Biomedical subjects

Benedikt Volk

Publications and source records attributed to Benedikt Volk.

At least 19 recordsLinked to original sources

PubMed2007

A new clinico-pathological classification system for mesial temporal sclerosis.

We propose a histopathological classification system for hippocampal cell loss in patients suffering from mesial temporal lobe epilepsies (MTLE). One hundred and seventy-eight surgically resected specimens were microscopically examined with respect to neuronal cell loss in hippocampal subfields CA1-CA4 and dentate gyrus. Five distinct patterns were recognized within a consecutive cohort of anatomically well-preserved surgical specimens. The first group comprised hippocampi with neuronal cell densities not significantly different from age matched autopsy controls [no mesial temporal sclerosis (no MTS); n = 34, 19%]. A classical pattern with severe cell loss in CA1 and moderate neuronal loss in all other subfields excluding CA2 was observed in 33 cases (19%), whereas the vast majority of cases showed extensive neuronal cell loss in all hippocampal subfields (n = 94, 53%). Due to considerable similarities of neuronal cell loss patterns and clinical histories, we designated these two groups as MTS type 1a and 1b, respectively. We further distinguished two atypical variants characterized either by severe neuronal loss restricted to sector CA1 (MTS type 2; n = 10, 6%) or to the hilar region (MTS type 3, n = 7, 4%). Correlation with clinical data pointed to an early age of initial precipitating injury (IPI < 3 years) as important predictor of hippocampal pathology, i.e. MTS type 1a and 1b. In MTS type 2, IPIs were documented at a later age (mean 6 years), whereas in MTS type 3 and normal appearing hippocampus (no MTS) the first event appeared beyond the age of 13 and 16 years, respectively. In addition, postsurgical outcome was significantly worse in atypical MTS, especially MTS type 3 with only 28% of patients having seizure relief after 1-year follow-up period, compared to successful seizure control in MTS types 1a and 1b (72 and 73%). Our classification system appears suitable for stratifying the clinically heterogeneous group of MTLE patients also with respect to postsurgical outcome studies.

Adult↗

PubMed2006

High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma.

PURPOSE: To improve survival and reduce toxicity in primary CNS lymphoma (PCNSL) treatment, we conducted a multicenter phase II study with early high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) followed by hyperfractionated whole-brain radiotherapy (WBRT) for newly diagnosed PCNSL patients younger than 65 years of age. PATIENTS AND METHODS: Chemotherapy included three steps: three cycles of methotrexate (8 g/m2); cytarabine (AraC; two doses of 3 g/m2) and thiotepa (40 mg/m2) followed by stem-cell harvest; HDT with carmustine (400 mg/m2) and thiotepa (two doses of 5 mg/kg body weight) followed by ASCT. WBRT (45 Gy, two doses of 1 Gy/d) was administered for consolidation. RESULTS: Thirty patients with PCNSL younger than 65 years of age (median, 54 years; range, 27 years to 64 years) were enrolled (nine pilot-phase; 21 phase II). Twenty-eight patients responded to methotrexate: six patients with complete remission (CR), 15 patients with partial remission (PR), and seven patients with stable disease (SD) with clinical improvement. Of 26 patients proceeding to AraC and thiotepa, 10 patients achieved CR, 14 patients achieved PR, one patient experienced SD with clinical improvement, and one patient suffered disease progression. Twenty-three patients received HDT plus ASCT, resulting in 15 patients with CRs and eight patients with PRs. After WBRT, 21 of 21 patients had CRs. One patient died from liver failure after methotrexate. HDT was well tolerated apart from WHO grade 3/4 cytopenia. With a median follow-up of 63 months (range, 4 months to 84 months), 5-year overall survival probability is 69% for all patients and 87% for the 23 patients receiving HDT plus ASCT. The 5-year probability of relapse-related death is 21% for all patients (n = 30) and 8.7% for patients treated with HDT plus ASCT (n = 23). CONCLUSION: Sequential systemic methotrexate and AraC and thiotepa followed by HDT plus ASCT and hyperfractionated WBRT is very effective with little toxicity as initial therapy for PCNSL.

Adult↗

PubMed2006

Clinical characteristics in focal cortical dysplasia: a retrospective evaluation in a series of 120 patients.

Focal cortical dysplasias (FCDs) are increasingly diagnosed as a cause of symptomatic focal epilepsy in paediatric and adult patients. However, little is known about the clinical characteristics of epilepsy in these patients. In order to elucidate the clinical characteristics of their epilepsy, 120 pharmacoresistant patients including children and adults with histologically proven FCD were studied retrospectively. Age at seizure onset was analysed in the total group and compared between subgroups with different localization and different histological subtypes of FCD. The role of febrile seizures with respect to dual pathology was investigated. Seizure semiology was analysed focusing on initial seizure type and change of seizure semiology during the course of disease. Finally, transient responsiveness to antiepileptic drug therapy was studied. In the majority of patients, epilepsy began in the first 5 years of life. However, onset of epilepsy could also occur in the second or third decade until the age of 60. Age at epilepsy onset was not significantly different between temporal, extratemporal and multilobar localization of FCD. Patients without cytoarchitectural abnormalities (mild malformations of cortical development, FCD 1a according to Palmini) had significantly later epilepsy onset (P= 0.001) compared with patients with cytoarchitectural abnormalities (FCD 1b, 2a and 2b according to Palmini). In patients with additional hippocampal sclerosis (dual pathology) febrile seizures were significantly more frequently reported (P = 0.02) than in patients without dual pathology. Moreover, patients with dual pathology and febrile seizures significantly more frequently presented with severe hippocampal sclerosis (Wyler Grade 3-4) as compared with patients with dual pathology in the absence of febrile seizures (P = 0.03). First observed seizures were mainly tonic or generalized tonic-clonic. A change of seizure semiology seemed to be age-dependent and occurred between the age of >1 and 14 years. About 15.8% of the patients presented with status epilepticus during the course of disease. About 17% of the patients showed transient responsiveness (> or =1 year seizure freedom) to antiepileptic drug therapy either after initial therapy (50%) or later in the course of epilepsy (50%). Patients with FCD represent a heterogeneous group. Different age at epilepsy onset and transient responsiveness to antiepileptic drugs in approximately 17% of patients may reflect different dynamics in epileptogenicity of the underlying FCD. Dual pathology may be associated with different pathomechanisms in patients with and without febrile seizures.

Adolescent↗

PubMed2006

Defining the actual sensitivity and specificity of the neurosphere assay in stem cell biology.

For more than a decade the 'neurosphere assay' has been used to define and measure neural stem cell (NSC) behavior, with similar assays now used in other organ systems and in cancer. We asked whether neurospheres are clonal structures whose diameter, number and composition accurately reflect the proliferation, self-renewal and multipotency of a single founding NSC. Using time-lapse video microscopy, coculture experiments with genetically labeled cells, and analysis of the volume of spheres, we observed that neurospheres are highly motile structures prone to fuse even under ostensibly 'clonal' culture conditions. Chimeric neurospheres were prevalent independent of ages, species and neural structures. Thus, the intrinsic dynamic of neurospheres, as conventionally assayed, introduces confounders. More accurate conditions (for example, plating a single cell per miniwell) will be crucial for assessing clonality, number and fate of stem cells. These cautions probably have implications for the use of 'cytospheres' as an assay in other organ systems and with other cell types, both normal and neoplastic.

Animals↗

PubMed2005

Anti-epileptic drug phenytoin enhances androgen metabolism and androgen receptor expression in murine hippocampus.

Epilepsy is very often related to strong impairment of neuronal networks, particularly in the hippocampus. Previous studies of brain tissue have demonstrated that long-term administration of the anti-epileptic drug (AED) phenytoin leads to enhanced metabolism of testosterone mediated by cytochrome P450 (CYP) isoforms. Thus, we speculate that AEDs affect androgen signalling in the hippocampus. In the present study, we investigated how the AED phenytoin influences the levels of testosterone, 17beta-oestradiol, and androgen receptor (AR) in the hippocampus of male C57Bl/6J mice. Phenytoin administration led to a 61.24% decreased hippocampal testosterone level as compared with controls, while serum levels were slightly enhanced. 17beta-Oestradiol serum level was elevated 2.6-fold. Concomitantly, the testosterone metabolizing CYP isoforms CYP3A11 and CYP19 (aromatase) have been found to be induced 2.4- and 4.2-fold, respectively. CYP3A-mediated depletion of testosterone-forming 2beta-, and 6beta-hydroxytestosterone was significantly enhanced. Additionally, AR expression was increased 2-fold (mRNA) and 1.8-fold (protein), predominantly in the CA1 region. AR was shown to concentrate in nuclei of CA1 pyramidal neurons. We conclude that phenytoin affects testosterone metabolism via induction of CYP isoforms. The increased metabolism of testosterone leading to augmented androgen metabolite formation most likely led to enhanced expression of CYP19 and AR in hippocampus. Phenytoin obviously modulates the androgen signalling in the hippocampus.

Androgens↗

PubMed2005

The brain tumor board: lessons to be learned from an interdisciplinary conference.

BACKGROUND: The aim of this study is to analyze the work of the interdisciplinary Brain Tumor Board (BTB) which was established at Freiburg University Hospital in 1998. PATIENTS AND METHODS: From January 1998 to December 2003, a total of 1,516 patients were discussed in 259 meetings of the BTB. The protocols of the BTB were analyzed retrospectively. RESULTS: In 79% of the patients, the diagnosis was based on histological findings or a typical radiological appearance of a lesion, or both. This group was composed of 4 subgroups: 28% benign skull base tumors (19% meningiomas, 4% pituitary adenomas, 3% acoustic schwannomas, 2% others), 24% primary brain tumors of glial origin (8% glioblastomas, 12% gliomas other than glioblastomas, 5% oligoastrocytomas or oligodendrogliomas), 19% brain metastases, and 8% other brain or skull base tumors. In 13% of the cases, the exact diagnosis was still unknown when the patient was presented. 8% of the presentations were motivated by nontumorous interdisciplinary problems (e.g. arterio-venous malformations). The recommendations given by the BTB included: 23% further diagnostic procedures (11% non-invasive examinations, 12% stereotactic biopsies), 57% active antitumoral therapy (22% resection, 17% fractionated radiotherapy, 13% radiosurgery, 5% chemotherapy, <1% embolization), 20% no treatment (14% watchful waiting, 6% supportive care). 91% of the BTB recommendations were realized within 3 months. CONCLUSION: Interdisciplinary care seems to be particularly necessary in patients with benign skull base tumors, gliomas and brain metastases. Decisions made in a small interdisciplinary group of experts have a high potential of subsequently being realized.

Academic Medical Centers↗

PubMed2005

Validation of intraoperative diagnoses using smear preparations from stereotactic brain biopsies: intraoperative versus final diagnosis--influence of clinical factors.

OBJECTIVE: Despite improvements in imaging techniques, histopathological diagnosis is still an important tool in neuro-oncology. At Freiburg University Hospital in Germany, approximately 450 patients per year undergo a serial stereotactic biopsy to obtain a diagnosis. We analyzed the accuracy of intraoperative diagnosis for rapid establishment of treatment options. Furthermore, we wanted to find out whether the location and histopathology of the tumors as well as the age and sex of the patients affected accuracy. Because of the large number of biopsies performed per year, parameters could also be evaluated for rare cerebral lesions. METHODS: We retrospectively analyzed 5000 consecutive stereotactic brain biopsies from 4589 patients. The digital database comprises the intraoperative and final diagnoses, the location of the tumors, and the sex and age of the patients. Regression analysis was performed to identify parameters that had a significant impact on the results. RESULTS: Intraoperative diagnosis was correct in 90.3% of biopsies. This included complete correlation in 81.3% of the biopsies and partial correlation in 9% of the biopsies. In 5.1% of the biopsies, no correlation between the intraoperative and final diagnosis was obtained. In 4.6% of the biopsies, no diagnosis could be made during or after surgery. A high correlation was found for World Health Organization Type II astrocytomas and, with regression analysis, for World Health Organization Type I astrocytomas, glioblastomas, and metastases. CONCLUSION: Intraoperative diagnosis with stereotactic biopsy has high validity. Immediate treatment based on the intraoperative diagnosis can be justified (e.g., for metastases or glioblastomas). Stereotactic biopsy with an exact histopathological diagnosis is strongly recommended for planning adequate therapy for patients with unidentified brain lesions.

Biopsy↗

PubMed2005

DNA topoisomerase IIalpha and Her-2/neu gene dosages in pediatric malignant gliomas.

Pediatric malignant non-brainstem glioma (PMNBG) is a rare tumor that accounts for only about five percent of childhood intracranial neoplasms. DNA topoisomerase IIalpha (TIIalpha) is a novel marker of cell-cycle turnover and a target of high-risk chemotherapy in PMNBG. We have shown that TIIalpha protein expression strongly correlates with event-free and overall survival in these malignancies. The molecular mechanism causing the varying TIIalpha protein expression in PMNBG remains unknown. Utilizing a combined approach of immunocytochemistry-based morphology guidance, laser-assisted microdissection and quantitative real-time PCR, we report a low-level co-amplification of the neighboring TIIalpha and Her-2/neu gene loci on chromosome 17q11-q22 in one of seventeen examined PMNBGs. Analysis of both genes by real-time PCR in the crude tumor samples without prior tissue heterogeneity reduction via laser microdissection, resulted in loss of detection of amplification of the syngeneic Her-2/neu locus. Gene dosage assessment in a microscopically distant tumor area revealed no amplification of either gene. Our results suggest that low-level amplification of the TIIalpha gene locus may be a sporadic mechanism of increased TIIalpha protein expression in PMNBG, which can coincide with low-level amplification of Her-2/neu. The observed intratumor genetic heterogeneity for TIIalpha in PMNBGs may have an impact on the relevance of TIIalpha as a biological constituent of outcome in these neoplasms.

Antigens, Neoplasm↗

PubMed2004

Acute hemorrhagic leukoencephalitis (Hurst's disease) linked to Epstein-Barr virus infection.

A 16-year-old girl presented signs of a common cold in combination with a hemolytic crisis. Within 3 days, she developed reduced consciousness and hemiparesis subsequently followed by coma. CT and MRI scans revealed evidence for raised intracranial pressure and an extensive inflammatory process extending from the brain stem up to the thalamus. The patient died within 3 weeks after onset of first symptoms of intracranial pressure despite maximum intensive care. Neuropathological examination revealed disseminated necrotic lesions and perivascular hemorrhages characteristic for acute hemorrhagic leukoencephalitis (Hurst's disease), mainly of the brain stem, diencephalon and cerebellum. Serological results, in situ hybridization and PCR analysis demonstrated an acute Epstein-Barr virus (EBV) infection of the central nervous system. To our knowledge, this is the first reported case of Hurst's disease linked to EBV.

Adolescent↗

PubMed2004

Neurogranin is expressed by principal cells but not interneurons in the rodent and monkey neocortex and hippocampus.

As a substrate of protein kinase C (PKC), neurogranin (NG) is involved in the regulation of calcium signaling and activity-dependent plasticity. Recently, we have shown that, in the rodent cerebellum, NG is exclusively expressed by gamma-aminobutyric acidergic Golgi cells, whereas, in the monkey cerebellum, brush cells were the only neuronal population expressing NG (Singec et al. [2003] J. Comp. Neurol. 459:278-289). In the present study, we analyzed the neocortical and hippocampal expression patterns of NG in adult mouse (C57Bl/6), rat (Wistar), and monkey (Cercopithecus aetiops). By using immunocytochemistry and nonradioactive in situ hybridization, we demonstrate strong NG expression by principal cells in different neocortical layers and in the hippocampus by granule cells of the dentate gyrus and pyramidal neurons of CA1-CA3. In contrast, double-labeling experiments in rodents revealed that neocortical and hippocampal interneurons expressing glutamate decarboxylase 67 (GAD67) were consistently devoid of NG. In addition, by using antibodies against parvalbumin, calbindin, and calretinin, we could demonstrate the absence of NG in interneurons of monkey frontal cortex and hippocampus. Together these findings corroborate the idea of different calcium signaling pathways in excitatory and inhibitory cells that may contribute to different modes of synaptic plasticity in these neurons.

Animals↗

PubMed2004

Focal cortical dysplasias: surgical outcome in 67 patients in relation to histological subtypes and dual pathology.

The purpose of this study was to assess whether the histological subtype of focal cortical dysplasia and dual pathology affect surgical outcome in patients with medically intractable epilepsy due to focal cortical dysplasia (FCD). We retrospectively analysed the outcome of 67 patients from 2 to 66 years of age at follow-up periods of 6 to 48 months after epilepsy surgery. Histological subtypes were classified according to Palmini and included a few cases with mild histological abnormalities corresponding to the definition of mild malformations of cortical development. The seizure outcome was classified according to Engel and evaluated at the last follow-up visit as well as at follow-up periods of 12 and 24 months after surgery. The outcome in patients with FCD and additional hippocampal pathology (dual pathology) was analysed separately. Distribution of histological subtypes differed in temporal and extratemporal localization, with a significantly higher extratemporal prevalence of FCD type 2. There was a tendency towards better postsurgical outcome related to the last follow-up visit in patients with more subtle abnormalities classified as mild malformations of cortical development (mMCD) (63% Engel Ia), FCD type 1a (67% Engel Ia) and FCD type 1b (55% Engel Ia) compared with patients with FCD type 2a (43% Engel Ia) and FCD type 2b (Taylor type) (50% Engel Ia). Considering the outcome at follow-up periods over 12 and 24 months, complete seizure-freedom was achieved significantly more often in patients with FCD type 1 and mMCD than with FCD type 2, and seizure reduction by less than 75% (Engel IV) occurred in more patients with FCD type 2a compared with the other subgroups. This tendency was seen in the whole patient group and in the extratemporal subgroup. Patients with dual pathology almost always had temporal lobe epilepsy; the outcome in this patient group was generally favourable (66% complete seizure-freedom at the last follow-up visit). The outcome remained almost constant with longer periods of follow-up. We conclude that patients with FCD type 1 and mMCD had a better outcome compared with those with more severe forms of cortical dysplasia. A higher incidence of FCD type 1 in temporal localization did not allow the effects of histological subtype and localization to be separated. A subanalysis of extratemporal FCDs, however, revealed a similar tendency for a better outcome with FCD type 1, suggesting that the histological subtype itself seems to be at least a relevant cofactor influencing postsurgical outcome.

Adolescent↗

PubMed2003

Neurogranin expression by cerebellar neurons in rodents and non-human primates.

Neurogranin (NG) is a brain-specific protein kinase C substrate involved in the regulation of calcium signaling and neuronal plasticity. A rostrocaudal expression profile, with large amounts in telencephalic brain regions and low expression levels in phylogenetically older brain structures, was reported previously. In the cerebellum, expression of NG has not been described. By using immunocytochemistry and in situ hybridization, we found that NG is expressed in the mouse (C57Bl/6), rat (Wistar), and monkey (Cercopithecus aetiops) cerebella. In the mouse cerebellum, Golgi cells were strongly immunoreactive for NG, whereas other cerebellar neurons were devoid of this protein. Cell counts showed 1.6-fold more immunopositive Golgi cells in the hemispheres (61.1 +/- 8.0 cells/mm(2)) than in the vermis (37.5 +/- 3.3 cells/mm(2)). Developmental studies showed detectable NG in the mouse cerebellum as early as on postnatal day 10 (P10). In contrast to the mouse, in the rat cerebellum we found only a few Golgi cells containing NG (hemispheres, 2.4 +/- 0.5 cells/mm(2); vermis, 1.5 +/- 0.3 cells/mm(2)). In the monkey cerebellum, unipolar brush cells, localized in the granular layer, were heavily labeled, whereas Golgi cells were devoid of NG. This study demonstrated that NG is strongly expressed in specific gamma-aminobutyric acidergic neurons in the rodent cerebellum. In addition, NG expression in the primate cerebellum by brush cells, which are excitatory, showed remarkable cell type-specific and species-specific expression patterns of a postsynaptic protein mediating calcium signaling mechanisms.

Animals↗

PubMed2003

Nucleus-specific alteration of raphe neurons in human neurodegenerative disorders.

Neurodegenerative diseases share symptoms suggested to be related to the serotonergic system. To evaluate the involvement of serotonergic raphe nuclei, we compared the percentage of neurons synthesizing serotonin in the nucleus centralis superior (NCS), raphe obscurus and pallidus (NROP) in Alzheimer's disease (AD), progressive supranuclear palsy (PSP), Parkinson's disease (PD), multiple system atrophy (MSA), and control brains. We used immunohistochemistry for tryptophan hydroxylase (TpOH), phosphorylated tau, and alpha-synuclein. We observed a significant decrease in the NCS in the NROP in AD, but a significant increase in PSP and MSA. Cytoskeletal pathology was present in the NCS and NROP to a variable degree. We conclude that there is disease- and nucleus-specific alteration of serotonin synthesis in the raphe.

Aged↗

PubMed2003

MR imaging of autopsy-proved paraneoplastic limbic encephalitis in non-Hodgkin lymphoma.

We report the case of a 26-year-old man with precursor T-cell acute lymphoblastic leukemia who developed paraneoplastic limbic encephalitis that was diagnosed on the basis of MR imaging findings and was proved post mortem. In our MR imaging studies, fluid-attenuated inversion recovery images and diffusion-weighted echo-planar images clearly depicted bilateral involvement of the medial temporal lobes and multifocal involvement of the brain, whereas T2-weighted turbo spin-echo images failed to show the changes.

Adult↗

PubMed2002

Anterograde tracing of human hippocampus in vitro-a neuroanatomical tract tracing technique for the analysis of local fiber tracts in human brain.

Hippocampal slices were obtained from hippocampi of patients with temporal lobe epilepsy or from patients with mass lesions located in the temporal lobe. Hippocampal slices were kept alive in a slice chamber and the anterograde tracer neurobiotin was iontophoretically injected into the granule cell layer of the dentate gyrus. Single injections resulted in the labeling of small groups of granule cells. The axonal arbor of these cells could be partially reconstructed and single mossy fibers could be followed from the soma to the inner molecular layer of the sclerotic dentate gyrus. Electron microscopy revealed asymmetric mossy fiber synapses on spiny neurons in the inner molecular layer, presumably granule cells. These data demonstrate that in vitro anterograde tracing can be employed to study the local connectivity of the human brain at the light and electron microscopic level.

Biotin↗

PubMed2002

Synaptic vesicle protein synaptoporin is differently expressed by subpopulations of mouse hippocampal neurons.

In the hippocampus, the synaptic vesicle protein synaptoporin (SPO) has been reported to be exclusively enriched in the granule cell axons, the mossy fibers. In this study, we show that in adult rats and mice SPO immunoreactivity (IR) is also detectable in strata oriens, radiatum, and lacunosum-moleculare of CA1-CA3, as well as perisomatically in the hippocampus proper and fascia dentata. In situ hybridization confirmed that SPO mRNA was present in granule cells and CA3 pyramidal cells but not in CA1 pyramidal cells. Importantly, cells scattered throughout the hippocampal layers resembling the distribution of interneurons were found to synthesize high amounts of SPO mRNA, too. Thus, these findings indicate that SPO expression in the hippocampus was underestimated until now. Moreover, double-labeling immunohistochemistry and confocal microscopy revealed selective colocalization of SPO and glutamate decarboxylase (GAD 65), a marker for gamma-aminobutyric acid (GABA)ergic terminals. To identify SPO expressing interneurons, in situ hybridization was combined with immunocytochemistry against parvalbumin (PV), calbindin (CB), calretinin (CR), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP). We found that SPO transcripts were differentially expressed by various interneuron subpopulations in the hippocampus of C57Bl/6 mice (PV 44.2%, CB 46.3%, CR 19.3%, CCK 38.6%, VIP 59.9%). Immunoelectron microscopy for SPO labeled synaptic vesicle profiles in distinct symmetric and asymmetric synapses. In conclusion, our data demonstrate that hippocampal principal cells and interneurons display a variety of synaptic vesicles that are likely to contribute to the functional characteristics of their output synapses.

Animals↗

PubMed2002

Malignant pineal parenchymal tumors in adult patients: patterns of care and prognostic factors.

OBJECTIVE: The aim of our study was to analyze patterns of care and to identify prognostic factors in patients at least 18 years of age who received radiotherapy for malignant pineal parenchymal tumors. METHODS: In a multicenter, retrospective study, we analyzed data for 37 previously published cases and 64 patients treated at the participating institutions. RESULTS: A total of 56 patients received postoperative radiotherapy, and 45 patients received primary radiotherapy. Chemotherapy was administered to 34 patients. The median follow-up period was 38 months, and median overall survival was 100 months. The variables that significantly influenced overall survival were the extent of disease (localized versus disseminated; P = 0.0002), differentiation (pineal parenchymal tumor of intermediate differentiation versus pineoblastoma; P = 0.001), and residual disease (> or = 50% versus < 50% reduction in size; P < 0.0001). In a multivariate analysis, the parameters turned out to be independent risk factors. The median survival in patients with local or spinal failure was 15 months. Local control was better in older patients (> or = 32 yr versus < 32 yr; P = 0.02). Spinal control was more successful in patients with pineal parenchymal tumors of intermediate differentiation than it was in patients with pineoblastomas (P = 0.03). Nine of 45 treatment failures occurred later than 5 years after treatment. CONCLUSION: Stage, histological characteristics, and response are independent risk factors in adults with malignant pineal parenchymal tumors. Late relapses are common.

Adolescent↗

PubMed2002

Problems in differential diagnosis of non Langerhans cell histiocytosis with pituitary involvement: case report and review of literature.

Differentiation among various non Langerhans cell histiocytoses granulomatous in adults is often difficult. Patients, moreover, may not have endocrinologic abnormalities. A 53-yr-old patient was admitted owing to central diabetes insipidus and partial hypopituitarism. Magnetic resonance imaging revealed a space-occupying lesion near the hypophyseal stalk, along with diffuse signal uptake in the cerebellar region. Laboratory chemistry showed monoclonal gammopathy of IgGkappa, and hormone tests disclosed insufficiency in the gonadotropic and somatotropic axes. The clinical picture was marked by multiple cutaneous xanthogranulomas, ataxic gait with blurred speech, compatible with pseudobulbar pontocerebellar symptomatology. Stereotactic pituitary biopsy was histologically classified as nonspecific granulomatous disease. Supplemental biopsies taken from the cutaneous periorbital xanthogranulomas were histologically and immunohistochemically consistent with non Langerhans cell histiocytosis. Systemic cortisone treatment as well as local radiotherapy to the pituitary lesion with a total of 18.0 gy had no impact on the progression of disease-growing tumor and progressing neurologic symptoms. Systemic granulomatoses cannot always be classified according to specific defined diseases. Differential diagnosis in the current patient should include the possibility of Erdheim-Chester disease, necrobiotic xanthogranuloma, and adult disseminated xanthoma.

Biopsy↗