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NMF: Haematology > Malignancy > Flashcards

Malignancy Flashcards

1
Q

Where do precursor cells come from?

A

progenitor cells that come from stem cells

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2
Q

What cells can self-renew?

A

stem cells

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3
Q

What is differentiation? When does it occur?

A

committing to a lineage

- when a multi-potent progenitor becomes either a myeloid or lymphoid progenitor

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4
Q

Describe a bone marrow sinusoid

A

discontinuous capillary increases permeability

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5
Q

How do blood cells pass through the sinusoid?

A

sinusoid dilates to increase blood flow and blood cells can pass through fenestrations

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6
Q

Which type of marrow is haemopoietically active?

A

red

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7
Q

What hormone regulates megakaryocytes and therefore, platelet production?

A

thrombopoietin

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8
Q

How can we investigate non-lymphoid cells?

A

blood count
cell indices
morphology on blood film

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9
Q

How can we investigate precursor cells?

A

bone marow aspiration

- immunophenotyping for lymphoid cells

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10
Q

Where do B cells mature?

A

bone marrow

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11
Q

Where do T cells mature?

A

thymus

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12
Q

Where do blood vessels enter and exit a lymph node?

A

hilum

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13
Q

Where does the thoracic duct carry lymph to?

A

left venous angle

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14
Q

Where does the right lymphatic duct drain lymph into?

A

right venous angle

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15
Q

Where do the venous angles drain into?

A

the internal jugular veins

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16
Q

What can cause regional lymphadenopathy?

A
  • infection (CMV, EBV, HIV
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17
Q

What can cause generalised lymphadenopathy?

A

systemic inflammatory process or widespread malignancy (lymphoma/leukaemia)

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18
Q

Where is the spleen located?

A

ULQ of abdomen

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19
Q

What are the parts of the spleen parenchyma?

A

red pulp

white pulp

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20
Q

What is the red pulp made up of?

A

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

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21
Q

What is the white pulp made up of?

A

lymphatic tissue cords containing B cells and T cells

+ branch of splenic artery (central artery)

+ nodules (made of B cells)

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22
Q

What do lymphocytes gather around the central artery to form?

A

PALS - peri arterial lymphatic sheath

made up of T cells

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23
Q

Symptoms of splenomegaly

A

dragging sensation in LUQ
discomfort with eating
pain (if infarction)

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24
Q

What is hypersplenism?

A

splenomegaly + decrease in blood component + cytopenia corrected by splenectomy

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25
Q

Causes of hyposplenism

A

splenectomy
coeliac disease
sickle cell disease
sarcoidosis

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26
Q

What characterises malignant haemopoiesis?

A

increase in abnormal, dysfunctional cells

loss of normal activity

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27
Q

What causes malignant haemopoiesis?

A

somatic mutations in regulatory genes (driver genes that confer growth advantage)

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28
Q

Features of histologically aggressive disease

A

large cells with high nuclear-cytoplasmic ratio, prominent nucleoli, rapid proliferation

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29
Q

What is a myeloma?

A

cancer of plasma cells

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30
Q

How can symptoms arise in myeloma?

A

plasma cells produce monoclonal antibodies called paraprotein that clog the kidneys and bone marrow

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31
Q

What is a lymphoma?

A

a cancer of mature lymphocytes in lymphoid tissue

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32
Q

What is acute leukaemia?

A

cancer of immature (blast) cells in the bone marrow

can be myeloid or lymphoid

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33
Q

How can acute leukaemia present?

A

failure of normal bone marrow function

  • increased white cells
  • anaemia
  • thrombocytopenia
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34
Q

What is the most common childhood cancer?

A

acute lymphoid leukaemia

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35
Q

What is chronic leukaemia?

A

cancer affecting mature cells in the bone marrow

can be myeloid or lymphoid

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36
Q

What are myeloproliferative disorders?

A

cancer affecting bone marrow cells that produce rbc, platelets or fibroblasts

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37
Q

Give examples of myeloproliferative disorders

A

polycythaemia rubra vera
essential thrombocythaemia
myelofibrosis
chronic myeloid leukaemia

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38
Q

What is myelodysplasia?

A

pre-cancerous disease of the bone marrow which may cause abnormal/inadequate blood cell production

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39
Q

What is involved in a chronic lymphocytic leukaemia

A

blood and lymph nodes

40
Q

Does pancytopenia always indicate bone marrow failure?

A

no can also be due to increased destruction

41
Q

What is pancytopenia?

A

anaemia + neutropenia + thrombocytopenia

42
Q

What is affected in bone marrow failure?

A

reduced production due to inherited syndromes or acquired causes

43
Q

How do inherited syndromes result in bone marrow failure?

A

defect in DNA repair or ribosomes

44
Q

Give an example of an inherited syndrome that results in bone marrow failure

A

Fanconi’s anaemia

45
Q

How does fanconi’s anaemia present?

A
  • short stature
  • cafe au lait spots
  • hypogenitilia
  • endocrinopathies
  • bone marrow failure
  • acute myeloid leukaemia
46
Q

Primary acquired causes of bone marrow failue

A

idiopathic aplastic anaemia
myelodysplastic syndromes
acute leukaemia

47
Q

Secondary acquired causes of bone marrow failure

A 
drug-induced aplasia
vitamin B12/folate deficiency
infections (viral, mycobacterial)
metastatic cancers
storage disorders
48
Q

What is the bone marrow like on examination in myelodysplastic syndrome?

A

hypercellular

49
Q

What is the bone marrow like on examination in aplastic anaemia?

A

hypocellular

50
Q

What can myelodysplastic syndrome become?

A

Acute myeloid leukaemia

51
Q

Causes of increased destruction resulting in pancytopenia

A

hypersplenism

  • congestion in portal hypertension, congestive cardiac failure
  • systemic disease eg rheumatoid
  • haematolgical disease eg splenic lymphoma
52
Q

Features of pancytopenia

A

anaemia –> fatigue, SOB, CV compromise

neutropenia –> infections

thrombocytopenia –> bleeding (purpura, petechiae, visceral bleeds)

53
Q

How can you treat congenital bone marrow failure?

A

transplant

54
Q

How can you treat idiopathic aplastic anaemia?

A

immunosuppression

55
Q

What test allows us to detect abnormal immunoglobulins?

A

serum electrophoresis

56
Q

Name some causes of paraproteinaemia

A

MGUS
myeloma
amyloidosis

57
Q

In a normal individual, what percentage of the bone marrow will be plasma cells?

A

under 5%

58
Q

In an individual with myeloma, what percentage of the bone marrow is plasma cells?

A

over 10%

59
Q

What else is produced in myeloma other than an excess of plasma cells?

A

immunoglobulins and free light chains

60
Q

What immunoglobulins are produced in myeloma?

A

most commonly IgG

then IgA

61
Q

Give some direct tumour cell effects in myeloma

A

bone lesions
hypercalcaemia
bone pain
marrow failure

62
Q

Give some paraprotein mediated effects of myeloma

A

renal failure
immunosuppression
hyperviscosity
amyloid

63
Q

How does hypercalcaemia present?

A

moans (tiredness, depression)
bones
stones (kidney)
abdominal groans

64
Q

How do light chains cause renal impairment

A
  • 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
65
Q

What are MGUS proteins?

A

monocloncal gammopathy of undetermined significance

  • paraproteins present but no end organ damage
  • 1% progress to myeloma per year
66
Q

Which gene mutation is associated with polycythaemia rubra vera?

A

JAK2

67
Q

In what condition, are Bence-Jones proteins seen in the urine?

A

myeloma

68
Q

Which targeted therapy is successful in chronic myeloid leukaemia?

A

tyrosine kinase inhibitors eg imatinib

69
Q

Give an example of a monoclonal antibody

A

rituximab

70
Q

What is the action of rituximab?

A

it binds to CD20 on B cells to treat Non-Hodgkin’s lymphoma

71
Q

Which gene is only present in CML? Why?

A

BCR-ABL due to presence of philadelphia chromosome

72
Q

Features of CML

A
  • Asymptomatic
  • Splenomegaly
  • Hypermetabolic symptoms
  • Gout
73
Q

Common features of myeloproliferative disorders

A
  • Asymptomatic
  • Increased cellular turnover (gout, fatigue, weight loss, sweats)
  • Splenomegaly
  • Marrow failure (fibrosis or leukaemic transformation)
  • Thrombosis
74
Q

What is polycythaemia rubra vera ?

A

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.

75
Q

Features of PRV?

A

headache
fatigue
itch after hot bath

76
Q

Treat PRV

A

venesect to <0.45
aspirin
hydroxycarbamide

77
Q

What is essential thrombocytosis?

A

Megakaryocyte proliferation results in an overproduction of platelets which have abnormal function causing bleeding and thrombosis

78
Q

What is myelofibrosis?

A

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

79
Q

Features of idiopathic myelofibrosis

A 
o	Marrow failure
o	Bone marrow fibrosis 
o	Extramedullary haematopoiesis
o	Leucoerythroblastic film appearances (See erythroblasts and myelocytes)
o	Teardrop RBCs
80
Q

What can chronic lymphocytic leukaemia transform in to?

A

non-Hodgkin’s lymphoma

81
Q

unexplained petechiae and hepatosplenomegaly in a young person

A

leukaemia

82
Q

What translocation is seen in the philadelphia chromosome?

A

t(9;22)(q34;q11

83
Q

What are the b symptoms of hodgkin’s disease? What do they mean?

A

weight loss > 10% in last 6 months
fever > 38ºC
night sweats

  • indicate poor prognosis
84
Q

What are smudge cells on blood film characteristic of?

A

CLL

85
Q

How does CML present?

A

anaemia
splenomegaly
weight loss
an increase in granulocytes at different stages of maturation +/- thrombocytosis

86
Q

Unexplained cytopenia + lymphadenopathy

A

? HIV

87
Q

Which type of lymphoma is associated with HIV?

A

Non-Hodgkin’s lymphoma

88
Q

Which type of lymphoma is associated with EBV?

A

Burkitt’s lymphoma

89
Q

What does starry-sky appearance on lymph node bioppsy indicate?

A

Burkitt’s lymphoma

90
Q

When is IgM paraproteinaemia seen?

A

waldenstrom’s macroglobulinaemia

91
Q

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?

A

Hodgkin’s lymphoma

lymph node biopsy

92
Q

Marked lymphocytosis would suggest what?

A

CLL

93
Q

How do you prevent tumour lysis syndrome?

A

IV allopurinol

94
Q

A raised ESR and osteoporosis indicate what?

A

multiple myeloma

95
Q

What is a disorder of

a) plasma cells?
b) clonal B cells?

A

a) myeloma

c) CLL

NMF: Haematology (8 decks)

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