Specialty Guide · Path-iQ Global Pathology Review
Paediatric pathology is the subspecialty concerned with diseases of infants, children, and adolescents — including tumours, developmental anomalies, perinatal pathology, inherited metabolic disorders, and sudden unexpected death in childhood. It requires mastery of normal developmental anatomy at every age from foetus to adolescence, making it one of the most knowledge-intensive and intellectually demanding subspecialties in anatomic pathology.
Childhood cancers differ fundamentally from adult cancers in their biology, histology, genetic drivers, and prognosis. Whereas adult cancers arise from accumulated somatic mutations over decades, most childhood tumours arise from aberrant developmental programmes — oncofetal genes, disrupted differentiation, or germline predisposition syndromes — and frequently carry single or few high-impact genetic events rather than the complex mutational landscapes of adult carcinomas.
| Feature | Paediatric Cancers | Adult Cancers |
|---|---|---|
| Primary tumour type | Leukaemia (most common), brain tumours, lymphoma, neuroblastoma, Wilms, soft tissue sarcoma, retinoblastoma, Ewing sarcoma | Carcinoma (breast, lung, prostate, colorectal) dominates; carcinoma rare in childhood |
| Mutational burden | Very low (<1 mut/Mb in most paediatric tumours); often single driver event | High (10–1000 mut/Mb in carcinoma); multiple sequential mutations over years |
| Carcinoma | Extremely rare; adrenocortical carcinoma, hepatocellular carcinoma (HBV-related), NPC in adolescents | Commonest malignancy type worldwide |
| Embryonal tumours | Frequent — Wilms tumour, neuroblastoma, hepatoblastoma, medulloblastoma, retinoblastoma all embryonal in origin | Absent (embryonal tumours resolve or transform by adulthood) |
| Overall prognosis | Much better — 5-year survival >85% in high-income countries for all childhood cancers combined | Highly variable; many adult cancers have 5-year survival <50% |
| Treatment response | Often exquisitely chemosensitive; high complete response rates | Chemoresistance common in carcinomas; targeted therapy required |
| Hereditary predisposition | Recognised in ~10% of childhood cancers (RB1, TP53 Li-Fraumeni, WT1, DICER1, SMARCA4, BRCA2, Beckwith-Wiedemann) | BRCA1/2, Lynch syndrome ~5–10% of adult cancers; majority sporadic |
Wilms tumour is the most common primary renal tumour of childhood (peak age 3–4 years; 95% of paediatric renal tumours). The classic triphasic histology consists of blastemal, stromal, and epithelial components in varying proportions. Histological risk stratification drives treatment intensity:
Neuroblastoma is the most common extracranial solid tumour of childhood, arising from neural crest-derived sympathetic precursors (adrenal medulla ~50%; paraspinal sympathetic chain; neck, chest, pelvis). The International Neuroblastoma Pathology Classification (INPC / Shimada system) stratifies tumours into favourable and unfavourable histology based on degree of Schwannian stromal development, differentiation, and mitosis-karyorrhexis index (MKI).
| INPC Category | Histology | Age / MKI Criteria | Prognosis |
|---|---|---|---|
| Neuroblastoma, FH | Poorly differentiated or differentiating; <50% Schwannian stroma | Age <1.5yr + low/intermediate MKI; OR age <5yr + low MKI | Favourable; excellent with risk-adapted therapy |
| Neuroblastoma, UFH | Undifferentiated OR high MKI for age | Undifferentiated at any age; OR age >1.5yr + intermediate/high MKI | Unfavourable; high-risk treatment required |
| Ganglioneuroblastoma, intermixed | >50% Schwannian stroma; nests of neuroblasts within stroma | Any age | Favourable |
| Ganglioneuroblastoma, nodular | Composite: ganglioneuroma / stroma-rich + neuroblastoma nodule(s) | Nodule histology determines risk (FH vs UFH) | Variable; determined by neuroblastoma nodule |
| Ganglioneuroma | >50% mature Schwannian stroma; fully mature ganglion cells; no neuroblasts | Any age; represents maturation of neuroblastoma | Benign; surgical excision curative |
MYCN amplification (>10 copies / cell by FISH) is the single most important adverse prognostic molecular marker in neuroblastoma, present in ~25% of cases and associated with aggressive biology. Additional molecular risk factors: ALK mutation/amplification; segmental chromosomal aberrations (1p del, 11q del, 17q gain); DNA ploidy (hyperdiploid = favourable in infants).
Hepatoblastoma is the most common primary liver tumour in children (peak age 1–2 years; rare after age 5). PRETEXT (pre-treatment extent of disease) staging by imaging guides surgical and chemotherapy planning. Histological subtypes per CHIC criteria: epithelial (pure fetal, embryonal, macrotrabecular, small cell undifferentiated) and mixed epithelial-mesenchymal. Pure fetal histology with low mitotic rate (<2/10 HPF) is associated with the best prognosis; small cell undifferentiated (SCUD) with INI1 loss (SMARCB1 inactivation) is highest risk.
Retinoblastoma arises from immature retinal precursors (retinoblasts) in children almost exclusively under age 5. Bilateral retinoblastoma (40% of cases) is virtually always hereditary, caused by germline RB1 mutation. Unilateral cases may be hereditary or sporadic. Histological high-risk features that predict metastasis and mandate adjuvant chemotherapy: massive choroidal invasion (>3 mm); optic nerve invasion posterior to the lamina cribrosa; scleral or anterior segment invasion; surgical margin involvement.
| Tumour | Peak Age | Location | Key Molecular Feature | Prognosis |
|---|---|---|---|---|
| Pilocytic astrocytoma (WHO grade 1) | 5–15 yr | Cerebellum (most common); optic pathway; hypothalamus | KIAA1549-BRAF fusion (~70% cerebellar); BRAF V600E (optic pathway); RAF1 fusions | Excellent; surgical cure in most cerebellar cases; 10-yr OS >95% |
| Medulloblastoma (WHO grade 4) | 5–9 yr (childhood); bimodal with adults | Posterior fossa (cerebellum / fourth ventricle) | WNT (best; CTNNB1); SHH (intermediate; TP53 status splits risk); Group 3 (worst; MYC amp); Group 4 | 5-yr OS: WNT >90%; SHH-TP53 wildtype 75%; Group 3 ~50%; Group 4 ~75% |
| Ependymoma (WHO grade 2–3) | Bimodal: <5yr (infratentorial) and adults | Posterior fossa (ZFTA-RELA in children: supratentorial); spinal in adults | ZFTA-RELA fusion (supratentorial, children, grade 3); YAP1 fusion (supratentorial, infants, better prognosis); PFA/PFB methylation groups (posterior fossa) | PFA (posterior fossa A) = worst; 5-yr OS ~65%; PFB = best |
| Diffuse intrinsic pontine glioma (DIPG) / DMG | 5–9 yr | Pons; thalamus; spine | H3 K27M mutation (H3.3 or H3.1); now classified as diffuse midline glioma, H3 K27-altered | Worst CNS tumour in children; median OS 9–15 months; ONC201 shows early promise |
| Atypical teratoid/rhabdoid tumour (AT/RT) | <3 yr | Posterior fossa and supratentorial | SMARCB1 (INI1) or SMARCA4 loss — diagnostic; three methylation subgroups (TYR, SHH, MYC) | Historically dismal (<20% 5-yr OS); intensive multimodal therapy improving outcomes in older children |
Placental pathological examination is indicated after all stillbirths, severe neonatal morbidity, IUGR, preterm birth <34 weeks, and preeclampsia with severe features. The Amsterdam Placental Workshop Group Consensus Statement (2016) provides standardised terminology for placental lesions classified by timing (acute vs chronic) and aetiology (maternal vascular malperfusion, foetal vascular malperfusion, inflammation, and other).
Authority on paediatric lymphoma, leukaemia immunophenotyping, and the WHO classification of haematolymphoid tumours as applied to childhood malignancies. Expert in EBV-associated lymphoproliferative disorders in immunocompromised children.
Pioneer in improving paediatric cancer diagnosis in Central America, focusing on the pathological classification of childhood leukaemia, Wilms tumour, and retinoblastoma in resource-limited settings. Recipient of SIOP global health awards.
Leading Scandinavian perinatal pathologist specialising in placental pathology, Amsterdam criteria classification, and the pathological investigation of stillbirth in Danish perinatal audit programmes.
Expert in paediatric and young adult sarcoma pathology — Ewing sarcoma, rhabdomyosarcoma, osteosarcoma — with experience in the largest paediatric sarcoma volume in South Asia. Contributor to WHO Classification of Soft Tissue Tumours 5th edition.
Authority on paediatric soft tissue tumours, rhabdomyosarcoma pathological classification (embryonal vs alveolar vs pleomorphic), FISH testing for PAX-FOXO1 fusion, and the Children's Oncology Group (COG) sarcoma pathology committee.
European authority on paediatric renal and hepatic tumours; contributor to SIOP nephroblastoma working group histological classification and the German Society of Paediatric Oncology pathology committee.