Medulloblastoma

Abstract

The histogenetic approach to the classification of embryonal tumors of the central nervous system has historically received wide acceptance as a scheme for histologic typing and nosologic definition. Medulloblastoma is a paradigm of a neuroblastic neoplasm whose origins and differentiation potential are traceable to cerebellar embryogenesis. Medulloblastomas show unequivocal neuroblastic maturational changes evidenced by neuritogenesis and expression of neuronal cytoskeletal and other neuronal differentiation-associated antigenic determinants. In addition, ganglion cells form in some lesions. Based on differential patterns of immunoreactivity for calbindin-D28k (a ventricular matrix (VM)-associated neuronal calcium binding protein, which is not expressed in the external granule layer (EGL) or its progeny) and the class III beta-tubulin isotype (beta III) (expressed metachronously in the neuronal descendants of both neuroepithelia), it is possible that distinct subsets of medulloblastomas may implicate clonally-related neuroblasts from two sources: VM for classic medulloblastomas and the EGL for desmoplastic (nodular) medulloblastomas. However, the possibility of two separate origins for the classic medulloblastomas cannot be entirely excluded. Origin from the VM is suggested for the rare subset of medulloblastomas with ganglion cells. It is, however, unclear whether these ganglion cells are neoplastic (products of terminal neuronal differentiation), or dysplastic (entrapped preexisting elements of cerebellar heterotopias). Glial differentiation (gliomatous transformation) in medulloblastomas is at issue but is documented in rare cases of classic medulloblastomas (presumed heteroclones of cotransformed VM glial precursors), or desmoplastic medulloblastomas (probable stromal glial transformation-induction). Astrocytic proliferations in desmoplastic medulloblastomas may be stroma-derived (neuronal differentiation-associated), analogous to Schwann cell contributions during maturation of peripheral neuroblastomas.