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Objective: Uniform cells with round, regular nuclei characterize the typical histologic aspect of medulloblastoma. Enlargement of nuclei distinguishes the large-cell medulloblastoma variant and is associated with a poor prognosis in pediatric medulloblastomas. The aim of the present study was to compare the size of nuclei between pediatric and adult medulloblastomas by a morphometric analysis., Material and Methods: In 79 neurosurgical specimens of cerebellar medulloblastomas, the maximum nuclear diameter of the largest nuclei was measured. Measurements were performed with a digital-image analysis system. The measure of the maximum diameter was chosen in order to reduce the split cell error., Results: The difference between the mean values in children and adults was statistically significant (p = 0,001). The distribution of maximum values measured in each case had two distinct peaks in the two age groups, in 3.5% of adult cases and in more than 30% of pediatric cases the maximum nuclear size was superior to 12 microm., Conclusions: The present results show that nuclei of tumor cells in pediatric medulloblastomas are larger than those in adult medulloblastomas and confirm that the phenotype of medulloblastoma is different in the two age groups. Distinct genetic events can, thus, underlie medulloblastoma in childhood and adult age, the prognostic role of genetic variables can differ by age.

Background: Lipomatous medulloblastoma is a recently identified clinicopathological entity, characterized by areas of lipomatous differentiation, manifestation in adults, and apparently by a favorable prognosis., Material and Methods: In our series of medulloblastomas of adults and children we have found lipidized cells within the tumor in 6 out of 78 cases of adults and in 8 out of 44 cases of children. In 3 adult cases and 3 children cases, lipidized cells were particularly numerous and clustered., Results: Neuronal differentiation was found in 4/6 cases; no case showed GFAP-positive tumor cells. Lipidized cells were constantly immunopositive for vimentin and some of them also for KP-1 and CR3/43. The proliferation potential was evaluated by the immunohistochemical demonstration of MIB-1; MIB-1-labeling index (LI) ranged from 20.8% to 40.5%. No case survived longer than 7 years after diagnosis and postoperative radiotherapy., Conclusion: The present 6 cases of heavily lipidized medulloblastoma are not uniform as for age of occurrence, proliferation potential and survival. They do not share the clinical and pathologic features of "lipomatous medulloblastoma". Therefore, the finding of large numbers of lipidized cells in a medulloblastoma does not authorize to diagnose the tumor as "lipomatous medulloblastoma", for which a favorable clinical prognosis is foreseen.

Medulloblastoma is one of the most common primary tumors of the central nervous system seen in children; in contrast, it is somewhat uncommon in adult age. Due to the infrequent occurrence, data on incidence rates are sparse. The present study was aimed at ascertaining the epidemiological characteristics of medulloblastoma in adult age in Piedmont during the period 1976-1995. Piedmont is a region in northwest Italy, which had a total population of 4.30 millions/year for the period mentioned. From the files of clinical records of patients hospitalized in neurologic and neurosurgical departments, 45 cases (32 males, 13 females) of histologically verified medulloblastoma were recorded. The incidence rate (annual per million) in the whole period studied was 0.5 (95% confidence interval, 0.36-0.67). The incidence rate was high in the age group 15 to 19 years (2.33/million/year) and decreased up to age 40, consistent with the embryonal origin of the tumor. No time-trend of incidence rate was found. Male excess was evident in all age groups and in each time period. Median survival time was 17.6 years; the 5-year survival rate was 69.9%. Survival rate in the present group of adult medulloblastoma is slightly better than that reported in clinical series. A comparison was made with incidence data concerning pediatric medulloblastoma reported in the Registry of Childhood Cancer of Piedmont: from 1980 to 1989, adult medulloblastomas represented 34% of medulloblastomas. The figure is higher than that generally assumed, and indicates that the occurrence of this embryonal tumor in adult age is relevant. Our epidemiological data are consistent with an embryonal origin of medulloblastoma.

Medulloblastoma is a highly malignant cerebellar tumor of children and, less frequently, of adults, with a tendency to early recurrence and dissemination through the cerebrospinal fluid. The prognosis has improved significantly in recent decades, in parallel with the improvement in neurosurgical techniques and the use of postoperative radiotherapy. An overview is given of the prognostic role of clinical and pathological features of individual cases as reported in the literature. Apart from the presence or absence of metastases at diagnosis and the radiotherapy modality, none of the factors studied was generally thought to have a definite significant prognostic role. The extent of surgical excision seems to influence survival more in pediatric cases than in adults. Ongoing cytogenetic studies and molecular biology investigations are aimed at better categorization of medulloblastomas and individualized postoperative treatment.

Isochromosome 17q (i[17q]) is the most frequent chromosomal abnormality in medulloblastoma, occurring in 30-60% of cases by karyotype analysis. In the present study i[17q] was demonstrated in routinely processed tissue sections of 20 medulloblastomas by in situ hybridization (ISH), using a chromosome 17 centromeric alpha satellite DNA probe. All medulloblastomas showed the i[17q] specific signal, i.e. two hybridization spots slightly apart from each other. The specific hybridization signal was not observed in ependymomas, cerebellar astrocytomas, haemangioblastomas, supratentorial neuroblastomas and ependymoblastomas. The constant finding of i[17q] in medulloblastoma depends on the much higher number of nuclei which can be analysed by ISH compared with cytogenetic techniques. Molecular data on medulloblastoma are consistent with the present results. The number of cells with i[17q] in medulloblastoma cases ranged from 3% to 9%; these figures are underestimated because of nuclear truncation in tissue sections. The percentage was not linked to patients' age, location of tumour, MIB-1 labelling index and histological type (classical vs desmoplastic). The present results indicate that i[17q] is a key event in the pathogenesis of medulloblastoma, and suggest a genetic difference between medulloblastoma and other primitive neuroectodermal tumours.

The appearance of medulloblastoma in adult age and the uncertain overlapping of prognostic factors in pediatric and adult populations stimulate the question of whether medulloblastoma is different in adults and in children. The pathologic features, proliferation potential and glial/neuronal differentiation have been investigated in 42 adult medulloblastomas and 42 medulloblastomas of children; the quantitative data have been compared between the two groups of age. Homer-Wright rosettes, nuclear polymorphism and histologic signs of neuronal differentiation were more frequent in children cases; GFAP-positive tumor cells and desmoplastic type were more frequent in adult cases. The mean, median and rage of Lis, with PCNA and MIB-1 were significantly (p < 0.05) higher in adults than in children. All cases, independently from age of the patients were immunoreactive with markers of neuronal commitment (class III beta tubulin isotype, MAP-2, neurofilaments). The immunoreactivity pattern suggested a more mature neuronal character in desmoplastic cases of adults than of children and in classic cases of children than of adults. In conclusion, some phenotypic differences between childhood and adult medulloblastoma exist, but do not support a substantially different course of the disease. The higher proliferation potential in adult than in childhood cases is unexpected in a tumor of embryonal origin, and reduces the applicability of Collin's law to medulloblastoma.

Aims and Background: Medulloblastoma in adults is a rare tumor. The small number of cases in the reported series has not permitted a definite assessment of the prognostic role of clinical, pathologic and cell kinetics factors. The largest series of medulloblastoma in adults treated in a single institution is herein reported., Methods: The clinical, therapeutic, pathologic and proliferation features of medulloblastoma in 44 adult patients (> 18 years) were analyzed retrospectively with regard to postoperative survival. The proliferation potential of each tumor was evaluated by the immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA) and Ki-67, clone MIB-1, in paraffin sections., Results: The overall 5- and 10-year survival rates were 40% and 35.6%, respectively. Significant factors in predicting a longer postoperative survival were: age < 37 years, decade of management (1977-1990), radiotherapy (50-55 Gy on the posterior fossa and 30-35 Gy on the spinal cord) and nuclear isomorphism. When corrected for adequacy of radiotreatment, desmoplastic type and differentiation were significantly correlated with a shorter survival. The PCNA-labelling index (LI) ranged from 34.5 to 82.2%, the MIB-1-LI ranged from 9.6 to 64.7%. No association was found between PCNA- or MIB-1-LI values and microscopic features, or between LI values and prognosis., Conclusions: Contrary to a general assumption, desmoplastic medulloblastoma and differentiated medulloblastoma are negative prognostic factors in adequately radiotreated adult patients. This may possibly be referred to lower radiosensitivity of these tumor variants. The LI with PCNA or Ki-67 is of no help in identifying aggressive tumors.

The distribution of proliferating cell nuclear antigen (PCNA)-(clone PC 10)- and Ki-67-(clone MIB-1)-positive nuclei was investigated in 60 medulloblastomas of childhood. Although the labeling index of the two markers did not coincide, both showed a wide range of parallel variations. The percentage of positive nuclei was similar in both classic and desmoplastic tumors. A variable proliferation capacity was found in the different tumor structures. Areas with neuronal and glial differentiation showed very few positive nuclei; these were very abundant in the infiltration areas, and along penetrating vessels from subarachnoidal growths. Pale islands were negative or positive only in their peripheral part. Large-cell areas were richer in positive nuclei than classic ones, accounting for their more malignant character. Hyperchromatic round nuclei, not belonging to necrotic foci and called lymphocyte-like nuclei, differently interpreted in the past, were variably found in every case. They are known, from previous experience, to stain orange with Acridine Orange fluorochroming, like single-stranded DNA. They were not easily distinguishable from mitoses and were stained by in situ end-labeling of DNA strand breaks, as demonstrated by incorporation of labeled nucleotides. They were regarded as possible apoptotic nuclei, representing either a peculiar type of cell death or the preservation of the cell deletion capacity, typical of the embryonal tissue of origin.

Two cases of medullomyoblastoma in children are described. The muscular component showed different features in the two cases and were associated with neuronal differentiation. Morphological, immunohistochemical, and electron microscopical findings are presented. The origin of the muscular component is discussed in relation to the findings in other cases of the literature. Both differentiation from primitive neuroepithelial cells and derivation from ectomesenchyme are considered.

The problem of differentiation of medulloblastoma is considered. In this regard 43 medulloblastomas, showing cells with glial or neuronal features by routine histologic methods, were studied. The investigation was carried out by means of the immunohistochemical demonstration of the glial fibrillary acidic protein (GFAP) and the neuron-specific enolase (NSE). In most cases, GFAP-positive cells are preexisting astrocytes; in two cases they correspond to the transitional cells of the subependymal layer. NSE was demonstrated in areas filled with cells with neuroblastic features. The relationship between medulloblastoma with neuron-differentiation and cerebellar neuroblastoma is discussed.

Objective: Uniform cells with round, regular nuclei characterize the typical histologic aspect of medulloblastoma. Enlargement of nuclei distinguishes the large-cell medulloblastoma variant and is associated with a poor prognosis in pediatric medulloblastomas. The aim of the present study was to compare the size of nuclei between pediatric and adult medulloblastomas by a morphometric analysis. Material and methods: In 79 neurosurgical specimens of cerebellar medulloblastomas, the maximum nuclear diameter of the largest nuclei was measured. Measurements were performed with a digital-image analysis system. The measure of the maximum diameter was chosen in order to reduce the split cell error. Results: The difference between the mean values in children and adults was statistically significant (p = 0,001). The distribution of maximum values measured in each case had two distinct peaks in the two age groups, in 3.5% of adult cases and in more than 30% of pediatric cases the maximum nuclear size was superior to 12 µm. Conclusions: The present results show that nuclei of tumor cells in pediatric medulloblastomas are larger than those in adult medulloblastomas and confirm that the phenotype of medulloblastoma is different in the two age groups. Distinct genetic events can, thus, underlie medulloblastoma in childhood and adult age, the prognostic role of genetic variables can differ by age. [ABSTRACT FROM AUTHOR]