Long-term survival and transmission of INI1-mutation via nonpenetrant males in a family with rhabdoid tumour predisposition syndrome.

Rhabdoid tumour predisposition syndrome (RTPS) is a rare syndrome caused by inheritance of a mutated INI1 gene for which only two multigeneration families have been reported. To further characterise the genotype and phenotype of RTPS, we present a third family in which at least three cousins developed an atypical teratoid/rhabdoid tumour (AT/RT) at a young age. Two of these patients showed unusual long survival, and one of these developed an intracranial meningioma and a myoepithelioma of the lip in adulthood. Mutation analysis of INI1 revealed a germline G>A mutation in the donor splice site of exon 4 (c.500+1G>A) in the patients and in their unaffected fathers. This mutation prevents normal splicing and concomitantly generates a stop codon, resulting in nonsense-mediated mRNA decay. Biallelic inactivation of INI1 in the tumours, except for the meningioma, was confirmed by absence of nuclear INI1-protein staining. The myoepithelioma of one of the patients carried an identical somatic rearrangement in the NF2 gene as the AT/RT, indicating that both tumours originated from a common precursor cell. In conclusion, this study demonstrates for the first time transmission of a germline INI1-mutation in a RTPS family via nonpenetrant males, long-term survival of two members of this family with an AT/RT, and involvement of INI1 in the pathogenesis of myoepithelioma.

Giant Brunner's hamartomas of the duodenum and obstructive jaundice. An overview of the literature and suspicion of malignancy in a case.

BACKGROUND/AIMS: 150 cases of Brunner's gland hamartoma (BGH) have been reported in the literature. BGHs are benign and are thought not to cause bile obstruction. METHODS: In this case report, a 60-year-old male is presented with unexplained obstructive jaundice who was also known for over 17 years with diffuse adenomatous hyperplasia of Brunner's glands in the duodenum. Despite the benign preoperative diagnosis, the choice of treatment was Whipple's procedure due to suspicion of a coexisting malignancy. RESULTS: Pathological analysis of the resection specimen revealed multiple BGHs and an adenocarcinoma of the papilla of Vater (PoV). Molecular pathology using loss of heterogeneity analysis was used to confirm that both were different entities. CONCLUSION: It is likely that previous reports of malignant degeneration of BGHs may actually have been cases involving the coexistence of a PoV adenocarcinoma. Physicians need to be alert when a patient presents with BGH accompanied with obstructive jaundice for simultaneously occurring PoV adenocarcinoma.

[Guideline 'Leptomeningeal metastases of solid tumours']. / Richtlijn 'Leptomeningeale metastasen van solide tumoren'.

In view of recent progressive insight in the diagnosis and treatment of leptomeningeal metastases of solid tumours, a new guideline has been designed on the initiative of the Dutch Association of NeuroOncology and the Netherlands Society of Neurology, with methodological support from the Dutch Institute for Healthcare Improvement (CBO). - There are no neurological symptoms or signs, nor MRI characteristics that are unique to leptomeningeal metastasis. However, clinical suspicion of leptomeningeal metastasis in a patient known to have cancer, in combination with specific MRI characteristics is sufficient to make the diagnosis. If MRI or CT results are negative or inconclusive cerebrospinal-fluid assessment should be conducted. - Management of care of patients with leptomeningeal metastasis without brain metastases can be based on a series of categories that have been developed using prognostic factors such as Karnofsky performance status, serious encephalopathy or neurological dysfunction, systemic disease, sensitivity of the tumour for chemotherapy or hormonal treatment - In the context of meaningful palliation, systemic treatment, if necessary in combination with radiotherapy to clinically relevant sites, is preferable to intrathecal chemotherapy. - Intrathecal chemotherapy combined with local radiotherapy is recommended if effective systemic treatment is not available, and if the tumour is potentially sensitive to methotrexate, cytarabine or thiotepa. The combination of intrathecal methotrexate and whole-brain radiotherapy should be avoided.

Stable incidence of childhood and adult glioma in The Netherlands, 1989-2003.

Time trends in the incidence of glioma may reflect changes in the prevalence of environmental risk factors for glioma. We therefore investigated trends in the incidence of childhood and adult glioma in The Netherlands from 1989 to 2003. We used population-based incidence data from the Netherlands Cancer Registry. We calculated European standardised incidence rates for glioma, and stratified for age, gender and glioma subgroups. Changes in the incidence were estimated by calculating the Estimated Annual Percentage Change. Similar to other countries, the overall incidence of glioma was fairly stable in The Netherlands during the period 1989 to 2003, for both children and adults. In adult astrocytic glioma, a significantly increasing incidence of high-grade astrocytoma was balanced by simultaneous decreases of low-grade astrocytoma, astrocytoma with unknown malignancy grade and glioma of uncertain histology. Most of these time trends can be explained by improving detection and diagnostic precision. Stable incidence rates of adult and childhood glioma suggest that no major changes in environmental risk factors have occurred, which influenced the incidence of glioma in the studied period.

Hypertension as a risk factor for glioma? Evidence from a population-based study of comorbidity in glioma patients.

BACKGROUND: Little is known about the aetiology of glioma. Research is often hampered by the low incidence and high mortality of the disease. Concomitant diseases in glioma patients may indicate possible aetiological pathways. We therefore studied comorbidity in glioma patients. PATIENTS AND METHODS: We performed a case-control study using population-based data from the Eindhoven Cancer Registry. We compared prevalences of concomitant diseases in 510 glioma patients with two reference cancer populations from the same registry. RESULTS: Compared with all other cancer patients, a significantly higher prevalence of hypertension was found in glioma patients for age categories 60-74 years [odds ratio (OR) 1.37; 95% confidence interval (CI) 1.02-1.84] and 75+ years (OR 2.37; 95% CI 1.34-4.21). The association was most pronounced in elderly men and in astrocytic glioma, with a maximum in age category 75+ years (OR 5.86; 95% CI 2.20-15.7). The prevalence of cerebrovascular disease was higher in glioma patients >45 years old (OR 1.67; 95% CI 1.12-2.47), whereas the prevalence of other cancers was lower (OR 0.64; 95% CI 0.48-0.87). No consistent associations were detected for several other concomitant diseases. CONCLUSIONS: Our data suggest an association between hypertension and glioma, although questions remain about causality and the possible mechanisms. We hypothesise that this association is mediated through potentially neurocarcinogenic effects of antihypertensive medication.

Contrast enhancement in Lhermitte-Duclos disease of the cerebellum: correlation of imaging with neuropathology in two cases.

Lhermitte-Duclos disease (LDD), also known as dysplastic gangliocytoma, is a rare cerebellar lesion. It has long been regarded as avascular. We report two patients with surgically proven LDD in whom contrast enhancement was observed on MRI. Neuropathological examination revealed proliferation of veins. We suggest that peripheral enhancement of LDD probably reflects vascular proliferation of the cerebellar venous draining system, and should be considered part of the imaging features of LDD.