Giant Cerebriform Nevus Lipomatosus Cutaneous- Superficialis with Diffuse Lipomatosis: An Unusual Presentation on the Neck.

A 25-year-old man presented with gradually increasing swelling of 15 years' duration on the left side of his neck. There had been occasional foul-smelling discharge from the swelling. Local examination revealed an 8 cm × 5 cm oblong-shaped, yellowish to skin-colored, soft, -cerebriform swelling. There were multiple open comedones (Figure 1a). The surrounding skin had small and soft skin-colored papules. On palpation, there was no ulceration, tenderness, induration, or bag of worms. A scar from the past surgery was visible. Systemic examina- tion was unremarkable. The differential diagnosis demonstrated plexiform neurofibroma and nevus lipomatosus cutaneous superficialis (NLCS; Figure 2).

Revisiting the NPcis mouse model: A new tool to model plexiform neurofibroma.

Neurofibromatosis Type I (NF1) is a rare genetic disorder. NF1 patients frequently develop a benign tumor in peripheral nerve plexuses called plexiform neurofibroma. In the past two decades, tissue-specific Nf1 knockout mouse models were developed using commercially available tissue-specific Cre recombinase and the Nf1 flox mice to mimic neurofibroma development. However, these models develop para-spinal neurofibroma, recapitulating a rare type of neurofibroma found in NF1 patients. The NPcis mouse model developed a malignant version of neurofibroma called malignant peripheral nerve sheath tumor (MPNST) within 3 to 6 months but intriguingly without apparent benign precursor lesion. Here, we revisited the NPcis model and discovered that about 20% display clinical signs similar to Nf1 tissue-specific knockout mice models. However, a systematic histological analysis could not explain the clinical signs we observed although we noticed lesions reminiscent of a neurofibroma in a peripheral nerve, a cutaneous neurofibroma, and para-spinal neurofibroma on rare occasions in NPcis mice. We also observed that 10% of the mice developed a malignant peripheral nerve sheath tumor (MPNST) spontaneously, coinciding with their earring tag identification. Strikingly, half of the sciatic nerves from NPcis mice developed plexiform neurofibroma within 1-6 months when intentionally injured. Thus, we provided a procedure to turn the widely used NPcis sarcoma model into a model recapitulating plexiform neurofibroma.

Selumetinib for children with neurofibromatosis type 1 and plexiform neurofibromas: A plain language summary of SPRINT.

WHAT IS THIS SUMMARY ABOUT?: This summary describes a publication about a study called SPRINT. The SPRINT study included 50 children with neurofibromatosis type 1 (NF1) and plexiform neurofibroma (PN) that could not be removed with surgery. PNs are tumors that grow along nerves and can cause various problems for children, such as pain, changes to appearance, and muscle weakness. In SPRINT, the study team wanted to learn whether a medication called selumetinib was able to shrink the PN caused by NF1 (also known as NF1-related PN), and if shrinking PNs helped relieve children of the problems caused by it. To assess how selumetinib might help, children had scans to measure the size of their PN, completed questionnaires, and had a variety of other tests done by their doctor. Their caregivers also completed questionnaires about their child. The children took selumetinib capsules twice a day on an empty stomach. WHAT WERE THE RESULTS?: The results showed that selumetinib was able to shrink the PN for most children (68%). The results also showed that the problems caused by the children's PNs mostly improved while on selumetinib treatment. SPRINT also showed that the side effects of selumetinib were mainly mild and could be managed by doctors. WHAT DO THE RESULTS MEAN?: Before SPRINT, there were not many treatment options for children with NF1 and PN as there were no medications that had been shown to shrink PN, and surgery was not always possible. SPRINT showed that this medication shrinks most PNs and could help children with NF1 and PN. In April 2020, selumetinib was approved by the US Food and Drug Administration (FDA) because of the results of SPRINT. Selumetinib was the first and, as of February 2024, is the only medicine that can be prescribed by doctors to help children with NF1-related PN. Clinical Trial Registration: NCT01362803 (SPRINT) (ClinicalTrials.gov).

Precision oncology in neurofibromatosis type 1: quantification of differential sensitivity to selumetinib in plexiform neurofibromas using single-cell RNA sequencing.

PURPOSE: Selumetinib is an FDA-approved targeted therapy for plexiform neurofibromas in neurofibromatosis type 1(NF1) with durable response rates seen in most, but not all patients. In this proof-of-concept study, we demonstrate single-cell RNA sequencing(scRNAseq) as a technique for quantifying drug response to selumetinib at the single cell level. METHODS: scRNAseq data from neurofibroma biopsies was obtained from a public genomics repository. Schwann cell populations were identified through standard clustering techniques and single-cell selumetinib sensitivity was quantified on a scale of 0(resistant) to 1(sensitive) based on the expression pattern of a 500 gene selumetinib sensitivity signature from the BeyondCell sensitivity library. RESULTS: A total of seven plexiform neurofibromas were included in our final analysis. The median absolute number of Schwann cells across samples was 658 cells (IQR: 1,029 cells, Q1-Q3: 135 cells to 1,163 cells). There was a statistically significant difference in selumetinib sensitivity profiles across samples (p < 0.001). The tumor with the highest median selumetinib sensitivity score had a median selumetinib sensitivity score of 0.64(IQR: 0.14, Q1-Q3: 0.59-0.70, n = 112 cells) and the tumor with the lowest median selumetinib sensitivity score had a median score of 0.37 (IQR: 0.21, Q1-Q3: 0.27-0.48, n = 1,034 cells). CONCLUSIONS: scRNAseq of plexiform neurofibroma biopsies reveals differential susceptibilities to selumetinib on a single cell level. These findings may explain the partial responses seen in clinical trials of selumetinib for NF1 and demonstrate the value of collecting scRNAseq data for future NF1 trials.

Intraparotid plexiform neurofibroma: A rare diagnostic challenge.

Isolated intraparotid neurofibromas are exceptionally rare and often associated with neurofibromatosis type 1 (NF1). Diagnosing these tumors proves challenging because of the clinical resemblance to primary salivary gland masses. This case report details an 18-year-old with a painful, enlarging parotid mass, diagnosed through fine needle aspiration biopsy (FNAB) revealing myxoid stroma and spindle cells. Magnetic resonance imaging confirmed a plexiform neurofibroma involving the parotid gland and facial nerve. Histopathology validated the diagnosis, emphasizing the importance of cytological and radiological correlation. Notably, the absent NF1 association makes this case unique. Surgical excision with facial nerve reconstruction was performed, highlighting the complexity of managing such rare intraparotid neurofibromas. Awareness of this entity is crucial for accurate diagnosis and appropriate management.

A Population Pharmacokinetic Assessment of the Effect of Food on Selumetinib in Patients with Neurofibromatosis Type 1-Related Plexiform Neurofibromas and Healthy Volunteers.

Selumetinib is clinically used for pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas. Until recently, selumetinib had to be taken twice daily, after 2 hours of fasting and followed by 1 hour of fasting, which could be inconvenient. This population analysis evaluated the effect of low- and high-fat meals on the pharmacokinetic (PK) parameters of selumetinib and its active metabolite N-desmethyl selumetinib. The dataset comprised 511 subjects from 15 clinical trials who received ≥1 dose of selumetinib and provided ≥1 measurable postdose concentration of selumetinib and N-desmethyl selumetinib. A 2-compartment model with sequential 0- and 1st-order delayed absorption and 1st-order elimination adequately described selumetinib PK characteristics. A 1-compartment model reasonably described N-desmethyl selumetinib PK characteristics over time simultaneously with selumetinib. Selumetinib geometric mean area under the concentration-time curve ratio (1-sided 90% confidence interval [CI] lower bound) was 76.9% (73.3%) with a low-fat meal and 79.3% (76.3%) with a high-fat meal versus fasting. The lower bound of the 1-sided 90% CI demonstrated a difference of <30% between fed and fasted states. Considering the flat exposure-response relationship within the dose range (20-30 mg/m2), the observed range of exposure, and the variability in the SPRINT trial, this was not considered clinically relevant.

C5aR plus MEK inhibition durably targets the tumor milieu and reveals tumor cell phagocytosis.

Plexiform neurofibromas (PNFs) are nerve tumors caused by loss of NF1 and dysregulation of RAS-MAPK signaling in Schwann cells. Most PNFs shrink in response to MEK inhibition, but targets with increased and durable effects are needed. We identified the anaphylatoxin C5a as increased in PNFs and expressed largely by PNF m acrophages. We defined pharmacokinetic and immunomodulatory properties of a C5aR1/2 antagonist and tested if peptide antagonists augment the effects of MEK inhibition. MEK inhibition recruited C5AR1 to the macrophage surface; short-term inhibition of C5aR elevated macrophage apoptosis and Schwann cell death, without affecting MEK-induced tumor shrinkage. PNF macrophages lacking C5aR1 increased the engulfment of dying Schwann cells, allowing their visualization. Halting combination therapy resulted in altered T-cell distribution, elevated Iba1+ and CD169+ immunoreactivity, and profoundly altered cytokine expression, but not sustained trumor shrinkage. Thus, C5aRA inhibition independently induces macrophage cell death and causes sustained and durable effects on the PNF microenvironment.

The PlexiQoL, a patient-reported outcome measure on quality of life in neurofibromatosis type 1-associated plexiform neurofibroma: translation, cultural adaptation and validation into the Dutch language for the Netherlands.

BACKGROUND: Half of the patients with Neurofibromatosis type 1 (NF1) develop one or more tumours called plexiform neurofibromas, which can have a significant impact on Quality of Life (QoL). The PlexiQoL questionnaire is a disease-specific QoL measure for adults with NF1-associated plexiform neurofibromas. The aim of this study was to adapt and validate a Dutch version of the PlexiQoL for the Netherlands. METHODS: The PlexiQoL was translated using the dual-panel methodology, followed by cognitive debriefing interviews to assess face and content validity. The psychometric properties were evaluated by administering the questionnaire on two separate occasions to a sample of adults with NF1 and plexiform neurofibromas. Feasibility was evaluated by the presence of floor/ceiling effects. Reliability was assessed by evaluating Cronbach's alpha coefficient and test-retest reliability, using Spearman's rank correlation coefficients. Mann-Whitney U tests were used to check for known group validity. The Nottingham Health Profile (NHP) questionnaire was used as comparator questionnaire to evaluate convergent validity. RESULTS: The translation and cognitive debriefing interviews resulted in a Dutch version of the PlexiQoL that reflected the original concept and underlying semantic meanings of the UK English version. Forty participants completed the validation survey. The Dutch PlexiQoL demonstrated excellent internal consistency (Cronbach's α 0.825) and test-retest reliability (Spearman correlation coefficient 0.928). The questionnaire detected differences in PlexiQoL scores between participants based on self-reported general health and disease severity. Convergent validity was confirmed for relevant NHP subsections. CONCLUSIONS: The Dutch PlexiQoL demonstrated excellent psychometric properties and can be reliably used to measure plexiform neurofibroma-related QoL in adults with NF1 in the Netherlands.

Efficacy and safety of selumetinib in patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas: a systematic review and meta-analysis.

BACKGROUND: The approval of selumetinib in patients with neurofibromatosis type 1(NF1) and inoperable plexiform neurofibromas (PN) has reshaped the landscape of clinical management of the disease, and further comprehensive evaluation of the drug's efficacy and safety is needed. METHODS: Original articles reporting on the efficacy and safety of elumetinib in patients with NF1 were comprehensively searched in the Pubmed database, Embase database, Cochrane Library, and Web of Science database and screened for inclusion of studies that met the criteria. We pooled the objective response rate (ORR), disease control rate (DCR), disease progression rate (DPR), and the rate of improvement in PN-related complications using meta-analysis. The incidence of drug-related adverse events was also statistically analyzed. RESULTS: This study included 10 clinical trials involving 268 patients. The pooled ORR was 68.0% (95% CI 58.0-77.3%), the DCR was 96.8% (95% CI 90.8-99.7%) and the DPR was only 1.4% (95% CI 0-4.3%). The pooled improvement rate was 75.3% (95% CI 56.2-90.9%) for pain and 77.8% (95% CI 63.1-92.5%) for motor disorders. Most adverse events were mild, with the most common being gastrointestinal reactions (diarrhea: 62.5%; vomiting: 54.5%). CONCLUSION: Our study demonstrates that selumetinib is effective in patients with NF1 and PN, significantly improving the serious complications associated with PN as well as having tolerable toxicities. Our findings help to increase clinicians' confidence in applying selumetinib and promote the clinical adoption and benefit of the new drug.

Cutaneous toxicities of mitogen-activated protein kinase inhibitors in children and young adults with neurofibromatosis-1.

PURPOSE: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder which commonly causes neoplasms leading to disfigurement or dysfunction. Mitogen-activated protein kinase inhibitors (MEKi) are generally well-tolerated treatments which target neural tumor progression in patients with NF1. However, cutaneous adverse events (CAEs) are common and may hinder patients' abilities to remain on treatment, particularly in children. We aim to characterize CAEs secondary to MEKi treatment in pediatric and young adult patients with NF1. METHODS: We reviewed institutional medical records of patients under 30 years with a diagnosis of "NF1," "NF2," or "other neurofibromatoses" on MEKi therapy between January 1, 2019 and June 1, 2022. We recorded the time-to-onset, type, and distribution of CAEs, non-cutaneous adverse events (AEs), AE management, and tumor response. RESULTS: Our cohort consisted of 40 patients with NF1 (median age, 14 years). Tumor types included low-grade gliomas (51%) and plexiform neurofibromas (38%). MEKi used included selumetinib (69%), trametinib (25%), and mirdametinib (6%). A total of 74 CAEs occurred, with 28 cases of acneiform rash (38%). Other common CAEs were paronychia, seborrheic dermatitis, eczema, xerosis, and oral mucositis. The most common treatments included oral antibiotics and topical corticosteroids. Most patients had clinical (stable or improved) tumor response (71%) while 29% had tumor progression while on a MEKi. There was no significant association between CAE presence and tumor response (p = 0.39). CONCLUSIONS: Improvement in characterization of MEKi toxicities and their management is important to develop treatment guidelines for pediatric and young adult patients with NF1 on MEKi therapy.

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.

Perceived transition readiness among adolescents and young adults with neurofibromatosis type 1 and plexiform neurofibromas: a cross-sectional descriptive study.

OBJECTIVES: Neurofibromatosis type 1 (NF1) is a genetic cancer predisposition syndrome that can impact multiple organ systems and is associated with plexiform neurofibroma tumors, requiring care from birth through adulthood. Adolescents and young adults (AYAs) with NF1 face several barriers to transition from pediatric to adult care. This cross-sectional study aimed to assess transition readiness in this population and to evaluate relationships between specific NF1 symptoms and transition readiness. METHODS: AYAs (aged 16-24) enrolled in existing studies related to NF1 were eligible. AYAs and their parents completed measures of transition readiness (Transition Readiness Assessment Questionnaire version 4 [TRAQ-4]), and AYAs also completed a transition readiness interview (UNC TRxANSITION). RESULTS: Thirty-eight AYAs (mean age = 19.95 ± 2.68 years) participated in the study. Average TRAQ scores indicated that AYAs were still learning Self-Management skills (M = 3.37, SD = 1.08) and Self-Advocacy skills (M = 3.98, SD = 0.67). Older AYAs had higher TRAQ scores for Self-Management (r = 0.70, p < .001) and Self-Advocacy (r = 0.41, p = .011) than younger AYAs. Parents and AYAs had similar TRAQ scores. About one third of AYAs (37.8%, n = 14) expressed uncertainty about how NF1 might affect them in the future. The remaining AYAs mostly expressed concerns regarding tumor growth, pain, or cancer. CONCLUSIONS: In this small study, preliminary findings suggest that AYAs with NF1 express confidence in many areas of transition readiness but continue to require support, particularly with Self-Management skills. Given the gaps in understanding of future health risks, AYAs with NF1 would benefit from early assessment, psychoeducation, and support for transition readiness to adult care.

Schwann cell derived pleiotrophin stimulates fibroblast for proliferation and excessive collagen deposition in plexiform neurofibroma.

Neurofibromatosis type 1 associated plexiform neurofibroma (pNF) is characterized by abundant fibroblasts and dense collagen, yet the intricate interactions between tumor-origin cells (Schwann cells) and neurofibroma-associated fibroblasts (NFAFs) remain elusive. Employing single-cell RNA sequencing on human pNF samples, we generated a comprehensive transcriptomics dataset and conducted cell-cell communication analysis to unravel the molecular dynamics between Schwann cells and NFAFs. Our focus centered on the pleiotrophin (PTN)/nucleolin (NCL) axis as a pivotal ligand-receptor pair orchestrating this interaction. Validation of PTN involvement was affirmed through coculture models and recombinant protein experiments. Functional and mechanistic investigations, employing assays such as CCK8, EdU, Western Blot, ELISA, Hydroxyproline Assay, and Human phospho-kinase array, provided critical insights. We employed siRNA or inhibitors to intercept the PTN/NCL/proline-rich Akt substrate of 40 kDa (PRAS40) axis, validating the associated molecular mechanism. Our analysis highlighted a subset of Schwann cells closely linked to collagen deposition, underscoring their significance in pNF development. The PTN/NCL axis emerged as a key mediator of the Schwann cell-NFAF interaction. Furthermore, our study demonstrated that elevated PTN levels enhanced NFAF proliferation and collagen synthesis, either independently or synergistically with TGF-ß1 in vitro. Activation of the downstream molecule PRAS40 was noted in NFAFs upon PTN treatment. Crucially, by targeting NCL and PRAS40, we successfully reversed collagen synthesis within NFAFs. In conclusion, our findings unveil the pivotal role of the PTN/NCL/PRAS40 axis in driving pNF development by promoting NFAFs proliferation and function. Targeting this pathway emerges as a potential therapeutic strategy for pNF. This study contributes novel insights into the molecular mechanisms governing pNF pathogenesis.

Treatment With Selumetinib for Café-au-Lait Macules and Plexiform Neurofibroma in Pediatric Patients With Neurofibromatosis Type 1.

This case report describes 4 patients with a rare autosomal dominant multisystem disorder resulting from NF1 variants that leads to café-au-lait macules and neurofibromas.

Giant gluteal and vesical plexiform neurofibromas in a patient with neurofibromatosis type 1: a case report.

BACKGROUND: Neurofibromatosis type 1 is a neurocutaneous genetic disorder caused by mutations in the NF1 gene, resulting in the formation of benign tumors called neurofibromas. The most common type of tumor seen in patients with neurofibromatosis type 1 is the slow-growing and benign neurofibroma, with a subtype called plexiform neurofibroma being particularly common and causing pain, functional impairment, and cosmetic disfigurement. CASE PRESENTATION: We report the case of a 20-year-old North African female patient with a history of neurofibromatosis type 1 who presented with a growing mass in her right gluteal region, which was later diagnosed as a giant cutaneous neurofibroma. Imaging studies revealed infiltration in several regions, including the urinary bladder wall, resulting in significant bilateral hydronephrosis. The patient is currently being monitored, and no excisional procedures are planned. CONCLUSIONS: Neurofibromatosis type 1 can cause a variety of clinical symptoms, including the development of large plexiform neurofibromas. It is important to closely monitor patients with neurofibromatosis type 1 for the early detection of neurofibromas. Early detection and prompt surgical intervention are essential for preventing complications.

Recommendations for assessing appearance concerns related to plexiform and cutaneous neurofibromas in neurofibromatosis 1 clinical trials.

BACKGROUND/AIMS: Individuals with neurofibromatosis 1 may experience changes in their appearance due to physical manifestations of the disorders and/or treatment sequelae. Appearance concerns related to these physical changes can lead to psychological distress and poorer quality of life. While many neurofibromatosis 1 clinical trials focus on assessing changes in tumor volume, evaluating patients' perspectives on corresponding changes in symptoms such as physical appearance can be key secondary outcomes. We aimed to determine whether any existing patient-reported outcome measures are appropriate for evaluating changes in appearance concerns within neurofibromatosis 1 clinical trials. METHODS: After updating our previously published systematic review process, we used it to identify and rate existing patient-reported outcome measures related to disfigurement and appearance. Using a systematic literature search and initial triage process, we focused on identifying patient-reported outcome measures that could be used to evaluate changes in appearance concerns in plexiform or cutaneous neurofibroma clinical trials in neurofibromatosis 1. Our revised Patient-Reported Outcome Rating and Acceptance Tool for Endpoints then was used to evaluate each published patient-reported outcome measures in five domains, including (1) respondent characteristics, (2) content validity, (3) scoring format and interpretability, (4) psychometric data, and (5) feasibility. The highest-rated patient-reported outcome measures were then re-reviewed in a side-by-side comparison to generate a final consensus recommendation. RESULTS: Eleven measures assessing appearance concerns were reviewed and rated; no measures were explicitly designed to assess appearance concerns related to neurofibromatosis 1. The FACE-Q Craniofacial Module-Appearance Distress scale was the top-rated measure for potential use in neurofibromatosis 1 clinical trials. Strengths of the measure included that it was rigorously developed, included individuals with neurofibromatosis 1 in the validation sample, was applicable to children and adults, covered item topics deemed important by neurofibromatosis 1 patient representatives, exhibited good psychometric properties, and was feasible for use in neurofibromatosis 1 trials. Limitations included a lack of validation in older adults, no published information regarding sensitivity to change in clinical trials, and limited availability in languages other than English. CONCLUSION: The Response Evaluation in Neurofibromatosis and Schwannomatosis patient-reported outcome working group currently recommends the FACE-Q Craniofacial Module Appearance Distress scale to evaluate patient-reported changes in appearance concerns in clinical trials for neurofibromatosis 1-related plexiform or cutaneous neurofibromas. Additional research is needed to validate this measure in people with neurofibromatosis 1, including older adults and those with tumors in various body locations, and explore the effects of nontumor manifestations on appearance concerns in people with neurofibromatosis 1 and schwannomatosis.

Neurofibroma: Case Series with Clinical Features and Recommendations.

Neurofibroma is an autosomal benign disorder. It can be localized, diffuse or invasive like plexiform neurofibroma that involves the nerves, muscle, tissues, skeleton. It represents itself as a destructive variant of neurofibroma, mostly present as orbital or periorbital neurofibroma or may be associated with autosomal dominant disease. Clinical diagnosis of neurofibromatosis (NF) according to National Institutes of Health (NIH) criteria should have more than two of the seven features including lisch nodules, cafe'- au-lait spots, plexiform neurofibroma, optic glioma, freckling, first degree relative with NF or dysplasia of cortical bones. However, proper early diagnosis is still crucial due to its various presentation such as cheek mass, painless swelling on skin, chalazion, intratracheal tumor, genital swelling or ptosis. It is reported that neurofibroma often represents as ocular or facial swelling. Here we are presenting features of neurofibroma of eight cases of patients from Civil Hospital, Karachi. These cases had main complain of overhanging skin mass mainly on orbital or periorbital region that damage the area and with poor daily activities. Multiple nodules on face and body along with them Cafe'-au-lait spots and lisch nodules were main signs. While, other signs i.e. ptosis, pterygium, telecanthus and muddy discoloration of conjunctiva need further evaluation for correlation with neurofibromatosis. Debulking surgery was planned for most of the cases but the huge disfigurement caused by overhanging skin mass and nodules made it a challenge for plastic surgeons to provide good outcomes with minimum damage. Keywords: neurofibroma; lisch nodules; ptosis; Cafe'-au-lait spot; periorbital; overhanging skin.

Neurofibromatosis laríngea pediátrica: reporte de localización atípica / Pediatric neurofibromatosis of the larynx: report of atypical location

Los neurofibromas laríngeos (NFL) son tumores benignos poco frecuentes de localización principalmente supraglótica. Se manifiestan con síntomas obstructivos de la vía aérea. El tratamiento es la resección completa del tumor mediante abordaje endoscópico; se reserva la cirugía abierta para tumores de gran extensión. Se presenta el caso de un paciente pediátrico con localización atípica de NFL asociado a neurofibromatosis tipo 1 (NF1). Se realizó resección endoscópica del tumor y la anatomía patológica informó neurofibroma plexiforme. Es importante sospechar de esta patología en todo niño con estridor inspiratorio atípico progresivo. Se sugiere seguimiento a largo plazo por la alta probabilidad de recidiva.

Laryngeal neurofibromas (LNFs) are rare benign tumors mainly located in the supraglottis. LNFs occur with airway obstruction symptoms. The treatment is complete resection via an endoscopic technique; the open approach is reserved for large tumors. Here we describe the case of a pediatric patient with LNF of atypical location associated with neurofibromatosis type 1 (NF-1). The tumor was resected with an endoscopic technique, and the pathological study reported a plexiform neurofibroma. It is important to suspect this condition in any child with atypical, progressive inspiratory stridor. Long-term follow-up is recommended due to the high rate of recurrence