Pediatric neoplasms differ fundamentally from adult cancers. They are predominantly embryonal tumors — derived from primitive, undifferentiated cells that recapitulate the histology of developing embryonic tissues. Their classification integrates morphology, IHC, and molecular genetics, and their treatment and prognosis differ markedly from histologically similar adult tumors.
Neuroblastoma
Neuroblastoma is the most common extracranial solid tumor in children, arising from the developing sympathetic nervous system (neural crest). The primary site is the adrenal medulla (40%) or para-spinal sympathetic ganglia. Histology shows small, round, blue cells with Homer-Wright rosettes (neoplastic cells arranged around a central fibrillary core). Differentiation is graded: undifferentiated (no neuropil), poorly differentiated (neuropil present), and differentiating (mature ganglion cells). Schwannian stroma — the presence of mature Schwann cells dividing the tumor into nests is associated with favorable histology. The International Neuroblastoma Pathology Classification (INPC) assigns favorable or unfavorable histology based on differentiation grade, mitosis-karyorrhexis index (MKI), and age.
Molecular markers: MYCN amplification (present in 25%) — the strongest negative prognostic factor, independent of stage; ALK mutations (10%) — targetable with ALK inhibitors; 1p deletion, 11q deletion, 17q gain — segmental chromosomal alterations associated with high-risk disease. IHC: synaptophysin+, chromogranin+, PHOX2B+ (nuclear, highly specific), CD56+. Treatment is risk-stratified: observation for low-risk, chemotherapy and surgery for intermediate-risk, intensive chemotherapy with stem cell transplant and anti-GD2 immunotherapy for high-risk.
Wilms Tumor (Nephroblastoma)
Wilms tumor is the most common renal tumor in children, arising from persistent metanephric blastema (nephrogenic rests). Histology shows a classic triphasic pattern of blastema (dense, small blue cells), stroma (mesenchymal elements — fibroblasts, smooth muscle, skeletal muscle, cartilage, fat), and epithelium (primitive tubules and glomeruli). Anaplasia (marked nuclear enlargement, hyperchromasia, atypical mitoses) defines the unfavorable histology group — present in 5-10% of cases and associated with TP53 mutation.
Molecular markers: WT1 mutation (10-20%), CTNNB1 (beta-catenin) mutation (15%), WTX mutation (30%), IGF2 overexpression (70%, from 11p15 loss of imprinting). Nephrogenic rests — persistent embryonal renal tissue present in 30-40% of Wilms tumor kidneys; they are precursors of Wilms tumor. Treatment: nephrectomy + chemotherapy (vincristine, actinomycin D) ± radiotherapy. Survival exceeds 90% for favorable histology.
Hepatoblastoma
Hepatoblastoma is the most common liver tumor in children under 3 years, arising from primitive hepatoblast (liver stem cells). Histology shows epithelial (fetal, embryonal, macrotrabecular, small cell undifferentiated) and mixed epithelial-mesenchymal patterns. The fetal pattern (well-differentiated) shows uniform small cells with clear cytoplasm (glycogen-rich) and is associated with excellent prognosis. The embryonal pattern shows more primitive cells with higher N/C ratio. Small cell undifferentiated pattern — aggressive, with INI1 loss in a subset.
IHC: HepPar1+, GPC3 (glypican-3)+, beta-catenin (nuclear accumulation in 80%), CK19+ (embryonal pattern). Molecular: CTNNB1 mutations (60-80%), activating beta-catenin pathway. Serum alpha-fetoprotein (AFP) is elevated in >90% of cases and is used for screening and monitoring. Treatment: surgical resection + chemotherapy (cisplatin, doxorubicin). Prognosis depends on PRETEXT stage and histological subtype.
Rhabdomyosarcoma
Rhabdomyosarcoma is the most common soft tissue sarcoma in children, arising from skeletal muscle precursors. The two major subtypes are embryonal (60-70%, botryoid variant) and alveolar (20-30%). Embryonal RMS shows spindle-shaped or round cells with variable rhabdomyoblastic differentiation (eosinophilic cytoplasm, cross-striations). The botryoid variant grows as polypoid grape-like clusters beneath mucosal surfaces (bladder, vagina, nasopharynx) with a characteristic cambium layer (dense tumor cell layer beneath the epithelium).
Alveolar RMS shows round cells arranged in nests separated by fibrovascular septa, with central loss of cohesion producing alveolar spaces. Molecular: PAX3/PAX7-FOXO1 fusion (80% of alveolar RMS) — fusion-positive alveolar RMS has a poor prognosis. Embryonal RMS shows RAS pathway mutations, FGFR4 mutations, and 11p15 loss of heterozygosity.
IHC: desmin+, MyoD1+, myogenin+, MYF4+. Treatment: multimodal chemotherapy (vincristine, actinomycin D, cyclophosphamide) + surgery + radiotherapy. Prognosis depends on subtype, stage, and fusion status.
Pediatric CNS Tumors
Pediatric CNS tumors are the second most common childhood malignancy. Medulloblastoma (posterior fossa, the most common malignant brain tumor in children) is classified by WHO into four molecular subgroups: WNT-activated (best prognosis), SHH-activated, group 3, and group 4. Histology shows small, round, blue cells with Homer-Wright rosettes. Craniopharyngioma — histologically benign but clinically aggressive tumor arising from Rathke pouch epithelium. Low-grade gliomas (pilocytic astrocytoma) are the most common pediatric brain tumor — WHO grade 1, BRAF alterations (KIAA1549-BRAF fusion in 70%), excellent prognosis after complete resection.
