Paediatriac Malignant Disease Flashcards
What are the core clinical problems that causes paediatric malignant disease?
1 Anaemia
4 Dying patient
5 Splenomegaly
8 Lymphadenopathy
20 Headache
60 Abdominal mass
Childhood cancer statistics
Cancer is rare in children
Less than 1% of all cases of malignancy
Average GP – will see 1 case in 15 years
Average DGH – will see 5 cases a year
When a diagnosis of cancer is made or suspected - what happens?
most children are referred to a regional centre.
There are 21 such centres in the UK and Ireland.
Children may receive all their treatment at the regional centre, or this may be done in conjunction with their local hospital in a variety of “shared care” arrangements.
Mortality rates in children
In 1st year mortality
580 deaths per 100,000 infants (UK)
After 1st year risk of death reduces:
27 deaths per 100,000 in children aged 1-4
12 deaths per 100,000 in children aged 5-14
Main causes of death in children (1999)
Injury 23.1%
Cancer 18.4%
CNS disorders 13%
Respiratory disease 9.6% (includes pneumonia)
Congenital anomalies 8.2%
Infectious causes 6.3%
What are the implications of improving survival?
Survival has improved over last 30 years
Today > 75% are cured
1 in 900 adults had cancer as child
Late effects from treatment
Some are well recognised
New problems identified (longer survival, new therapy)
Life long follow up essential
Differences in cancers between children and adults?
Carcinomas very rare in children
Embryonal tumours very rare in adults
- Wilms
- Neuroblastoma
- Rhabdomyosarcoma
Leukaemia occurs at all ages
- More common in younger children
Bone tumours and lymphomas
- Peak incidence: early adolescence, early adulthood
What is the difference in biological behaviour in lymphoma between children and adults
with indolent “low grade” lymphomas being much more common in adults and extremely rare in childhood where “high grade” types predominate.
Difference in leukaemia between children and adults
children the predominant type is acute lymphoblastic leukaemia, which is much less common in adults. Chronic leukaemia is extremely rare in childhood, in particular chronic lymphoid leukaemia is not seen.
What is the most common malignancy seen in childhood?
Acute leukaemia is the commonest malignancy seen in childhood – accounting for around 30-33% with the majority of these (80-85%) being acute lymphoblastic leukaemia. The peak incidence of acute leukaemia in “resource rich” countries is 2-6 years. This is not seen in less privileged countries. Acute myeloblastic leukaemia does not have such variation in incidence. Environmental factors are responsible for the very high incidence of B cell lymphomas in equatorial Africa.
Some common cancer incidence
Leukaemia
CNS tumours
Lymphoma
Neuroblastoma
Soft tissue sarcoma
Wilms
Bone tumours
Retinoblastoma
Other
Which tumour’s incidence seems to be increasing?
The incidence of some tumours appears to be increasing. For example there has been an average 0.7% annual increase in ALL of precursor B cell origin and Hodgkins lymphoma (1.2% per year) in the North West of England since the mid 1950s. Other studies have shown small increases in incidence of other solid tumour types. The reasons for these increases are not clear
What is the aetiology of childhood cancers
Most cases – cause is unknown
< 5% due to identifiable genetic abnormality
Double Hit theory: interaction between environment and genetic susceptibility
Mutations in cellular genes
Oncogenes, tumour suppressor genes
Inherited (e.g. retinoblastoma) or sporadic
Some children at increased risk of cancer
Downs, immune-compromised, NF1
WAGR syndrome and cancer
Studies of children with the WAGR syndrome (Wilms tumour, aniridia, genital abnormalities and mental retardation) led to greater understanding of genetics and cancer. A number of children with the syndrome were found to have a deletion of 11p13, and subsequently the WT1 gene was located to this region. Mutations of this gene are found in the tumour cells of many (but not all) children with Wilms who do not have the WAGR or similar syndromes
What is the presentation of children with possible malignant disease?
Localised mass
- Lymphadenopathy
- Organomegaly
- Soft tissue or bony mass
Problems from disseminated disease
- Bone marrow infiltration
Problems from localised mass
- Airway obstruction from lymphadenopathy
Cervical lymphadenopathy is not uncommon in childhood but most children with this do not have cancer
Abdominal distension may be due to tumour in organ such as kidney, or constipation
Aches and pains are a frequent complaint in childhood – only very rarely due to leukaemia
Breathlessness and wheeze much more likely to be due to asthma than lymphoma
Headaches very unlikely to be due to CNS tumour, but frequently are present in child with brain tumour
What are some possible presentations of malignant disease in paediatrics?
Recent URTI, pale & tired
Post viral or leukaemia?
Lump in neck, otherwise well
Atypical mycobacteria or Hodgkin’s?
Early morning headache
Sinusitis or brain tumour?
Recurrent fever & bone pain
Arthritis, Leukaemia, Ewing’s, Neuroblastoma?
Easier differentials in those with paediatric malignancy?
Abnormal red reflex in eye
Retinoblastoma
Proptosis
Infection, Neuroblastoma, Rhabdomyosarcoma
Recurrent discharging ear
Infection, Rhabdomyosarcoma, LCH
Key messages to remember for children with possible malignancy?
Consider malignancy in any child whose condition does not resolve or respond to treatment in the normal way
Do not be afraid to challenge the original diagnosis
If in doubt, retake a full history, from the beginning
Presentation of acute leukaemia?
Fever
Fatigue
Frequent infections
Lymphadenopathy
Hepatomegaly and/or splenomegaly
Anaemia
Bruising,petechiae
Bone or joint pain
What do children with ALL usually present with?
signs and symptoms that reflect bone marrow infiltration and/or extramedullary disease. Because leukaemic blasts replace the bone marrow, patients present with signs of bone marrow failure, including anaemia, thrombocytopenia, and neutropaenia.
What are the S + S of CNS involvement?
Signs or symptoms of CNS involvement, even when it occurs, are rarely seen at presentation. The signs and symptoms include headache, nausea and vomiting, lethargy, irritability, nuchal rigidity, papilloedema. Cranial nerve involvement (most frequently involves 3rd, 4th, 6th and 7th nerves) may occur. Rarely there may be an intracranial or spinal mass, which causes symptoms due to nerve compression.
Testicular involvement at diagnosis is rare. However, if present, it appears as painless testicular enlargement and is most often unilateral
What are the clinical manifestations of ALL in children?
fatigue and pallor, petechiae and bleeding, and fever. In addition, leukaemic spread may manifest as lymphadenopathy and hepatosplenomegaly. Other signs and symptoms of leukemia include weight loss, bone pain, and dyspnoea.
What are the investigations of ALL?
Blood film
Serum chemistry
CXR
Bone marrow aspirate
Lumbar puncture
Imaging studies: Chest radiography Procedures: Bone marrow aspirate & biopsy
What happens in chest radiography?
Evaluate for a mediastinal mass. In general, no other imaging studies are required. If physical examination reveals enlarged testes, then ultrasound of testes should be done - to evaluate for testicular infiltration.
What happens in bone marrow aspirate & biopsy?
The results confirm the diagnosis of ALL. In addition, special stains (immunohistochemistry), immunophenotyping, cytogenetic analysis, and molecular analysis help in classifying each case.
Lumbar puncture with cytospin morphologic analysis: These tests are performed before systemic chemotherapy is administered to assess for CNS involvement and to administer intrathecal chemotherapy.
ALL treatment
Chemotherapy – 5 phases
Induction, Consolidation, Interim maintenance
Delayed intensification, Maintenance
Haemopoietic stem cell transplantation
High risk patients in first remission
Relapsed patients
