haemopoietic cancers

Question 1

what are the causes of sx in haemopoietic cancers

Answer 1

bone marrow failure

infections recurrent or severe

accumulation of malignant cells

systemic

Question 2

sx of bone marrow failure in haemopoietic cancer

Answer 2

anaemia

infection

bleeding

Question 3

infections in haemopoietic cancer

Answer 3

AML -> neutropenia fatal gram -ve septicaemia eg proteus e coli. lack of neutrophils = no resisentance to gram-ve septicaemia and death

Failure of lymphoid – loss of lymphocytes – herpes zoster, recurrent chest and throat infections (sino-pulmonary infections), candida, pneumocystis

Question 4

sx from accumulation of malignant cells in haemopoietic cancer

Answer 4

Chronic myeloid – extramedullary haemopoiesis -> hepatosplenomegaly

chronic lymphoid -> hepatosplenomegaly and lymphadenopathy

Acute don’t get hepatosplenomegaly - die of infection before accumulate

Lymphoid – lesions from lymophoid infiltration = SVC obstruction in hodgkins, lymph nodes in abdo obstruct bowel ureter, bv in abdo cavity

Lymphoid progress and leave the lymphatic system – extralymphatic – lymphoid infiltration into liver, lung, kidney

Immune privalidged site eg eye, brain, testes – don’t have normal lymphocytes, but can get lymphoid infiltration in ca

Question 5

systemic sx in haemopoietic cancer

Answer 5

hypermetabolism

B sx - fever, night sweats, weight loss

fatigue

tumour lysis - rapid breakdown of intracellular contents

autoimmune with lymphoid

Question 6

epidemiology of haematopoietic cancers

Answer 6

16% of tumours that people develop in adults

in adults - lymphoma 9%, myeloma/leukaemia 7%

51% of childhood tumours – acute lymphoblastic leukaemia is most common cancer of childhood

No myeloma in childhood

Question 7

what can cause BM damage

Answer 7

infiltrating cancer

drugs - cytotoxic

radiation

Question 8

pathogenesis of blood cancers

Answer 8

acquired somatic DNA damage in lympho-haemopoietic prescursor

may be background of inherited DNA instability - panconi’s anaemia, dyskeratosis congenita

rapid turnover = risk of DNA mutations, and chronosomal translocations during mitosis

Lymphoid – adaptive immune system = lymphocytes have an unstable genome – DNA recombination involved in Ab diversity

Maturation of immune response with class switching Ig adn varial diversity joining region recombination to make Ab

somatic hypermutation needed for Ab maturation

Question 9

cells involved in myeloid malignancies

Answer 9

mast cell/basophils

eosinophils

neutrophils

monocyte/macrophages

Question 10

lymphoid tumour cells

Answer 10

B or T cell

Question 11

B cell development

Answer 11

1. haemopoietic stem cell
2. lymphoid stem cell
3. lymphoblast
4. pre-germinal centre cell
5. germinal centre cell
6. post-germinal centre cell
7. return ot circ as memory B cell, or return to BM as plasma cell

if tumour develops at blast level - acute lymphoblastic lymphoma

Question 12

multiple myeloma

Answer 12

tumour of fully differentiated Ab producing plasma cells

Question 13

which lymphoid malignancy is more common

Answer 13

B 80%

T 20%

Question 14

Answer 14

in mature stage can get T cell lymphoma involving the skin, as well as LN

Question 15

dx of blood cancer

Answer 15

All requires tissue dx

Peripheral blood – under microscope

• FBC - cytology, flow cytometry (see Ag expression in cells), cytogenics and culture

Bone marrow – origin of the cells

if large hepatic lesion in someone suspect with lymphoma – could see lymphoid cells in liver

LN - fine needle aspirate, core biopsy, excision biopsy

Question 16

bone marrow analysis for blood cancer

Answer 16

aspirate - cytology, flow cytometry, cytogenetics and microculture

• From posterior iliac crest – smaller needle in and aspirate cells – get picture of the individual cells – cytology
• Liquid tumour: stain with monoclonal Ab – flow cytometry – CD or Ag expression of cell – distinguish between T (CD3 CD4 CD8) and B cell (CD19 CD20)

trephine biopsy - architecture, cytology, immunochemistry, FISH, cytogenetics

Question 17

LN core biopsy

Answer 17

Fine needle into LN - per-cutaneous US guided

No anaesthetic, day case, No scar

Useful to look in LN for non-lymphoid material eg TB, mets

Immunophenotyping – see cells expressing squamous cell marking or adenoca marking in LN – suggest cancer – axilla met from breast, cervical – drainage from pharynx

limitation - no lymphatic architecture, limits use in lymphoma dx unless heavily abnormal

Question 18

LN excision biopsy

Answer 18

• Need surgery and GA
• Scar
• Optimal for lymphoma dx and classification – impression of architecture of LN
• see TB and granulomas, and mets

Question 19

investigations for haemato-oncology dx

Answer 19

Morphology of cells - Ln or core biopsy – architecture of tumour

Immunophenotype through flow cytometry if liquid

Immunohistochemistry if solid

Cytogenetics

• FISH if know what lesions looking for
• Conventional karyotyope of want to know general type

Question 20

what do you do whne you get an abnormal blood result

Answer 20

request film

analyse groups of info (anaemia-> Hb, MCV, reticulocytes), (leukocytes - differential and film)

is it isolated in single lineage or all (all suggest BM, low plt - ITP, low MCV - IDA)

prev FBC normal more likely acquired

plan ix - haematinics, Hb electrophoresis, BM biopsy, infection screen, inflammation

Question 21

what is the top dx

Answer 21

BM met from breast cancer, high BR because of liver mets

not pernicious anaemia - FH means possibility – B12 needed for all dividing cells – low Hb, ret, WCC, could give high BR because haemolysis. If pure pernicious anaemia = MCV higher than here

not autoimmune haemolytic anaemia - SLE – autoAb against brain and kidney could be against red cells – low Hb, borderline high MCV fit with reticulocytosis, but with healthy marrow would only involve the red cells, not pancytopenia. Would be high reticulocyte and high BR

Question 22

causes of pancytopenia

Answer 22

failure of blood cell production:

• B12 or folate deficiency
• aplastic anaemia
• toxicity - drugs (cytotoxic/idiosynchratic drug reaction eg chloramphenicol), radiation

malignant infiltration/involvement of marrow

• blood cancer
• mets - prostate, breast, adenocarcinoma from stomach

Question 23

interpretation of bone marrow trephine

Answer 23

Normal – 50 50 of cells and fat

Aplastic or hypocellular – lack of cells and a lot of fat spaces

Leukaemia – infiltrated eg leukaemia loss of space, loss of precusers, lots of malignant cells

Question 24

summarise B12 deficiency and mx

Answer 24

Question 25

summarise folate deficiency and mx

Answer 25