WHO pediatric tumor classification reflects transition to molecular diagnosis
Click Here to Manage Email Alerts
A first-ever pediatric blue book has been developed as part of the fifth edition of the WHO Classification of Tumors series.
The blue book presents an updated collection of all tumor types, divided by organ sites, that may occur in childhood or adolescence.
A review article published in Cancer Discovery summarized significant changes in a systematic approach for all tumor types that specifically occur in children.
“This blue book focuses on the pediatric age group and not on the organ or organ system, comprising an important change in perspective. So far, pediatric tumors were ‘buried’ in the different organ-specific classifications, despite pediatric tumors being quite dramatically different from those occurring in adults in terms of tumor types, molecular/genetic features and response to therapy,” Stefan M. Pfister, MD, director of the Hopp Children’s Cancer Center Heidelberg and head of the division of pediatric neuro-oncology at German Cancer Research Center, told Healio.
“Pediatric solid tumors are frequently ‘embryonal’ tumors — reproducing the morphologic, as well as many biologic, features of embryonal tissues with a maturation block as an initial oncogenic hit — often driven by a single genetic alteration and typically showing a relatively simple genetic profile. Their immune infiltration is often minimal,” Pfister added. “These characteristics are crucial for the modern approach to the diagnosis of malignancies evolving from a histogenesis-based taxonomy recognized by the traditional optic microscopy to an integrated diagnosis combining molecular, genetic and epigenetic features with morphological patterns. In fact, a multilayered diagnostic strategy is the key to diagnostic precision to optimally inform therapeutic decisions and prognostication. Pediatric tumor classification is based on these premises and reflects the current state of the art in terms of biology and clinicopathologic features for the different tumor types in a holistic perspective. This complex system is represented by a still-developing pediatric or adolescent patient with the specificity related to the young age and the need to find a balance between cure and quality of future life. All these patients, once cured, expect to live for another 70 to 80 years, so it’s crucial to minimize collateral damage of therapies for these patients. Having all these rare diseases described in one classification, written by the most specialized experts in the field, is a milestone in the challenging field of childhood tumor diagnostics.”
New classifications
Special relevance has been given to molecular and epigenetic features in the classification of pediatric tumors, according to Rita Alaggio, MD, head of the pathology unit in the department of laboratories at Bambino Gesù Children’s Hospital in Rome.
“In brain tumors, the classification has almost completely shifted from a primarily histology-based definition to molecularly defined entities and their integration with histology — with many of them for the first time listed as a distinct entity,” Alaggio told Healio. “DNA methylation profiling was also added as a new diagnostic tool, which is listed as an essential or desirable diagnostic criterion for most brain tumor types.”
In mesenchymal tumors, for the first time the classification of vascular tumors and vascular malformations has been adjusted to the International Society for the Study of Vascular Anomalies (ISSVA) classification — a clinicopathologic classification used mostly in dermatopathology, Alaggio added.
“This is an example of the need for a pediatric-specific perspective. The border between vascular malformations and tumors has been a subject of debate for many years, and the current classification is remarkable for establishing a ‘shared’ language between different disciplines,” Alaggio said.
In addition, Pfister said an emphasis has been placed on pediatric tumors in the context of tumor predisposition syndromes.
“About 10% of pediatric malignancies are related to a tumor predisposition syndrome, but this may be an underestimate, considering the rarity of pediatric tumors, thus potentially limiting the identification of new familial predisposition syndromes,” Pfister said. “The specific pediatric approach also clearly emerges in the sections on hepatoblastoma, neuroblastoma and other embryonal tumors, for which the classification is strictly related to clinical trial protocols through a well-established multidisciplinary approach by integrating morphology, molecular alterations and prognosis.”
Moreover, hematolymphoid tumors are currently in transition and novel entities have been included in the upcoming fifth edition, according to Pfister.
“However, these diseases in the past have spearheaded the transition from a morphology-based to an integrated, molecularly based approach,” Pfister said. “Thus, the majority hematolymphoid tumor types are actually defined by certain cytogenetic aberrations or prototypic translocations rather than their microscopic appearance.”
Researchers noted one limitation of this effort is the fact that tumor classification and molecular characterization are moving targets. Therefore, any classification only provides a current snapshot that reflects the current knowledge.
For this reason, WHO has implemented mechanisms to update specific aspects of the classifications between editions and has all tumor classifications in an online format where they can be updated in real time, according to Alaggio.
Implications
This blue book highlights the need for a multidisciplinary approach to pediatric tumors that has the developing organism in mind, according to Alaggio.
“It sets a new standard regarding common language, common understanding of disease entities, and necessary and desirable diagnostic tests, and it forms the basis for stratified and precision oncology treatment protocols,” Alaggio said. “The upper age limit of the pediatric age group is still being debated, since adolescents and young adults comprise an age continuum for many diseases and are still a highly understudied and underserved patient population.”
Pfister said the multilayered classification approach is extremely important because it implies different techniques starting with classic morphology and reaching all the way to more genome-wide molecular/genetic/epigenetic tests, which may not be accessible in all countries.
“The introduction in the classification of ‘essential’ and ‘desirable’ diagnostic criteria for each tumor type reflects the need to allow formulating a diagnosis based on available techniques in individual countries, while at the same time integrating the state-of-the art knowledge of tumor biology to allow for the best care for our children with cancer,” Pfister said.
For more information:
Stefan M. Pfister, MD, can be reached at s.pfister@kitz-heidelberg.de.
Rita Alaggio, MD, can be reached at rita.alaggio@gmail.com.
Collapse
Click Here to Manage Email Alerts