Key Facts

Childhood cancer differs fundamentally from adult cancer in histological type, behaviour, and treatment response. Embryonal tumours and haematological malignancies predominate. Cure rates are high with modern multi-modal therapy, but long-term treatment effects require lifelong surveillance.

Epidemiology

Approximately 1,900 children aged 0-14 are diagnosed with cancer annually in the UK. Childhood cancer accounts for <1% of all cancer diagnoses but is the leading cause of disease-related death in children aged 1-14. Age distribution: peak incidence in children under 5 (especially leukaemia and embryonal tumours). Overall 5-year survival is approximately 80-85%.

Aetiology

Most childhood cancers arise from errors in normal development rather than cumulative mutations:

• Genetic predisposition (~5-10%): Li-Fraumeni (TP53), hereditary retinoblastoma (RB1), Beckwith-Wiedemann syndrome (Wilms'), NF1 (optic glioma, MPNST), familial adenomatous polyposis, MEN syndromes
• Chromosomal: Down syndrome (20× risk of ALL), Turner syndrome
• Environmental: Ionising radiation, previous chemotherapy (secondary malignancy)
• Infections: EBV (Burkitt lymphoma, Hodgkin), HHV8 (Kaposi sarcoma)
• Idiopathic: The majority have no identifiable cause

Pathophysiology

Childhood cancers are predominantly embryonal (arising from primitive cell types) or haematological:

• Leukaemia: Clonal proliferation of immature haematopoietic cells in bone marrow
• CNS tumours: Arise from neural, glial, or embryonal tissue (medulloblastoma, astrocytoma, ependymoma)
• Embryonal tumours: Neuroblastoma (neural crest), Wilms' tumour (metanephric mesenchyme), retinoblastoma (retinal cells), rhabdomyosarcoma (skeletal muscle)
• Lymphoma: Clonal lymphocyte proliferation — Hodgkin or non-Hodgkin

Leukaemia

• Pallor, fatigue (anaemia)
• Bruising, petechiae, bleeding (thrombocytopenia)
• Recurrent infections, fever (neutropenia)
• Bone/joint pain (marrow infiltration)
• Hepatosplenomegaly, lymphadenopathy

CNS Tumours

• Persistent headache (especially early morning, worse lying flat)
• Vomiting (especially early morning, without nausea)
• Visual disturbance (diplopia, visual field loss)
• Gait abnormality, coordination difficulties
• Personality/behavioural change
• Head tilt (posterior fossa tumour)
• Cushing's triad in raised ICP: hypertension, bradycardia, irregular respiration

Lymphoma

• Painless lymphadenopathy (>2cm, persistent >6 weeks, non-tender, firm)
• B symptoms: Fever, night sweats, weight loss >10%
• Mediastinal mass (SVC obstruction, stridor)

Abdominal Tumours

• Palpable abdominal mass (Wilms' — smooth, does not cross midline; neuroblastoma — firm, irregular, crosses midline)
• Haematuria (Wilms')
• Periorbital bruising, opsoclonus-myoclonus (neuroblastoma)

Red Flags (NICE NG12)

• Unexplained petechiae or bruising
• Unexplained persistent bone pain
• Unexplained lymphadenopathy >2cm lasting >6 weeks
• Persistent headache with vomiting
• New neurological deficit or gait abnormality
• Proptosis, absent red reflex (white pupil — retinoblastoma)
• Abdominal mass

Bedside

• Full clinical examination: Lymphadenopathy, organomegaly, abdominal masses, neurological signs, skin (petechiae, bruising, café-au-lait spots)
• Fundoscopy: Papilloedema (raised ICP), absent red reflex (retinoblastoma)
• Growth: Plot height and weight
• BP: May be elevated in Wilms' tumour, neuroblastoma

Bloods

• FBC and blood film: Anaemia, thrombocytopenia, neutropenia, blast cells on film
• LDH: Non-specific tumour marker; elevated in leukaemia, lymphoma
• Uric acid: Elevated with high cell turnover (tumour lysis syndrome risk)
• U&Es, calcium, phosphate: Metabolic derangement, tumour lysis
• LFTs: Baseline, hepatic infiltration
• Coagulation screen: DIC risk in acute promyelocytic leukaemia
• Urinary catecholamines (VMA, HVA): Elevated in neuroblastoma (>90% sensitivity)
• AFP, β-hCG: Germ cell tumours

Imaging

• Ultrasound: First-line for abdominal masses
• MRI brain with contrast: Gold standard for CNS tumours
• CT chest/abdomen/pelvis: Staging for lymphoma, solid tumours
• PET-CT: Staging and response assessment in lymphoma
• MIBG scan: Neuroblastoma staging
• Bone scan: Bone metastases
• CXR: Mediastinal mass (lymphoma), pulmonary metastases

Special Tests

• Bone marrow aspirate and trephine: Essential for leukaemia diagnosis — morphology, immunophenotyping, cytogenetics, molecular genetics
• Lymph node biopsy: Excisional preferred for lymphoma
• Tumour biopsy: Histology and molecular characterisation
• Lumbar puncture: CNS involvement in leukaemia/lymphoma

Non-pharmacological

• Specialist centre care: All childhood cancers treated in or managed through a PTC
• MDT approach: Paediatric oncologist, surgeon, radiologist, pathologist, clinical nurse specialist, psychologist, play specialist, social worker, dietitian
• Psychological support: For child and family throughout treatment and beyond
• Education: Hospital school/home tutoring during treatment
• Fertility preservation: Discuss sperm banking (post-pubertal males), ovarian tissue/oocyte cryopreservation where appropriate before gonadotoxic treatment

Pharmacological

• Chemotherapy: Backbone of treatment for most childhood cancers
  • ALL: Multi-agent protocols (e.g., UKALL2011) — vincristine, dexamethasone, asparaginase, methotrexate, 6-mercaptopurine, cyclophosphamide; treatment lasts ~2-3 years
  • Lymphoma: ABVD (Hodgkin), multi-agent regimens (NHL)
• Supportive care: Anti-emetics (ondansetron 0.15mg/kg), PCP prophylaxis (co-trimoxazole), antifungals, blood product support, G-CSF
• Targeted therapy: Imatinib for Philadelphia chromosome-positive ALL; crizotinib for ALK-positive tumours; checkpoint inhibitors emerging

Surgical/Interventional

• Tumour resection: Primary surgery for Wilms' tumour, neuroblastoma, brain tumours (where feasible)
• Central venous access: Hickman line or port-a-cath insertion for chemotherapy
• Radiotherapy: CNS tumours, Hodgkin lymphoma, some solid tumours — sparing approaches to minimise late effects
• Stem cell transplant: High-risk ALL, relapsed leukaemia, some solid tumours

Referral Criteria

• Any suspected childhood cancer — immediate 2-week-wait referral (NICE NG12)
• Unexplained blood count abnormalities with blast cells — same-day haematology/oncology discussion
• CNS symptoms with suspected tumour — urgent MRI and neurosurgical referral

• Overall 5-year survival: ~80-85% (UK, all childhood cancers combined)
• ALL: ~90% 5-year survival (standard risk); ~70% high-risk
• Hodgkin lymphoma: >95% 5-year survival
• Brain tumours: Variable — low-grade glioma >90%; high-grade glioma/DIPG <10%
• Wilms' tumour: ~90% 5-year survival
• Neuroblastoma: Variable — >95% low-risk; <50% high-risk
• Late effects: >60% of survivors experience at least one late effect; ~25% have severe/life-threatening late effects
  • Cardiotoxicity (anthracyclines)
  • Endocrine (growth, thyroid, gonadal failure)
  • Secondary malignancy (5-10% at 30 years)
  • Neurocognitive (especially cranial radiotherapy)
  • Psychosocial

Common Childhood Cancers by Frequency

Key Genetic Predisposition Syndromes