Pasado, presente y futuro en el tratamiento del meduloblastoma / Past, present and future in the treatement of medulloblastoma

Hacemos una breve historia del manejo de los meduloblastomas desde la primera descripción hecha por Bailey y Cushing en 1924, hasta nuestros días en que el tratamiento es multidisciplinario incluyendo a neurocirujanos, neuropatólogos, neurorradiólogos, radioterapeutas, oncólogos,etc. y también señalamos los pasos futuros basados en los valiosos aportes de la biología molecular y la genética.

We present a short history of the management of medulloblatomas, from the first description done by Bailey and Cushing in 1924 up to our days when treatment is multidisciplinary, involving neurosurgeons, neuropathologists, neuroradiologists, radiotherapists and, oncologists among others; and we also show the future steps based on the valuable contributions of genetics molecular biology.

On the neuronal/neuroblastic nature of medulloblastomas: a tribute to Pio del Rio Hortega and Moises Polak.

The concept that medulloblastomas represent cerebellar neuroblastic tumours was championed by del Rio Hortega in the 1930s and was critically reappraised in the 1960s by Moises Polak. Whereas the aetiology and molecular pathogenesis of medulloblastomas remain unresolved, there is now compelling evidence in support of a fundamentally neuronal tumour phenotype. Tumour cells express in a differentiation-dependent manner a repertoire of neuronal cytoskeletal, synaptic, and other lineage-associated proteins. Neuronal differentiation is more pronounced in the so-called nodular/desmoplastic medulloblastomas, which are typified by areas of neoplastic neuritogenesis ("pale islands") marked by the co-expression of neuronal marker proteins and neurotrophin receptors TrkA and TrkC, low proliferative indices, and apoptosis. The pale islands contain meshworks of reactive astrocytes as part of mutually inductive tumour-stromal cell interactions. However, overt glial differentiation or gliomatous transformation are uncommon. There is growing evidence to support the hypothesis that distinct subtypes of medulloblastomas may implicate transformed neuroblasts from two separate neuroepithelial sources: (a) the velum medullare for a subset of classic medulloblastomas, and (b) the external granule layer for the nodular/desmoplastic medulloblastomas as well as certain classic medulloblastomas. The nosological position of medulloblastomas is discussed in the context of the so-called embryonal central nervous system tumours with emphasis on the cerebral and cerebellar neuroblastomas. We give credence to the view that the medulloblastoma belongs to a group of central neuronal/neuroblastic tumours and call for a critical re-evaluation of its present taxonomic placement.

The influence of Harvey Cushing on neuroradiologic therapy.

Harvey Cushing was largely responsible for the establishment of neurosurgery as a separate discipline. He demonstrated how careful attention to technique could make surgery acceptably safe, established classifications and clinical-pathologic correlations of a wide variety of tumors, and trained dozens of future neurosurgical department heads. Less well known, however, is Cushing's contribution to the early clinical use of radiation therapy for a variety of intracranial disorders. With the aid of his meticulous clinical follow-up, large case volume, and willingness to try new treatment methods, he demonstrated the utility of therapeutic radiation in patients with pituitary tumor, medulloblastoma, and arteriovenous malformation. His less impressive results with the irradiation of patients with glioma are also worthy of note and include trials of brachytherapy. Neurosurgeons and radiation oncologists exploring new methods of delivering therapeutic radiation to the central nervous system should be aware of the lessons learned from Cushing's experience.