Paediatric cancers are rare and differ substantially from adult cancers in their tumour spectrum, biology and treatment. The lecture describes cancer as the second leading cause of childhood death after accidents; treat this as a historical local teaching statement, not a timeless international ranking. This note covers recognition, the major paediatric malignancies, oncological emergencies and long-term survivorship. ^[1][2]

1. Understand the epidemiology and how paediatric cancers differ from adult cancers
2. Recognise common presentations of childhood cancers
3. Know the major paediatric cancer types, their age distribution, clinical features, investigations, and management principles
4. Understand oncological emergencies in paediatrics
5. Appreciate the late effects of cancer treatment in survivors ^[2]

ALL is the most common childhood malignancy, accounting for ~30% of all childhood cancers. ALL accounts for ~80% of childhood leukaemia. Peak incidence is 2–5 years. Males > Females. ^[8]

Why does ALL present the way it does? The malignant lymphoblasts crowd out the normal bone marrow → pancytopenia:

• ↓ RBC → anaemia → pallor, fatigue
• ↓ Platelets → thrombocytopenia → bruising, petechiae, bleeding
• ↓ Functional neutrophils → infection risk; the total WBC may be low, normal or very high because circulating blasts are non-functional
• Infiltration: bone pain (marrow expansion), hepatosplenomegaly, lymphadenopathy, CNS (cranial nerve palsies, headache), testes

Investigations:

• CBC + blood film: anaemia, thrombocytopenia, ↑/↓ WCC with blasts
• Bone marrow aspirate: ≥ 25% blasts = ALL (< 25% → lymphoblastic lymphoma)
• Flow cytometric immunophenotyping establishes lineage; cytogenetic and molecular testing defines the disease more precisely than the old morphology-only categories
• Examples shown in the historical genetics pie include high hyperdiploidy and ETV6::RUNX1, BCR::ABL1, TCF3::PBX1, KMT2A rearrangements, hypodiploidy and iAMP21. Their frequencies and implications are age- and protocol-dependent
• Measurable residual disease (MRD), usually assessed after induction and again at protocol-defined time points, is a major independent risk-stratification variable; genetics and MRD must be interpreted together ^[23]
• Lumbar puncture is performed for CNS assessment and protocol-directed intrathecal therapy only when clinically safe; defer it in major coagulopathy or instability
• CXR: mediastinal mass (T-cell ALL) ^[8][3]

AML in children: ^[1]

• ALL >> AML; CML and MDS are rare; CLL is almost non-existent in children
• The deck's FAB M0–M7 scheme and morphology-to-disease flowchart are historical. Current AML classification integrates morphology with recurrent genetic abnormalities (for example RUNX1::RUNX1T1, CBFB::MYH11 and PML::RARA) and other molecular findings
• Non-APL AML usually uses intensive induction and consolidation; allogeneic HSCT is selected according to genetics, response/MRD, relapse risk and protocol—not offered automatically to every “high-risk” child. Routine maintenance is not standard for most childhood AML
• APL is a haemorrhagic emergency: suspected APL with coagulopathy requires immediate paediatric haematology involvement, prompt ATRA (tretinoin) while confirming PML::RARA, and aggressive blood-product support. Do not perform a diagnostic lumbar puncture until coagulopathy has resolved. Current risk-adapted regimens use ATRA + ATO, with additional therapy for selected high-risk disease ^[24]

Management principles:

• Multiagent induction → consolidation/intensification → maintenance, with CNS-directed therapy integrated through the protocol
• Exact drugs, phase names and duration vary by immunophenotype, genetics, age, toxicity and treatment protocol
• MRD response and molecular risk guide treatment intensity; HSCT in first remission is reserved for selected indications rather than “high risk” as a single blanket category ^[23]

Childhood ALL is the first disseminated cancer shown to be curable. ^[8]

Historical phase diagram in the deck: ^[1]

1. Induction → 2. Consolidation → 3. CNS Prophylaxis → 4. 2nd Consolidation → 5. Maintenance

• Intensive phases (Induction through 2nd Consolidation): ~4–6 months
• Maintenance phase: ~1.5–2 years
• The labels and durations illustrate the broad sequence used by the lecture-era HK protocol; they are not a prescription. Contemporary protocols distribute CNS-directed therapy across phases and make transplant decisions using subtype, MRD/response and relapse risk

What the clonal-evolution diagram adds: a relapse is not necessarily a simple regrowth of an unchanged diagnostic clone. In the historical series shown, relapse could arise from the diagnostic clone, an evolved descendant or an ancestral pre-leukaemic clone; a small minority represented a genetically unrelated second leukaemia. This is why relapse is re-characterised rather than assumed to be biologically identical. ^[1]

Slide-era context: CNS tumours formed a major childhood-cancer group and dominated deaths in the historical HKPHOSG charts. They are the most common group of paediatric solid tumours and cause substantial mortality and neurological morbidity, but rankings depend on the population, period and classification used. ^[1][9][10]

Historical HK CNS-tumour grouping in the deck: ^[1][9][10]

1. Astrocytoma / Other gliomas
2. “PNETs,” including medulloblastoma (older terminology)
3. Germ cell tumours (GCTs)
4. Ependymoma

The 1999–2009 local pie (n = 357) used astrocytoma, brainstem tumour, “other glioma,” germ-cell tumour, PNET, ATRT, ependymoma and other morphology/site labels. Do not transpose these percentages into the current WHO system. “CNS PNET” is no longer a single diagnostic entity; current diagnosis integrates histology and molecular testing. ^[1][25]

Site distribution:

• Infratentorial (posterior fossa) tumours predominate in ages 1–10 years → medulloblastoma, juvenile pilocytic astrocytoma (JPA) ^[9][10]
• Supratentorial tumours predominate in < 1 year and > 10 years
• This is opposite to adults where ~80% are supratentorial ^[11]

Why does location matter?

• Posterior fossa tumours → obstruct 4th ventricle → obstructive hydrocephalus → ↑ICP → morning headache, vomiting, papilloedema
• Supratentorial tumours → focal neurological deficits, seizures
• Brainstem tumours → cranial nerve palsies, long tract signs
• Cerebellar/posterior-fossa tumours → gait or limb ataxia, nystagmus and loss of fine motor control (the case slide pairs worsening morning vomiting with unsteadiness and deteriorating handwriting)
• Suprasellar tumours → visual-field loss, endocrine dysfunction, growth disturbance or diabetes insipidus; pineal-region tumours may cause hydrocephalus or Parinaud syndrome
• Optic-pathway glioma → progressive visual impairment, proptosis or nystagmus depending on site and age

Presentation clues by tumour type:

CNS GCT subtypes (HK data): ^[1]

• Germinoma 73%, non-germinoma 27% (yolk sac tumour ↑AFP, choriocarcinoma ↑βhCG, teratoma, mixed)
• 60% arise at pineal/suprasellar region
• Germinoma has better prognosis than non-germinomatous GCT ^[1]

Medulloblastoma — translating the four-colour molecular diagram: ^[1]

• This is a historical four-group teaching model. Current WHO terminology includes WNT-activated, SHH-activated and TP53-wildtype, SHH-activated and TP53-mutant, and non-WNT/non-SHH medulloblastoma, with further molecular subdivisions. Treatment remains specialist, risk-adapted and trial-informed; de-escalation or targeted therapy is not inferred from the colour group alone. ^[25]

Astrocytoma/glioma classification safety update: the slide's linear “grade I pilocytic → grade II low-grade → grade III anaplastic → grade IV glioblastoma” arrows can misleadingly imply inevitable progression. Current paediatric gliomas include biologically distinct circumscribed and diffuse, low- and high-grade molecular entities (for example pilocytic astrocytoma, diffuse midline glioma H3 K27-altered and diffuse hemispheric glioma H3 G34-mutant); one category is not simply a mandatory step toward the next. ^[25]

Brain tumour treatment modalities: ^[1]

• Surgery, radiotherapy, chemotherapy, targeted therapy and CSF diversion are selected by an integrated tumour diagnosis, site, dissemination, age and treatment protocol
• The slide's examples (temozolomide, bevacizumab, nimotuzumab, mTOR inhibitors and VP shunt) are not a generic regimen for paediatric brain tumours. Hydrocephalus requires urgent neurosurgical assessment; the appropriate temporary or permanent diversion procedure is individualised
• The historical local outcome graphs (medulloblastoma, germinoma/non-germinomatous GCT) show that stage and biology separate prognoses, but should not be used for current individual counselling

Hodgkin Lymphoma (HL):

• Bimodal age distribution (adolescents and older adults)
• Painless cervical lymphadenopathy, mediastinal mass
• Reed-Sternberg cells on biopsy
• B-symptoms: fever, night sweats, weight loss > 10%
• Often highly curable; current therapy is risk- and response-adapted, and radiotherapy is not automatic for every child

Non-Hodgkin Lymphoma (NHL):

• More common in younger children than HL

• Often extranodal, disseminated at presentation

• Major subtypes include mature B-cell lymphomas (especially Burkitt lymphoma and DLBCL), lymphoblastic lymphoma and anaplastic large-cell lymphoma (ALCL). The slide's “Working Formulation,” “small non-cleaved,” “lymphoblastic” and “Ki-1” labels are historical; current classification combines morphology, immunophenotype and molecular findings ^[26]

• More aggressive than HL but chemosensitive

• ALCL: may involve lymph nodes, skin, bone, soft tissue or viscera; pleural effusion and skin nodules are useful slide examples, not required features ^[1]

• Tissue is required for diagnosis. Choose excisional, incisional or image-guided core biopsy with the multidisciplinary team according to site, procedural risk and the amount needed for morphology, flow/immunophenotyping and molecular testing; “needle biopsy is always inferior” is too absolute

• The 1995–2016 HK survival curves (small subtype cohorts) are historical service outcomes, not current subtype-specific counselling estimates ^[1]

Neuroblastoma is the most common extracranial solid tumour of childhood and is especially common in infants and young children. ^[4]

Origin: Neural crest cells → arises anywhere along the sympathetic chain

• Most commonly: adrenal medulla (40%), abdominal paraspinal ganglia
• Also: thorax, pelvis, neck

Pattern, not a rule: a large neuroblastoma often crosses the midline and encases vessels, whereas a Wilms tumour is intrarenal and usually displaces structures. Either pattern can have exceptions. ^[4]

Presentation depends on location:

• Abdominal mass (most common): may be large and irregular, cross the midline, encase vessels and contain calcification
• Thoracic: SVCO, Horner syndrome (miosis, ptosis, anhidrosis)
• Metastatic disease: periorbital ecchymosis ("raccoon eyes") — orbital metastasis; bone pain; skin nodules ("blueberry muffin" in infants)
• Paraneoplastic: opsoclonus-myoclonus syndrome ("dancing eyes–dancing feet"), secretory diarrhoea (VIP)

Investigations:

• Urine VMA/HVA (vanillylmandelic acid / homovanillic acid) — catecholamine metabolites ^[3]
• MIBG scan (meta-iodobenzylguanidine — taken up by sympathetic tissue)
• CT/MRI, bone marrow biopsy
• Histology: small round blue cell tumour, Homer-Wright rosettes

Unique biology:

• Some infants with the special metastatic pattern historically called stage 4S may undergo spontaneous regression; the current INRG equivalent is stage MS (metastases limited to skin, liver and/or a small degree of marrow involvement in a child younger than 18 months) ^[27]
• MYCN amplification = poor prognosis
• Older age at diagnosis = worse prognosis

Prognosis and treatment cannot be reduced to whether a mass is “detected late.” Current pretreatment risk assessment combines INRG stage (L1, L2, M or MS), age, histology/differentiation, MYCN, 11q status and ploidy. Low-risk disease may be observed or treated with surgery alone; intermediate-risk disease usually receives chemotherapy with selective surgery; high-risk treatment is multimodal. ^[27]

The “early-stage neuroblastoma” cyclophosphamide/doxorubicin flowchart is explicitly labelled HKPHOSG-ESNB-96. It is a 1996 protocol diagram and must not be used as a current dosing or management algorithm. ^[1]

High-risk neuroblastoma — immunotherapy: ^[1]

• The ANBL0032 graph is a landmark historical trial: adding anti-GD2 immunotherapy to isotretinoin after consolidation improved EFS and OS in that study. It established the importance of anti-GD2 therapy, but the exact antibody, cytokines and sequence now depend on the contemporary protocol; do not copy the 2010 trial combination as a stand-alone prescription. ^[1][27]

Wilms tumour is the most common primary renal malignancy in children < 15 years, accounting for 95% of renal tumours and ~6% of all childhood malignancy. ^[5][6]

Key facts:

• Peak incidence at age 3 years (majority diagnosed 1–5 years)
• 5% bilateral involvement
• 10% multifocal within single kidney
• Usually remains centred on and expands the kidney, although a very large tumour can cross the midline

Associated syndromes: ^[5][6]

Presentation:

• Abdominal mass — typically smooth, non-tender, does not cross midline, often discovered incidentally by parent
• Haematuria (20%), hypertension, abdominal pain
• Metastasis: haematogenous to lung (most common), liver, bone, brain ^[5]

Investigations:

• USS abdomen → intrarenal mass (distinguishes from neuroblastoma which is extrarenal)
• CT/MRI for staging
• Chest CT (lung metastases)
• Biopsy is pathway-dependent. In the COG immediate-nephrectomy pathway, a resectable unilateral mass with typical imaging is generally removed without pre-operative biopsy because biopsy upstages it. Biopsy is appropriate for selected atypical or initially unresectable masses and is integral to some pre-operative-treatment pathways; discuss with the specialist renal-tumour team ^[28]

Management:

Surgery (nephrectomy) + chemotherapy ± radiotherapy. Good prognosis if early stage. ^[4]

• SIOP (European) approach: neoadjuvant chemotherapy → surgery
• COG (North American) approach: upfront nephrectomy → adjuvant chemotherapy
• Favourable histology (most cases) → excellent prognosis (~90% survival)
• Anaplastic Wilms histology carries higher risk. Clear-cell sarcoma of kidney and malignant rhabdoid tumour are separate childhood renal cancers, not “unfavourable Wilms histology” ^[28]

Rhabdomyosarcoma (RMS):

• Most common soft tissue sarcoma in children
• Arises from skeletal muscle precursors
• Common sites: head and neck (orbit, nasopharynx), genitourinary tract, extremities
• Two main subtypes: embryonal (younger children, better prognosis) and alveolar (older children/adolescents, worse)
• Treatment: multimodal — surgery + chemotherapy + radiotherapy

Osteosarcoma:

• Most common primary bone malignancy in children/adolescents
• Peak incidence during pubertal growth spurt (10–20 years)
• Typically around the knee (distal femur, proximal tibia)
• Presentation: pain, swelling, pathological fracture
• X-ray: "sunburst" periosteal reaction, Codman triangle
• Metastases: lung (pulmonary nodules)
• Treatment: neoadjuvant chemotherapy → limb-sparing surgery → adjuvant chemotherapy

Ewing Sarcoma:

• Second most common bone tumour in children
• Younger age than osteosarcoma (5–15 years)
• Diaphysis of long bones, pelvis, ribs
• X-ray: "onion-skin" periosteal reaction
• t(11;22) translocation — EWS-FLI1 fusion
• Highly chemosensitive; treatment: chemo + surgery/RT

Reading the bone-tumour slide: osteosarcoma classically centres in the metaphysis and may form cloud-like osteoid with sunburst spicules or a Codman triangle; Ewing sarcoma more often involves the diaphysis and may produce layered “onion-skin” periosteal reaction. These appearances overlap with other aggressive lesions and infection. Obtain MRI/staging imaging and involve an orthopaedic oncology team before biopsy, because an ill-planned biopsy tract can compromise limb-sparing surgery. ^[29][30]

The slide's “EWS/pPNET” label is historical: peripheral PNET was grouped within the Ewing sarcoma family. Modern diagnosis requires compatible morphology plus molecular confirmation (usually an EWSR1–ETS fusion); the old small local “EWS versus pPNET” survival curves should not be treated as current separate-disease prognoses.

Retinoblastoma is the commonest intraocular tumour of childhood. 40% are heritable (related to RB1 gene on chromosome 13q14). The commonest presenting finding is leukocoria (white pupillary reflex). ^[13]

Genetics — Knudson's Two-Hit Hypothesis:

• Heritable (40%): First hit is germline (inherited or de novo); second hit is somatic. Often bilateral, earlier onset, risk of second primary cancers (e.g., osteosarcoma)
• Non-heritable: Both hits are somatic and disease is usually unilateral. Unilateral presentation does not by itself exclude a germline RB1 variant

Presentation:

• Leukocoria — white reflex instead of red reflex on fundoscopy/photos
• Strabismus, nystagmus, red eye
• Late: proptosis, orbital cellulitis-like picture (advanced disease)

Management goals (in priority order): ^[14]

1. Life-saving: eradicate disease
2. Organ-saving: preserve normal appearance of eye
3. Vision-saving: preserve vision

Treatment modalities: ^[14]

• Focal: cryotherapy, laser photocoagulation (small tumours)
• Regional: ophthalmic artery chemosurgery (OAC), intravitreal chemotherapy, episcleral plaque brachytherapy
• Systemic: systemic chemotherapy
• Enucleation: for advanced unilateral disease (Group E)
• External beam RT: rarely used now due to risk of second cancers

Hepatoblastoma is the most common primary liver malignancy in young children. It usually presents before age 5 years. ^[5][6]

Associated conditions: FAP, Beckwith-Wiedemann, Trisomy 18 (Edwards), Trisomy 21 (Down), Li-Fraumeni, GSD Ia ^[5][6]

Presentation:

• Abdominal mass, pain, distension
• Constitutional symptoms (weight loss, fever, night sweats)
• Paraneoplastic: precocious puberty in males (hCG secretion) ^[5]

Investigations:

• Serum AFP elevated in ~90% — this is the key tumour marker ^[3][5]
• CBC: anaemia, thrombocytosis
• LFT: usually normal
• Imaging: ultrasound followed by contrast-enhanced cross-sectional liver imaging and chest staging according to the specialist protocol; PET is not a routine universal next step
• Liver biopsy for histological confirmation

Staging: ^[5]

• PRETEXT/SIOPEL (Europe): Pre-surgical staging based on number of liver sectors involved (I–IV)
• COG (North America): Post-surgical staging (I–IV based on resection completeness and metastasis)

Management: ^[5]

• Complete resection is the primary goal — major determinant of survival
• Neoadjuvant chemotherapy to reduce tumour size before surgery
• Liver transplantation for unresectable tumours

• Arise from primordial germ cells
• Can occur in gonadal (testis, ovary) or extragonadal sites (sacrococcygeal, mediastinum, retroperitoneum, intracranial—especially pineal/suprasellar); older East Asian registry series reported a higher CNS GCT proportion
• Tumour markers: AFP (yolk sac tumour), βhCG (choriocarcinoma), LDH ^[3]
• Sacrococcygeal teratoma is the most common GCT in neonates
• Treatment: surgery ± chemotherapy (platinum-based)

Slides 48–60 contain multiple Kaplan–Meier plots from small HKPHOSG cohorts treated from the mid-1990s to 2016. Their enduring lessons are comparative, not numerical:

• “Childhood cancer” is not one prognosis: lymphoma subtype, tumour biology, stage, resectability and metastatic pattern separate outcomes
• The renal-tumour table shows Wilms tumour was the dominant kidney tumour, while clear-cell sarcoma, rhabdoid tumour, renal-cell carcinoma and other rare entities behaved differently and must not be folded into “Wilms”
• Extracranial germ-cell tumours in that cohort were treated mainly with surgery plus JEB (carboplatin, etoposide and bleomycin); this is historical protocol context, not a regimen to prescribe from the slide
• Localised osteosarcoma had substantially better outcome than metastatic osteosarcoma; the same stage effect is visible in several solid-tumour panels
• RMS, hepatoblastoma, Ewing sarcoma and the old “peripheral PNET” group have disease-specific risk systems, so the plotted plateaus cannot be reused as current individual survival estimates

Paediatric oncology combines surgery, systemic therapy, radiotherapy, immunotherapy/targeted therapy and/or HSCT according to the disease and risk group. Many common childhood tumours are chemosensitive, but children are not simply “more tolerant”: treatment can cause acute toxicity, developmental injury and lifelong late effects. Curative and palliative/supportive care should both be proportionate and family-centred.

What the treatment-modality diagrams mean: “rescue/protection” agents are paired with a specific exposure (for example folinic acid after high-dose methotrexate and mesna with urotoxic oxazaphosphorines); they are not general antidotes. The cell-expansion diagrams (CIK/LAK/NK/dendritic-cell/CTL products) illustrate experimental immunotherapy concepts from the lecture era. They should not be listed alongside HSCT or established anti-GD2/CAR-T indications as interchangeable routine treatments.

Targeted and immune therapies may reduce some off-target effects but can still cause serious, mechanism-specific toxicity; “targeted” does not mean side-effect free.

• Anticipate transfusion needs, infection and tumour lysis rather than reacting after decompensation
• Treat pain, nausea, mucositis, nutrition, mobility and sleep; involve psychology, social work, play/school services and palliative care according to need
• Support parents, siblings and the child's wider network. The concentric-circle slide emphasises that illness affects development, education and the whole family, not only the tumour-bearing organ

• Induction: Rapid tumour kill
• Consolidation/Intensification: Eliminate residual disease
• Maintenance: Prevent relapse (e.g., ALL maintenance for 2–3 years)
• CNS-directed therapy: Intrathecal methotrexate (blood-brain barrier prevents systemic chemo from reaching CNS)

• Primary resection for localised tumours (Wilms, hepatoblastoma)
• Delayed primary surgery after neoadjuvant chemo (neuroblastoma, hepatoblastoma)
• Biopsy for unresectable tumours

• Used in selected settings (Hodgkin lymphoma, Ewing sarcoma, CNS tumours)
• Avoided when possible in young children due to growth and development effects

• Selected very-high-risk or relapsed leukaemia and consolidation in defined high-risk neuroblastoma protocols; indication depends on disease, response/MRD and protocol
• Autologous (patient's own stem cells) or allogeneic (donor)