-
what fraction of childhood cases does leukaemia account for?
one third
-
what are the 3 important causative factors in childhood cancer?
- genetic
- infections
- environmental
-
what is the gene defect in retinoblastoma?
chromosome 13 deletion of tumour suppressor gene
-
what is the gene defect in Li-Fraumeni?
p53 mutation
-
what is the inheritance of Li-Fraumeni?
autosomal dominant
-
which cancers are people with Li-Fraumeni at risk of getting?
- breast
- brain
- leukaemia
- sarcoma - soft tissue & bone
- adrenal cortical
-
what is the genetic defect with ataxia telangiectasia?
DNA repair defect
-
what is the gene defect assoc with downs?
trisomy 21
-
which are the 2 main infections that are associated with malignancy?
- EBV: disruption of c-myc oncogene on chromosome 8 leading to malignant change eg Burkitt's lymphoma
- HIV: lymphoma
-
name an environmental risk factor for childhood cancers?
previous treatment of malignancy in a child
-
how do lymphomas usually present?
- constitutional symptoms
- weight loss
- fevers
- night sweats
-
if there is a localised mass in the abdomen, which 2 cancers could that be?
- wilms tumour (nephroblastoma)
- neuroblastoma (most common extracranial solid cancer in childhood)
-
if there is a localised mass in the thorax, what cancer could that be?
non hodgkins lymphoma
-
if there is a localised mass in a soft tissue, what cancer could that be?
rhabdomyosarcoma
-
what cancer causes LN enlargement?
lymphoma
-
what cancer causes symptoms of bone marrow failure?
acute leukaemia
-
which 2 cancers can cause bone pain?
-
how does a primary CNS tumour present?
signs of raised ICP
-
what are the 5 main long term problems in survivors of childhood cancer?
- secondary tumours
- reduced fertility: from alkylating chemotherapy
- cognitive/psychosocial difficulties: methotrexate, school absence
- reduced growth and endocrine problems: irradiated glands
- auditory: platinum drugs
- cardiac: doxorubicin
-
what is the most common malignancy of childhood?
leukaemia
-
how do you characterise leukaemia?
proliferation of immature white cells
-
what is the onset of leukaemia?
insiduous onset
-
what are the signs/symptoms of acute leukaemia? what causes them?
- infiltration of bone marrow/other organs with leukaemia blast cells
- anaemia: pallor & malaise
- thrombocytopenia: purpura, easy bruising, epistaxis
- neutropenia: infection
- reticuloendothelial cell infiltration: hepatosplenomegaly, lymphadenopathy
- expansion of marrow cavity: bone pain
- general: malaise, anorexia
-
how do you confirm the diagnosis of leukaemia?
bone marrow aspiration
-
what % of leukaemias are ALL?
80%
-
what is the peak age for incidence of ALL?
between 3-6 years old
-
is ALL more in boys or girls?
boys
-
how is ALL classified?
according to cell surface antigens = immunophenotype
-
what are the 3 immunophenotypes of ALL?
- non-T, non-B cell ALL: 80% are mostly early B cell clone
- T cell ALL: 15%
- B cell aLL: 1%
-
what are the 3 main prognostic factors taken into consideration for ALL and what is poor?
- age, WBC, lineage
- age: < 1yr
- WBC > 50
- lineage: T cell or B cell
-
which children get T cell ALL?
older children and teenagers
-
what are 2 features of T cell ALL?
- high peripheral WCC
- mediastinal mass
-
what % of ALL can be cured?
65%
-
which cell type of ALL have the best prognosis?
- null cell (common)
- ie non-T, non-B cell
-
what % of children with ALL go into remission? and what % survive beyond 5 years?
75% both
-
which 3 ares of the body can relapses occur?
-
if there is a relapse of leukaemia, what needs to be done?
- high dose chemo
- total body irradiation
- BM transplant
-
why do boys need longer treatment than girls?
as relapses can occur in their testes
-
what has a worse prognosis ALL or AML?
AML and has more intensive treatment
-
what are 80% of AML cases associated with?
chromosomal abnormalities
-
what is the tumour marker for neuroblastoma?
VMA
- what is the tumour marker for germ cell tumour/liver tumour?
- AFP
- which oncogene is associated with poor prognosis in neuroblastoma?
- N-myc
- which 2 chromosomes are translocated in Ewings sarcoma?
- 11 and 12
-
before treatment of ALL is started, what needs to be ensured?
- anaemia is corrected with blood transfusion
- risk of bleeding minimised with platelet infusion
- hydration/allopurinol to protect renal function against effects of rapid cell lysis
-
what does remission mean?
eradication of the leukaemic blasts and restoration of normal marrow function
-
why are blocks of intensification chemotherapy given? give one adv and one disadv
- to consolidate remission
- they improve cure rates but at expense of increased toxicity
-
what is given for CNS protection? why?
- intrathecal methotrexate
- because systemic treatment of cytotoxic drugs poorly penetrate into CNS
-
how many years is maintenance chemotherapy continued for in boys and girls?
- boys 3 years (as testes involvement)
- girls 2 years
-
what prophylaxis treatment is given during chemotherapy and why?
- co-trimoxazole
- to prevent PCP
-
what are the 6 main short term SE of chemotherapy?
- BM suppression: anaemia, low plt, low neutrophils
- immunosuppression: infection
- GI: anorexia, N+V, gut mucosal damage - leading to undernutrition
- alopecia
-
what is the specific SE with doxorubicin?
cardiotoxicity
-
what are the 2 specific SE with cisplatin?
-
what are the 2 SE of cyclophosphamide?
haemorrhagic cystitis
-
what is the SE of vincristine?
neuropathy
-
which type of lymphoma is more common in childhood?
NHL
-
which type of lymphoma is more common in adolescence?
Hodgkins lymphoma
-
how do T cell malignancies usually present?
- as ALL or NHL
- both - mediastinal mass & BM infiltration
-
how do B cell malignancies more commonly present?
- as NHL
- localised lymph node disease usually head, neck, abdomen
-
how does abdominal lymphoma usually present?
- pain
- palpable mass
- intussusception if the ileum is involved
-
how does hodgkins lymphoma usually present?
painless lymphadenopathy - neck usually
-
how can you tell between benign lymphadenopathy and lymphoma?
LN are larger and firmer
-
can HL be cured even if disseminated?
yes, 60% can be cured
-
which age group is NHL more common in?
young children
-
which age group is HL more common in?
-
what increases your risk of NHL?
immunocompromised eg HIV, SCID
-
what is the growth of NHL like?
aggressive, rapidly growing
-
what are the different ways NHL may present?
- peripheral LN enlargement: B cell
- intrathoracic mass: T cell
- mediastinal mass or pleural effusion
- abdominal mass: advanced B cell disease
- Gut of LN masses
-
what is the mainstay of Rx of lymphoma?
chemotherapy
-
what extra Rx may be needed for abdominal tumours NHL?
debulking surgery
-
what are the 2 complications of NHL in the acute setting?
- SVC syndrome: SOB, face or arm swelling, distended veins
- tumour lysis syndrome: occurs after Rx of cancer due to breakdown products of cancer cells eg high K, high phosphate (causing low calcium - tetany seizures), high uric acid - renal failure
-
which cell is HL characterised by?
Reed Sternberg cell
-
does HL affect f or m more?
female adolescents
-
how does HL usually present?
- painless cervical or supraclavicular lymphadenopathy
- systemic symptoms are uncommon
-
where does mets of HL occur?
-
how is HL diagnosed?
LN biopsy and histological examination
-
what aerate 4 subtypes of HL and how does this affect prognosis?
- lymphocyte predominance: best prognosis
- mixed cellularity
- nodular sclerosing: most common in children and adolescents
- lymphocyte deplete: worse prognosis
-
which subtype of HL has best prognosis?
lymphocyte predominance
-
which subtype of HL has worse prognosis?
lymphocyte deplete
-
which is most common subtype of HL in children?
nodular sclerosing
-
what is Rx of HL?
- stage first by imaging chest mediastinum abdomen
- Rx with combo chemo except if localised disease - radiotherapy
-
what is overall prognosis of HL?
-
what is the 2nd most common form of childhood cancer?
brain tumour
-
what is the commonest solid tumour of childhood?
brain tumour
-
where are 60% of brain tumours in children located?
infratentorially
-
what are signs and symptoms of brain tumours DUE TO?
- increased ICP
- cerebellar dysfunction
-
what are the 3 main types of brain tumours?
- astrocytomas
- PNET - primitive neuroectodermal tumours (medulloblastoma)
- craniopharyngioma
-
where are high grade astrocytomas located?
supratentorial
-
where are low grade astrocytomas located?
cerebellar
-
what age do children get astrocytoma?
6-9 years
-
how do cerebellar astrocytomas present?
- headache and vomiting: due to obstructive hydrocephalus
- papilloedema
- cerebellar: ATAXIA, nystagmus, incoordination
- eyes: diplopia, SQUINT due to CN6 palsy
-
how do supratentorial astrocytomas present?
- focal neurological signs
- seizures
-
how do brainstem gliomas present?
- CN palsy
- ataxia
- pyramidal tract signs
-
what are worrying features of headache?
- especially worse when lying down
- worse first thing in morning - as due to high ICP
-
what are worrying features of vomiting?
- especially on waking in mornings
- no nausea assoc with it
-
what is the most common MALIGNANT brain tumour in childhood?
PNET - medulloblastoma
-
which gender and age does PNET occur in?
-
where do PNET arise and where do they invade?
- arise in MIDLINE
- invade 4th ventricle and cerebellar hemispheres
-
what is different about PNET tumours from the other brain tumours?
- they seed through the CNS
- 20% have spinal mets at diagnosis
-
what are the presenting features of PNET?
-
what is Rx of PNET?
- surgical removal
- whole CNS irradiation
-
what are 5yr survival rates of PNET?
50%
-
where do craniopharyngiomas arise from?
remnant of Rathke's pouch
-
how do craniopharyngiomas present?
- visual field loss: compression of optic chasm
- pituitary dysfunction: growth failure, diabetes insipidus
-
which Ix do craniopharyngiomas show up on and why?
-
what is Rx of craniopharyngioma?
- surgical excision
- may need radiotherapy
-
what is prognosis and sequelae of craniopharyngioma?
- good prognosis
- sequelae: visual impairment, endocrine deficiency
-
what is neuroblastoma?
malignancy of NEURAL CREST CELLS
-
what do neural crest cells normally give rise to?
- paraspinal SYMPATHETIC ganglia
- adrenal medulla
-
what age children does neuroblastoma occur in?
-
what do clinical features of neuroblastoma depend on?
location
-
what is the most common mode of presentation of neuroblastoma?
- firm
- non tender abdominal mass
-
what are clinical features of neuroblastoma? top to toe
- eyes: opsoclonus myoclonus from immune response, unilateral proptosis due to mets to eye
- mediastinum: mass on CXR
- abdominal mass: firm, non tender
- GI: diarrhoea due to secretion of VIP
- liver: hepatomegaly
- Lymphadenopathy
- systemic: pallor, weight loss
- bone pain: disseminated disease
-
which Ix can be used to help diagnose neuroblastoma?
raised urinary catecholamines - VMA
-
how do you do a confirmatory diagnosis?
MIBG radiolabelled tumour specific agent
-
what is Rx of neuroblastoma?
- surgical resection
- chemotherapy
- irradiation
-
what makes prognosis worse in neuroblastoma?
- older children
- metastatic disease
- overexpression of N-myc oncogene
-
what is the proper name for Wilms tumour?
nephroblastoma
-
what age does wilms present?
first 5 years
-
what is the most common clinical presentation of wilms?
- asymptomatic abdominal mass
- that does not cross the midline
-
why would you get abdominal pain in wilms?
haemorrhage into the tumour
-
what are the 2 causes of hypertension in wilms?
- compression of renal artery
- renin production by tumour cells
-
what are other features of a wilms apart from abdominal mass?
- abdominal pain if bleeding into tumour
- haematuria
- hypertension - compression of renal artery or renin production by tumour cells
-
what other abnormalities is Wilms associated with?
- hemihypertrophy - one side of body is larger than other
- GU tract abnormalities
- mental retardation
- aniridia - absence of iris
-
which cells does wilms tumour arise from?
embryonic renal cells
-
how do you make diagnosis of wilms?
- CT characteristic appearance: INTRINSIC renal mass with MIXED solid and cystic densities
- biopsy
-
where are the most common mets of Wilms?
-
what is Rx of wilms?
- surgical resection
- chemo
- radio if advanced disease
-
what is prognosis of wilms?
good 80% cure rate if no mets
-
what age group and gender does bone tumours affect?
-
what are the 2 main types of bone tumours in children? which is most common?
- osteogenic sarcoma - most common
- ewing's sarcoma
-
what age group does osteosarcoma affect?
older children
-
what age group does ewings sarcoma affect?
younger children
-
what part of the bone is osteosarcoma a tumour of?
- bone producing mesenchyme
- m:f 2:1
-
what is the usual presenting feature of osteosarcoma?
- local pain - persistent
- swelling
-
where do most cases of osteosarcoma occur?
around knee joint - metaphysis of distal femur or proximal tibia
-
where do osteosarcoma metastasise to?
lungs
-
what does bone x-ray of osteosarcoma show?
- destruction
- sunburst appearance as tumour breaks through the cortex and spicules of new bone are formed
-
what is Rx of osteosarcoma?
- surgery of primary AND metastatic deposits
- aggressive chemo to treat micromets
-
what is survival of osteosarcoma?
>50%
-
what is the origin of ewings - what type of tissue?
- undifferentiated sarcoma
- uncertain tissue of origin - bone and sometimes soft tissues
-
which 2 types of bones does ewing's most commonly affect?
- long bones - mid to proximal femur
- also flat bones - pelvis
-
what are the presenting features of ewing's?
-
what does XR of Ewing's look like?
- destructive lesion
- periosteal elevation
- OR soft tissue mass - onion skin appearance
-
where do Ewing's mets occur to?
lung and other bones
-
what is Rx of Ewing's?
- radiotherapy to primary tumour
- combo with chemotherapy for prevention or Rx of mets
-
what is the genetic abnormality in retinoblastoma and which chromosome?
- deletion of tumour suppressor gene
- chromosome 13
-
what % of retinoblastoma is bilateral?
bilateral in 40%
-
how does retinoblastoma present?
absent red reflex
-
what is the pattern of inheritance in Rb?
dominant but with incomplete penetrance
-
when do most cases of Rb present?
first 3 yrs
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