History of Management of Supratentorial Low-Grade Gliomas in Children

Understanding of Disease

Historical development of tumor classification

CNS tumors have a wide variety of histological appearances and cytological origins, reflecting the complexity of the tissue from which they are derived. The successive diagnostic classifications for different brain tumors have arbitrarily emphasized one histological characteristic or another so as to provide simultaneous information on the cellular origin of the tumor, its etiology, and patient prognosis.

• Early classifications: At the end of the 1940s a classification of brain tumors based on cytology was established. The concept was that the different CNS tumors would originate from each of the mature brain cell types. In addition, the importance of location began to be factored into the evaluation of the prognosis, and the differences between tumor types were assessed as much by their morphology as by their behavior and location.
• Grading classifications: In an attempt to simplify classifications and provide a prognostic criterion based on grade, a grading system was developed by Kernohan et al. in 1949 (26). The authors assigned tumors to one of four grades depending on their differentiation, ranging from well differentiated (grade I) to poorly differentiated (grade IV).
• Histological grade: The Kernohan classification system determines histological grade according to the recognition of cellular anaplasia, defined as pleomorphism, cell density, number of mitotic figures, atypical mitoses, level of cell differentiation, presence of giant cells, vascular proliferation, necrosis with or without pseudo-palisades, rapid growth with infiltration, and metastasis.
• Zülch classification: The need to include concrete prognostic criteria led to a meeting of experts in 1971 under the leadership of Zülch (3). This meeting presented a classification system with only a few conceptual modifications to the 1970 Zülch classification (28), basically including the concept of grade. This classification, created in 1956, classified the tumors into categories and subcategorized the neuroepithelial tumors (27).

W.H.O. tumor classification

The CNS tumor classification systems described above ignored the special characteristics of pediatric CNS tumors, particularly the histological variation present in the same mass and the differences in how the tumors evolve. Considering the above characteristics, as well as the variability of tumor evolution depending on its location, the age of the patient, and the different histological features, in 1985 Gilles proposed the need for a classification system that could predict prognosis, i.e., survival and response to treatment (4, 29). He proposed that the classification of pediatric CNS tumors should consider, rather than solely histogenetic criteria, other criteria with prognostic significance, such as localization of the tumor mass, and, consequently, the possibility for total resection; age at presentation; the histological variability/variation within the mass; and the evaluation of certain histological characteristics that might have a prognostic significance that differed from that in adults (4). These thoughts influenced the subsequent evolution in tumor classification and resulted in the classification systems that are in current use.

• 2007 W.H.O. CNS tumor classification: CNS tumor classification is very complicated in children because masses present greater variability in children than in adults. The same mass may present different histological cell types that may change during the evolution of the tumor. In 2007 the W.H.O. CNS Tumor Classification was released to reflect these facts (30). 

Technological Development

• Imaging advances have improved surgical targeting and assessment of therapies: The use of new PET and MRI techniques has revealed the pathological changes occurring within tumors such as neovascularization (with MR perfusion images), infiltration of surrounding parenchyma, increased cellularity (diffusion weighted and diffusion MR spectroscopy and FDG PET) and proliferation (spectroscopy and methionine PET). These advances provide guidance during biopsy or surgical therapy and also allow for evaluation of the response to the chosen therapy.

Surgical Technique

• Surgical resection: The advances in surgical resection in recent years have revolutionized the management of glial tumors. Surgical improvements have been achieved through the combination of new diagnostic techniques that enable appropriate presurgical planning together with the development of microsurgical instruments and the surgical microscope, laser, ultrasonic aspirator, and other equipment.
• Intraoperative techniques: Techniques for intrasurgical localization and control, such as neuronavigation and intrasurgical ultrasound, have made it possible to locate the tumor, differentiate it from vital neurological structures, and control the extent of the resection.