Neurofibroma Size Research Articles

Vitamin D and Bone Metabolism in Adult Patients with Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is a genetic multisystemic autosomal dominant disorder determining reduced life expectancy due to higher risk of developing benign and malignant tumors. Low levels of vitamin D and reduced bone mineral density (BMD) have been reported in young patients with NF1. However, correlation between vitamin D and NF1 phenotype needs to be elucidated. Aim of this study was to assess vitamin D levels and bone metabolism in NF1 patients, analyzing potential correlations with clinical phenotype. A cross-sectional study was carried out in a monocentric series of NF1 patients, evaluating genotype, clinical phenotype, BMD, biochemical evaluation with focus on serum 25OH-vitamin D, parathyroid hormone (PTH), calcium and phosphate levels. Correlations between clinical manifestations, neurofibromas, and vitamin D status have been studied in comparison with healthy controls. 31 NF1 adult patients were matched for sex, age and body mass index with 31 healthy controls. A significantly difference in vitamin D level emerged in NF1 patients compared to controls. Interestingly low vitamin D levels correlated with a more aggressive phenotype and with a bigger size of neurofibromas. These data underline that vitamin D deficiency/insufficiency may play a role in clinical severity of neurofibromas in patients with NF1, suggesting the need to check bone status and replace vitamin D in these patients.

APPLICATION OF KSHARASUTRA OVER SURGICAL EXCISION OF NEUROFIBROMA (NF1): A CASE REPORT

Neurofibromatosis type 1 (NF1) or Von Recklinghausen's disease is a rare genetic disorder characterized by the development of multiple noncancerous tumors of nerves and skin (neurofibromas). Head and neck neurofibroma are generally located in the soft tissue. Here, a case of a 42-year-old man with NF1 has been presented. The disease started in childhood with the appearance of multiple hyperpigmented skin macules. He has generalized freckling and café-au-lait spots all over the body and cutaneous nodules with multiple sizes. The diagnosis of NF1 was made according to presence of two or more diagnostic criteria of the National Institute of Health Consensus Development Conference. On the basis of symptoms, it was closely related to the Kaphaja Arbuda. Acharya Sushruta mentioned Kshara and Ksharasutra in Arbuda Chikitsa. So, Ksharasutra was tied on the root of one of the neurofibroma size of 4 x 2.5 cm present on medial side of the mid arm. The Fibroma was shed-off completely after 7 days and no recurrence was observed in a follow up at the end of 12 months after application of Ksharasutra.

Sarcomatous transformation of Recklinghausen´s disease

Neurofibromatosis type I is a common genetic disease. Affected patients are 4 times more likely to develop a tumor. Most tumors are benign (neurofibromas). Although these rarely result in malignant tumors, they represent the leading cause of death in patients, thus making neurofibromatosis type I a severe disease. It mainly develops to melanoma, pheochromocytoma, astrocytoma, optic glioma, Wilms tumor of and leukemia. Sarcomatous transformation is exceptional. Early diagnosis is essential. It arises from isolated nodular or plexiform neurofibromas. During the monitoring of patients with NF1 and with plexiform neurofibromas, clinicians should consider the possibility of its transformation into neurofibrosarcoma. This is also the case for rapid increase in tumor size, its hardening, its extremely painful nature or the occurrence of neurological signs. We report the case of a 42-year-old female patient, with childhood history of Von Recklinghausen disease, presenting with pain, bleeding and an increase in plexiform neurofibroma size in the right lower limb (A, B, C). Clinical examination showed coffee-with-milk colored spots, cutaneous neurofibromas and large size ulcerated and painful mass involving all the right lower limb. Computed tomography (CT) scan of the limb objectified a tumoral process at the level of the posterior region of the lower limb. Biopsy of the mass showed malignant peripheral nerve sheath tumor.

Selumetynib — pierwszy lek skuteczny w terapii nerwiakowłókniaków splotowatych w przebiegu neurofibromatozy typu 1

Plexiform neurofibromas progress and increase their size throughout the patient’s life, causing body deformity, disability, and higher mortality. Complete tumour resection is often dificult due to the large size of the plexiform neurofibroma and nerve infiltration. Treatment with MEK inhibitors appears to be a promising therapeutic option that allows reducing the mass of tumours. In the clinical trial NCT01362803 on the effect of selumetinib on inoperable plexiform neurofibromas in type 1 neurofibromatosis, children aged 3 to 18 years were involved. 74% of patients showed a partial response, defined as a reduction of at least 20% in tumour volume. Progression-free time was on average 3 years. The best results were observed after the 16th cycle of therapy. In addition to reducing tumour volume, a significant clinical reduction in pain intensity has also been demonstrated, which has resulted in an improvement in overall quality of life and daily functioning. At the same time, 78% of children from the control sample showed an increase of at least 20% in neurofibroma size. The results of studies on the effects of selumetinib in the adult population are also promising. Selumetinib treatment was well tolerated in both age groups. Gastrointestinal and skin complaints were most commonly observed. Most symptoms could be alleviated by appropriate treatment. More serious but rarer complications were cardiomyopathy and ophthalmic complications.

Cardiac overload resolved by resection of a large plexiform neurofibroma on both the buttocks and upper posterior thighs in a patient with neurofibromatosis type I: a case report

BackgroundA large plexiform neurofibroma in patients with neurofibromatosis type I can be life threatening due to possible massive bleeding within the lesion. Although the literature includes many reports that describe the plexiform neurofibroma size and weight or strategies for their surgical treatment, few have discussed their possible physical or mental benefits, such as reducing cardiac stress. In addition, resection of these large tumors can result in impaired wound healing, partly due to massive blood loss during surgery.Case presentationA 24-year-old man was diagnosed with neurofibromatosis type I and burdened with a large plexiform neurofibroma on the buttocks and upper posterior thighs. The patient was 159 cm in height and 70.0 kg in weight at the first visit. Cardiac overload was indicated by an echocardiography before surgery. His cardiac output was 5.2 L/min with mild tricuspid regurgitation. After embolism of the arteries feeding the tumor, the patient underwent surgery to remove the neurofibroma, followed by skin grafting. Follow-up echocardiography, performed 6 months after the final surgery, indicated a decreased cardiac output (3.6 L/min) with improvement of tricuspid regurgitation. Because the blood loss during the first surgery was over 3.8 L, malnutrition with albuminemia was induced and half of the skin graft did not attach. Nutritional support to improve the albuminemia produced better results following a second surgery to repair the skin wound.ConclusionCardiac overload may be latent in patients with neurofibromatosis type I with large plexiform neurofibromas. As in pregnancy, the body may compensate for this burden. In these patients, one stage total excision may improve quality of life and reduce cardiac overload. In addition, nutritional support is likely needed following a major surgery that results in either an extensive skin wound or excessive blood loss during treatment.

A Proof-of-Concept Assessment of the Safety and Efficacy of Intralesional Diclofenac in the Treatment of Cutaneous Neurofibromas

The objectives of this study were to assess the safety and efficacy of intralesionally administered diclofenac in the treatment of cutaneous neurofibromas in patients with NF1. This was a proof-of-concept, prospective, safety and efficacy study of the effect of intralesionally administered diclofenac 25 mg/ml given once a week to 3 target cutaneous neurofibromas for 4 consecutive weeks. Overall, there was no significant change in neurofibroma size. During the study, some treated lesions developed signs of necrosis and fell off after a few weeks, but none of the control neurofibromas fell off. There were no significant changes in patient’s vital signs. A few adverse events occurred, mostly at the injection sites. During the study, some neurofibromas developed necrosis after the diclofenac injections and eventually detached from the patient. Overall, diclofenac was well tolerated, suggesting minimal systemic exposure, which required confirmation and further studies, including bioavailability analysis.

Visual Outcomes in Children With Neurofibromatosis Type 1 and Orbitotemporal Plexiform Neurofibromas

To describe the visual outcomes and volumetric magnetic resonance imaging (3D MRI) in children with neurofibromatosis type 1 (NF1) and orbitotemporal plexiform neurofibromas. Multicenter retrospective case series. Two institutions with dedicated NF1 clinical research programs queried their established clinical databases for children with orbitotemporal plexiform neurofibromas. Visual acuity, refractive error, ambylopia, and treatment history were abstracted. Extent of orbitotemporal plexiform neurofibroma involvement was assessed clinically and with 3D MRI analysis. Children with optic pathway gliomas or ocular causes of decreased visual acuity (ie, cataracts, glaucoma) other than strabismus or anisometropia were excluded. Twenty-one children met inclusion criteria (median age 8 years, range 0.33-23 years). Orbitotemporal plexiform neurofibroma location was classified as isolated eyelid (n= 6), eyelid and orbit (n= 7), orbit and temporal region (n= 7), or diffuse orbit (n= 1). Three subjects had bilateral orbital involvement. Amblyopia secondary to the orbitotemporal plexiform neurofibroma was present in 13 subjects (62%) and was caused by strabismus (n= 2, 10%), occlusion from ptosis (n= 9, 43%), or anisometropia (n= 9, 43%), or a combination of factors (n= 6, 29%). MRI-derived volumes were measured in 19 subjects (median 41.8mL, range 2.7-754mL). All subjects with amblyopia had orbitotemporal plexiform neurofibroma volumes greater than 10mL. In our series, amblyopia occurs in more than half of NF1 children with orbitotemporal plexiform neurofibromas, most commonly because of ptosis and anisometropia. The 3D MRI analysis allowed for sensitive measurement of orbitotemporal plexiform neurofibroma size, and larger volumes were associated with development of amblyopia.

Spinal anesthesia for emergency cesarean section in a preeclampsia patient diagnosed with type 1 neurofibromatosis

Spinal anesthesia for emergency cesarean section in a preeclampsia patient diagnosed with type 1 neurofibromatosis

Solitary giant neurofibroma of the neck subjected to photodynamic therapy: case study

Photodynamic therapy (PDT) - the fourth modality - has been successfully used in the management of early and advanced pathologies of the head and neck. We studied the effect of this modality on a giant solitary neurofibroma of the neck. A 70-year-old Caucasian female presented with left neck pain and disfigurement associated with slight shortness of breath and dysphagia. Examination revealed a large mass in the neck with no neurovascular compromise. Magnetic resonance imaging (MRI) reported a heterogeneously enhancing mass extending from the left angle of the mandible to the base of the neck. A core biopsy was performed and histopathological examination revealed a disorganised array of peripheral nerve fascicles. The patient elected to receive photodynamic therapy as the primary intervention. The multi-disciplinary meeting approved the treatment plan. The photosensitizing agent was mTHPC (0.15 mg/kg), which was systemically administered 96-hours prior to ultrasound (US)-guided light delivery to the mass, which was undertaken under general anaesthesia. Recovery was uneventful.Post-PDT follow-up showed that the patient’s pain, dysphagia and shortness of breath issues had improved. The disfigurement of the neck caused by the mass was no longer a problem. Three months post-PDT, MRI revealed a significant reduction in the neurofibroma size. PDT was proven as a successful primary intervention for this pathology. However, higher evidence-based studies are required before this therapy can be proposed as a replacement to any of the other conventional therapies.

The role of steroid hormones in the NF1 phenotype: Focus on pregnancy

The Neurofibromatosis Type 1 (NF1) gene functions as a tumor suppressor gene. Loss of its protein, neurofibromin, in the autosomal dominant disorder NF1 is associated with peripheral nervous system tumors, particularly neurofibromas, benign lesions in which the major cell type is the Schwann Cell (SC). Benign and malignant human tumors found in NF1 patients are heterogeneous with respect to their cellular composition. The number and size of neurofibromas in NF1 patients has been shown to increase during pregnancy, with, in some cases, post-partum regression, which suggests hormonal involvement in this increase. However, in this review, we consider evidence from the literature that both direct hormonal influence on tumor growth and on angiogenesis may contribute to these effects.

Influence of hormones and hormone metabolites on the growth of schwann cells derived from embryonic stem cells and on tumor cell lines expressing variable levels of neurofibromin

Loss of neurofibromin, the protein product of the tumor suppressor gene neurofibromatosis type 1 (NF1), is associated with neurofibromas, composed largely of Schwann cells. The number and size of neurofibromas in NF1 patients have been shown to increase during pregnancy. A mouse embryonic stem cell (mESC) model was used, in which mESCs with varying levels of neurofibromin were differentiated into Schwann-like cells. NF1 cell lines derived from a malignant and a benign human tumor were used to study proliferation in response to hormones. Estrogen and androgen receptors were not expressed or expressed at very low levels in the NF1+/+ cells, at low levels in NF1+/-cells, and robust levels in NF1-/-cells. A 17beta-estradiol (E2) metabolite, 2-methoxy estradiol (2ME2) is cytotoxic to the NF1-/- malignant tumor cell line, and inhibits proliferation in the other cell lines. 2ME2 or its derivatives could provide new treatment avenues for NF1 hormone-sensitive tumors at times of greatest hormonal influence.

Serum IgE levels in neurofibromatosis 1

A descriptive case study was performed on 75 patients with NF1 (neurofibromatosis type 1) from the CNNF (Brazil) database. Serum IgE levels were determined using the IgE radioimmunosorbent test, with the reference values of 75-502 IU mL(-1). The patients were divided into groups, with 25 patients presenting plexiform neurofibromas, 25 presenting neurofibromas and 25 presenting no neurofibromas. The purposes of this study were to determine the serum IgE levels of patients with NF1 presenting plexiform neurofibromas, neurofibromas and no neurofibromas, as well as to determine possible correlations between serum IgE levels and the size of the plexiform neurofibromas and neurofibromas presented by these patients. Elevated serum IgE levels were observed in all the patient groups. We did not observe a correlation between IgE levels and age in these patients; however, we did observe correlations between IgE levels and neurofibroma and plexiform neurofibroma size. We suggest further studies to confirm these results and to investigate in greater depth the possible role of IgE in the development and growth of neurofibromas and plexiform neurofibromas in NF1.

A role for modifier genes in genome imprinting.

It is, by now, an old observation that the phenotype elicited by a mutant allele at a particular locus is not the sole result of the DNA sequence of that allele. The truth of this statement may be easily recognized by comparing different individuals within the same family, each of whom has the same genetic disease. Siblings who have neurofibromatosis, for example, all share the same disease allele at the NF1 locus but the manifestations of disease (number and size of cafe au lait spots, number and size of neurofibromas, presence of neurofibrosarcoma, etc.) among the siblings may vary dramatically (Easton et al. 1993). These variations in disease phenotype between individuals who carry the same mutant allele have been subsumed under the mechanistically vague concept that many diseases exhibit variable expressivity (Thompson et al. 1991). Such differences in disease phenotype may result from many factors, including stochastic processes and environmental influences, but at least some of these differences are thought to result from the collective action of additional genetic factors that differ between individuals. These additional genetic factors are said to modify the phenotype and are, therefore, called modifier genes.KeywordsMutant AlleleModifier GeneFamilial Adenomatous PolyposisImprint GeneAngelman SyndromeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

New Hope for Neurofibromatosis? The Mast Cell Connection

Neurofibromatosis is a common and progressive illness.^1,2The spectrum of disease varies from the mildest of formes frustes to highly destructive and disfiguring syndromes. (It now seems that the most famous putative severe example, that of Joseph Merrick, "The Elephant Man," was not neurofibromatosis at all.³) The primary, if not the only, treatment has been surgery. In the August issue of the American Medical Association's<i>Archives of Dermatology</i>,⁴Riccardi presents his early experience in treating neurofibromatosis with ketotifen, a mast cell stabilizer.⁵During a three-year period, 15 patients received oral ketotifen. The conditions of 11 patients improved in one or more of the following variables: pain, itching, or the general feeling of well-being. In addition, most of these patients also had an apparent decrease in neurofibroma size, or a slowing of tumor growth, and a decrease in the profuse bleeding that accompanies surgery in this illness.