Plexiform Neurofibroma: A Case Report.

Neurofibromatosis is a group of genetic disorders that primarily impact the growth of neural tissues, leading to multiple tumors on nerve tissues in the brain, spinal cord, and peripheral nerves. As an autosomal dominant condition, it involves mutations in the neurofibromatosis type 1 (NF1) tumor-suppressor gene, inherited in a recessive manner. Plexiform neurofibroma is a rare manifestation. It is a benign peripheral nerve sheath tumor that grows beneath the skin or deeper within tissues without clear boundaries. The diverse presentations of NF1 necessitate careful, personalized medical management to address the disorder's effects on various organs. Due to its progressive nature, early diagnosis is crucial to prevent complications. Comprehensive care, including psychological support and long-term monitoring, is essential for enhancing the quality of life of NF1 patients. By adopting a proactive and holistic approach, healthcare providers can better assist patients in managing this complex condition.

Plexiform's perplexities: a tale of two plexiform neurofibromas.

Plexiform neurofibroma (PF) is a rare benign variant belonging to a subtype of neurofibromatosis type 1 that forms bulging or deforming masses arising from the peripheral nerve sheath. These masses involve surrounding connective tissue or dermal layers, leading to multiple cutaneous changes and certain characteristic appearances. It is these appearances that aid in the diagnosis of PF. We have encountered two distinct patients diagnosed with this disorder. While one patient was clinically and pathologically confirmed for PF, the other had no characteristic cutaneous changes. The diagnosis was made with postoperative histopathology and confirmed with an immunohistochemical examination. There are various modalities in the management of PFs, with surgery being a mainstay in the treatment of disfiguring large PFs, especially in resource-restrained settings. In view of high recurrence rates, postoperative clinical follow-up is a must. This paper describes these patients' typical and atypical clinical presentation and subsequent management.

Pulmonary Arterial Hypertension in Neurofibromatosis Type 1: A Case with a Novel NF1 Gene Mutation.

Neurofibromatosis type 1 (NF1) is an autosomal dominant multi-organ disease. The clinical manifestations include not only skin lesions and malignant tumors but also lung complications, including pulmonary arterial hypertension (PAH). However, the association between gene mutations in NF1 and the occurrence of PAH has not yet been elucidated. We herein report a case of isolated PAH in a 67-year-old woman with NF1, presumably caused by a novel heterozygous mutation, c.4485_4486delinsAT (p.Lys1496Ter), in the NF1 gene.

Solitary Isolated Oropharyngeal Neurofibroma Presenting With Dysphagia in the Setting of Von Recklinghausen's Disease.

A 24-year-old man with von Recklinghausen's disease presented with complaints of difficulty in swallowing for 6 months and change of voice for 3 months. He also had recent-onset difficulty in breathing. Telelaryngoscopy and subsequent contrast-enhanced computed tomography scan revealed a well-defined, smooth submucosal mass in the oropharynx (attached to the posterior pharyngeal wall, superior to the level of left aryepiglottic fold), obscuring the ipsilateral pyriform fossa, and nearly blocking the pharyngeal lumen. The mass was removed with endoscopic coblation-assisted laryngeal surgery, and subsequent histopathology revealed it to be neurofibroma. Neurofibromas are rare neoplasms to be encountered in the oropharynx. However, in the setting of von Recklinghausen's disease (neurofibromatosis type 1), one or more well-demarcated, submucosal nodular lesions in the upper aerodigestive tract may be considered as neurofibromas, and workup and treatment should be directed accordingly based on this clinical presumption. Endoscopic coblation during laryngeal surgery can effectively be used as a surgical tool to excise such lesions. It provides a relatively bloodless field compared to the conventional cold steel excision, and reduces the risk of complications at surgery and during the follow-up period. This clinical record illustrates the presentation and management of a solitary, isolated oropharyngeal neurofibroma in a man suffering from von Recklinghausen's disease. It further emphasizes the role of endoscopic coblation-assisted laryngeal surgery in this setup, and the need to maintain a low threshold of suspicion in having a provisional clinical diagnosis of such lesions.

Robotic resection for splenic artery aneurysm associated with neurofibromatosis type 1: a case report.

BACKGROUND: Neurofibromatosis type 1 is an autosomal-dominant disease characterized by café-au-lait spots and neurofibromas, as well as various other symptoms in the bones, eyes, and nervous system. Due to its connection with vascular fragility, neurofibromatosis type 1 has been reported to be associated with vascular lesions, such as aneurysms. However, there have been few reports of abdominal visceral aneurysms associated with neurofibromatosis type 1. Furthermore, there have been no reports of robotic treatment of aneurysms associated with neurofibromatosis type 1. In this report, we describe the case of a patient with neurofibromatosis type 1 with a splenic artery aneurysm who was successfully treated with robotic surgery. CASE PRESENTATION: This report describes a 41-year-old Asian woman with a history of neurofibromatosis type 1 who was referred to our hospital for evaluation of a 28 mm splenic artery aneurysm observed on abdominal ultrasound. The aneurysm was in the splenic hilum, and transcatheter arterial embolization was attempted; however, this was difficult due to the tortuosity of the splenic artery. Thus, we suggested minimally invasive robotic surgery for treatment and resection of the splenic artery aneurysm with preservation of the spleen. The postoperative course was uneventful, and the patient was discharged on the eighth day after surgery. At 1 year of follow-up, the patient was doing well, with no evidence of recurrence. CONCLUSION: We encountered a rare case of splenic artery aneurysm in a patient with neurofibromatosis type 1 who was successfully treated with robotic surgery. There is no consensus on treatment modalities for neurofibromatosis-related aneurysms, and endovascular treatment is considered safe and effective; however, surgery remains an important treatment modality. Especially in patients with stable hemodynamic status, robotic surgery may be considered as definitive treatment. To our knowledge, this is the first successfully treated case of a splenic artery aneurysm in a patient with neurofibromatosis type 1.

Patient characteristics, treatment patterns, healthcare resource utilization, and costs among patients diagnosed with neurofibromatosis type 1 with and without plexiform neurofibromas in Japan.

OBJECTIVES: The objectives of this study were to retrospectively investigate the patient characteristics, treatment patterns, healthcare resource utilization (HCRU), and healthcare costs related to management of neurofibromatosis type 1 (NF1) in Japan. METHODS: Cohorts of NF1 patients with or without plexiform neurofibromas (PN) were identified from the Medical Data Vision database in 2008-2019. Baseline characteristics, NF1 medications, HCRU, and associated costs were assessed using descriptive statistics. All-cause HCRU and costs following the first confirmed NF1 diagnosis date were analyzed per patient per year (PPPY) in Japanese Yen (JPY) and United States Dollar (USD). RESULTS: A total of 4394 NF1 patients without PN and 370 NF1 patients with PN were identified. The mean age was 35.0 and 36.9 years, respectively. The proportion of patients with PN treated with medications was higher than that in patients without PN (except for antirheumatic/immunologic agents). Analgesics/non-steroidal anti-inflammatory drugs were the most frequently prescribed NF1 medications (44.3% and 56.0% in patients without and with PN, respectively), followed by inpatient prescriptions of opioids/opioid-like agents (17.8% and 27.6%, respectively). Inpatient admissions accounted for the highest costs in both cohorts with the average cost PPPY being JPY 2,133,277 (USD 19,861) for patients without PN and JPY 1,052,868 (USD 9802) for patients with PN. CONCLUSIONS: NF1 is treated primarily with supportive care with analgesics/non-steroidal anti-inflammatory drugs being the most frequently prescribed NF1 medications in Japan. Findings underscored the unmet need and substantial economic burden among patients with NF1 and highlighted the need for new treatment options for patients with this disease.

Multimodal Imaging of Choroidal Nodules in Neurofibromatosis Type I.

AIM: To clarify the possibilities and role of posterior segment imaging in patients with neurofibromatosis type I (NF1), and to show the prevalence of this disease in the pediatric population in Slovakia. MATERIAL AND METHODS: Until recently, ophthalmologic consultations in patients with NF1 were limited mainly to the observation of Lisch nodules of the iris and the presence of optic nerve glioma. However, advances in imaging capabilities have made it possible to investigate and describe new f indings concerning the ocular manifestations of this disease. Between October 2020 and November 2021, we examined the anterior and posterior segment of 76 eyes (38 children ­ 12 boys and 26 girls) with genetically confirmed NF1 gene mutation at our clinic. The age of the patients ranged from 4 to 18 years. The anterior segment was checked for the presence of Lisch nodules biomicroscopically with a slit lamp. On the posterior segment, the presence of choroidal nodules was checked by various imaging methods ­ fundus camera, infrared confocal selective laser ophthalmoscopy, MultiColor imaging, OCT, and OCT angiography. All the patients had magnetic resonance imaging performed in order to detect potential optic nerve gliomas for the purpose of diagnosis. We observed the correlation between the patients' age, presence of Lisch nodules and the presence of choroidal nodules. Eight patients also had other manifestations of the disease ­ optic nerve gliomas or microvascular changes (so-called "corkscrew" vessels). RESULTS: Out of 38 patients, Lisch iris nodules were present in 20 patients (53%) and choroidal nodules in 24 patients (63%). There was no positive correlation between the presence of these two manifestations within the same patient or eye, but there is a clear correlation between the presence of choroidal nodules and patient age. CONCLUSION: The results suggest that a previously unknown ocular manifestation of neurofibromatosis type I, namely choroidal nodules, has a higher prevalence than Lisch nodules also in the pediatric population and can be easily visualized using various imaging modalities. It will be important to include follow-up observation of this finding among the standard controls for ocular findings in NF1, and it will be very interesting to correlate this f inding with the exact NF1 mutation

Duodenal neuroendocrine tumor after bilateral breast cancer with type 1 neurofibromatosis: a case report.

BACKGROUND: Young women with NF1 are at a high risk of developing breast cancer. Although they are at risk for abdominal tumors, such as gastrointestinal stromal tumors and neuroendocrine tumors, follow-up strategies for other tumors after breast cancer have not yet been established. Here, we present a case of duodenal neuroendocrine tumor found during follow-up after bilateral mastectomy for breast cancer with type 1 neurofibromatosis (NF1), for which pancreaticoduodenectomy (PD) and lymphadenectomy were performed. CASE PRESENTATION: A 46-year-old woman with NF1 was referred to our hospital for treatment of a duodenal submucosal tumor. Her previous operative history included bilateral mastectomy for breast cancer: right total mastectomy and left partial mastectomy performed 9 and 5 years ago, respectively. Her daughter was confirmed to have NF1, but her parents were unclear. Although she had no recurrence or symptoms during the follow-up for her breast cancer, she wished to undergo 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) for systemic screening. FDG-PET demonstrated FDG accumulation in the duodenal tumor with a maximum standardized uptake value of 5.78. Endoscopy revealed a 20-mm-diameter tumor in the second duodenal portion, and endoscopic biopsy suggested a NET G1. We performed PD and lymphadenectomy for complete. She was doing well without recurrence and was followed up with PET tomography-computed tomography. CONCLUSIONS: Early detection of gastrointestinal tumors is difficult, because most of them are asymptomatic. Gastrointestinal screening is important for patients with NF1, and PD with lymphadenectomy is feasible for managing duodenal neuroendocrine tumors, depending on their size.

Neurofibromatosis type1, type 2, tuberous sclerosis and Von Hippel-Lindau disease.

Neurocutaneous syndromes (also known as phakomatoses) are heterogenous group of disorders that involve derivatives of the neuroectoderm. Each disease has diagnostic and pathognomonic criteria, once identified, thorough clinical examination to the patient and the family members should be done. Magnetic resonance imaging (MRI) is used to study the pathognomonic findings withing the CNS (Evans et al. in Am J Med Genet A 152A:327-332, 2010). This chapter includes the 4 most common syndromes faced by neurosurgeons and neurologists; neurofibromatosis types 1 and 2, tuberous sclerosis and Von Hippel-Lindau disease. Each syndrome has specific genetic anomaly that involves a tumor suppressor gene and the loss of inhibition of specific pathways. The result is a spectrum of cutaneous manifestations and neoplasms.

Minimal intervention for neurofibromatosis type I manifestations: A case report.

INTRODUCTION AND IMPORTANCE: Neurofibromatosis type I (NF1, OMIM: 162200) is a benign, autosomal dominant, tumorigenic predisposing syndrome with variable manifestations. Both neurofibromatosis and soft tissue sarcomas are associated with the formation of hematomas. Moreover, skeletal manifestations of NF1 include focal or generalized forms and expansive or infiltrative growth types. CASE PRESENTATION: A 19-year-old NF1 female patient presented with an expanding post-traumatic facial hematoma that resembled a soft-tissue tumor at initial presentation. A congenital neck mass was noted ipsilateral to her craniofacial skeletal deformities. Multiple imaging modalities were used to aid diagnosis, and urgent surgical intervention of the expanding facial lesion was performed. Her neck lesion and skeletal deformities were monitored, and her recovery was uneventful at 1-year follow-up, with no progression. CLINICAL DISCUSSION: A palpable, non-pulsatile soft tissue mass is a common clinical presentation with a diverse differential diagnosis. Despite the low incidence of post-traumatic vascular injuries and lesions in the maxillofacial region, neurofibromatosis-associated vasculopathy remains an underestimated and serious manifestation of NF1. The reported zygomatic arch deformity is believed to be unique. However, the NF1 tumor-associated skeletal malformations are not linearly related. CONCLUSION: NF1 is a multisystem disorder necessitating an early multidisciplinary team approach. Minimal intervention can help convert an emergent operation into an urgent one and preclude the need for major surgery. The case illustrated a rare example of simultaneous affection of soft tissue and jaw bones in NF1 patients.

Burden of adult neurofibromatosis 1 questionnaire: translation and psychometric properties of the Persian version.

BACKGROUND: The notion of "burden" has taken a key place in the evaluation of care, particularly in the case of rare diseases. The aim of this study was to evaluate the psychometric properties of the burden of neurofibromatosis 1 questionnaire (BoN) and to determine the perceived disease burden. RESULTS: The 15-item BoN was translated into Persian, and no items were removed based on content validity. The adequacy of the sample was acceptable (KMO = 0.902), and Bartlett's test of sphericity revealed statistically significant results (P < 0.001). Exploratory factor analysis revealed three factors. The reliability of the scale was good (Cronbach's alpha: 0.90), and the intraclass coefficient was 0.85. The severity of the burden of neurofibromatosis was moderate, and the total mean burden score was 33.12 ± 16.12. CONCLUSIONS: The Persian version of the BoN is an acceptable tool in terms of structure and content, and it specifically assesses the practical aspects of daily activities for patients with neurofibromatosis.

Diffuse Neurofibroma in a Micronesian Male.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, with variable clinical features, most commonly including café-au-lait macules and neurofibromas. The incidence of NF1 is approximately one in 3,000 individuals. Diffuse neurofibroma is the rarest subtype of neurofibromas. We present a case of a 39-year-old Micronesian male presenting with a substantially large and heavy overgrowth on his back, found to be consistent with diffuse neurofibroma on histopathologic examination. The patient also met the diagnostic criteria for NF1 based on clinical examination. Imaging showed the dermal and subcutaneous thickening without deep extension into the underlying fascial layer or muscles. A patient-centered, multidisciplinary approach was taken in the workup and management of this case. Our patient expressed disinterest in surgical interventions.

Rapid airway stenosis due to ruptured occipital artery in a patient with neurofibromatosis type I.

Background: Neurofibromatosis type I is rarely associated with vascular abnormalities. Here, we report a case of rapid airway stenosis caused by a ruptured occipital artery that was treated with surgical airway management. Case Presentation: A 40-year-old woman, with no medical history, presented with a chief complaint of a sudden neck pain on the left side. She had a prominent mass in the outer left side of the neck. After arrival at the emergency room, the patient complained of severe dyspnea and experienced a rapid drop in oxygen saturation. Supplemental ventilation was ineffective, and tracheal intubation was attempted; however, laryngeal expansion could not be observed because of the enlarged cervical mass. Therefore, to manage the surgical airway, a cricothyrotomy was first carried out, which resulted in an immediate increase in oxygen saturation. Two percutaneous embolizations and one surgical procedure were carried out, and the patient was discharged without any complications. Conclusion: For a sudden onset cervical mass, airway management should be undertaken, keeping in mind the possibility of worsening rapid airway narrowing due to bleeding.

Modified facelift in severe plexiform neurofibromatosis associated with venous vascular malformation: Case report.

Neurofibromatosis is an autosomal dominant disorder characterized by tumors of the nervous system and skin. Plexiform neurofibromas are common complications of neurofibromatosis type 1 and can cause large facial deformities. Vascular anomalies are in turn a rare manifestation of neurofibromatosis. We present the case of a 48-year-old female patient with right hemifacial neurofibromatosis associated with venous vascular malformation, previously treated surgically and then with sclerosing agents, determining severe residual facial deformity. Her surgical approach using a modified facelift technique associated with partial tumor debulking and lipofilling seems to be a valid technical alternative for these highly complex cases that require a customized approach after exhaustive preoperative evaluation.

A fortuitous discovery of a neurofibroma in a female patient with type 1 neurofibromatosis: a case report.

Neurofibromatosis type 1 (NF1) is a neurocutaneous condition with an autosomal dominant pattern of inheritance. This congenital disease is characterized by a wide spectrum of clinical manifestations and degree of severity. This case report describes a female patient in her early 20s who presented with a complaint of lumbosciatica-like pain evolving for several months. The condition initially escaped the attention of clinicians until a lumbar computed tomography scan and spinal magnetic resonance imaging were performed. The patient was then transferred to the general surgery department, where a clinical diagnosis of NF1 was established. The clinical manifestations were specific for this disease, including café-au-lait macules, plexiform neurofibroma, and a history of neurofibromatosis in her mother. The patient underwent surgical resection of the neurofibroma, which resulted in a favorable outcome. However, 2 years later, a new mass attached to the second lumbar spinal nerve was revealed by a follow-up computed tomography scan. Long-term and close follow-up of NF1 is required because of the high risk of malignancy and recurrence in NF1 patients.

Systematic Review of Pediatric Brain Tumors in Neurofibromatosis Type 1: Status of Gene Therapy.

As oncology practice is rapidly shifting away from toxic chemotherapy, gene therapy provides a highly specific therapeutic approach for brain tumors. In this systematic review, we investigate gene therapy's status in pediatric brain tumors and future recommendations. The search was conducted systematically using PubMed, Cochrane, Google Scholar, and ClinicalTrials.gov databases. The field search used in the process was selected based on the keywords and Medical Subject Headings (MeSH), depending on the database used. We included cases of neurofibromatosis type 1 (NF1) brain tumors in all age groups with the additional inclusion of English language, free full text, articles published within the last 20 years, randomized controlled trials (RCTs), observational studies, systematic reviews, and meta-analyses. We excluded case reports, case studies, and editorials. The search identified a total of 1,213 articles from the databases. We included 19 studies with 16 narrative reviews, one systematic review, and two randomized clinical trials with 43 patients. After reviewing all data in the articles, we found that gene therapy can improve standard treatment efficacy when used as adjuvant therapy. It can be used to overcome barriers such as chemotherapy resistance by downregulating resistance genes. It is associated with mild toxicity when compared with other available treatment options, but given the overall poor prognosis in pediatric brain tumors, further studies are warranted.

[Lisch nodules: an ophthalmic marker of neurofibromatosis type 1]. / Nodules de Lisch: marqueur ophtalmologique de la neurofibromatose de type 1.

Von Recklinghausen disease or neurofibromatosis type I (NF1) is the most common phacomatosis. It is inherited in an autosomal dominant manner. Lisch nodules are the most common ophthalmic manifestation of NF1. They are reported in 73-95% of cases. We here report the case of a 49-year-old female patient referred for a consultation with an ophthalmologist for routine eye check-up after the onset of the following symptoms: coffee-with-milk colored spots and multiple neurofibromas (A). She reported similar family history. Visual acuity was 10/10 P2 in both eyes. Examination of the anterior segment showed several Lisch nodules in both irises. They were scattered over the entire iris surface and varied in size (B). Fundus examination was unremarkable. CT scan of the brain and the orbit as well as thoracoabdominal CT scan showed no associated lesion. The patient met NIH diagnostic criteria for NF1. Lisch nodules are small brown dome-shaped lesions developing on the surface of the iris, with well-defined edges, embedded in the stroma and lighter than iris pigmentation. Differential diagnosis includes iris mammillations, iris naevi, iris melanoma, iris granulomatous nodules. Unlike skin signs, the presence of multiple Lisch nodules are considered a specific indication of NF1. These nodules may occur in childhood and their prevalence and number increase with age. Thus, periodic eye examinations in subjects with suspected neurofibromatosis type I may help to improve early diagnosis.

Case report: Bilateral spinal neurofibromatosis.

Spinal neurofibromatosis (SNF) is a rare form of Neurofibromatosis in which neurofibromas exist bilaterally throughout all spinal roots. Despite previous attempts made to characterize and classify the disease as a separate clinical form of the disease, the low incidence rate of the disease and scarcity of previous reports calls for further studies and reports to elaborate this clinical entity. The patient in this report was a 36-year-old man presenting with lower limb weakness, unsteady gait, and paresthesia. The patient also presented with multiple cutaneous café-au-lait spots, cutaneous neurofibromas, and a large neurocutaneous neurofibroma of right facial nerve. Magnetic resonance imaging (MRI) of spine revealed bilateral spinal neurofibromas across all spinal cord roots. MRI study of head revealed no abnormalities in the brain and optic tract. The patient fulfilled both NIH criteria as well as revised criteria for NF1. Despite total spinal cord involvement, surgical intervention was withheld from the patient due to high propensity of recurrence as seen with previous attempts in removing peripheral neurofibromas, slow progression of symptoms, and lack of significant pain and impairment. SNF is often described as a form of disease with infrequent presentation of classical NF1 symptoms other than spinal tumors. The case presented here however, presented with several cutaneous neurofibromas and café-au-lait spots. Considering the positive outcome of surgical intervention in a few other reports, the decision to surgically intervene should be left to the clinical judgement of the participating surgeon, patient preference and socioeconomic background in a case-by-case manner.