Malignant Diseases

What is the epidemiology, aetiology, and overall prognosis of childhood cancer, and how does it differ between continents?

Cancer is the most common disease causing death in childhood beyond the neonatal period.
This improvement over 40 years is attributed to multi-agent chemotherapy, improved supportive care, and specialist multidisciplinary management.
Age variation:
leukaemia peaks in early childhood;
neuroblastoma and Wilms tumour (embryonal tumours) are almost always seen in the first 6 years;
Hodgkin lymphoma and bone tumours peak in adolescence and early adult life.
Aetiology: mostly unclear, likely involving environmental factors (viral infections) + host genetic susceptibility.
Established examples: bilateral retinoblastoma (RB gene, chromosome 13 mutation);
Down syndrome and leukaemia;
neurofibromatosis and glioma.
Infection-related: Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma (EBV); liver carcinoma (HBV); Kaposi sarcoma (HIV + HHV-8).

What are the short-term side-effects of chemotherapy and cancer treatment, and how are they managed?

Bone marrow suppression: anaemia → blood transfusions; thrombocytopenia → risk of bleeding and extensive blood product support (especially in leukaemia, BMT, and intensive solid tumour protocols); neutropenia → risk of serious infection.

Infection from immunosuppression: fever + neutropenia = emergency → immediate hospital admission, cultures, and broad-spectrum antibiotics.

Key opportunistic infections: Pneumocystis jiroveci pneumonia (especially in leukaemia — prevented by cotrimoxazole prophylaxis); disseminated fungal infections (aspergillosis, candidiasis); coagulase-negative staphylococcal CVC infections.

Measles and varicella zoster may have atypical presentations and can be life-threatening → if non-immune child exposed, give immunoglobulin (measles) or zoster immune globulin (varicella); treat established varicella with aciclovir.

Live vaccines contraindicated during chemotherapy and for 6–12 months after; reimmunization recommended after this period. GI damage: mouth ulcers, nausea and vomiting (partially prevented by antiemetics), diarrhoea, gut mucosal damage → predisposes to Gram-negative sepsis; significant nutritional compromise may require NG or parenteral nutrition.

Drug-specific toxicities: cardiotoxicity (doxorubicin),
renal failure and deafness (cisplatin),
haemorrhagic cystitis (cyclophosphamide),
neuropathy (vincristine).

Pain management: from disease infiltration, treatment side-effects, or surgical procedures — paediatric palliative care specialists are part of the MDT.

Fertility preservation: sperm banking for mature boys; surgical relocation of gonads from radiotherapy field; cryopreservation of ovarian/testicular cortical tissue (still experimental).
Venous access: tunnelled central venous catheters (Hickman lines) or implantable ports avoid repeated venepunctures; risk of infection, blockage, or splitting.
Psychosocial support: counselling for patient, parents, and siblings; practical help with transport, finances, accommodation; early return to school; written information for parents.

What are the clinical features, investigations, management, and prognosis of Acute Lymphoblastic Leukaemia (ALL)?

ALL accounts for 80% of childhood leukaemia; remaining 20% is mostly AML/ANLL; chronic myeloid leukaemia is rare.

Peak presentation: 2–5 years of age.
Presentation is usually insidious over several weeks (occasionally rapid). Signs and symptoms (from bone marrow infiltration and dissemination): pallor/lethargy (anaemia); infection/fever (neutropenia); bruising, petechiae, epistaxis (thrombocytopenia); bone pain; hepatosplenomegaly; generalized lymphadenopathy; superior mediastinal obstruction (T-cell disease); testicular enlargement (rare at diagnosis, more often at relapse); headache, vomiting, nerve palsies (CNS infiltration).

Investigations:
FBC (low Hb, thrombocytopenia, leukemic blasts on film — but count may be normal); bone marrow aspiration (essential — confirms diagnosis and provides immunological and cytogenetic data); coagulation screen (10% have DIC at diagnosis); lumbar puncture (CSF involvement); chest X-ray (mediastinal mass in T-cell disease).

Classification: morphology; immunophenotyping — common B-cell (75%) and T-cell (15%) most frequent.
Prognostic factors: age <1 or >10 years; WBC >50 × 10⁹/L at presentation; cytogenetic/molecular abnormalities (MLL rearrangement, t(4;11), hypodiploidy <44 chromosomes); slow response to initial chemotherapy; persistence of blasts in bone marrow; detectable MRD (minimal residual disease) by PCR after induction.

Management: Pre-treatment — correct anaemia, platelets; allopurinol/urate oxidase + hydration for tumour lysis syndrome prevention.

Remission induction (combination chemo + steroids; 95% remission rate). Intensification (consolidation).

CNS-directed therapy (intrathecal chemotherapy; extra doses if CNS disease at diagnosis).

Continuing therapy (up to 3 years; cotrimoxazole prophylaxis for Pneumocystis pneumonia).

Relapse: high-dose chemo ± total body irradiation + BMT; CAR T-cell therapy for relapsed B-cell ALL.

What are the types, clinical features, and management of brain tumours in children?

Brain tumours are the most common solid tumour in children and the leading cause of childhood cancer deaths.

In contrast to adults, they are almost always primary (not metastatic) and 60% are infratentorial.

Types: Astrocytoma (~40%) — varies from low grade to highly malignant (glioblastoma multiforme);
found in cerebral hemispheres, thalamus, hypothalamus, and posterior fossa (cystic, slow-growing, good prognosis in posterior fossa).

Medulloblastoma (~20%) — midline posterior fossa; may seed through CNS via CSF; up to 20% have spinal metastases at diagnosis; 5-year survival ~50%.

Ependymoma (~8%) — most common at 4th ventricle; 10% are slow-growing low grade; remainder are aggressive and require complete resection + radiotherapy for cure.

Brainstem glioma (6%) — malignant, very poor prognosis (<10% survival); too hazardous to biopsy; treated with palliative radiotherapy.

Craniopharyngioma (4%) — developmental tumour from squamous remnant of Rathke's pouch; not truly malignant but locally invasive; grows slowly in suprasellar region; good survival but risk of long-term visual impairment and lifelong complex pituitary insufficiency.

Atypical teratoid/rhabdoid tumour — rare, aggressive, most common in young children.

Clinical features (age-dependent): Infants — developmental delay/regression, progressive head circumference increase, bulging fontanelle, separated sutures, lethargy.
Children/teenagers — persistent/recurrent headache, vomiting, balance/coordination/walking problems, blurred/double vision, seizures (without fever), abnormal eye movements, behavioural change, deteriorating school performance, delayed/arrested puberty, slow growth, wry neck/persistent head tilt, facial asymmetry.
Site-specific:
Supratentorial cortex → seizures, hemiplegia, focal neurological signs.
Midline → visual field loss (bitemporal hemianopia), pituitary failure (growth failure, diabetes insipidus, weight gain).
Cerebellar/4th ventricle → truncal ataxia, coordination difficulties, abnormal eye movements.
Brainstem → cranial nerve defects, pyramidal tract signs, ataxia.

Investigations: MRI (best characterization); MR spectroscopy (biological activity); lumbar puncture for CSF staging (NEVER without neurosurgical advice if raised ICP suspected).

Management:
Surgery first (treat hydrocephalus, tissue diagnosis, maximum safe resection);
some tumours cannot be biopsied (brainstem, optic pathway);
chemotherapy and/or radiotherapy varies by tumour type and age;
cranial radiotherapy in children <3 years risks severe cognitive damage. Neurorehabilitation: physiotherapy, OT, SLT in acute phase; long-term complex care for growth, endocrine, neuropsychological, and educational problems.

What are the clinical features, investigations, management, and prognosis of Hodgkin and Non-Hodgkin Lymphoma in children?

Hodgkin lymphoma (HL): peaks in adolescence.

Classic presentation: painless lymphadenopathy (most frequently neck); nodes are larger and firmer than benign lymphadenopathy; long clinical history (several months); systemic 'B' symptoms (sweating, weight loss, fever, pruritus) are uncommon even in advanced disease;
may cause airway or SVC obstruction.

Investigations: lymph node biopsy; radiological staging of all nodal sites; bone marrow biopsy; PET scanning used in the UK to monitor treatment response and guide further management.

Management: combination chemotherapy ± radiotherapy; PET-guided response assessment.

Prognosis: ~80% of all patients cured; ~60% of those with disseminated disease cured.

Non-Hodgkin lymphoma (NHL): more common in childhood.
T-cell NHL: usually presents with a mediastinal mass ± bone marrow infiltration; may cause SVCO presenting with dyspnoea, facial swelling, flushing, venous distension in neck, and distended veins in upper chest and arms → requires rapid assessment at a unit with Paediatric ICU facilities.
B-cell NHL: presents with lymphadenopathy in head/neck or abdomen; abdominal disease → pain from intestinal obstruction, palpable mass, or intussusception (especially with ileal involvement).

Management: intensive multi-agent chemotherapy; treatment based on histological subtype and stage; overall prognosis has improved significantly over decades.

What are the clinical features, investigation, management, and prognosis of Neuroblastoma?

Neuroblastoma is a tumour of the sympathetic nervous system arising from neural crest cells.

It is an embryonal tumour almost always occurring in the first 6 years of life. It can arise anywhere along the sympathetic chain — most commonly the adrenal medulla, but also paraspinal ganglia (chest, abdomen, pelvis).

It is the most common solid extracranial tumour in children and the most common cancer in infants.

Clinical features reflect the primary site and extent of metastatic spread: Abdominal mass (most common), often crossing the midline (unlike Wilms tumour which is unilateral).
Hypertension (catecholamine secretion).
Horner syndrome (cervical sympathetic chain involvement).
Spinal cord compression (dumbbell tumour via intervertebral foramina).
Periorbital ecchymoses ('raccoon eyes') from orbital metastases.
Bone pain and bone marrow infiltration (causing anaemia, thrombocytopenia).
Opsoclonus-myoclonus ('dancing eyes/dancing feet' syndrome) — a paraneoplastic syndrome indicating favourable histology.

Investigations:
Urinary catecholamines — elevated VMA (vanillylmandelic acid) and HVA (homovanillic acid) in the urine are diagnostic;
MIBG scan (metaiodobenzylguanidine) — highly specific for neural crest tumours, used for staging and detecting metastases;
CT/MRI for anatomy; bone marrow biopsy; histology; MYCN oncogene amplification — associated with poor prognosis.

Staging and prognosis:
International Neuroblastoma Staging System (INRG):
stage 1–2 (localized) — surgery often curative;
stage 3 (unresectable, crossing midline);
stage 4 (widely metastatic) — poor prognosis; stage 4S (infants with specific spread pattern) — may spontaneously regress. Age and MYCN are the most important prognostic factors.

Management: Low-risk: surgery ± observation.
Intermediate-risk: surgery + chemotherapy.
High-risk: intensive chemotherapy; surgery; radiotherapy; high-dose chemotherapy with autologous stem cell rescue;
anti-GD2 monoclonal antibody (dinutuximab); MIBG therapy; isotretinoin (differentiation agent); 5-year survival for high-risk disease ~30–40%.

What are the clinical features, investigations, management, and prognosis of Wilms Tumour (Nephroblastoma)?

Wilms tumour (nephroblastoma) is an embryonal tumour of the kidney arising from remnants of primitive metanephric blastema.
It is one of the most common solid tumours of childhood, occurring predominantly in the first 5 years of life (peak 3–4 years), and is rare after age 10.

Associated conditions:
WAGR syndrome (Wilms tumour, aniridia, genitourinary anomalies, intellectual disability — associated with WT1 gene deletion on chromosome 11p13);

Denys–Drash syndrome (WT1 mutation — Wilms tumour, pseudohermaphroditism, nephropathy);

Beckwith–Wiedemann syndrome (WT2/IGF2 — Wilms tumour, macroglossia, organomegaly, hemihypertrophy);

Horseshoe kidneys and other urinary tract anomalies.

Clinical features:
Usually presents as a large, smooth, unilateral abdominal mass (may be incidentally found by parent or clinician);
haematuria (macroscopic or microscopic);
hypertension; abdominal pain; rarely bilateral.

Important distinction:
Wilms tumour tends to be unilateral and does not cross the midline — in contrast to neuroblastoma which commonly crosses the midline.

Investigations: ultrasound (first-line — shows renal origin, IVC extension); CT chest and abdomen for staging; histology (nephroblastoma — blastemal, epithelial, and stromal components; anaplasia is associated with poor prognosis).

Management: In Europe (SIOP protocol) — pre-operative chemotherapy (actinomycin D + vincristine) to shrink the tumour → nephrectomy → further chemotherapy ± radiotherapy depending on stage and histology. In North America (COG/NWTS protocol) — primary nephrectomy then chemotherapy.

Prognosis: Excellent overall (best prognosis among all paediatric solid tumours)

What are soft tissue sarcomas in children — their types, presentations, and management?

The most common type in children is rhabdomyosarcoma (RMS) — a tumour arising from primitive mesenchymal cells that would normally develop into striated muscle; it can arise anywhere in the body even where no muscle is normally found.

Common primary sites: head and neck (including orbit, nasopharynx, middle ear — 40%); genitourinary tract (bladder, prostate, vagina, paratesticular — 25%); extremities (20%); trunk and other sites (15%).

Histological subtypes: Embryonal RMS (most common, better prognosis); Alveolar RMS (worse prognosis, associated with chromosomal translocations t(2;13) and t(1;13)).

Clinical features vary by site:
orbital → proptosis;
nasopharyngeal → nasal obstruction, epistaxis; genitourinary → haematuria, urinary obstruction;
paratesticular → painless scrotal mass; extremity → soft tissue mass.

Investigations: MRI for local staging; CT chest for metastases; bone marrow biopsy; bone scan; MIBG scan to exclude neuroblastoma; histology with immunohistochemistry and molecular studies.

Management: Combination of surgery (wide local excision if feasible), chemotherapy (vincristine, actinomycin D, ifosfamide ± doxorubicin), and radiotherapy (for unresectable or residual disease).

Non-RMS soft tissue sarcomas (e.g. synovial sarcoma, undifferentiated/unclassified sarcoma) are treated similarly. Prognosis: localized resectable disease → ~80% 5-year survival; metastatic disease → <30% 5-year survival. PET scanning increasingly used for staging and response assessment.