✓ The embryonal central nervous system (CNS) neoplasms are reviewed with special reference to their differentiating potential and in the light of current neuro-oncogenetic concepts partly derived from the experimental induction of neural tumors. The conceptual (and, occasionally, practical) distinction between adult-type and embryonal CNS tumors raises a complex problem, because neoplastic transformation essentially involves replicating stem cells in tissues of renewal and because in the human brain such cells are found mostly in the course of CNS development. A cytogenetic scheme is therefore needed to serve as a frame of reference for a classification of embryonal CNS tumors that will account for the different histological entities documented so far and for the range and the restrictions of their differentiating capabilities. Most embryonal CNS tumors can be fitted into such a scheme. The cerebral medulloepithelioma, the cerebral and cerebellar neuroblastomas, the primitive polar spongioblastoma, and the ependymoblastoma show characteristic morphological features and a correspondingly distinctive cellular differentiating potential. The differentiating capabilities of the cerebellar medulloblastoma, the pineoblastoma, and the retinoblastoma are also distinctive, and are apparently determined by the cytogenesis of the area of the CNS in which the tumors originate. The indiscriminate application of a simplistic concept that would include all the so-called “primitive neuroectodermal tumors” into a single neuroepithelial tumor entity is unlikely to bring further understanding to the problem.
A cytogenetic view of a complex neuro-oncological problem
Lucien J. Rubinstein
Its contributions to neurosurgical diagnosis
Jose M. Bonnin and Lucien J. Rubinstein
✓ Immunofluorescence and immunoperoxidase (peroxidase-antiperoxidase, PAP) techniques for the demonstration of neural and non-neural cell markers are contributing greatly to increase the diagnostic accuracy of difficult tumors of the central nervous system. Well characterized nervous system markers include glial fibrillary acidic (GFA) protein, the three protein subunits of neurofilaments, neuron-specific enolase (NSE), myelin basic protein, and S-100 protein. The most important and reliable of these is GFA protein, which is widely in use for the immunohistochemical diagnosis of tumors of the glioma group. Its many practical applications are reviewed and illustrated. Other neural markers, in particular the specificity of NSE and S-100 protein, need to be critically evaluated. Problems related to the immunohistochemical diagnosis of central neuroepithelial tumors of putative neuroblastic origin remain complex and still need to be resolved. Non-neural markers, such as vimentin, desmin, cytokeratins, Factor VIII, alpha-fetoprotein, human chorionic gonadotropin, and immunoglobulins have well defined, although more restricted, applications in surgical neuropathology.
Gary W. Ross and Lucien J. Rubinstein
✓ It is widely believed that an important determinant of clinical behavior and prognosis in patients harboring an ependymoma is the histological grade of malignancy of the tumor. Excluding from the present analysis examples of ependymoblastoma (a highly cellular, embryonal tumor occurring in children, with a notably poor prognosis and a tendency to subarachnoid spread), an attempt was made to correlate 15 cases of histologically malignant ependymoma with clinical recurrence and postoperative patient survival times. Ten patients (67%) were alive from 15 months to 14 years after surgery (median survival time 8.8 years); one patient had a histologically benign recurrence 11 years after surgical resection. Five patients (33%) died from a local recurrence of their tumor; their postoperative survival times ranged from 13 months to 6 years (median 2.5 years).
The prognosis of malignant ependymomas is therefore highly variable. No correlation was possible between the tumor's histological features, site, or likelihood of recurrence. This lack of clinicohistopathological concordance contrasts with the known correlations that exist in astrocytomas.
Ann E. Hamilton, Lucien J. Rubinstein and G. Joseph Poole
✓ A case of esthesioneuroblastoma (olfactory neuroblastoma) is reported. Its onset was that of an intracranial tumor, and it subsequently recurred four times. At autopsy, 4 years and 8 months after the onset of symptoms, metastases were found in the cerebrospinal pathways and visceral organs. The literature on this relatively rare neoplasm is reviewed with special reference to the unusual clinical presentation and biological behavior of the tumor.
Desmoplastic supratentorial neuroepithelial tumors of infancy with divergent differentiation potential (“desmoplastic infantile gangliogliomas”)
Report on 11 cases of a distinctive embryonal tumor with favorable prognosis
Scott R. VandenBerg, Estelle E. May, Lucien J. Rubinstein, Mary M. Herman, E. Perentes, S. A. Vinores, V. Peter Collins and T. S. Park
✓ Eleven cases of supratentorial neuroepithelial tumor presenting in infancy are reported. The tumors were characterized by their voluminous size, their intense desmoplasia, and the frequent presence of divergent astrocytic and ganglionic differentiation as demonstrated by special neurohistological and immunohisto- and immunocytochemical techniques. All the tumors presented in subjects below the age of 18 months, usually within the first 4 months of life. They most often involved the frontal and parietal regions and were composed predominantly of a dense desmoplastic tissue superficially resembling a moderately cellular fibroma. The fibroblastic elements were admixed with variable numbers of pleomorphic neuroepithelial cells. Divergent astrocytic and neuronal differentiation was demonstrable in nine of the 11 tumors. All showed astrocytic differentiation. The study of one example by electron microscopy, immunocytochemistry, and tissue culture disclosed that the astrocytic tumor cells were partly invested by a pericytoplasmic basal lamina. Successful total or near-total surgical resection has been followed by a favorable postoperative course extending in some cases over many years of tumor-free survival. The name “desmoplastic infantile ganglioglioma” is proposed for this apparently distinct clinicopathological entity, whose massive size is indicative of a pre- or perinatal origin. Its identification can be achieved by careful histological analysis and is of obvious prognostic significance.