Congenital lumbosacral lipomas can be responsible for progressive defects. The general feeling is that tethering of roots, filum, or cord probably explains this evolution, and that untethering of these structures could prevent late deterioration. Like the vast majority of neurosurgeons, we too have routinely and systematically operated on lumbosacral lipomas, even in the absence of neurological deficits. This policy stemmed from our belief that spontaneous neurological deterioration was frequent, recovery from preoperative deficits rare, and surgery both efficient and benign in nature. After 22 years of experience, we felt that it was necessary to review our series of 291 lipomas (38 lipomas of the filum and 253 of the conus) operated on from 1972 to 1994. To reassess the value of prophylactic surgery, we attempted an accurate evaluation of (1) the risk of pathology, (2) the risks involved in surgery, (3) the postoperative outcome with respect to preoperative deficits, and (4) the postoperative outcome in asymptomatic patients at 1 year and at maximum follow-up. Special attention was paid to 93 patients whose postoperative follow-up was more than 5 years (average 8.7, median 8, range 5-23 years). Of these 93 patients, 39 were asymptomatic preoperatively (7 with lipoma of the filum and 32 with lipoma of the conus). Lipomas of the filum and of the conus are entirely different lesions and were studied separately. In 6 cases prenatal diagnosis had been possible. The mean age at surgery was 6.4 years. Low back skin stigmata were present in 89.4% of cases. Preoperative neurological deficits existed in 57% of the patients and were congenital in 22%. Clinical signs and symptoms recorded were pain in 13.3% of the patients and/or neurological deficits affecting sphincter (52%), motor (27.6%) and sensory (22.4%) functions. Deficits were progressive in 22.4% of cases, slowly progressive in 58.8% of these and rapidly progressive in the remaining 41.2%. In 36 patients (13.2%) the lipomas were seen to grow either subcutaneously or intraspinally. Among these patients, 21 were infants, 2 were obese adolescents, and 10 were pregnant women. The metabolism of the fat within the lipomas was studied in 11 patients and found to be similar to that at other sites. Lipomas were associated with various other malformations, either intra- or extraspinal. These associated anomalies were rare in the case of lipomatous filum (5.2%) but frequent with lipomas of the conus, except for intracranial malformations (3.6%). Therapeutic objectives were spinal cord untethering and decompression, sparing of functional neural tissue and prevention of retethering. Procedures used to achieve these goals were subtotal removal of the lipoma, intraoperative monitoring, duroplasty, and sometimes closure of the placode. Histologically, lipomas consisted of normal mature fat. However, 77% of them also included a wide variety of other tissues, originating from ectoderm, mesoderm, or entoderm. This indicates that lipomas are either simple or complex teratomas. The r...

Medulloblastoma is the most frequent malignant paediatric brain tumour. The activation of the Wnt/beta-catenin pathway occurs in 10-15% of medulloblastomas and has been recently described as a marker for favourable patient outcome. We report a series of 72 paediatric medulloblastomas evaluated for beta-catenin protein expression, CTNNB1 mutations, and comparative genomic hybridization. Gene expression profiles were also available in a subset of 40 cases. Immunostaining of beta-catenin showed extensive nuclear staining (>50% of the tumour cells) in six cases and focal nuclear staining (<10% of cells) in three cases. The other cases either exhibited a signal strictly limited to the cytoplasm (58 cases) or were negative (five cases). CTNNB1 mutations were detected in all beta-catenin extensively nucleopositive cases. The expression profiles of these cases documented strong activation of the Wnt/beta-catenin pathway. Remarkably, five out of these six tumours showed a complete loss of chromosome 6. In contrast, cases with focal nuclear beta-catenin staining, as well as tumours with negative or cytoplasmic staining, never demonstrated CTNNB1 mutation, Wnt/beta-catenin pathway activation or chromosome 6 loss. Patients with extensive nuclear staining were significantly older at diagnosis and were in continuous complete remission after a mean follow-up of 75.7 months (range 27.5-121.2 months) from diagnosis. All three patients with focal nuclear staining of beta-catenin died within 36 months from diagnosis. Altogether, these data confirm and extend previous observations that CTNNB1-mutated tumours represent a distinct molecular subgroup of medulloblastomas with favourable outcome, indicating that therapy de-escalation should be considered. International consensus on the definition criteria of this distinct medulloblastoma subgroup should be achieved.

The hSNF5/INI1 gene which encodes a member of the SWI/SNF chromatin ATP-dependent remodeling complex, is a new tumor suppressor gene localized on chromosome 22q11.2 and recently shown to be mutated in malignant rhabdoid tumors. We have searched for hSNF5/INI1 mutations in 229 tumors of various origins using a screening method based on denaturing high-performance liquid chromatography. A total of 31 homozygous deletions and 36 point alterations were identified. Point mutations were scattered along the coding sequence and included 15 nonsense, 15 frameshift, three splice site, two missense and one editing mutations. Mutations were retrieved in most rhabdoid tumors, whatever their sites of occurrence, indicating the common pathogenetic origin of these tumors. Recurrent hSNF5/INI1 alterations were also observed in choroid plexus carcinomas and in a subset of central primitive neuroectodermal tumors (cPNETs) and medulloblastomas. In contrast, hSNF5/INI1 point mutations were not detected in breast cancers, Wilms' tumors, gliomas, ependymomas, sarcomas and other tumor types, even though most analyzed cases harbored loss of heterozygosity at 22q11.2 loci. These results suggest that rhabdoid tumors, choroid plexus carcinomas and a subset of medulloblastomas and cPNETs share common pathways of oncogenesis related to hSNF5/INI1 alteration and that hSNF5/INI1 mutations define a genetically homogeneous family of highly aggressive cancers mainly occurring in young children and frequently, but not always, exhibiting a rhabdoid phenotype.

Several types of glioneuronal tumors are known to induce intractable partial seizures in children and adults. The most frequent are dysembryoplastic neuroepithelial tumors (DNETs) and gangliogliomas. We report here a new clinicopathological entity within the spectrum of glioneuronal tumors observed in 10 children who underwent surgery for refractory epilepsy. These tumors demonstrate a unique, pathognomonic histological pattern and a specific appearance at magnetic resonance imaging (MRI). The most striking neuropathological feature is an angiocentric polarity of the tumor with gliofibrillary acidic protein (GFAP) positive fusiform and bipolar astrocytic cells arranged around blood vessels (perivascular cuffing with tumoral astrocytes). Characteristic MRI findings include involvement of cortical gray and white matter, intrinsically high signal on T1-weighted images, as well as a stalk like extension to the ventricle. Immunohistochemical neuronal markers (neurofilament protein, synaptophysin and chromogranin) confirm the presence of a neuronal cell component. Therefore, the term angiocentric neuroepithelial tumor (ANET) is proposed.

Object Choroid plexus tumors are rare intraventricular tumors (1% of all intracranial tumors) that occur mainly in children. The physiopathological characteristics of associated hydrocephalus, surgical management, and oncological issues related to these tumors remain a matter of debate. To understand more about these tumors, the authors have reviewed their experience with the management of 38 children with choroid plexus tumors. Methods There were 25 cases of papilloma and 13 of carcinoma. The mean age of the patients at presentation was 22.5 months and one-half of the patients were younger than 2 years of age. Hydrocephalus was present in 33 patients and poorly correlated with the size, site, and pathological characteristics of the tumor. In nine children, a ventriculoperitoneal shunt was required after tumor excision, calling into question the notion that cerebrospinal fluid oversecretion is the only cause of hydrocephalus. Complete excision was achieved in 96% of the cases of papilloma and 61.5% of the cases of carcinoma. These surgical procedures were complicated by the risks of perioperative hemorrhage, which proved to be fatal in two cases, and postoperative brain collapse, which led to subdural fluid collections requiring subdural shunt placement in six patients. Preoperative embolization was partially successful in four cases and significantly assisted surgery. Preoperative controlled drainage of excessively dilated ventricles and intraoperative gluing of the cortical incision have been used to address the problem of postoperative brain collapse. Patients with carcinomas were treated postoperatively by chemotherapy alone (seven cases), radiotherapy (one case), or chemotherapy plus radiotherapy (one case). The overall 5-year survival rate was 100% for patients with papillomas and 40% for those with carcinomas. Conclusions Total surgical excision is curative in cases of papillomas. For carcinomas, the most effective treatment remains total surgical excision; however, adjuvant treatment in the form of chemotherapy in patients younger than 3 years, supplemented by radiation therapy in older children, can moderately reduce the risk of recurrence.

The presence of brainstem involvement (tumor in the transitional form) emerged as a significant negative prognostic factor and should be treated as a distinct nosological entity. The extent of surgical excision has a significant bearing on the risk of tumor recurrence.

Rhabdoid tumours (RTs) are rare but highly aggressive tumours of childhood. Their rarity and their miscellaneous locations make the diagnosis particularly challenging for pathologists. Central nervous system and peripheral RTs have been associated with biallelic inactivation of the hSNF5/INI1/SMARCB1 (hSNF5/INI1) tumour suppressor gene. Immunohistochemistry (IHC) with a monoclonal anti-hSNF5/INI1 antibody has recently been proposed as an efficient diagnostic tool for RTs. We have conducted a retrospective study of 55 tumours referred to our institution with a suspicion of RT. This analysis included pathological review, IHC with anti-hSNF5/INI1 antibody, and molecular investigation using quantitative DNA fluorescent analysis and sequencing of the nine exons of hSNF5/INI1. The molecular lesion could be detected in 37 of the 39 cases exhibiting negative staining for hSNF5/INI1. In the two discrepant cases, the lack of detection of genetic abnormality was probably owing to the presence of a high number of non-tumour cells in the samples. This indicates that hSNF5/INI1 IHC is very sensitive and highly specific for the detection of hSNF5/INI1 loss-of-function. Among the 38 cases with typical RT histological features, six failed to exhibit hSNF5/INI1 mutation and stained positive for hSNF5/INI1. This strongly supports the evidence of a second genetic locus, distinct from hSNF5/INI1, associated with RT. Conversely, seven tumours with histological features poorly compatible with RT stained negative for hSNF5/INI1; they nevertheless exhibited an age of onset and a clinical behaviour similar to RT. This suggests that hSNF5/INI1 inactivation is not strictly limited to typical RT but characterizes a wider family of hSNF5/INI1-deficient tumours. Consequently, we believe that anti-hSNF5/INI1 IHC should be performed widely, even when the pathological characteristics are not typical. The molecular investigation should be performed in infants when a rhabdoid predisposition syndrome is suspected.

Total surgical excision is curative in cases of papillomas. For carcinomas, the most effective treatment remains total surgical excision; however, adjuvant treatment in the form of chemotherapy in patients younger than age 3 years, supplemented by radiation therapy in older children, can moderately reduce the risk of recurrence.