In some parts of the world, access to modern pathology and methodology is still a rate-limiting step. However, according to the authors, shifting to unbiased and reproducible (molecular) diagnostic criteria, which form the basis for the current classification, may eventually help middle- and low-income countries that typically suffer from a significant shortage in subspecialized pathologists and pathology training to increase diagnostic precision. This will additionally require the development of affordable tests and supporting networks for middle- and low-income countries, complemented by artificial intelligence approaches to potentially predict molecular classes from histology samples in the future.

While sporadic (non-hereditary) genetic alterations play a key role in the development of the majority of pediatric tumors, approximately 10 percent of the cases are associated with hereditary cancer predisposition syndromes. The pediatric blue book contains a classification of the cancer predisposition syndromes and identifies the challenges associated with diagnosis and treatment.


According to the authors, the inaugural edition of the WHO Classification of Pediatric Tumors has been an ambitious project involving a large number of contributors from all over the world. This joint effort was aimed at collecting state-of-the-art knowledge on all pediatric tumors from different perspectives involving multiple disciplines, emphasizing the specific needs and challenges of the pediatric and adolescent age groups.

“Spending 2-3 percent of the cost of a modern cancer therapy to establish a precise, unbiased, and unambiguous diagnosis that harmonizes molecular tumor typing, prognostic and predictive biomarkers, and potential cancer predisposition is an extremely good investment to improve patient outcomes and spare treatment side effects,” said Pfister.

One limitation of this effort is that tumor classification and molecular characterization are moving targets, so any classification can only provide an up-to-date snapshot reflecting the current knowledge. “For this reason, the WHO has implemented mechanisms to update specific aspects of the classifications between editions,” commented Alaggio. “Additionally, the WHO will have all tumor classifications in an online format where they can also be updated in real time.”

This study was funded by the German Childhood Cancer Foundation, the German Federal Ministry of Education and Research, the Everest Centre for Research Into Low-grade Paediatric Brain Tumours (The Brain Tumour Charity), the Pediatric Low-Grade Astrocytoma Fund at the Pediatric Brain Tumor Foundation, the German Research Foundation (Deutsche Forschungsgemeinschaft), the Marjorie K. Harmer Endowment for Research in Pediatric Pathology, University of Pittsburgh School of Medicine, the National Institutes of Health, Children with Cancer UK, Great Ormond Street Hospital Children’s Charity, Olivia Hodson Cancer Fund, Cancer Research UK, and the U.K. National Institute of Health Research. The authors declare no conflicts of interest.

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