7. Paediatric tumours

Introduction to Pediatric Tumors

• Pediatric tumors are the leading cause of cancer-related deaths in children, despite being relatively uncommon.

• Unique characteristics of pediatric tumors include origins from a single genetic driver event and different diagnostic challenges than adult tumors.

• First World Health Organization (WHO) Classification of Pediatric Tumors aims to tackle these challenges through a multilayered diagnostic approach, incorporating morphology, immunohistochemistry (IHC), and molecular traits.

Significance of the WHO Classification

• This inaugural classification highlights a rapid transition to a molecular-driven classification system based on recent findings in pediatric tumor genomics.

• Special emphasis on blastomas: Tumors that reflect the morphologic maturation of the organs from which they originate.

Why Separate Classification is Necessary

• Pediatric tumors are qualitatively distinct from adult tumors; though they account for about 1% of total tumor diagnoses, they commonly involve tumors of mesodermal or neuroectodermal origins.

• Pediatric tumors typically involve:

  • Lower genetic burden: Often driven by a single clonal genetic event (e.g., translocations).

  • Immune infiltration: Generally have limited immune infiltration, posing challenges in treatment.

• The distinct nature of pediatric tumors justifies the need for a specific WHO classification.

New WHO Classification Features

• Pediatric tumors are classified separately in the fifth edition of the WHO classification.

• The classification includes details by site, category, family, and type, with new guidelines on standards and characterizations, including the addition of molecular evidence.

• Inclusion of recent genomic findings and updated recommendations for tumor grading.

Diagnostic Technologies

• Transition from morphology to molecular analysis: significant advancements include:

  • Next-generation sequencing (NGS)

  • Methylome analysis

  • Proteomics

• Methylation patterns help estimate tumor lineage.

• NGS is critical for identifying tumor-specific alterations.

Integrated Diagnoses

• Pathological diagnoses facilitate communication regarding prognosis and treatment options, requiring incorporation of a comprehensive set of data. Key components include:

  1. Morphologic evaluation

  2. Tumor grade

  3. Molecular information level

• Use of a multilayered diagnosis ensures that the complexity and variety of pediatric tumors are communicated effectively.

Entity-Specific Developments: Leukemias and Lymphomas

• Hematolymphoid neoplasms account for a significant proportion (38.7%) of cancers in children and adolescents.

• The WHO classification is evolving to integrate clinical and molecular characteristics, significantly impacting diagnosis and treatment.

• Genetic aberrations are important diagnostic criteria in leukemias.

Tumor Classifications and Characteristics

• Classification of various tumor types is detailed, including:

  • Leukemias and Lymphomas: Includes specific children-oriented subcategories.

  • Soft-tissue Tumors: Incorporates traditional morphology with increasing genetic insights.

  • Bone Tumors: Focus on Ewing sarcoma and osteosarcoma.

  • CNS Tumors: Integration of classic histologic diagnoses with molecular tools.

Conclusion:

• Pediatric tumors demand a precise classification due to their rarity, heterogeneity, and distinct pathogenesis compared to adult tumors.

• Continued updates and research in genetic predisposition and molecular classification of tumors are essential. The WHO's new classification aims to guide pathologists and clinical teams in improving diagnosis, therapies, and outcomes for pediatric cancer patients.