The Hopp Children’s Cancer Center Heidelberg (KiTZ) is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital (UKHD) and the University of Heidelberg (Uni HD).

Even though childhood cancers are rare, they are the most common cause of disease-related death in children. The diagnosis of cancer in children and adults is based on the WHO (World Health Organization) classifications. A tumor sample is classified and precisely characterized on the basis of its tissue properties, its molecular characteristics and the localization of the tumor. Thus, the tumor is given a uniform and internationally valid label which provides the basis for its treatment.

However, childhood tumors are unique in many ways. "Tumors in childhood and adolescence are fundamentally different from tumors in adults in terms of tumor types, causes of development, biology and therapeutic approaches," emphasizes Stefan Pfister, director of the Hopp Children's Cancer Center Heidelberg (KiTZ), department head at the German Cancer Research Center (DKFZ), and pediatric oncologist at Heidelberg University Hospital (UKHD), who is one of the lead authors of the current publication. Many childhood cancers are caused by a single genetic event which occurs in a cell during its developmental phase and subsequently leads to uncontrolled cell division. In contrast, malignancies in adults are usually due to multiple genetic events, often caused by external chronic influences such as smoking, alcohol, infections or UV light. Consequently, tumors whose tissues look similar under the microscope and which occur in the same organ can still have a completely different origin, an entirely different biology, and a different course of disease.

The new WHO classification of childhood tumors, which was jointly developed by scientists at KiTZ, UKHD, DKFZ, and numerous other international experts, is therefore based on a modern, multi-layered approach which incorporates not only all microscopically visible features but also numerous molecular ones into the diagnosis. The book, now published as Volume 7 of the fifth edition of the WHO Classification of Tumors, represents the first reference work to date of all tumor types which can occur in childhood and adolescence. "Until now, childhood tumors were only listed in the organ-specific WHO classifications among the numerous types of cancer which practically only occur in adulthood," says Andreas von Deimling, medical director of neuropathology at the UKHD and head of the Clinical Cooperation Unit Neuropathology at DKFZ. In addition to the usual classification by organ, a distinction is also made between cancers which typically occur in infants, older children, and adolescents. "Finally, a holistic view should consider a child's tumor not only as a disease of an organ, but as a disease of an organ in a developing child," explains co-author Rita Alaggio, Head of the Department of Pathology at the Bambino Gesù Children's Hospital in Rome.

By adding genetic and other molecular tumor characteristics, it is also possible to identify entirely new tumor types, identify therapeutic targets, and make assessments of the course of the disease, the authors say. For example, while tumors of the connective tissue are still classified mainly on the basis of tissue structures, tumors of the central nervous system and leukemia are nowadays mostly classified on the basis of recurrent molecular or epigenetic changes or patterns.

In the medium term, low- and middle-income countries could also benefit from the new, more precise diagnostic criteria for treating children with cancer, the experts hope. "An important prerequisite for this is the development of affordable tests, and links to pathology and pediatric oncology networks," says Stefan Pfister. Especially in such countries, which have too few specialized pathologists to evaluate tumor samples, these methods could help to use more precise diagnostic approaches specifically for children with cancer as standard. Pfister is convinced that early precision diagnostics can already decisively improve the situation of many patients: "If we invest only two to three per cent of the costs of modern cancer therapy in an objective, precise, and unambiguous diagnosis in which we bring together molecular tumor profiles, biomarkers for predicting the course of the disease, and hereditary cancer predispositions, this is an extremely good investment for patients. To be able to recommend tailored treatments and avoid side effects."

About the WHO tumor classifications:
The World Health Organization (WHO) tumor classification classifies cancers based on defined criteria. Since 1956, the WHO has promoted the publication of the classification of tumors, better known as the WHO "Blue Books". Each book contains a state-of-the-art, scientific classification of tumors for each organ. Previously, pediatric tumors were included exclusively with adult tumors in organ-specific tumor classifications.

 

Original Publication:
Pfister, S.M. et al. A summary of the inaugural WHO Classification of Pediatric Tumors:
Transitioning from the optical into the molecular era. In: Cancer Discovery (Online Publikation 17. Dezember 2021) DOI: 10.1158/2159-8290.CD-21-1094

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