Neurofibromatosis

Distribution by Scientific Domains
Distribution within Medical Sciences

Terms modified by Neurofibromatosis

  • neurofibromatosis type i

  • Selected Abstracts


    Regulation of the Neurofibromatosis 2 gene promoter expression during embryonic development

    DEVELOPMENTAL DYNAMICS, Issue 10 2006
    Elena M. Akhmametyeva
    Abstract Mutations in the Neurofibromatosis 2 (NF2) gene are associated with predisposition to vestibular schwannomas, spinal schwannomas, meningiomas, and ependymomas. Presently, how NF2 is expressed during embryonic development and in the tissues affected by neurofibromatosis type 2 (NF2) has not been well defined. To examine NF2 expression in vivo, we generated transgenic mice carrying a 2.4-kb NF2 promoter driving ,-galactosidase (,-gal) with a nuclear localization signal. Whole-mount embryo staining revealed that the NF2 promoter directed ,-gal expression as early as embryonic day E5.5. Strong expression was detected at E6.5 in the embryonic ectoderm containing many mitotic cells. ,-gal staining was also found in parts of embryonic endoderm and mesoderm. The ,-gal staining pattern in the embryonic tissues was corroborated by in situ hybridization analysis of endogenous Nf2 RNA expression. Importantly, we observed strong NF2 promoter activity in the developing brain and in sites containing migrating cells including the neural tube closure, branchial arches, dorsal aorta, and paraaortic splanchnopleura. Furthermore, we noted a transient change of NF2 promoter activity during neural crest cell migration. While little ,-gal activity was detected in premigratory neural crest cells at the dorsal ridge region of the neural fold, significant activity was seen in the neural crest cells already migrating away from the dorsal neural tube. In addition, we detected considerable NF2 promoter activity in various NF2-affected tissues such as acoustic ganglion, trigeminal ganglion, spinal ganglia, optic chiasma, the ependymal cell-containing tela choroidea, and the pigmented epithelium of the retina. The NF2 promoter expression pattern during embryogenesis suggests a specific regulation of the NF2 gene during neural crest cell migration and further supports the role of merlin in cell adhesion, motility, and proliferation during development. Developmental Dynamics 235:2771,2785, 2006. © 2006 Wiley-Liss, Inc. [source]


    Exploring the "two-hit hypothesis" in NF2: Tests of two-hit and three-hit models of vestibular schwannoma development

    GENETIC EPIDEMIOLOGY, Issue 4 2003
    Ryan Woods
    Abstract Neurofibromatosis 2 (NF2) is a genetic disease that occurs in approximately 1 in 40,000 live births. Almost all affected individuals develop bilateral tumors of Schwann cells that surround the vestibular nerves; these tumors are known as vestibular schwannomas (VS). Evidence from molecular genetic studies suggests that at least two mutations are involved in formation of VS in patients with NF2. Several authors proposed probabilistic models for this process in other tumors, and showed that such models are consistent with incidence data. We evaluated two different probabilistic models for a "2-hit" hypothesis for VS development in NF2 patients, and we present results from fitting these models to incidence data. Molecular evidence does not exclude the possibility that additional hits are necessary for the development of VS, and we also assessed a "3-hit" model for tumor formation. The "3-hit" model fits the data marginally better than one of the "2-hit" models and much better than the other "2-hit" model. Our findings suggest that more than two mutations may be necessary for VS development in NF2 patients. Genet Epidemiol 24:265,272, 2003. © 2003 Wiley-Liss, Inc. [source]


    Melanocytic nevi are associated with neurofibromas in neurofibromatosis, type I, but not sporadic neurofibromas.

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2005
    A study of 226 cases
    Background:, Neurofibromatosis, type 1, is associated with cutaneous melanin pigmentation, but an association with ordinary melanocytic nevi has not been described. Methods:, This retrospective case-control study was designed to see if neurofibromas in patients with neurofibromatosis, type 1 (NF-1) differ from sporadic neurofibromas (SN) in their incidence of associated melanocytic nevi and other histologic features. Slides from 114 NF-1 were compared with 112 SN and 300 intradermal melanocytic nevi (IDN). Results:, Small lentiginous melanocytic nevi were identified over 13 NF-1 (11%) but no SN (P = 0.0002). Compared with other NF-1, NF-1 with nevi were more frequently associated with melanocytic hyperplasia, giant melanosomes and diffuse neurofibroma (P < 0.03). Compared with SN, NF-1 were also more frequently associated with melanocytic hyperplasia, lentigo simplex-like changes, diffuse neurofibroma and plexiform neurofibroma (P < 0.001). Sebaceous hyperplasia (14%), dermal elastosis (9%), lipomatous change (8%), epithelial cysts (4%) and keratin granulomas or folliculitis (3%) were not significantly different in prevalence between NF-1, SN and the control group of IDN. Conclusions:, This study suggests that there is a difference in the potential for melanocytic proliferation in NF-1 compared with SN. NF-1, SN and IDN are associated with a similar range of incidental histologic changes. [source]


    Forensic Considerations in Cases of Neurofibromatosis,An Overview

    JOURNAL OF FORENSIC SCIENCES, Issue 5 2007
    Roger W. Byard M.B.B.S.
    Abstract:, Neurofibromatosis types 1 and 2 are inherited neurocutaneous disorders characterized by a variety of manifestations that involve the circulatory system, the central and peripheral nervous systems, the skin, and the skeleton. Significant reduction in lifespan occurs in both conditions often related to complications of malignancy and hypertension. Individuals with these conditions may also be the subject of medicolegal autopsy investigation if sudden death occurs. Unexpected lethal events may be associated with intracranial neoplasia and hemorrhage or brainstem compression. Vasculopathy with fibrointimal proliferation may result in critical reduction in blood flow within the coronary or cerebral circulations, and aneurysmal dilatation may be associated with rupture and life-threatening hemorrhage. An autopsy approach to potential cases should include review of the history/hospital record, liaison with a clinical geneticist (to include family follow-up), a full external examination with careful documentation of skin lesions and nodules, measurement of the head circumference in children, photography, possible radiologic examination, a standard internal autopsy examination, documentation of the effects of previous surgery and/or chemo/radiotherapy, examination for specific tumors, specific examination and sampling of vasculature (renal, cerebral, and cardiac), formal neuropathologic examination of brain and spinal cord, possible examination of the eyeballs, examination of the gastrointestinal tract, histology to include tumors, vessels, gut, and bone marrow, toxicological testing for anticonvulsants, and sampling of blood and tissue for possible cytogenetic/molecular evaluation if required. [source]


    Neurofibromatosis 2 with peripheral neuropathies: Electrophysiological, pathological and genetic studies of a Taiwanese family

    NEUROPATHOLOGY, Issue 5 2010
    Hung-Chou Kuo
    The objective of this study was to assess peripheral nerve involvement and DNA mutation of the neurofibromatosis type 2 (NF2) gene (NF2) in a Taiwanese family with classic NF2. Eleven members (six symptomatic and five asymptomatic) of a family carrying NF2 underwent clinical examination, neuroimaging, and electrophysiological analysis. Mutation and linkage analyses were conducted on DNA samples prepared from peripheral blood (all individuals), a sural nerve biopsy specimen (one symptomatic member), and a tumor specimen (another symptomatic member). Six of the 11 members were diagnosed with classic NF2. DNA sequencing of the tumor specimen demonstrated a frameshift mutation with 756delC on exon 8 of NF2. Three affected subjects showed clinical variability of the neuropathic disorders. Electrophysiological studies demonstrated variation in the disease pattern and severity of peripheral nerve involvement in five affected subjects. The morphometric assessment of the sural nerve biopsy specimen showed a marked reduction in both large myelinated and unmyelinated fibre density and increased density of non-myelinating Schwann cell nuclei. Apart from numerous pathological nuclei of isolated Schwann cells, multiple profiles of non-myelinating Schwann cell subunits were apparent in the endoneurium. Schwann cell proliferation in association with first-hit mutation of the merlin gene might be responsible for the NF2-associated neuropathy. Sural nerve biopsy showed a progressive neuropathy in the disease. Further, we suggest nonmyelinating Schwann cells are involved in NF2 neuropathy. [source]


    Neurofibromatosis: A Handbook for Patients, Families, and Health Care Professionals

    PEDIATRIC DERMATOLOGY, Issue 6 2008
    KEVIN P. BOYD M.D.
    No abstract is available for this article. [source]


    Juvenile Xanthogranuloma Associated with Neurofibromatosis 1: 14 Patients without Evidence of Hematologic Malignancies

    PEDIATRIC DERMATOLOGY, Issue 2 2004
    Stefano Cambiaghi M.D.
    Mean follow-up in 11 of these patients was 4.3 years (range 1,10 years). None of the children developed hematologic malignancies during this period. The onset of JXG was in the first 2 years of life in 13 of the patients. In this series, the association between JXG and six or more café au lait spots more than 5 mm in diameter was a good marker for NF1 in the first few years of life. Overall the JXG in these patients did not show any features distinguishable from those of "classical" JXG. [source]


    Impact of neurofibromatosis 1 upon quality of life in childhood: a cross-sectional study of 79 cases

    BRITISH JOURNAL OF DERMATOLOGY, Issue 4 2009
    P. Wolkenstein
    Summary Background, Neurofibromatosis 1 (NF1) has a significant impact on quality of life (QoL). Objectives, To evaluate QoL in NF1 according to phenotype from the viewpoint of children and proxy. Methods, One hundred and forty families with a child aged between 8 and 16 years, seen consecutively at the National Academic Paediatric Referral Centre for NF1 for a phenotype evaluation, were contacted by mail. Families agreeing to participate were sent two questionnaires, the DISABKIDS for children and proxy and the cartoon version of the Children's Dermatology Life Quality Index (CDLQI). QoL scores were compared with those in other major diseases and were analysed according to age, gender and phenotype. Results, Eighty families agreed to participate, and 79 returned the questionnaires. Using DISABKIDS, NF1 had a higher impact on health-related QoL than asthma (mean ± SD 75·18 ± 18·22 vs. 79·78 ± 13·41; P = 0·005). The total score was more altered when assessed by proxy than by children (71·20 ± 17·94 vs. 75·18 ± 18·22; P = 0·002). Orthopaedic manifestations, learning disabilities and presence of at least two plexiform neurofibromas were independently associated with a higher impact (P < 0·01). The CDLQI score was slightly altered (11·3%). Dermatological signs, such as café-au-lait spots and freckling, did not have a significant impact. Conclusions, Orthopaedic manifestations, learning disabilities and plexiform neurofibromas are the main complications impacting on QoL during childhood NF1. QoL could be considered as an endpoint for intervention studies in this context. [source]


    Symptoms associated with malignancy of peripheral nerve sheath tumours: a retrospective study of 69 patients with neurofibromatosis 1

    BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2005
    L. Valeyrie-Allanore
    Summary Background, Neurofibromatosis 1 (NF1) is a common genetic disorder with variable clinical manifestations and an unpredictable course. Plexiform neurofibromas are common complications of NF1. Their malignant transformation is the main cause of mortality in adult patients with NF1. Objectives, To identify clinical factors associated with malignant transformation of plexiform neurofibromas. Methods, Using the database of our neurofibromatosis clinic we included in a retrospective study all patients with NF1 having at least one peripheral nerve sheath tumour for which they underwent surgery or surgical biopsy. Predictive values for malignant transformation of three clinical symptoms, i.e. pain, enlargement of mass and neurological symptoms, were evaluated in association with histological parameters. Results, Of 69 patients studied, 48 had at least one plexiform neurofibroma and 21 had a malignant peripheral nerve sheath tumour. Only enlargement of the tumour had high negative and positive predictive values for malignant transformation: 0·92 and 0·95, respectively. In multivariate analysis, tumour enlargement was independently associated with malignant transformation (odds ratio 167·8, 95% confidence interval 14·0,2012·1). Conclusions, From a practical point of view, pain, neurological deficit and enlargement of a pre-existing peripheral nerve sheath tumour in NF1 must lead to deep surgical biopsy to rule out malignant transformation. [source]


    GASTRIC SCHWANNOMA WITH ADJACENT EXTERNAL PROGRESSION HARBORED ABERRANT NF2 GENE

    DIGESTIVE ENDOSCOPY, Issue 3 2009
    Naotaka Ogasawara
    Gastric schwannomas are rare benign mesenchymal tumors. We describe a schwannoma of gastric origin with adjacent external progression. Sections showed a spindle cell tumor arranged in interlaced bundles and fascicles that was S-100 and CD34 positive but c-KIT protein negative. Histology and immunohistochemistry revealed the typical appearance of a gastric schwannoma. Genetic evaluation revealed that the tumor harbored a point mutation in exon 6 of the tumor suppressor neurofibromatosis 2 (NF2) gene, which resulted in an amino acid substitution of NF2 protein, and no mutation in exon 4b of the NF1 gene. In conclusion, we identified a rare mutation of the NF2 gene in gastric schwannoma. A diagnosis can only be definitive when based on histological and immunohistochemical findings. Digestive tract schwannomas are rare mesenchymal tumors that are differentiated from gastrointestinal stromal tumors by the absence of KIT protein. Follow up suggested that complete resection is an effective long-term treatment strategy. [source]


    Neurocutaneous syndrome with mental delay, autism, blockage in intracellular vescicular trafficking and melanosome defects

    EUROPEAN JOURNAL OF NEUROLOGY, Issue 8 2006
    S. Buoni
    We evaluated a 11-year-old male patient with mental delay, autism and brownish and whitish skin spots. The former resembled those of neurofibromatosis, the latter those of tuberous sclerosis. The patient received a complete clinical work-up to exclude neurofibromatosis, tuberous sclerosis, or any other known neurocutaneous disease, with biochemistry, chromosome analysis and analysis of skin specimens. Being all the other tests not significant, two main ultrastructural defects were observed. The first was a blockage in intracellular vescicular trafficking with sparing of the mitochondria; the second an aberrant presence of melanosomes in vacuoles of several cell lines and abnormal transfer of these organelles to keratinocytes. This patient presented with a unique clinical picture distinct from neurofibromatosis or tuberous sclerosis or any other known neurocutaneous disease. The ultrastructural abnormalities suggested a defect in cell trafficking involving several cell lines and compartments. [source]


    Early primary tooth eruption in neurofibromatosis 1 individuals

    EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 5 2007
    Marga Lammert
    No abstract is available for this article. [source]


    Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours

    HISTOPATHOLOGY, Issue 3 2008
    J Lasota
    Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Despite clinicopathological differences, GISTs share oncogenic KIT or platelet-derived growth factor-alpha (PDGFRA) mutations. Imatinib, KIT and PDGFRA inhibitor, has been successfully used in the treatment of metastatic GISTs. There are primary KIT or PDGFRA mutations diagnosed before imatinib treatment, linked to GIST pathogenesis, and secondary mutations detected during treatment, causing drug resistance. KIT exon 11 mutations are the most common. Gastric GISTs with exon 11 deletions are more aggressive than those with substitutions. KIT exon 11 mutants respond well to imatinib. Less common KIT exon 9 Ala502_Tyr503dup mutants occur predominantly in intestinal GISTs and are less sensitive to imatinib. An Asp842Val substitution in exon 18 is the most common PDGFRA mutation. GISTs with such mutation are resistant to imatinib. PDGFRA mutations are associated with gastric GISTs, epithelioid morphology and a less malignant course of disease. GISTs in neurofibromatosis 1, Carney triad and paediatric tumours generally lack KIT and PDGFRA mutations. Secondary KIT mutations affect exons 13,17. GISTs with secondary mutations in exon 13 and 14 are sensitive to sunitinib, another tyrosine kinase inhibitor. KIT and PDGFRA genotyping is important for GIST diagnosis and assessment of sensitivity to tyrosine kinase inhibitors. [source]


    The distribution of constitutional and somatic mutations in the neurofibromatosis 2 gene,

    HUMAN MUTATION, Issue 4 2006
    Michael E. Baser
    Abstract Constitutional heterozygous inactivating mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene cause the autosomal dominant disease NF2, and biallelic inactivating somatic NF2 mutations are found in a high proportion of unilateral sporadic vestibular schwannoma (USVS) and sporadic meningioma. We surveyed the distributions of constitutional NF2 mutations in 823 NF2 families, 278 somatic NF2 mutations in USVS, and 208 somatic NF2 mutations in sporadic meningioma. Based on the available NF2 mutation data, the most dominant influence on the spectra of mutations in exons 1,15 are C>T transitions that change arginine codons (CGA) to stop codons (TGA) due to spontaneous deamination of methylcytosine to thymine in CpG dinucleotides. The paucity of reported mutations in exon 9 and the absence of reported mutations in exons 16 and 17 may be related to structure,function relationships in the NF2 protein. Hum Mutat 27(4), 297-306, 2006. © 2006 Wiley-Liss, Inc. [source]


    Constitutional NF1 mutations in neurofibromatosis 1 patients with malignant peripheral nerve sheath tumors,,

    HUMAN MUTATION, Issue 5 2003
    Lan Kluwe
    Abstract Neurofibromatosis type 1 (NF1) patients have 10% of lifetime risk for developing malignant peripheral nerve sheath tumors (MPNST), one of the most aggressive cancers. We examined the spectrum of constitutional NF1 mutations among 24 NF1 patients with MPNST. We found mutations in 18 patients: four megabase deletions involving the NF1 gene, 13 truncating mutations, and only one missense mutation. One deletion included both exonic and intronic sequences. No typical splicing mutation was found. Five of these mutations were novel: c.3686delA, c.197_204+9del17, c.3044T>C (p.Leu1015Pro), c.2497delT, and c.6020_6027dup. The proportion of megabase deletions of the NF1 gene found in patients with MPNST (17%=4/24) was higher than that in a group of unselected NF1 patients (5.4%=27/500). © 2003 Wiley-Liss, Inc. [source]


    Cutaneous sclerosing perineurioma of the digit

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 9 2006
    Toshitsugu Nakamura MD
    An 11-year-old Japanese girl noticed a small nodule, with mild tenderness, on the right index finger 5 years before visiting our outpatient clinic. She had no familial history of neurofibromatosis or past history of traumatic injury at the site of the tumor. Physical examination revealed a slightly elevated, subcutaneous, nodular tumor in the volar aspect between the proximal and distal interphalangeal joints of the digit (Fig. 1A). By magnetic resonance imaging examination, the tumor showed low density on both T1- and T2-weighted images, and was located just adjacent to the tendon with no invasive signs. The tumor was extirpated; at operation, it was well circumscribed and mobile without adhesion to adjacent tendon or nerve, and was easily removed. Figure 1. (a) Slightly elevated subcutaneous tumor (arrow) on the volar aspect of the right index finger. (b) gross appearance of the extirpated tumor, showing a well-circumscribed, whitish solid nodule Grossly, the tumor was a well-circumscribed, firm nodule (10 mm × 8 mm × 5 mm in size) (Fig. 1B). The cut surface was whitish, homogeneous, and solid without cystic lesions. Histologically, it was an unencapsulated, paucicellular dense, fibrous nodule with a concentric circular arrangement of collagen bundles (Fig. 2A). Amongst the fibrous bundles, a small number of ovoid/epithelioid or plump spindle cells were arranged in a corded, trabecular, or whorled (onion bulb-like) pattern (Fig. 2B); a storiform pattern was not noted. These cells were relatively uniform and had a somewhat elongated, slightly hyperchromatic nucleus with fine granular chromatin. Neither nuclear pleomorphism nor multinucleated cells were evident, and necrosis and mitotic figures were not observed. Periodic acid,Schiff (PAS) stain after diastase digestion highlighted the corded or whorled pattern of the tumor cells by encasing them. For immunohistochemical examination, formalin-fixed, paraffin-embedded serial tissue sections were stained by a labeled streptavidin,biotin method. The tumor cells were positive for vimentin and epithelial membrane antigen (EMA) (Fig. 3A), and negative for pan-cytokeratin, carcinoembryonic antigen (CEA), CD34, ,-smooth muscle actin, desmin, and CD68. Type IV collagen and laminin (Fig. 3B) were detected along the cords or whorls of the tumor cells, similar to the staining pattern of the diastase-PAS reaction. Schwann cells and axonal components, immunoreactive for S100 protein and neurofilament, respectively, were focally detected just adjacent to the cords or whorls, although the tumor cells per se did not express these proteins. Consequently, the tumor was found to be perineurial in origin and was diagnosed as cutaneous sclerosing perineurioma. Figure 2. (a) Low-power view of the tumor, showing an unencapsulated, paucicellular, dense, fibrous nodule with a concentric circular arrangement of collagen bundles (hematoxylin and eosin stain: original magnification, ×15). (b) Higher magnification of the tumor, showing ovoid or epithelioid cells arranged in cords or whorls in the abundant collagen bundles (hematoxylin and eosin stain: original magnification, ×150) Figure 3. Immunohistochemical profiles of the tumor. The tumor cells are positive for epithelial membrane antigen (a) and are surrounded by laminin (b) (original magnification, ×150) [source]


    Multiple nodular plexiform neurofibromas in a neurofibromatosis 1 family: a familial tendency?

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 5 2003
    A case report, review of the literature
    No abstract is available for this article. [source]


    All in the family: Using inherited cancer syndromes to understand de-regulated cell signaling in brain tumors

    JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2007
    S. Sean Houshmandi
    Abstract The cell signaling pathways that are tightly regulated during development are often co-opted by cancer cells to allow them to escape from the constraints that normally limit cell growth and cell movement. In this regard, de-regulated signaling in cancer cells confers a number of key tumor-associated properties, including increased cell proliferation, decreased cell death, and increased cell motility. The identification of some of these critical signaling pathways in the nervous system has come from studies of inherited cancer syndromes in which affected individuals develop brain tumors. The study of brain tumors arising in patients with neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and tuberous sclerosis complex (TSC) has already uncovered several key intracellular signaling pathways important for modulating brain tumor growth. An in-depth analysis of these intracellular signaling pathways will not only lead to an improved understanding of the process of brain tumorigenesis, but may also provide important molecular targets for future therapeutic drug design. J. Cell. Biochem. 102: 811,819, 2007. © 2007 Wiley-Liss, Inc. [source]


    Cutaneous melanocytoneuroma: the first case of a distinctive intraneural tumor with dual nerve sheath and melanocytic differentiation

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 2007
    Ilan Weinreb
    Many melanocytic nevi contain areas similar to nerve sheath tumors (NST) and NSTs with melanin have been described. There are some NSTs with at least partial intraneural location, including neurofibromas, plexiform neurofibromas, granular cell tumors and the recently described, dendritic cell neurofibroma with pseudorosettes. We describe the case of an NST with melanocytic differentiation and intraneural location, for which we suggest the term ,melanocytoneuroma' (MCN). It arose in the skin of a 67-year-old woman with no previous history of melanoma or neurofibromatosis. The lesion presented as a papule and histologically consisted of a dermal nodule without junctional melanocytic activity. The lesion comprised an intraneural proliferation of large epithelioid eosinophilic cells with prominent cell borders imparting a ,plant-like' appearance. The cells were also seen within adjacent nerve twigs and were positive for S100, Melan-A, HMB-45, microphthalmia transcription factor and PGP 9.5. The lesion was entirely surrounded by an epithelial membrane antigen-positive-perineurial coat and the individual tumor cells were invested by laminin and collagen type-IV-positive basal lamina-like material. The lesion did not show any evidence of atypia and following complete excision, no recurrence has been documented. In conclusion, this unusual lesion represents an intraneural proliferation with melanocytic and nerve sheath cell differentiation, to which we have accorded the appellation, MCN. [source]


    Soft-tissue perineurioma in a 20-year-old patient with neurofibromatosis type 1 (NF1): report of a case and review of the literature

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2007
    Gregory G. Ausmus
    Background:, Perineurioma is a rare benign soft-tissue tumor composed of cells showing differentiation toward the perineurial cells of the nerve sheath. Although mutations in the neurofibromatosis 2 (NF2) gene have been documented in this tumor, there is no known association between perineuriomas and type 1 or 2 NF. Methods:, This is the first report of a case of soft-tissue perineurioma occurring in a patient with NF1. Results:, Histopathologic examination revealed a 2.0-cm well-circumscribed, spindle-cell neoplasm with slender, elongated, bipolar, wavy cytoplasmic processes and wavy, elongated nuclei in a hyalinized stroma with focal myxoid areas. The architecture was composed predominantly of short fascicles with areas exhibiting a storiform pattern. Immunohistochemistry showed positive labeling for epithelial membrane antigen (EMA) but no staining for S-100 and smooth muscle actin (SMA). Conclusion:, This case illustrates that perineurioma can occur in association with NF1. Perineuriomas can be confused with other spindle-cell neoplasms, and relevant features and immunohistochemistry of these lesions are outlined. The patient has not had a recurrence with limited follow-up. [source]


    Melanocytic nevi are associated with neurofibromas in neurofibromatosis, type I, but not sporadic neurofibromas.

    JOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2005
    A study of 226 cases
    Background:, Neurofibromatosis, type 1, is associated with cutaneous melanin pigmentation, but an association with ordinary melanocytic nevi has not been described. Methods:, This retrospective case-control study was designed to see if neurofibromas in patients with neurofibromatosis, type 1 (NF-1) differ from sporadic neurofibromas (SN) in their incidence of associated melanocytic nevi and other histologic features. Slides from 114 NF-1 were compared with 112 SN and 300 intradermal melanocytic nevi (IDN). Results:, Small lentiginous melanocytic nevi were identified over 13 NF-1 (11%) but no SN (P = 0.0002). Compared with other NF-1, NF-1 with nevi were more frequently associated with melanocytic hyperplasia, giant melanosomes and diffuse neurofibroma (P < 0.03). Compared with SN, NF-1 were also more frequently associated with melanocytic hyperplasia, lentigo simplex-like changes, diffuse neurofibroma and plexiform neurofibroma (P < 0.001). Sebaceous hyperplasia (14%), dermal elastosis (9%), lipomatous change (8%), epithelial cysts (4%) and keratin granulomas or folliculitis (3%) were not significantly different in prevalence between NF-1, SN and the control group of IDN. Conclusions:, This study suggests that there is a difference in the potential for melanocytic proliferation in NF-1 compared with SN. NF-1, SN and IDN are associated with a similar range of incidental histologic changes. [source]


    Endovascular treatment for bilateral vertebral arteriovenous fistulas in neurofibromatosis 1

    JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 4 2003
    W Siddhartha
    Summary We report a rare case of a 36-year-old woman with neurofibromatosis 1 (NF1) with bilateral vertebro-vertebral arteriovenous fistulas. The patient presented with quadriparesis and had neck pain. Angiography revealed vertebral arteriovenous fistulas bilaterally with dilated epidural venous plexuses compressing the cervical cord resulting in quadriparesis. Endovascular treatment using coils and balloons resulted in successful occlusion of both fistulas. At 6-months postembolization, the patient had improved significantly and is now able to walk with support. [source]


    In vitro studies of steroid hormones in neurofibromatosis 1 tumors and schwann cells

    MOLECULAR CARCINOGENESIS, Issue 7 2007
    Lauren Fishbein
    Abstract The most common NF1 feature is the benign neurofibroma, which consists predominantly of Schwann cells. Dermal neurofibromas usually arise during puberty and increase in number throughout adulthood. Plexiform neurofibromas, associated with larger nerves, are often congenital and can be life threatening. Malignant peripheral nerve sheath tumors (MPNST) in NF1 are believed to arise from plexiforms in 5%,10% of patients. There are reports of increased potential for malignant transformation of plexiform tumors and increase in dermal neurofibromas, during pregnancy. These observations suggest that steroid hormones influence neurofibroma growth, and our work is the first to examine steroid hormone receptor expression and ligand-mediated cell growth and survival in normal human Schwann cells and neurofibroma-derived Schwann cell cultures. Immunohistochemistry and real-time PCR showed that estrogen receptors (ERs), progesterone receptor (PR), and androgen receptor are differentially expressed in primary neurofibromas and in NF1 tumor-derived Schwann cell cultures compared to normal Schwann cells. However, there is substantial heterogeneity, with no clear divisions based on tumor type or gender. The in vitro effects of steroid hormone receptor ligands on proliferation and apoptosis of early passage NF1 tumor-derived Schwann cell cultures were compared to normal Schwann cell cultures. Some statistically significant changes in proliferation and apoptosis were found, also showing heterogeneity across groups and ligands. Overall, the changes are consistent with increased cell accumulation. Our data suggest that steroid hormones can directly influence neurofibroma initiation or progression by acting through their cognate receptor, but that these effects may only apply to a subset of tumors, in either gender. © 2007 Wiley-Liss, Inc. [source]


    Pigmented neurofibroma: Report of two cases and literature review

    PATHOLOGY INTERNATIONAL, Issue 7 2001
    Mayumi Inaba
    Two cases of pigmented neurofibroma of the skin are reported. In case 1, the tumor was removed from the back of a 55-year-old man with no associated neurofibromatosis. In case 2, the tumor was removed from the abdominal wall of a 21-year-old woman with neurofibromatosis. Both tumors consisted of benign, short spindle cells and multiple foci of scattered melanin-laden cells. In case 1, the spindle cells were arranged in a storiform pattern, resembling features of dermatofibrosarcoma protuberans. Immunohistochemically, the spindle cells of both cases were demonstrated to be positive for S-100 protein and CD34. The melanin-laden cells stained positively for HMB-45. This report describes an additional two cases of pigmented neurofibroma that conform to the new diagnostic criteria for this disease. [source]


    Malignant peripheral nerve sheath tumor arising in benign ancient schwannoma: A case report with an immunohistochemical study

    PATHOLOGY INTERNATIONAL, Issue 2 2000
    Yoshiki Mikami
    A rare example of malignant transformation in an ancient schwannoma arisng in the right side of the neck of a 51-year-old man without any clinical manifestations suggesting neurofibromatosis is described. The tumor, approximately 4 cm at its largest dimension, was well circumscribed and had a direct connection with the sympathetic nerve. Microscopically, the central portion of the tumor showed features of ancient schwannoma characterized by extensive hyalinization with cystic degeneration, scattered spindle cells with hyperchromatic and tapered nuclei, and some symplastic changes. However, predominantly in the outer portion, a proliferation of spindle-shaped cells with enlarged nuclei was present. The nuclei of these cells showed irregular contours, coarse granular chromatin texture, and conspicuous nucleoli. Mitotic figures and small necrotic foci with scattered apoptotic bodies were also seen. Immunohistochemically, S-100 protein was almost negative in areas consisting of overtly atypical cells where the mitotic index evaluated with MIB-1 antibody was 30.5%. In contrast, S-100-positive bland spindle cells were scattered in an extensively hyalinized area with a labeling index less than 3%. P53 protein was strongly positive in atypical spindle cells. Although it is a very uncommon event, definite nuclear atypia, frequent mitotic figures, and the existence of small necrotic foci should be recognized as indicating a diagnosis of malignant degeneration of benign schwannoma. Immunohistochemistry would be useful as an ancillary technique in such a setting. [source]


    Juvenile papillomatosis of the breast associated with neurofibromatosis 1

    PEDIATRIC BLOOD & CANCER, Issue 3 2007
    Tiong Yang Tan MBBS
    No abstract is available for this article. [source]


    Pseudoatrophic Macules Associated with Neurofibromatosis-1

    PEDIATRIC DERMATOLOGY, Issue 2 2009
    CHIEN-SHAN CHIU M.D.
    This clinical presentation of neurofibroma has rarely been reported in patients with neurofibromatosis. [source]


    Localized Hypertrichosis in a Pediatric Patient,What Is the Mechanism for Excess Hair Growth?

    PEDIATRIC DERMATOLOGY, Issue 3 2007
    Kyle Wagamon M.D.
    We highlight an instance of localized hypertrichosis due to an underlying diffuse neurofibroma in a patient with known neurofibromatosis 1. The classification and possible underlying pathogenic mechanisms of localized hypertriehosis in pediatric patients is discussed. [source]


    Treatment of pigmented lesions of neurofibromatosis 1 with intense pulsed,radio frequency in combination with topical application of vitamin D3 ointment

    THE JOURNAL OF DERMATOLOGY, Issue 4 2007
    Yuichi YOSHIDA
    ABSTRACT Cafe-au-lait spots and pigmented freckling are found in most of patients with neurofibromatosis 1 (NF1). Although many modalities have been used for treating the pigmented lesions, the response to treatment has been variable. Therefore, we performed the treatment of pigmented lesions with NF1 by intense pulsed,radio frequency (IPL,RF) in combination with topical application of vitamin D3 ointment. Eight patients were treated in this study and the improvement was moderate to good in six cases (75%) although the response was relatively mild. Thus, results from our study indicate that IPL,RF irradiation in combination with topical application of vitamin D3 ointment would be useful as new modalities, especially for treatment of numerous small pigmented lesions in patients with NF1. Although further studies with large groups of patients should be performed for a better conclusion, it could improve quality of life with NF1 patients who are concerned with serious cosmetic and social problems. [source]


    Vestibular Schwannoma Quantitative Polymerase Chain Reaction Expression of Estrogen and Progesterone Receptors,

    THE LARYNGOSCOPE, Issue 8 2008
    Andrew K. Patel MD
    Abstract Objectives/Hypothesis: Determine the role of estrogen receptor (ER) and progesterone receptor (PR) expression in sporadic and neurofibromatosis 2 (NF2)-related vestibular schwannomas (VS). Growth and proliferation signaling in human VS tumorigenesis may play a key role in molecular therapeutic targeting. VS carry mutations of the NF2 gene encoding the tumor suppressor, merlin, which interacts with ErbB2 in Schwann cells, implicating ErbB receptors in VS tumorigenesis. ErbB receptor family members are overexpressed or constitutively activated in many human tumors, and are effective therapeutic targets in some human cancers. VS occur more frequently in women and are larger, more vascular, and demonstrate increased growth rates during pregnancy. ER and PR may play a role in ErbB pathway activation and VS progression. Study Design: Quantitative real-time polymerase chain reaction (qRT-PCR) for ER and PR messenger RNA was performed using greater auricular and vestibular nerve controls (n = 8), sporadic VS (n = 23), and NF2-related VS (n = 16) tissues. Methods: The qRT-PCR data were normalized with standardization to a single constitutively expressed control gene, human cyclophylin. Results: Reverse transcription of messenger RNA from control and tumor specimens followed by RT Q-PCR demonstrated differences in ER and PR gene expression between sporadic and NF2-related VS. Conclusions: ER and PR expression in VS might have implications for development of a VS-specific drug delivery system using antihormone and ErbB pathway small molecule inhibitors, due to crosstalk between these receptors. These signals may be critical for re-establishing ErbB-mediated cell density dependent growth inhibition. [source]