin)
ACD (anaemia of chronic disease)
Sideroblastic anaemia

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49
Q

What is the link between serum ferritin and IDA?

A

Low serum ferritin always indicated low RES iron stores (but remember it’s an acute phase protein)

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50
Q

What are some physical signs of iron deficiency anaemia?

A

Koilonychia
Atrophic glossitis
Angular stomatitis

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51
Q

What are some causes of IDA?

A

DIetary (premature neonates, adolescent females), malabsorption, blood loss

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52
Q

What is the golden rule of IDA?

A

IDA in males and post-menopausal females is due to GI blood loss until proven otherwise

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53
Q

How is IDA treated?

A

The treatment is iron replacement and not blood transfusion
Ferrous sulphate 200mg
Ferrous gluconate 300mg
IV iron

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54
Q

When would you use IV iron replacement?

A

Intolerance of oral iron
Compliance issues
Renal anaemia and EPO replacement

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55
Q

What is anaemia of chronic disease?

A

Failure of iron utilisation eg Fe trapped in RES

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56
Q

What are the basic causes of anaemia of chronic disease?

A

Infection
Inflammation
Neoplasia

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57
Q

What does anaemia of chronic renal failure involve?

A

ACD + reduced EPO

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58
Q

What would the lab values be in anaemia of chronic disease?

A 
MCV/MCH (mean corpuscular volume) N/down
ESR up 
Ferritin N/up
Iron down 
TIBC (total iron binding capacity) down
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59
Q

What are RBC rouleaux?

A

Aggregations of RBCs

These occur when ESR is raised

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60
Q

What mechanisms cause anaemia of chronic disease?

A

RES iron blockade; iron trapped in macrophage; raised hepcidin levels
Reduced EPO response
Depressed marrow activity

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61
Q

why are B12 and folate needed?

A

They’re essential for DNA synthesis and nuclear maturation
Required for all dividing cells, deficiency noted first in red cells
Deficiency results in megaloblastic anaemia initially

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62
Q

What processes is vitamin B12 needed for?

A

B12 = cobalamin
Methylation of homocysteine to methionine
Methylmalonyl-CoA isomerisation

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63
Q

How is vitamin B12 absorbed in the gut?

A

Binds to intrinsic factor
Absorbed in ileum
Binds to transcobalamin

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64
Q

How is folate absorbed in the gut?

A

Mostly in the small bowel. No carrier molecule is required.

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65
Q

How does lack of B12/folate cause anaemia?

A

Disparity in rate of synthesis of precursors of DNA - leads to abnormal cell division
ie dissociation between nuclear and cytoplasmic development

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66
Q

What is B12/folate deficiency anaemia?

A

Dissociation between nuclear and cytoplasmic development
Ineffective eryhtropoiesis - death of mature cells while still in marrow
Raised bilirubin, raised LDH

67
Q

What tissues are affected by B12/folate deficiency?

A

Bone marrow, epithelial surfaces (mouth, stomach, small intestine, urinary, female genital tract)

68
Q

What does clinical B12 deficiency result in?

A

Blood abnormalities: megaloblastic anaemia (leucopaenia, thrombocytopaenia)
Neurological manifestations: bilateral peripheral neuropathy or demyelination of posterior and pyramidal tracts of spinal cord

69
Q

What does clinical folate deficiency result in?

A

Blood abnormalities: megaloblastic anaemia (leucopaenia, thrombocytopenia)
Growing foetus: in 1st 12 weeks deficiency causes neural tube defects

70
Q

What are the symptoms/signs of anaemia/cytopaenia?

A 
tired (macrocytic/megaloblastic), 
easy bruising (thrombocytopaenic),
mild jaundice (haemolysis),
neurological problems (nerve disturbance after B12 deficiency)
71
Q

What are some causes of general deficiency?

A

Intake
Absorption
Utilisation
Loss

72
Q

What is pernicious anaemia?

A

Anaemia caused by vitamin B12 deficiency

73
Q

What are causes of folate deficiency?

A

Dietary
Extensive small bowel disease (coeliac/severe Crohns)
Increased cell turnover (haemolysis, skin disorders)

74
Q

What are the causes of B12 deficiency?

A

Dietary
Pernicious anaemia
Gastrectomy/achlorhydria
Terminal ileum problem (Crohn’s/resection)

75
Q

What are causes of macrocytosis other than B12/folate deficiency?

A

Reticuocytosis

Cell wall abnormality

76
Q

What are haemoglobinopathies?

A

Relative lack of normal globin chains due to absent genes

77
Q

What does the severity of haemoglobinopathies depend on?

A

Amount of abnormal haemoglobin
Type of abnormal haemoglobin
Ameliorating factors

78
Q

What are the genetics of Hb production?

A

Haem synthesis takes place from proerythroblast to reticulocyte stage of red cell precursor
Transcription of each gene is controlled by promoter genes at 5’ end and influenced by upstream locus control elements

79
Q

What are thalassaemias?

A

A relative lack of globin genes
4 alpha globin genes
2 beta globin genes

80
Q

What is the clinical significance of alpha thalassaemia?

A

missing one gene = mild microcytosis
missing two genes = microcytosis, inc red cell count, ver mild anaemia
missing three genes = significant anaemia and bizarre shaped small red cells
missing four genes = incompatible with life

81
Q

What is HbH disease?

A

Haemoglobin H disease
Missing 3 alpha genes
Lack of alpha chains -> excess beta chains
Beta chains end up joining together

82
Q

What is beta thalassaemia?

A

Missing B genes

Common in Greek Cypriots (1/7)

83
Q

What is beta thalassaemia major?

A 
Missing both beta globin genes 
Autosomal recessive 
Unable to make adult haemoglobin 
Significant dyserythropoiesis
Transfusion dependant from early life (iron overload has major effect on life expectancy)
84
Q

What are some haemoglobin variant diseases?

A 
Thalassaemia
Sickle cell anaemia
Hb C
Hb D
Hb E
85
Q

What is the pathogenesis of sickle cell disease?

A

Polymerisation of Hb S occurs which results in altered beta Hb chains

86
Q

What is the clinical result of sickle cell anaemia?

A

Reduced red cell survivial (haemolysis), vasoocclusion (tissue hypoxia/infarction)

87
Q

How does sickle cell anaemia affect other systems?

A

Brain - stroke, moya moya
Lungs - acute chest syndrome
Bones - dactilytis
Spleen - hyposplenic

88
Q

What is the treatment of sickle cell disease?

A
  1. PREVENTING CRISES - hydration, prophylactic vaccine/antibiotics, folic acid
  2. MANAGING CRISES - O2, fluids, analgesia, antibiotics, bone transfusion
  3. BONE MARROW TRANSPLANT
89
Q

What is haemolytic anaemia?

A

Increased red cell destruction
Anaemia related to reduced RBC lifespan
No blood loss
No haematinic deficiency

90
Q

What is congenital haemolytic anaemia?

A

Abnormality of RBC membrane

91
Q

What is hereditary spherocytosis?

A 
A congenital haemolytic anaemia 
Abnormality of RBC membrane 
Autosomal dominant 
RBC spherocytic and polychromatic 
Jaundice 
Splenomegaly 
Treatment = splenectomy and hyposplenic prophylaxis
92
Q

What is the hyposplenic state?

A

Hyposplenism = acquired disorder
caused by several haematological and immunological diseases
Rises from encapsulated organisms - pneumococcus, meningococcus, haemophilus, immunisation, long term penicillin V

93
Q

What is pyruvate kinase deficiency anaemia?

A

Chronic/extravascular haemolytic anaemia
ATP depletion
Autosomal recessive

94
Q

What is Glucose-6-phosphate dehydrogenase deficinecy?

A

Acute episodic intravascular haemolysis
X linked recessive
Acute haemolysis from oxidative stress (Favism, Drugs - antimalarials, sulphonamides)

95
Q

What are the types of acquired haemolytic anaemia?

A

Autoimmune - warm type (IgG), cold type (IgM)
Isoimmune - haemolytic disease of newborn
Non-immune - fragmentation haemolysis

96
Q

What is cold autoimmune haemolytic anaemia?

A

Autoantibody IgM + complement
Mycoplasma infection
Idiopathic

Treatment: self limiting mycoplasma, idiopathic, keep warm

97
Q

What are cold agglutinins?

A

Autoantibodies that mistakenly target red blood cells.
They cause RBCs to clump together when exposed to cold temperatures and increase the likelihood that the affected RBCs will be destroyed by the body.

98
Q

What is warm autoimmune haemolytic anaemia?

A 
Autoantibody IgG (+/- complement)
Cause: Idiopathic 30%, lymphoproliferative disorder, other autoimmune disease, drug induced
RBC spherocytic and polychromatic

Treatment: stop drugs, steroids, immunosuppression, splenectomy

99
Q

What is the direct coombs test?

A

Purpose is to detect antibody on RBC surface. Positive means AIHA or haemolytic disease of newborn

100
Q

What is the purpose of the indirect coombs test?

A

To detect RBC antibodies in plasma

101
Q

How can leukaemia be classified?

A

Acute - AML, ALL

Chronic - CML, ALL

102
Q

What is leukaemia?

A

Accumulation of white blood cells (leucocytes)
Blood cancer
Accumulation of abnormal leucocytes in marrow/blood/other tissues

103
Q

What’s the difference between chronic and acute leukaemia?

A 
Chronic = symptoms from accumulation of cells 
Acute = symptoms from marrow failure
104
Q

What is MDS (myelodysplastic syndrome)?

A

A clonal blood disorder

Characterised by failure of effective haemopoiesis and dysplastic blood and marrow

105
Q

How do you establish between low risk and high risk MDS?

A

Proportion of blast cells in marrow and cytogenetic profile

106
Q

How is MDS treated?

A

It is untreatable other than stem cell transplant

107
Q

What are myeloproliferative disorders?

A

Clonal blood disorders. The JAK2 mutation is prevalent. Characterised by too much haemaopoiesis

108
Q

What are examples of MPDs?

A

Too many platelets = essential thrombocythaemia
Too many RBC = polycythaemia vera/ primary polycythaemia
Too much fibrous tissue = myelofibrosis

109
Q

What is myelofibrosis?

A 
Too much fibrous tissue
Difficult to manage 
Large spleen
Systemic symptoms 
Incurable other than SCT
Can use JAK2 inhibtors
110
Q

What is acute leukaemia?

A

A clonal blood disorder
Blastic proliferation in bone marrow
Rapid onset
Serious compromise of normal marrow elements

111
Q

What is the aetiology of AML?

A

largely unkown
Chemicals
Chemo/radiotherapy
genetics

112
Q

What are signs of AML?

A 
rapid onset of symptoms 
lethargy 
infection 
bone pain 
lymphadenopathy
113
Q

How is AML diagnosed?

A

Peripheral bloods - anaemia, neutropaenia, thrombocytopaenia, blasts

114
Q

How is AML managed?

A

Intensive chemo
Low dose chemo
Supportive care only

115
Q

What is the clinical presentation in ALL?

A

Limping child
purpuric rash
Unexplained bone pain

116
Q

How is ALL managed?

A

Chemo: Prednisolone, cyclophosphamide, vincristine. Initial aggressive therapy then oral maintenance
Supportive: blood transfusion, platelet transfusion, ABx, G-CSF

117
Q

What are the presenting features of CLL?

A 
none
lethargy 
night sweats 
weight loss 
anaemia symptoms 
lymphadenopathy 
infection
118
Q

How is CLL diagnosed?

A

Clonal population of B lymphocytes

Unique immunophenotype

119
Q

How is CLL staged?

A 
With BINET staging 
Stages:
A = <3 nodes involved 
B = >3 nodes involved 
C = anaemia or thrombocytopaenia
120
Q

What is BINET?

A

A type of clinical staging for CLL
A = <3 nodes involved
B = >3 nodes invovled
C = anaemia or thrombocytopaenia

121
Q

What are the immune complications of CLL?

A

Autoimmune haemolytic anaemia

Autoimmune thrombocytopaenia

122
Q

When do you treat patients with CLL?

A

Symptoms = sweat, weight loss, symptomatic nodes
Bone marrow failure = anaemia, thrombocytopaenia
Don’t treat asymptomatic patients

123
Q

What is the clinical presentation of CML?

A 
Fatigue 
Weight loss 
Night sweats 
Abdominal discomfort 
Splenomegaly 
Asymptomatic
124
Q

What is the natural history of CML?

A
  1. 3-5 years = chronic phase
  2. 12 - 18 months = accelerated phase
  3. 3-6 months = myeloid blast phase
125
Q

How is CML diagnosed?

A

Blood film and clinical features
MOlecular test on blood (BCR-ABL)
Cytogenetic analysis (karyotype)

126
Q

What mutation must people have for CML

A

Philadelphia translocation - BCR-ABL

127
Q

How is CML treated?

A

Imatinib - blocks action of BCR-ABL

128
Q

What are complications in CML treatment?

A

Imatinib resistance
Imatinib intolerance
Need for 2nd/3rd line TKI inhibitors
Accelerated phase/blast crisis

129
Q

In what ways do chronic and acute leukaemias differ?

A 
Cell of origin 
Biology and genetics 
presentation 
complications 
management 
outcome
130
Q

What are lymphocytes

A

White blood cells that form part of the immune system
They help protect the body against infective and other foreign agents
Some produce antibodies and others have a direct action against pathogens

131
Q

Describe B cells

A

Produced in bone marrow from stem cell progenitor
mature B cells circulate in peripheral blood and populate lymphoid and other organs
Interaction with antigens results in: memory B cells, plasma cells

132
Q

Describe T cells

A

T cells originate in bone marrow from stem cell progenitor
Precursor T cells migrate to the thymus where they develop into mature T cells
Mature T cells circulate in peripheral blood and populate lymphoid and other organs

133
Q

What is the size of a lymphocyte population determined by?

A

Rate of division

Rate of programmed cell death/apoptosis

134
Q

What is lymphoma?

A

Malignancy derived from lymphocytes.
Generally presents with a tumour mass
Commonly in lymph nodes

135
Q

What are risk factors for lymphoma?

A

Immuno-suppressive disorders/treatments
Infections
Age
Genetics

136
Q

How does lymphoma arise?

A

Genetic abnormalities in lymphocytes result in altered gene expression. So there’s altered growth and the balance between cell birth and death favours net growth of the tumour

137
Q

What’s the difference between leukaemia and lymphoma?

A 
Leukaemia = widespread involvement of bone marrow and peripheral blood 
Lymphoma = discrete tissue masses
138
Q

How is lymphoma diagnosed?

A

Biopsy (excision or core)

139
Q

What are the problems in diagnosis of lymphoma?

A

Malignant lymphocytes in NHL look like normal lymphocytes

Morphology alone may not be able to tell if tissue is malignant

140
Q

How is lymphoma classified?

A

Based on: morphology, immunophenotype, genetic features

141
Q

What are the general categories of lymphoma?

A

Non Hodgkins

Hodgkins

142
Q

What is low grade lymphoma?

A

Neoplastic cells mostly of small side (low rate of proliferation, low rate of apoptosis)
Cell cycle characteristics result in slow accumulation of neoplastic lymphocytes

143
Q

What is high grade lymphoma?

A

Neoblastic cells usually of large size with activated blast like appearance (dispersed nuclear chromatin, prominent nucleoli)
Cell cycyel characteristics result in rapid accumulation of neoplastic lymphocytes

144
Q

What is Ki67?

A

A protein expressed by cells in the S phase (ie dividing or proliferating cells)

145
Q

What is follicular lymphoma?

A 
Neoplasm of follicle centre B cells
Presents as painless lymphadenopathy 
Incurable bur indolent course
Treatment: alleviate symptoms 
Low grade lymphoma characterised by: low rate of proliferation, low rate of cell death
146
Q

What is diffuse large B-cell lymphoma?

A

Biologically heterogenous group of lymphoma
Prsents with rapidly enlarging mass at single nodal or extranodal site
Varied immunophenotype
Usually a complex karyotype and many other genetic abnormalities are also present

147
Q

What is Burkitt lymphoma?

A

Neoplasm of proliferating follicle centre (germinal centre) B cells
Highly aggressive but curable (with intensive chemo)

148
Q

What are the epidemiological variants of Burkitt lymphoma?

A

Endemic Burkitt lymphoma - equatorial Africa and Papua new Guinea, associated with EBV
Sporadic Burkitt lymphoma - in Western Europe and North America
Immunodeficiency Burkitt lymphoma - HIV, post transplant

149
Q

What are the genetics of Burkitt lymphoma?

A

Majority have chromosomal translocation involving MYC and IG gene partner

150
Q

What is Hodgkin lymphoma?

A

Lymphoid neoplasm affecting lymph nodes.

Characterised by: large neoplastic B cells (Reed Sternberg cell), prominent background of reactive WBC

151
Q

What are the 2 subtypes of Hodgkins lymphoma?

A

Nodular lymphocyte predominant Hosgkin lymphoma

Classic Hodgkin lymphoma

152
Q

What is classic Hodgkin lymphoma?

A

A subtype of Hodgkin lymphoma
Bimodal age incidence (peaks in YA, elderly)
Usually presents with painless lymphadenopathy
May have systemic symptoms

153
Q

What is the morphology of classic Hodgkin lymphoma?

A

Neoplastic cell is very large with blast like morphology - Reed Sternberg cells

Abundant cytoplasm
Binucleate
Prominent nucleolus

154
Q

What is nodular sclerosing?

A

Bands of sclerosis divide node into cellular nodes

155
Q

What is plasma cell myeloma?

A

A neoplastic proliferation of plasma cells in bone (lytic bone lesion)
Abnormal immunoglobulin detectable in peripheral blood or urine
Incurable

156
Q

What are plasma cells?

A

Immunoglobulin producing cells of the immune system: IgG>IgA>IgM

157
Q

What is plasma cell myeloma diagnosis based on?

A

Neoplastic plasma cells in bone marrow
Evidence of end organ damage attributable to plasma cell proliferation: hypercalcaemia, renal insufficiency, anaemia
Biomarkers of malignancy

158
Q

What is plasma cell myeloma morphology?

A

Neoplastic cells resemble normal mature plasma cells
Eccentric nucleus with clock face chromatin
Abundant cytoplasm with perinuclear clearing

159
Q

What is smouldering (asymptomatic) myeloma?

A

Presence of 10-60% clonal plasma cells in bone marrow but no other myeloma defining event
May be stable for many years but ultimate progression to symptomatic plasma cell myeloma

160
Q

What is monoclonal gammopathy of uncertain significance?

A

Serum M protein <30g/l
Clonal plasma cells in bone marrow <10%
Absence of end organ damage
Low risk of progression to myeloma

161
Q

What is plasmacytoma?

A

Single localised tumours consisting of monoclonal plasma cells
M protein may be detectable but no other typical features of plasma cell myeloma present
Normally managed by local radiotherapy

162
Q

How do patients with lymphoma normally present?

A

Lymphadenopathy: painless, rubbery
Splenomegaly
B symptoms: night sweats, weight loss, fever
Anaemia

163
Q

What do you need to consider when deciding fitness for treatment?

A 
renal function 
liver function 
bone marrow function 
cardiac disease
respiratory disease
164
Q

What system is used to stage lymphoma?

A

Ann-Arbor classification system
I: single lymph node group
II: more than one lymph node group same side of diaphragm
III: lymph node groups both side of the diaphragm (inc spleen)
IV: extranodal involvement eg liver, bone marrow
A or B can be added to signify presence of B symptoms

MBChB Phase 3 (15 decks)

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