haemopoietic cancers Flashcards
what are the causes of sx in haemopoietic cancers
bone marrow failure
infections recurrent or severe
accumulation of malignant cells
systemic
sx of bone marrow failure in haemopoietic cancer
anaemia
infection
bleeding
infections in haemopoietic cancer
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
sx from accumulation of malignant cells in haemopoietic cancer
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
systemic sx in haemopoietic cancer
hypermetabolism
B sx - fever, night sweats, weight loss
fatigue
tumour lysis - rapid breakdown of intracellular contents
autoimmune with lymphoid
epidemiology of haematopoietic cancers
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
what can cause BM damage
infiltrating cancer
drugs - cytotoxic
radiation
pathogenesis of blood cancers
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
cells involved in myeloid malignancies
mast cell/basophils
eosinophils
neutrophils
monocyte/macrophages
lymphoid tumour cells
B or T cell
B cell development
- haemopoietic stem cell
- lymphoid stem cell
- lymphoblast
- pre-germinal centre cell
- germinal centre cell
- post-germinal centre cell
- return ot circ as memory B cell, or return to BM as plasma cell
if tumour develops at blast level - acute lymphoblastic lymphoma
multiple myeloma
tumour of fully differentiated Ab producing plasma cells
which lymphoid malignancy is more common
B 80%
T 20%
in mature stage can get T cell lymphoma involving the skin, as well as LN
dx of blood cancer
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
bone marrow analysis for blood cancer
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
LN core biopsy
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
LN excision biopsy
- Need surgery and GA
- Scar
- Optimal for lymphoma dx and classification – impression of architecture of LN
- see TB and granulomas, and mets
investigations for haemato-oncology dx
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
what do you do whne you get an abnormal blood result
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
what is the top dx
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
causes of pancytopenia
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
interpretation of bone marrow trephine
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
summarise B12 deficiency and mx
summarise folate deficiency and mx
