Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “NEUROFIBROMA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,783 records · Page 99Linked to original sources
PubMed2000

Hypermethylation of the neurofibromatosis type 1 (NF1) gene promoter is not a common event in the inactivation of the NF1 gene in NF1-specific tumours.

Neurofibromatosis type 1 (NFI) is a common autosomal dominant disorder characterised by café-au-lait spots, neurofibromas and iris hamartomas. Since the NF1 gene product neurofibromin contains a GAP-related domain involved in the down-regulation of p21(ras) oncogene activity, the NF1 gene has come to be regarded as a tumour-suppressor gene. One common mechanism of tumour-suppressor gene inactivation during tumorigenesis is promoter hypermethylation, this "epi-mutation" being functionally equivalent to a second-hit somatic mutation. To assess the importance of promoter hypermethylation in NF1 gene inactivation in NF1-related tumours, the methylation status of the NF1 promoter region was determined by bisulphite-modified genomic sequencing in NF1-specific tumours and peripheral blood lymphocytes (PBL) from both NF1 patients and normal controls. Tumour-specific CpG methylation of six distinct CpG sites was identified at positions -609, -429, 406, -383, -331 and -315 relative to the transcriptional start site. However, since all other CpG sites were unmethylated in all tissues examined, it is unlikely that CpG hypermethylation within the NF1 promoter represents a common mutational mechanism leading to neurofibroma formation.

Case-Control Studies↗
PubMed1997

Identification of de novo deletions at the NF1 gene: no preferential paternal origin and phenotypic analysis of patients.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder. To date, a relatively small number of NF1 mutations have been characterized, thus precluding genotype-phenotype correlations. By genotyping 75 NF1 families, we have detected six hemizygous patients (two of whom are members of the same family). The five presumed deletions were confirmed by two quantitative methods of analysis of NF1 copy number: Southern hybridization with cDNA probes and a single-strand conformation polymorphism analysis that discriminates between the NF1 gene and the pseudogene sequences. The five deletions remove most of the NF1 gene, at least 225 kb, from exon 9 to the 3' end of the coding sequence. The origin of de novo mutations in the NF1 gene has been reported to be mainly paternal but we have determined that four of the de novo deletions involved the maternal chromosome and one the paternal chromosome. The six patients with deletions exhibited precocious, multiple clinical features of the disease. The incidence of tumor complications, particularly plexiform neurofibromas and intracranial tumors, among this group of patients is higher than the observed incidence in our NF1 population, suggesting that NF1 haploinsufficiency may cause a more severe phenotype with regard to tumor development. In contrast to other reports that associated large deletions with mildly dysmorphic facies, mental retardation and a large number of cutaneous neurofibromas, only one out of our six patients presented this phenotype.

Adolescent↗
PubMed2006

Novel NF1 gene mutation in a Japanese patient with neurofibromatosis type 1 and a gastrointestinal stromal tumor.

Many mutations of the NF1 gene have been reported in patients with neurofibromatosis type 1 (NF1); however, there have been no documented NF1 gene mutations in Japanese NF1 patients. In the present study, we used the polymerase chain reaction (PCR) and DNA sequencing analysis to characterize the NF1 gene in a 53-year-old Japanese patient with NF1 who suffered from neurofibroma, pheochromocytoma, and gastrointestinal stromal tumor (GIST). Direct sequence analyses revealed a single base substitution in the splicing donor site of intron 6 (IVS6 888+1, G --> A) in one NF1 allele, resulting in an altered splice site (ss) in the mutated allele. Splicing at the cryptic 5' ss in the mutated allele generated mRNA with an insertion of 60 nucleotides. In addition, we screened for mutations in exons 9, 11, 13, and 17 of the c-kit gene in GIST and the succinate dehydrogenase subunit D (SDHD) gene in the pheochromocytoma, but we did not detect any somatic mutations. We report here the first case of an NF1 patient with four neoplasms: neurofibroma, pheochromocytoma, astrocytoma and GIST. Our results suggest that the molecular pathogenesis of GISTs in NF1 patients is different from that in non-NF1 patients.

Female↗
PubMed2005

Ophthalmological manifestations in VHL and NF 1: pathological and diagnostic implications.

Von Hippel-Lindau disease (VHL) and neurofibromatosis type 1 (NF 1) are hereditary multitumor syndromes that show associated ocular manifestations. Capillary retinal angioma, a benign vascular tumor, is the classical ocular lesion in VHL. It often appears as the first manifestation of the disease and may thus lead to the diagnosis of VHL. Since small angiomas can be treated easily by laser photocoagulation, a regular ocular screening of VHL patients is recommended. Ocular manifestations of NF 1 are more diverse as compared to VHL. Lisch nodules of the iris are an important diagnostic criteria of NF 1 since they can be found in almost every affected patient. Optic glioma can occur both intraorbitally and intracranially. The intraorbital form causes progressive protrusion of the globe and eventually blindness. Extension of the tumor beyond the chiasm worsens the prognosis quoad vitam. The hallmark of NF 1, namely cutaneous neurofibroma can cause visual impairment when affecting the skin of the eyelids. The rare intraorbital pexiform neurofibroma is associated with abnormal development of the orbital bones and infantile glaucoma. It may result in orbital mass effects and therefore may need surgical excision.

Hemangioma↗
PubMed2006

Acute monocular blindness resulting from transformation of von Recklinghausen's neurofibromatosis to malignant melanocytic schwannomas.

A 59-year-old male was transferred to our facility after initial workup for left eye blindness revealed multiple brain lesions. The patient presented with scant pedunculated skin lesions on his neck and arms, axillary freckling and bilateral subcutaneous ankle nodules suggestive of neurofibromatosis type 1 (NF-1). Neurological examination revealed left-sided blindness, diminished pupillary response to light, incomplete eyelid closure and facial droop. A CT series of the chest/abdomen/pelvis demonstrated several lesions in the lungs, liver and left kidney. CT-guided biopsy of the renal lesion was "consistent with metastatic melanoma" based on the presence of malignant cell staining for the melanocyte differentiation antigen MART-1, as well as the calcium binding protein S-100. A dermatology consultant confirmed neurofibromas and a café au lait macule. No dysplastic nevi or primary melanoma were identified. An ophthalmology consultant noted gray choroidal lesions on fundoscopic examination thought to be metastatic disease of unknown primary. Despite treatment with whole brain irradiation and intravenous steroids, the patient died on hospital day 10. A full autopsy showed diffuse neurofibromas and café au lait macules consistent with NF-1 and malignant melanocytic schwannomas with multiple metastases.

Blindness↗
PubMed1987

Hepatic neurofibromatosis, malignant schwannoma, and angiosarcoma in von Recklinghausen's disease.

Liver involvement by neurofibromatosis is rare. This report describes a young man with von Recklinghausen's disease and hepatic neurofibromas who developed a large right hepatic lobe malignancy and died of massive intratumor hemorrhage. Postmortem examination showed the tumor to be composed of both malignant schwannoma and angiosarcoma and to have arisen from contiguous neurofibromas in portal tracts. Widespread pulmonary metastases consisted of the angiosarcomatous elements alone. The expression of malignant schwannoma and angiosarcoma phenotypes in this tumor may be related to a common histogenesis from cells of the neural crest.

Adult↗
PubMed1994

Immunohistochemical demonstration of the lysosome-associated glycoprotein CD68 (KP-1) in granular cell tumors and schwannomas.

The monoclonal antibody KP-1 that recognizes the lysosome-associated glycoprotein CD68 was used together with antibodies to other antigens (actin, glial fibrillary acidic protein, keratin, neurofilaments, chromogranin, synaptophysin, S-100 protein, HMB-45, lysozyme, and HLA-DR) in a labeled streptavidin biotin immunoperoxidase method to phenotypically characterize 27 granular cell tumors, five schwannomas, five neurofibromas, two ganglioneuromas, three ganglioneuroblastomas, five carcinoid tumors, five malignant melanomas, and five examples of histiocytosis X. The neoplastic cells in all 27 of the granular cell tumors and four of the five schwannomas strongly stained for CD68, whereas none of the neurofibromas, ganglioneuromas, ganglioneuroblastomas, or carcinoid tumors contained CD68-positive tumor cells. These findings further strengthen previous observations, suggesting a histogenetic relationship between granular cell tumors and Schwann cells. KP-1 reactivity also was demonstrated in cells of histiocytosis X and malignant melanoma, complementing other studies that extend the tumor types positive in immunoperoxidase stains using this antibody.

Antigens, CD↗
PubMed1991

Malignant peripheral nerve sheath tumor (malignant schwannoma) of urinary bladder in von Recklinghausen neurofibromatosis.

Von Recklinghausen neurofibromatosis occurs in 1 in 3,000 live births; however, urologic manifestations are rare. There have been over 40 reported cases of neurofibroma of the bladder. Malignant degeneration of subcutaneous neurofibroma occurs in about 5 to 10 percent of patients. We believe we present the second reported case of a malignant peripheral nerve sheath tumor involving the bladder in a patient with this disorder.

Adult↗
PubMed2006

Malignant peripheral nerve sheath tumour of the cervical vagus nerve in a neurofibromatosis type 1 patient.

One serious complication of neurofibromatosis type 1 (NF1) is the development of malignant peripheral nerve sheath tumours (MPNSTs). These malignancies often develop within pre-existing plexiform neurofibromas and their development is now thought to be associated with both tumour suppressor gene mutations and dysregulated growth factor signalling. Recent work demonstrates that the lifetime risk of malignant transformation is significantly greater than previously thought. Ionising radiation, a long-standing disease, particularly the presence of a large number of plexiform neurofibromas from an early age, are suggested risk factors. We present an NF1 patient who developed an MPNST of the cervical vagus nerve which was successfully treated with surgery. Close monitoring of patients with NF and a high level of suspicion towards rapidly enlarging and painful swellings is merited as these features may signify malignant transformation. Whether a positive history of MPNST in other affected family members predisposes the individual to a higher risk of malignant transformation is unclear.

Adult↗
PubMedDate not supplied

Rare syndromes.

Dermatologists may also encounter patients presenting with skin lesions that reflect an underlying endocrine disorder not commonly seen in daily practice. Some of these endocrine disorders include glucagonoma, neurofibromatosis type 1, McCune-Albright syndrome, multiple endocrine neoplasia, the Carney complex, carcinoid tumors, and mastocytosis. The clinical syndrome classically associated with glucagonoma includes necrolytic migratory erythema, weight loss, diabetes mellitus, anemia, cheilitis, venous thrombosis, and neuropsychiatric symptoms. The hallmarks of neurofibromatosis type 1 are the multiple café-au-lait spots and associated cutaneous neurofibromas. Other presenting features include freckling, peripheral neurofibromas, Lisch nodules, bone abnormalities, tumors, neurologic abnormalities and hypertension. McCune-Albright syndrome is characterized by café-au-lait spots, polyostotic fibrous dysplasia, sexual precocity, and hyperfunction of multiple endocrine glands. Multiple endocrine neoplasia type 2A is characterized by medullary thyroid cancer, pheochromocytoma, and primary parathyroid hyperplasia. In some patients with multiple endocrine neoplasia type 2A, cutaneous lichen amyloidosis may also be present. Multiple endocrine neoplasia type 2B is characterized by medullary thyroid cancer and pheochromocytoma but not hyperparathyroidism. The syndrome also includes mucosal neuromas, typically involving the lips and tongue, intestinal ganglioneuromas and a marfanoid habitus. Multiple endocrine neoplasia type 1 is an autosomal dominant predisposition to tumors of the parathyroid glands (four-gland hyperplasia), anterior pituitary, and pancreatic islet cells; hence, the mnemonic device of the "3 Ps"; multiple cutaneous lesions (angiofibromas and collagenomas) are frequent in patients with multiple endocrine neoplasia type 1. Carney complex may be viewed as a form of multiple endocrine neoplasia because affected patients often have tumors of two or more endocrine glands, including primary pigmented nodular adrenocortical disease (some with Cushing's syndrome), pituitary adenoma, testicular neoplasms, thyroid adenoma or carcinoma, and ovarian cysts. Additional unusual manifestations include psammomatous melanotic schwannoma, breast ductal adenoma, and a rare bone tumor, osteochondromyxoma. Carcinoid syndrome is the term applied to a constellation of symptoms mediated by various humoral factors elaborated by some carcinoid tumors; the major manifestations are diarrhea, flushing, bronchospasm, and cardiac valvular lesions. Mast cell diseases include all disorders of mast cell proliferation. These diseases can be limited to the skin, referred to as "cutaneous mastocytosis," or involve extracutaneous tissues, called "systemic mastocytosis." Patients present with urticaria pigmentosa, mastocytoma, or diffuse cutaneous mastocytosis. Systemic involvement may be gastronintestinal, hematologic, neurologic, and skeletal.

Endocrine System Diseases↗
PubMed2004

The neurofibromatoses: hereditary predisposition to multiple peripheral nerve tumors.

Neurosurgeons must be aware of the neuro-fibromatoses because they frequently present with nervous system tumors. Such patients develop numerous peripheral nerve sheath tumors; fortunately, only a few of these tumors are symptomatic or malignant. The tumor burden in individual patients can be remarkable, however, producing significant morbidity and requiring extensive or repeated care by a skilled neurosurgeon. Because it is impossible to predict which of the deep neurofibromas will undergo malignant transformation, it behooves clinicians and patients to be aware of any change in symptoms or growth of tumors, because early resection of MPNST offers the only chance for cure. Neurosurgical professionals should be familiar with the diagnostic criteria of the neurofibromatoses, because the patient who presents with an initial neurofibroma or schwannoma immediately falls into a category in which those disorders must be ruled out. In this regard, a family history of nerve sheath tumors is revealing and should prompt referral for a clinical genetics evaluation. Cutaneous manifestations of NFI can confirm the diagnosis at initial presentation. Missing the initial presentation of a patient with NF2 can lead to marked morbidity, such as deafness,because surveillance for subsequent tumors was inadequate. Tumorigenesis in all neurofibromatoses involves loss of tumor suppressor genes. These disorders illustrate that the two-hit loss of tumor suppressor gene model, which applies best for NF2, is oversimplified. As with most cancers,a theory of multistep progressive acquisition of genetic changes that promote unregulated grow this emerging in schwannomatosis. In addition, the hyperpigmentation and learning disability of NF 1 highlight that loss of one copy of the gene is sufficient to cause nontumoral manifestations of the disorder. Genetic counseling and testing have an important role in the diagnosis of NFI and NF2 as well as in the management of all the neurofibromatoses.

Genetic Predisposition to Disease↗
PubMed2005

[Neurofibromatosis type 1 or Von Recklinghausen's disease].

OBJECTIVES: Neurofibromatosis 1(NF1) is one of the most common genetic diseases. NF1 is an autosomal dominant genetic disorder and half of affected individuals have NF1 as the result of a new gene NF1 mutation. The offspring of an affected individual have a 50% risk of inheriting the altered NF1 gene. The disease manifestations are extremely variable, even within a family. NF1 is characterized by multiple cafe au lait spots, axillary and inguinal freckling, multiple discrete dermal neurofibromas, and iris Lisch nodules. Learning disabilities are frequent. Less common but potentially more serious manifestations include plexiform neurofibromas, optic and other central nervous system gliomas, malignant peripheral nerve sheath tumors, vasculopathy, and osseous lesions. CURRENT KNOWLEDGES AND KEY POINTS: Since the original National Institutes of Health consensus Development Conference in 1987, there have been significant progress toward a more complete understanding of the molecular-bases for neurofibromatosis 1 and the routine follow-up for the care of the NF1 patients. The authors review the present data on the clinical and molecular aspects of the neurofibromatosis 1. FUTURE PROSPECTS AND PROJECTS: NF1 requires life-long management adapted to age and multidisciplinary structures are particularly well adapted to the diversity of the manifestations of this pathology. The French NF-France Network has been created in 2001 to federate the French multidisciplinary structures for neurofibromatosis and harmonize the follow-up of NF1 patients in France.

Genes, Neurofibromatosis 1↗
PubMed1993

Case report: imaging of widespread plexiform neurofibromatosis.

Although the cutaneous, bony and retroperitoneal appearances of peripheral von Recklinghausen neurofibromatosis are well known, involvement of intra-abdominal organs and of the mediastinum is less well recognised. We present the case of a woman with peripheral neurofibromatosis who presented with loin pain. In addition to cutaneous neurofibromas, plexiform neurofibromas were present in the mediastinum, liver, mesentery and psoas muscles.

Adult↗
PubMed1989

Optic gliomas in children with neurofibromatosis type 1.

To determine the frequency and natural history of tumors of the optic nerves and chiasm in patients with neurofibromatosis type 1, we obtained computed tomographic scans of 65 children who had no known visual or ocular abnormalities before their initial evaluation. Optic gliomas were detected in 10 children (15%). The median age of children with gliomas was 4.3 years (mean 5.8 years, range 9 months to 21 years). Three children (30%) had isolated, unilateral tumors, three (30%) had bilateral tumors, and four (40%) had involvement of the optic chiasm and of one or both nerves. Definite abnormalities of vision were found in only two children (20%). Five additional children were referred to the clinic after evaluation of ophthalmologic complaints led to the diagnosis of neurofibromatosis type 1: three had unilateral exophthalmos and two had plexiform neurofibromas of the eyelid with associated glaucoma. Ipsilateral optic gliomas were found in all five children; one child also had a contralateral tumor. Optic gliomas are commonly identified in young children with neurofibromatosis type 1 who have no ocular or visual abnormalities. Optic nerve gliomas may be associated with plexiform neurofibromas of the eyelid and glaucoma.

Adolescent↗
PubMed1983

Ocular neurofibromatosis.

A 4 1/2-month-old girl with unilateral congenital glaucoma of the left eye subsequently underwent five surgical procedures that proved to be unsuccessful in controlling the intraocular pressure. Neurofibromatosis was diagnosed at the age of 5 1/2 years when she was found to have a plexiform neuroma of the left eyelids and multiple café au lait spots including in the left temple. Two years later the buphthalmic left globe was enucleated. Histopathologic findings included a diffuse neurofibroma of the ciliary body and choroid, peripheral anterior synechiae, total angle closure, and endothelialization of the iris, all of which probably contributed to the glaucoma. Other interesting features were melanocytic hamartomas of the iris, an anterior subcapsular cataract and ovoid bodies in the diffuse neurofibroma of the choroid.

Child, Preschool↗
PubMed2003

Quantitative RT-PCR reveals a ubiquitous but preferentially neural expression of the KIS gene in rat and human.

KIS is the only known protein kinase that possesses an RNA recognition motif. This original structure indicates a role for KIS in the maturation of RNAs possibly by phosphorylating and regulating the activities of RNA associated factors. Another function of KIS has recently been unravelled--it negatively regulates the cdk inhibitor p27Kip1 and thus promotes cell cycle progression through G1. In order to explore the functional expression of this kinase, we quantified its mRNA in a wide range of rat and human tissues, during development and in tumors. In both species, the highest level of KIS gene expression was in adult neural tissues. Interestingly, within the adult rat brain, KIS mRNA is enriched in several areas including the substantia nigra compacta and nuclei of the brain stem. Furthermore, KIS gene expression increases dramatically during brain development. Altogether our results point to a ubiquitous function for KIS together with a particular implication during neural differentiation or in the function of mature neural cells. No dysregulation of KIS gene expression was detected in human tumors from breast, bladder, prostate, liver and kidney origins. On the other hand, the KIS gene was overexpressed in NF1-associated plexiform neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs) as compared to dermal neurofibroma which suggests a possible implication of KIS in the genesis of NF1-associated tumors.

Age Factors↗
PubMed2003

Pedunculated presentation of dermatofibrosarcoma protuberans.

A 26-year-old patient had a dermatofibrosarcoma protuberans that clinically was considered to represent either a skin tag or neurofibroma. Histopathologically, this lesion could easily have been misinterpreted as a neurofibroma, particularly in the context of the clinical findings.

Adult↗
PubMed1986

Myxoma of the jaws. An analysis of 15 cases.

A retrospective study on 15 patients with myxomas of the jaws was carried out. The series consisted of 3 males and 12 females. The mean age was 26 years. The maxilla was involved in 4 cases whereas the tumour was situated in the mandible in 11 cases. Of the 9 patients who underwent conservative treatment, one exhibited recurrent tumour. Six patients were treated by resection including uninvolved adjacent tissue; none of them has so far exhibited recurrence. These results indicate that carefully performed conservative treatment for myxomas is justified in some instances. Histologically, myxomas of the jaw exhibit mitotic activity in the majority of cases which indicates a distinct proliferative activity. Myxomatous degeneration in neurofibromas may mimic myxoma. Therefore the present cases were compared with 2 cases of intramandibular neurofibroma. It is concluded that differences in nuclear morphology are sufficient to distinguish between both neoplasms.

Adolescent↗