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We present the case of a patient with neurofibromatosis-1, also known as von Recklinghausen's disease, and hepatic neurofibromatosis, and in which during the evaluation for abdominal pain syndrome, an imaging study was performed that defined the process as a mass extensive, occupying, with a compressive effect on the liver parenchyma, and distortion of both the intrahepatic and extrahepatic bile ducts. The development of extensive plexiform neurofibromas is an unusual presentation of the condition and even more so with abdominal involvement, as in this case, which is much less frequent. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is associated with below average writing achievement. However, little is known about specific aspects of written language impacted by NF1, changes in writing over time, and associations between cognitive aspects of the NF1 phenotype and writing. At three timepoints over six years, children with NF1 and plexiform neurofibromas (PNs) completed Woodcock-Johnson tests of writing mechanics (Spelling, Punctuation & Capitalization, handwriting), written expression of ideas (Writing Samples), writing speed (Writing Fluency), and tests of general cognitive ability, executive function, memory, and attention. Children (N = 76, mean age = 12.8 ± 3.4 years) completed at least one baseline writing subtest. Overall writing scores were in the Average range (M = 93.4, SD = 17.4), but lower than population norms (p = 0.002). Scores were highest on Writing Samples (M = 95.2, SD = 17.3), and lowest for Punctuation & Capitalization (M = 87.9, SD = 18.8, p = 0.034). Writing scores were mostly stable over time. Nonverbal reasoning was related to some tests of writing mechanics and written expression of ideas. Short-term memory and inattention explained additional variance in Writing Samples and Spelling. Poor handwriting was associated with writing content beyond the impact of cognitive factors. Children with NF1 and PNs may benefit from early screening and writing support. Interventions should address the contribution of both cognitive and handwriting difficulties in written language. [ABSTRACT FROM AUTHOR]

Pelvicoabdominal plexiform neurofibroma is a rare and complicated form of type 1 neurofibromatosis (NF1), distinguished by developing benign nerve sheath tumors in the pelvis and abdomen. A male patient, aged 26, came to our center with dysuria, abdominal bloating, rectal mucosa prolapses, and trouble walking and moving legs. Physical examination revealed a palpable mass of solid consistency fixed in the pelvic cavity to the abdominal cavity. A large and extensive mass in the pelvic to the abdominal region can be evaluated with multimodality radiological imaging, including ultrasound, computed tomography, and magnetic resonance imaging. Imaging is crucial for diagnosis, evaluation of extension, and early detection of potential malignant transformation in these patients. The patient was scheduled for palliative surgical resection due to the extensive mass; however, he did not survive while waiting for the operation. Pathology examination and immunohistochemical staining revealed positive S-100 protein, indicating the neural crest originate lesion. We report the clinical and radiological features of plexiform neurofibroma in a young male patient, confirmed by pathology examination.

Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders that predisposes patients to benign and malignant tumors of the peripheral nervous system. Plexiform and cutaneous neurofibromas are NF1-associated benign tumors. Despite their benign nature, they can cause tremendous morbidity in patients with NF1. Therapeutic drug options are limited to the MEK inhibitor, selumetinib, which is the only approved drug for pediatric patients with plexiform neurofibromas. Antifibrotic strategies have substantial therapeutic potential for NF1-associated neurofibromas. This review discusses the fibrotic features of plexiform and cutaneous neurofibromas focusing on the pathological composition of the extracellular matrix. It also highlights the core pathways implicated in the biochemical and biophysical regulation of the extracellular matrix remodeling in tumor imitation and progression. Finally, this review provides a brief outlook on how exploring novel vulnerabilities residing in the aberrant extracellular matrix and their underlying pathways can benefit the treatment of NF1-associated 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Plexiform neurofibromas in neurofibromatosis type 1 (pNF1), characterized by aggressive growth and local invasiveness, are comprised primarily of Schwann cell-derived tumor cells (Nf1−/−) and the tumor microenvironment (TME). Fibroblasts (Nf1+/−), the most abundant cell type in the TME, are known to significantly contribute to pNF1 formation, but their precise role in the subsequent tumor progression is poorly understood. Using our established three-dimensional (3D) culture models with patient-derived pNF1 cells and fibroblasts, we observed that the fibroblast-derived secretome stimulates the growth and local invasiveness of pNF1 spheroids. Depletion of small extracellular vesicles (sEVs) from the fibroblast secretome completely eliminated the paracrine effect on pNF1 spheroid growth. These results suggest that targeting paracrine interactions between pNF1 tumor cells and fibroblasts may offer a potential therapeutic approach for reducing pNF1 tumor progression. Plexiform neurofibromas (PNs) occur in about a half of neurofibromatosis type 1 (NF1) patients and have garnered significant research attention due to their capacity for growth and potential for malignant transformation. NF1 plexiform neurofibroma (pNF1) is a complex tumor composed of Schwann cell-derived tumor cells (Nf1−/−) and the tumor microenvironment (TME). Although it has been widely demonstrated that the TME is involved in the formation of neurofibromas, little is known about the effects of the TME on the subsequent progression of human pNF1. Elucidating the molecular interactions between tumor cells and the TME may provide new therapeutic targets to reduce the progression of pNF1. In the present study, we focused on the contributions of fibroblasts, the most abundant cell types in the TME, to the growth of pNF1. To simulate the TME, we used a three-dimensional (3D) coculture model of immortalized pNF1 tumor cells (Nf1−/−) and primary fibroblasts (Nf1+/−) derived from pNF1 patients. We performed live-cell imaging of 3D/4D (3D in real-time) cultures through confocal microscopy followed by 3D quantitative analyses using advanced imaging software. The growth of pNF1 spheroids in 3D cocultures with fibroblasts was significantly greater than that of pNF1 spheroids in 3D monocultures. An increase in the growth of pNF1 spheroids also occurred when they were cultured with conditioned media (CM) from fibroblasts. Moreover, fibroblast-derived CM increased the invasive outgrowth and further local invasion of pNF1 spheroids. Interestingly, when small extracellular vesicles (sEVs) were depleted from the fibroblast-derived CM, the stimulation of the growth of pNF1 spheroids was lost. Our results suggest that fibroblast-derived sEVs are a therapeutic target for reducing the growth of pNF1. [ABSTRACT FROM AUTHOR]

This is a case report on how an 18 year old had to live with a growth on her back since last twelve years due to lack of medical facilities and taboos associated with these growths in developing nations like India. The girl had stunted growth due to the weight she was carrying and associated deformities in her spine. She was evaluated and finally underwent surgery for the same. Plexiform neurofibromas are tumors of the peripheral nerve sheaths. They occur in people born with genetic disease called neurofibromatosis. They are slow growing tumors and keep on growing with age. They are soft to begin with. There are instances when plexiform neurofibromas have shown rapid growth. Neurofibromas are generally considered benign and not removed until they cause any complication or for cosmetic reasons. We hereby present a case of plexiform neurofibroma which grew to reach a weight of 28 kgs and ended up causing spinal deformities in a young girl. Background: Plexiform neurofibromas are tumors of the peripheral nerve sheaths. They occur in people born with genetic disease called neurofibromatosis. They are slow growing tumorsand keep on growing with age. They are soft to begin with. There are instances when plexiform neurofibromas have shown rapid growth. Neurofibromas are generally considered benign and not removed until they cause any complication or for cosmetic reasons. Methods:. We hereby present a case of plexiform neurofibroma which grew to reach a weight of 28 kgs and ended up causing spinal deformities in a young girl. Results:This is a case report on how an 18 year old had to live with a growth on her back since last twelve years due to lack of medical facilities and taboos associated with these growths in developing nations like India. The girl had stunted growth due to the weight she was carrying and associated deformities in her spine. She was evaluated and finally underwent surgery for the same. Conclusions:in India, the lack of medical facilities and the negligence still met to the girl child is responsible for such humungous growths presenting at the tertiary centres even in the 21st century. It is the need of the hour to work on both these challenges. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome, occurs when NF1 gene variants result in loss of neurofibromin, a negative regulator of RAS activity. Plexiform neurofibromas (PN) are peripheral nerve sheath tumors that develop in patients with NF1 and are associated with substantial morbidity and for which, until recently, the only treatment was surgical resection. However, surgery carries several risks and a proportion of PN are considered inoperable. Understanding the genetic underpinnings of PN led to the investigation of targeted therapies as medical treatment options, and the MEK1/2 inhibitor selumetinib has shown promising efficacy in pediatric patients with NF1 and symptomatic, inoperable PN. In a phase I/II trial, most children (approximately 70%) achieved reduction in tumor volume accompanied by improvements in patient-reported outcomes (decreased tumor-related pain and improvements in quality of life, strength, and range of motion). Selumetinib is currently the only licensed medical therapy indicated for use in pediatric patients with symptomatic, inoperable NF1-PN, with approval based on the results of this pivotal clinical study. Several other MEK inhibitors (binimetinib, mirdametinib, trametinib) and the tyrosine kinase inhibitor cabozantinib are also being investigated as medical therapies for NF1-PN. Careful consideration of multiple aspects of both disease and treatments is vital to reduce morbidity and improve outcomes in patients with this complex and heterogeneous disease, and clinicians should be fully aware of the risks and benefits of available treatments. There is no single treatment pathway for patients with NF1-PN; surgery, watchful waiting, and/or medical treatment are options. Treatment should be individualized based on recommendations from a multidisciplinary team, considering the size and location of PN, effects on adjacent tissues, and patient and family preferences. This review outlines the treatment strategies currently available for patients with NF1-PN and the evidence supporting the use of MEK inhibitors, and discusses key considerations in clinical decision-making.

Abstract 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.

Objective: The aim of this study is to evaluate neurofibromatosis type 1 (NF1) patients with whole-body MRI (WBMRI) to investigate the frequency of plexiform neurofibromas (pNFs), diffuse neurofibromas (dNFs), and malignant peripheral nerve sheath tumors (MPNSTs). Materials and methods: In this retrospective cross-sectional study, between the years 2015 and 2023, 83 consecutive patients with known NF1 underwent a total of 110 WBMRI screenings for MPNST using a standardized institutional protocol. The lesions are categorized as discrete lesions, pNFs, dNFs, and MPNSTs. Histopathology served as the reference standard for all MPNSTs. Results: Among the 83 patients analyzed, 53 (64%) were women and 30 were men (36%) of ages 36.94±14.43 years (range, 15–66 years). Of the 83 patients, 33 have a positive family history of NF1 and positive genetic studies. Seven of 83 (8%) have only dNF, 20/83 (24%) have pNF, 28/83 (34%) have both dNF and pNF, and 28/83 (34%) have neither. Of the 83 patients, eight (9.6%) were diagnosed with nine total MPNSTs. Age range for patients with MPNSTs at time of diagnosis was 22–51, with an average age of 33.4 years. Only one MPNST (11%) developed from underlying pNF 4 years after WBMRI along the right bronchial tree. Three of eight (37.5%) patients with MPNST died within 5 years of pathologic diagnosis. Conclusion: This study suggests the absence of a predisposition for development of MPNST from pNFs and dNFs in the setting of NF1. As such, these lesions may not need special surveillance compared to discrete peripheral nerve sheath tumors. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is a rare neurogenetic disorder characterized by multiple organ system involvement and a predisposition to benign and malignant tumor development. With revised NF1 clinical criteria and the availability of germline genetic testing, there is now an opportunity to render an early diagnosis, expedite medical surveillance, and initiate treatment in a prompt and targeted manner. The authors review the spectrum of medical problems associated with NF1, focusing specifically on children and young adults. The age-dependent appearance of NF1-associated features is highlighted, and the currently accepted medical treatments are discussed. Additionally, future directions for optimizing the care of this unique population of children are outlined. The appearance of NF1-related medical problems is age dependent, requiring surveillance for those features most likely to occur at any given age during childhood. As such, we advocate a life stage-focused screening approach beginning in infancy and continuing through the transition to adult care. With early detection, it becomes possible to promptly institute therapies and reduce patient morbidity. Importantly, with continued advancement in our understanding of disease pathogenesis, future improvements in the care of children with NF1 might incorporate improved risk assessments and more personalized molecularly targeted treatments. [ABSTRACT FROM AUTHOR]

Background/Aims: We developed an observer disfigurement severity scale for neurofibroma-related plexiform neurofibromas to assess change in plexiform neurofibroma–related disfigurement and evaluated its feasibility, reliability, and validity. Methods: Twenty-eight raters, divided into four cohorts based on neurofibromatosis type 1 familiarity and clinical experience, were shown photographs of children in a clinical trial (NCT01362803) at baseline and 1 year on selumetinib treatment for plexiform neurofibromas (n = 20) and of untreated participants with plexiform neurofibromas (n = 4). Raters, blinded to treatment and timepoint, completed the 0–10 disfigurement severity score for plexiform neurofibroma on each image (0 = not at all disfigured, 10 = very disfigured). Raters evaluated the ease of completing the scale, and a subset repeated the procedure to assess intra-rater reliability. Results: Mean baseline disfigurement severity score for plexiform neurofibroma ratings were similar for the selumetinib group (6.23) and controls (6.38). Mean paired differences between pre- and on-treatment ratings was −1.01 (less disfigurement) in the selumetinib group and 0.09 in the control (p = 0.005). For the disfigurement severity score for plexiform neurofibroma ratings, there was moderate-to-substantial agreement within rater cohorts (weighted kappa range = 0.46–0.66) and agreement between scores of the same raters at repeat sessions (p > 0.05). In the selumetinib group, change in disfigurement severity score for plexiform neurofibroma ratings was moderately correlated with change in plexiform neurofibroma volume with treatment (r = 0.60). Conclusion: This study demonstrates that our observer-rated disfigurement severity score for plexiform neurofibroma was feasible, reliable, and documented improvement in disfigurement in participants with plexiform neurofibroma shrinkage. Prospective studies in larger samples are needed to validate this scale further. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Neurofibromatosis Type 1 (NF1) is a common neurogenic condition characterized by heterozygous loss of function mutations in the neurofibromin gene. NF1 patients are susceptible to the development of neurofibromas, including plexiform neurofibromas (pNFs), which occurs in about half of all cases. Plexiform neurofibroma are benign peripheral nerve sheath tumors originating from Schwann cells after complete loss of neurofibromin; they can be debilitating and also transform into deadly malignant peripheral nerve sheath tumors (MPNSTs). Here, our data indicates that silver nanoparticles (AgNPs) may be useful in the treatment of pNFs. We assessed the cytotoxicity of AgNPs using pNF cells and Schwann cells derived from the same NF1 patient. We found that AgNPs are selectively cytotoxic to pNF cells relative to isogenic Schwann cells. We then examined the role of neurofibromin expression on AgNP-mediated cytotoxicity; restoration of neurofibromin expression in pNF cells decreased sensitivity to AgNP, and knockdown of neurofibromin in isogenic Schwann cells increased sensitivity to AgNP, outlining a correlation between neurofibromin expression and AgNP-mediated cytotoxicity. AgNP was able to selectively remove pNF cells from a co-culture with patient-matched Schwann cells. Therefore, AgNPs represent a new approach for clinical management of NF1-associated pNF to address significant clinical need. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review, we explore how interactions between tumorigenic Schwann cells and infiltrating immune cells shape the development and malignant transformation of peripheral nerve sheath tumors in neurofibromatosis type 1. We summarize the current state of the field and address key knowledge gaps surrounding the impact of neurofibromin haploinsufficiency on immune cell function, as well as the impact of Schwann cell lineage states on immune cell recruitment and activation within the tumor microenvironment. Furthermore, we discuss emerging evidence suggesting a dueling role of the immune system in promoting benign tumor initiation while potentially restraining malignant outgrowth. Finally, we highlight the potential implications of these findings and suggest future directions for research relevant to the diagnosis, risk-assessment, and treatment of peripheral nerve sheath tumors, utilizing immunomodulatory therapeutics. Neurofibromatosis type 1 (NF1) is a common genetic disorder resulting in the development of both benign and malignant tumors of the peripheral nervous system. NF1 is caused by germline pathogenic variants or deletions of the NF1 tumor suppressor gene, which encodes the protein neurofibromin that functions as negative regulator of p21 RAS. Loss of NF1 heterozygosity in Schwann cells (SCs), the cells of origin for these nerve sheath-derived tumors, leads to the formation of plexiform neurofibromas (PNF)—benign yet complex neoplasms involving multiple nerve fascicles and comprised of a myriad of infiltrating stromal and immune cells. PNF development and progression are shaped by dynamic interactions between SCs and immune cells, including mast cells, macrophages, and T cells. In this review, we explore the current state of the field and critical knowledge gaps regarding the role of NF1(Nf1) haploinsufficiency on immune cell function, as well as the putative impact of Schwann cell lineage states on immune cell recruitment and function within the tumor field. Furthermore, we review emerging evidence suggesting a dueling role of Nf1+/- immune cells along the neurofibroma to MPNST continuum, on one hand propitiating PNF initiation, while on the other, potentially impeding the malignant transformation of plexiform and atypical neurofibroma precursor lesions. Finally, we underscore the potential implications of these discoveries and advocate for further research directed at illuminating the contributions of various immune cells subsets in discrete stages of tumor initiation, progression, and malignant transformation to facilitate the discovery and translation of innovative diagnostic and therapeutic approaches to transform risk-adapted care. [ABSTRACT FROM AUTHOR]

Purpose: Plexiform neurofibromas (PNF) are rare tumors arising from peripheral nerve sheath cells. PNF are a hallmark in patients with neurofibromatosis type 1 (NF1), a tumor predisposition syndrome. PNF often grow invasively and destructively, what may complicate surgical treatment. Data on frequency, location, and surgical procedures of patients with NF1-associated FPNF are scarce. This study provides treatment data of NF1 patients. Methods: Localization and treatment data of 69 NF1 patients with neck PNF were analyzed. Frequency of lesions was recorded in coded colors on schematic neck drawings. Results: The tumors showed no side preference, were located in the entire area under investigation, and did not respect anatomical units/dermatomes. However, the sternocleidomastoid region was particularly frequently affected. The mean number of surgical measures per patient was 1.33. Complications were extensive swelling, hematoma, and bleeding. Histological assessment usually confirmed the clinical assessment of neoplasm. However, histologic differentiation of PNST reveals differences in between tumors that have been unified in clinical assessment as PNF. Conclusion: The color-coded, schematic overview of the frequency distribution of surgical neck interventions in NF1 patients with PNF proved a useful tool to gain assessment of preferred treatment needs. The imaging procedure may be suitable for controlling the external aspect of natural tumor development (growth, effects of aging) in the same way as the documentation of the post-surgical course. Treatment plans for patients with these tumors should consider that repeated interventions may be necessary to achieve a longer-term stable result. [ABSTRACT FROM AUTHOR]

Abstract 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.

To present a simplified technique in management of complete ptosis secondary to neurofibromatosis. This prospective, non-comparative, clinical interventional study included 13 patients with complete ptosis secondary to histologically proved plexiform neurofibromas. It was conducted at the Orbital Unit of Assiut University Hospital, the referral center of Upper Egypt in the period between June 2013 and October 2021. In all cases, a simplified technique of 5 surgical steps was applied: (A) Division of the involved eyelid surgically into three parts by drawing 2 curvilinear lines, the superior line 11 mm below and parallel to the lower eyebrow hairline and the inferior one 10 mm above the lid margin, (B) Resection (full-thickness) of the large middle part which involves the main pathology and lies between the 2 lines, (C) Preservation of the upper part with identification, dissection and clamping of the levator muscle, (D) Refinement of the lower part by removal of any tissue between the skin and the debulked tarsus and (E) Re-suturing of the upper and lower parts in layers; conjunctiva to conjunctiva, levator to tarsus (after resection of a part that corrects the ptosis) and skin to skin. Ptosis was completely corrected in 8 cases (61.5%) and residual mild ptosis occurred in 5 patients (38.5%). No exposure keratopathy or tumor growth was reported during the follow-up period of minimum 1 year. This simplified technique could be considered as a surgical basis for correction of complete ptosis in neurofibromatosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 is one of the most common autosomal dominant disorders, presenting a higher risk of developing plexiform tumors and neurofibromas, whose conventional treatment, based on surgical, chemotherapy, or radiotherapy procedures, still has limitations. Comorbidities such as neuralgic, muscular, or paretic, and paralytic pain may occur depending on the tumor situation or the plexiform neurofibroma. Given the difficult approach to these patients, and to expand research and homeopathic knowledge about these cases, we present a case of pain associated with lumbosacral plexiform neurofibroma during oncological treatment for Glioma of the Optic Pathways, without surgical indication, but with difficult pain. control, even when using analgesics and antidepressants. Chemotherapy oncological treatment, due to crises and maintenance of pain, had been postponed. As an aid in controlling the symptoms, considering the ascending paretic pain syndrome of the left lower limb, the homeopathic medicine Conium maculatum was used as a complementary aid to the therapy. The patient's symptoms improved and she was able to continue with the chemotherapy treatment indicated, with a progressive reduction in the use of analgesics until they were discontinued. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type I (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis represent a diverse group of genetic tumor predisposition syndromes with a shared feature of tumors affecting the peripheral nerve sheaths. Purpose of Review: Many advancements have been made in understanding the biologic underpinnings of these conditions, and in 2016 the first drug was approved by the FDA to treat pediatric symptomatic unresectable plexiform neurofibromas. Recent Findings: Mek inhibitors have provided a much-needed therapeutic avenue for NF1 patients with unresectable plexiform neurofibromas (PN), both for reduction of tumor bulk and for improvement in symptoms. Selumetinib is the first FDA approved drug for PN, but is only approved for children. Some research suggests that alternative Mek inhibitors and other mixed tyrosine kinase inhibitors may have better efficacy in adults. Vascular endothelial growth factor (VEGF) inhibitor bevacizumab can prolong hearing and delay the need for surgery in NF2 patients with bilateral vestibular schwannomas. Summary: This article provides an update regarding considerations and approaches when treating the tumors associated with the neurofibromatoses (NF), including risk and prognosis metrics, clinical trial results, surgical techniques, and radiation therapy recommendations. [ABSTRACT FROM AUTHOR]

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Plexiform neurofibroma (PN) is an uncommon benign tumor, usually associated with neurofibromatosis type 1. As most PNs involve the craniomaxillofacial region, PN of the colon is very rare. Here we present a case of PN involving the sigmoid colon. A 43-year-old male patient presented to the outpatient clinic for the evaluation of an incidentally discovered sigmoid colon mass. A colonoscopic biopsy was performed for the mass, and the result revealed neuronal proliferation. The patient visited the outpatient clinic a year later with symptoms of abdominal pain and stool caliber change. Biopsy was repeated for the sigmoid colon mass, and the results showed mucosal Schwann cell proliferation and S-100 immunostaining positivity. Computed tomography and magnetic resonance imaging were performed for further evaluation, and neurofibroma or schwannoma was suspected based on the imaging studies. For an accurate diagnosis, the patient underwent surgery to remove the sigmoid colon mass. The final diagnosis of the mass was confirmed as PN. We hereby report a rare case of PN involving the sigmoid colon that could not be diagnosed before surgery.

Abstract Neurofibromatosis type 1 (NF1), the most common tumor predisposition syndrome, occurs when NF1 gene variants result in loss of neurofibromin, a negative regulator of RAS activity. Plexiform neurofibromas (PN) are peripheral nerve sheath tumors that develop in patients with NF1 and are associated with substantial morbidity and for which, until recently, the only treatment was surgical resection. However, surgery carries several risks and a proportion of PN are considered inoperable. Understanding the genetic underpinnings of PN led to the investigation of targeted therapies as medical treatment options, and the MEK1/2 inhibitor selumetinib has shown promising efficacy in pediatric patients with NF1 and symptomatic, inoperable PN. In a phase I/II trial, most children (approximately 70%) achieved reduction in tumor volume accompanied by improvements in patient-reported outcomes (decreased tumor-related pain and improvements in quality of life, strength, and range of motion). Selumetinib is currently the only licensed medical therapy indicated for use in pediatric patients with symptomatic, inoperable NF1-PN, with approval based on the results of this pivotal clinical study. Several other MEK inhibitors (binimetinib, mirdametinib, trametinib) and the tyrosine kinase inhibitor cabozantinib are also being investigated as medical therapies for NF1-PN. Careful consideration of multiple aspects of both disease and treatments is vital to reduce morbidity and improve outcomes in patients with this complex and heterogeneous disease, and clinicians should be fully aware of the risks and benefits of available treatments. There is no single treatment pathway for patients with NF1-PN; surgery, watchful waiting, and/or medical treatment are options. Treatment should be individualized based on recommendations from a multidisciplinary team, considering the size and location of PN, effects on adjacent tissues, and patient and family preferences. This review outlines the treatment strategies currently available for patients with NF1-PN and the evidence supporting the use of MEK inhibitors, and discusses key considerations in clinical decision-making.

Introduction: Neurofibromatosis type 1 (NF1) is an is an autosomal dominant heritable tumor predisposition syndrome.. Peripheral nerve sheath tumors (PNST) are a hallmark of NF1. Plexiform neurofibromas (PNF) are neoplasms that are characteristic of NF1, often causing disfiguring effects (e.g., on the face), and are considered precancerous lesions. Previous studies have shown that facial PNF (FPNF) have an impact on the shape of facial bones. This study examines deviations of mandibular symmetry from cephalometric reference planes considering the topography of FPNF.Material and methods: The posterior-anterior (PA) cephalograms of 16atients with NF1 were examined. We compared three groups: patients with FPNF (n=74), with disseminated cutaneous neurofibroma (DNF (n=94)), and control subjects without NF1 (n=23). The PNF group was subtyped with respect to facial PNST type and location. Typical mandibular cephalometric reference points were determined (condyle, antegonion, and menton). Results: The skeletal measurement points of the mandible in FPNF patients often differ significantly from those of the DNF group. It has been proven that typical asymmetries of the median-sagittal measurement points are indicators of PNF. Differences within the trigeminal tumor spread patterns are indicated in the measured values. A local tumor effect (PNF) on the relation of the measurement points to the reference planes is made plausible by the study results. The investigations prove that tumor type (FPNF) and the number of FPNF affected branches of the trigeminal nerve may correlate with significant deviations of mandible from symmetry on PA projections.Conclusion: The presented study shows that characteristic patterns of mandibular deformity can be measured on standardized radiographs in NF1 patients with FPNF. Mandibular deformities imaged on standardized radiographs may be initial indicators of a previously unrecognized NF1. Tumor-associated alterations of the mandible should be considered in the classification systems of pathognomonic, diagnostically pioneering osseous findings in NF1. The radiological findings provide clues for planning mandibular osteotomies in NF1 patients, especially for assessing facial regions typically highly vascularized by tumor spread. Furthermore, the radiological findings are an indication of a tumor potentially invading and destroying adjacent masticatory and mimic muscle, findings that may have an influence on surgical measures (function, aesthetics, and wound healing).

Plexiform schwannoma is an uncommon benign tumour that grows in a plexiform pattern. We report a 47-year-old man with a mass on the palmar aspect of the metacarpophalangeal joint of the right index finger that had been growing gradually for more than 10 years. The mass was palpated from the distal carpal tunnel to the ulnar aspect of the proximal interphalangeal joint of the index finger, with tingling and numbness sensation. The tumour was a multinodular tumour involving the first common palmar digital nerve to the ulnar proper palmar digital nerve. It was resected and reconstructed with a sural nerve graft. Plexiform schwannoma is rare in the digital nerve, with only six cases reported. Generally, classic schwannomas can be enucleated without causing neurologic deficits; however, plexiform schwannoma may require nerve resection. There have been reports of recurrence of plexiform schwannoma; definitive resection and long-term follow-up are necessary. Level of Evidence: Level V (Therapeutic) [ABSTRACT FROM AUTHOR]

Neurofibromatosis (NF) and schwannomatosis (SWN) are genetic conditions characterized by the risk of developing nervous system tumors. Recently revised diagnostic criteria include the addition of genetic testing to confirm a pathogenic variant, as well as to detect the presence of mosaicism. Therefore, the use and interpretation of both germline and tumor‐based testing have increasing importance in the diagnostic approach, treatment decisions, and risk stratification of these conditions. This focused review discusses approaches to genetic testing of NF‐ and SWN‐related tumor types, which are somewhat rare and perhaps lesser known to non‐specialized clinicians. These include gastrointestinal stromal tumors, breast cancer, plexiform neurofibromas with or without transformation to malignant peripheral nerve sheath tumors, gliomas, and schwannomas, and emphasizes the need for inclusion of genetic providers in patient care and appropriate pre‐ and post‐test education, genetic counseling, and focused evaluation by a medical geneticist or other healthcare provider familiar with clinical manifestations of these disorders. [ABSTRACT FROM AUTHOR]

Introduction: Facial plexiform neurofibromas (FPNF) are rare tumors frequently diagnosed in patients with neurofibromatosis type 1 (NF1), a tumor predisposition syndrome. FPNF often grows invasively and destructively, which may complicate surgical treatment. Data on the frequency, location, and surgical procedures of patients with NF1-associated FPNF are scarce. This study provides treatment data from a nationally networked reference center for the treatment of NF1 patients. Material and Methods: The localization and treatment data of 179 NF1 patients with FPNF were analyzed. Photographically documented tumors of the study area, further determined by imaging, were manually transferred to a facial scheme and digitized. The digitized registrations of the facial extensions of the tumors of each patient were overlaid in a single image (Photoshop™), so that the file of the facial scheme contained the sum of the tumor localization. Finally, the frequency of tumor localization was indicated with a color code. The frequency of tumor extension-related coded colors was applied to outline the lesions' topography on schematic face drawings (heat map). Results: The distribution of the tumors showed no side preference. The need for the treatment of patients with orbital/periorbital manifestations became evident in the graphic representations. Tumors do not respect anatomical units. However, the classification of the face according to dermatomes, especially the trigeminal nerve, offers indications of tumor spread and guides treatment planning. The mean number of surgical measures per patient was 2.21 (median: 1). Extensive swelling, hematoma, and delayed wound healing were all common postoperative complications. Conclusion: The color-coded, schematic overview of the frequency distribution of cutaneous tumor spread in NF1 patients with FPNF illustrates the importance of orbital/periorbital and cheek tumor manifestations in patients' treatment needs. The imaging procedure is suitable for controlling natural tumor growth in the same way as the documentation of the post-surgical course. Repeated interventions in the region are included in surgical planning of the progressing tumor disease. [ABSTRACT FROM AUTHOR]

A 3-year-old male patient was diagnosed with neurofibromatosis type 1(NF1) for two years. The patient has multiple neurofibromas in retroperitoneum, lumbococcygeal paravertebral, lumbosacral spinal canal, and foramina. Due to retroperitoneal mass compression, the child suffered from urological complications such as hydronephrosis, ureterdilation, neurogenic bladder, etc., which seriously affected the urination function and resulted in multiple surgical treatments. Currently, the patient has been treated with mitogen activates extracelluar signal-regulated kinases(MEK) inhibitor selumetinib targeted therapy, and has voluntarily urinated, and his general state is better than before medication. The diagnosis and treatment of this case reflects the importance of multidisciplinary collaboration in the diagnosis and treatment of rare diseases.

An 11‐year‐old female with neurofibromatosis type 1 (NF‐1) and history of optic glioma presented with a progressive cutaneous plexiform neurofibroma of the breast. The lesion was treated with topical application of a mitogen‐activated protein kinase inhibitor, trametinib, resulting in stable, non‐progression cutaneous plexiform neurofibroma for greater than 2 years. This case demonstrates the potential application of topical trametinib for NF1‐associated superficial cutaneous plexiform neurofibroma without the toxicities associated with systemic treatment. [ABSTRACT FROM AUTHOR]

Neurofibromatosis Type 1 (NF1) is a common neurogenic condition characterized by heterozygous loss of function mutations in the neurofibromin gene. NF1 patients are susceptible to the development of neurofibromas, including plexiform neurofibromas (pNFs), which occurs in about half of all cases. Plexiform neurofibroma are benign peripheral nerve sheath tumors originating from Schwann cells after complete loss of neurofibromin; they can be debilitating and also transform into deadly malignant peripheral nerve sheath tumors (MPNSTs). Here, our data indicates that silver nanoparticles (AgNPs) may be useful in the treatment of pNFs. We assessed the cytotoxicity of AgNPs using pNF cells and Schwann cells derived from the same NF1 patient. We found that AgNPs are selectively cytotoxic to pNF cells relative to isogenic Schwann cells. We then examined the role of neurofibromin expression on AgNP-mediated cytotoxicity; restoration of neurofibromin expression in pNF cells decreased sensitivity to AgNP, and knockdown of neurofibromin in isogenic Schwann cells increased sensitivity to AgNP, outlining a correlation between neurofibromin expression and AgNP-mediated cytotoxicity. AgNP was able to selectively remove pNF cells from a co-culture with patient-matched Schwann cells. Therefore, AgNPs represent a new approach for clinical management of NF1-associated pNF to address significant clinical need.

This case report describes a 4-year-old girl with an isolated neurofibroma in the sacrococcygeal region. Although initially resembling sacrococcygeal teratoma, histopathology revealed a benign nerve sheath tumor. Wide local excision was performed, and the final diagnosis was plexiform neurofibroma. Diagnostic challenges in rare childhood tumors require stepwise evaluation and multidisciplinary team discussions. [ABSTRACT FROM AUTHOR]

Background: Neurofibromatosis type-1 (NF-1) is an inherited neuro-ectodermal disorder primarily defined by the presence of six or more café-au-lait macules, intertriginous freckles, two or more neurofibromas, plexiform neurofibroma, lisch nodules, bony defects like sphenoid dysplasia, and optic gliomas. Due to gross cosmetic disfigurement and multisystem involvement, it can have heavy psychological and physical burdens, especially in countries like India, wherein skin disease is significantly stigmatized. Aim: The aim of the study was to understand various clinical and epidemiological patterns and complications of NF-1. Material and methods: We conducted a cross-sectional study on 47 clinically diagnosed patients with NF-1 at a tertiary care center in Bihar to understand various presentations and life-threatening complications in patients with Neurofibromatosis type-1. A detailed history was taken regarding onset, symptoms, family history, and associated co-morbidities. A comprehensive cutaneous, ophthalmological, neurological, and psychiatric evaluation was done. Ophthalmological screening via slit-lamp examination was done in all patients. Magnetic resonance imaging (MRI) was done in patients having neurological complaints and findings were subsequently analyzed. Results: A total of 47 newly diagnosed patients were enrolled in the study out of which 36 (76.6%) were males and 11 (23.4%) were females. The majority of patients belonged to the 40 to 49 years age group (29.78%) followed by the 30 to 39 years age group (27.65%). The mean age of total patients was 31.68 ± 13 years ranging from seven years to sixty-eight years. A family history of NF1 was positive in 22 patients (46.8%), with six (12.76%) patients reporting consanguineous marriage of their parents. All the cases of NF-1 presented with one consistent finding, that is, the prerequisite number and size of café au lait macules. The next most common presenting lesions were cutaneous neurofibromas and axillary freckling present in 38 (80.8%) and 26(55.31%) patients respectively. Plexiform neurofibroma was present in twelve (25.5%) patients. Clinical severity was assessed by DNB (dermatological, neurological, and bone manifestations) classification of Japan and the majority of patients (38.29%) were classified as Stage 3 followed by Stage 4 (23.4%). The most common ocular finding was lisch nodules, present in 28 patients. The most common neurological abnormality present was cognitive dysfunction (12.7%) followed by seizures (4.2%). Conclusion: Neurofibromatosis type-1 is a life-long neurocutaneous disorder with an extremely unpredictable clinical course. Although the majority of patients have a benign course, there's a small subset of patients who develop debilitating and life-threatening complications. To provide optimal care, treating physicians must be aware of its diverse presentations and rare complications, so as to prevent them at comparatively earlier stages and prevent chronic disabilities. [ABSTRACT FROM AUTHOR]

Lateral neck masses are common in children, ranging from simple benign diseases to pathologies with malignant potential. Plexiform neurofibromas are extremely rare peripheral nerve sheath tumours involving multiple nerve sheath fascicles. They are typically seen in the paediatric population, with the majority affecting the craniofacial area and neck. Due to the close clinical and histological resemblance with other benign neck lesions such as lymphadenitis and branchial cysts, these cases can often go misdiagnosed. We describe a lesion in a young girl who presented with a progressive lateral neck swelling and how it was managed. [ABSTRACT FROM AUTHOR]

Background: Neurofibromatosis type 1 (NF1) is a multi-system autosomal dominant disorder affecting 1 in 3000 individuals. The diagnostic criteria of NF1 includes ocular manifestations. Objective: To study the ophthalmic manifestations of neurofibromatosis type 1 and evaluate complications, if any. Methodology: A total of 30 eyes of 15 neurofibromatosis cases presenting to the ophthalmology outpatient department (OPD) underwent a detailed ocular examination, and clinical manifestations in each case were analyzed. Results: Lisch nodules were the most common presentation. Twenty-eight eyes of 14 patients had bilateral and one had unilateral presentation. Six eyes of three patients had ectropion uveae, one eye had plexiform neurofibroma, and one eye had pulsatile proptosis with absence of lesser wing of sphenoid. Other manifestations seen were optic nerve glioma, secondary optic atrophy, closed angles with raised intraocular pressure (IOP), medullated nerve fiber and retinal pigment epithelium (RPE) atrophic changes. Conclusion: This case series represents a spectrum of ocular manifestations of NF1 and highlights the importance of ocular examination and regular follow-up in these patients.

Simple Summary: Neurofibromatosis type 1 (NF1) is a genetic neurophakomatosis (neuroectodermal disorder) associated with a wide array of skin findings. The most recognizable feature is cutaneous neurofibromas; however, less common dermatologic stigmata may also occur. Currently, there are limited therapeutic options for the cutaneous manifestations of NF1. This review summarizes the dermatologic sequelae of NF1 and provides an update on emerging treatments. Appropriate care of these patients often requires interdisciplinary collaboration between neurologists, oncologists, and dermatologists, among other specialties. Increased awareness of these conditions is crucial for providing adequate care to patients with NF1. Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that increases one's risk for both benign and malignant tumors. NF1 affects every organ in the body, but the most distinctive symptoms that are often the most bothersome to patients are the cutaneous manifestations, which can be unsightly, cause pain or pruritus, and have limited therapeutic options. In an effort to increase awareness of lesser-known dermatologic associations and to promote multidisciplinary care, we conducted a narrative review to shed light on dermatologic associations of NF1 as well as emerging treatment options. Topics covered include cutaneous neurofibromas, plexiform neurofibromas, diffuse neurofibromas, distinct nodular lesions, malignant peripheral nerve sheath tumors, glomus tumors, juvenile xanthogranulomas, skin cancer, and cutaneous T-cell lymphoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Limited effective therapies exist for the treatment of neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN). The aim of our prospective clinical trial was to evaluate the activity and safety of vinblastine and methotrexate (conventional cytotoxic chemotherapies) given on a metronomic schedule in children and young adults with NF1 and PN. Of the 23 participants evaluable for treatment outcomes and toxicities, 14 completed all protocol therapy. There were no participants that discontinued therapy due to dose-limiting toxicities. In addition, there were no participants that demonstrated a partial response. VBL/MTX was well-tolerated but did not result in objective volumetric responses. Limited therapies exist for neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN). For this reason, the activity of vinblastine (VBL) and methotrexate (MTX) was evaluated in children and young adults with NF1 and PN. Patients ≤ 25 years of age with progressive and/or inoperable NF1-PN received VBL 6 mg/m2 and MTX 30 mg/m2 weekly for 26 weeks, followed by every 2 weeks for 26 weeks. Objective response rate was the primary endpoint. Of 25 participants enrolled, 23 were evaluable. The median age of participants was 6.6 years (range 0.3–20.7). The most frequent toxicities were neutropenia and elevation of transaminases. On two-dimensional (2D) imaging, 20 participants (87%) had stable tumor, with a median time to progression of 41.5 months (95% confidence interval 16.9, 64.9). Two of eight participants (25%) with airway involvement demonstrated functional improvements including decreased positive pressure requirements and apnea-hypopnea index. A post hoc three-dimensional (3D) analysis of PN volumes was completed on 15 participants with amenable imaging; 7 participants (46%) had progressive disease on or by the end of therapy. VBL/MTX was well-tolerated but did not result in objective volumetric response. Furthermore, 3D volumetric analysis highlighted the lack of sensitivity of 2D imaging for PN response evaluation. [ABSTRACT FROM AUTHOR]

A 4-year-old boy who was treated at the Santa Clara Health Center in Koulikoro by the medical team of the European Union Training Mission Mali XIX for a facial tumor that developed left ocular proptosis, causing a significant facial asymmetry at the level of the left eye. Medical examination revealed light brown stains, axillary ephelid and Lisch nodules in both eyes. Because of the suspicion of neurofibromatosis type 1 and following civil-military cooperation procedures, he is transferred to Spain. Civil-military cooperation is essential in the new forms of conflict, where these relationships are a fundamental tool in the coordination of all operations in the area. At the Miguel Servet University Hospital, in association with the General Defense Hospital of Zaragoza, the earlier diagnosis is confirmed (left trigeminal plexiform neurofibroma) with a genetic study and complementary imaging tests. It is decided to start treatment with selumetinib. [ABSTRACT FROM AUTHOR]

Simple Summary: The EUropean Network for RAre CANcers (EURACAN) Task Force on Ultrarare Brain Tumors (domain 10, subdomain 10) has reviewed the evidence of diagnostic and therapeutic interventions and drawn recommendations on peripheral and cranial nerve sheath tumors. The authors have provided an extensive revision of the clinical features, anatomical location, histological and molecular markers, and peculiar imaging findings of such unique entities, as well as some recommendations of local (e.g., surgery and radiotherapy) and systemic therapies (traditional chemotherapy and targeted agents) when feasible. The 2021 WHO classification of the CNS Tumors identifies as "Peripheral nerve sheath tumors" (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly. Tumor diagnosis is primarily based on hematoxylin and eosin-stained sections and immunohistochemistry. Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. MRI is the gold-standard to delineate the extension with respect to adjacent structures. Gross-total resection is the first choice, and can be curative in benign lesions; however, the extent of resection must be balanced with preservation of nerve functioning. Radiotherapy can be omitted in benign tumors after complete resection and in NF-related tumors, due to the theoretic risk of secondary malignancies in a tumor-suppressor syndrome. Systemic therapy should be considered in incomplete resected plexiform neurofibromas/MPNSTs. MEK inhibitor selumetinib can be used in NF1 children ≥2 years with inoperable/symptomatic plexiform neurofibromas, while anthracycline-based treatment is the first choice for unresectable/locally advanced/metastatic MPNST. Clinical trials on other MEK1-2 inhibitors alone or in combination with mTOR inhibitors are under investigation in plexiform neurofibromas and MPNST, respectively. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Aim: Neurofibromas (NF) are the most common benign nerve sheath tumors in the tongue, gingiva, major salivary glands, and jaw bones. Nowadays, tissue engineering is a revolutionary technique for reconstructing tissues. To explore the feasibility of using stem cells derived from NF teeth to treat orofacial bone defects, the differences in cell biological properties between an NF teeth group and Normal teeth group. Patients and Methods: The intra-dental pulp tissues from each tooth were extracted. The cell survival rates, morphology, proliferation rates, cell activity, and differentiation abilities were contrastively analyzed between the NF teeth group and Normal teeth group. Results: Between the two groups, there were no differences in the primary generation (P0) cells (p>0.05), the cell yield, and the time required for the cells to grow out of the pulp tissue and attach to the culture plate. Furthermore, no differences were found at the first generation (passage) between the two groups in colony formation rate and cell survival rate. The proliferation capacity, cell growth curve, and surface marker expression of dental pulp cells was not altered in the third generation (p>0.05). Conclusion: Dental pulp stem cells from NF teeth were successfully obtained and were not different from normal dental pulp stem cells. Although, clinical research using tissue-engineered bone to repair bone defects is still in its infancy, it will eventually enter the clinic and become a routine means of bone defect reconstruction treatment as related disciplines and technologies develop. [ABSTRACT FROM AUTHOR]

Neurofibromatosis of the genitourinary tract is rare, with a prevalence of 0.65%, and it is exceedingly rare to involve the external genitalia. Involvement of the clitoris, labia majora, and prepuce was reported with clitoromegaly being the most frequently occurring. Herein, we are reporting the case of a 6-year-old girl who was diagnosed with a neurofibroma of the clitoris; measuring 9.4 cm in its largest dimension. To the best of our knowledge, this is the largest clitoral neurofibroma reported in the literature. Due to the rarity of such cases and reports limitations in the literature, the diagnosis of neurofibroma of the external genitalia requires a high index of suspicion by health-care providers. Surgical excision and postoperative follow-up for possible recurrence remain the gold standard of management.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare but aggressive neoplasms associated with neurofibromatosis type 1. Specifically, children with deep plexiform neurofibromas are 18 times more likely to develop MPNSTs compared to the general population. However, there is currently no standard surveillance imaging protocol for children diagnosed with deep plexiform neurofibromatosis. We present a case of a boy with neurofibromatosis type 1 and scoliosis, who later developed MPNST. This case highlights the need for more frequent surveillance imaging and the challenges of diagnosing MPNST in a patient with scoliosis. In order to facilitate early detection of malignant transformation, we suggest annual surveillance MR imaging for patients known to have deep plexiform neurofibromatosis.

Simple Summary: Malignant peripheral nerve sheath tumor (MPNST) is a soft tissue sarcoma with limited therapeutic interventions and a poor prognosis. This review summarized the current understanding of the pathogenic mechanisms behind MPNST and the latest concepts in clinical management from diagnosis to therapeutic intervention. Additionally, the developments in molecular diagnosis and targeted therapies for MPNST are highlighted. It concluded with the challenges and prospects of MPNST management. Malignant peripheral nerve sheath tumor (MPNST) is an aggressive soft tissue sarcoma with limited therapeutic options and a poor prognosis. Although neurofibromatosis type 1 (NF1) and radiation exposure have been identified as risk factors for MPNST, the genetic and molecular mechanisms underlying MPNST pathogenesis have only lately been roughly elucidated. Plexiform neurofibroma (PN) and atypical neurofibromatous neoplasm of unknown biological potential (ANNUBP) are novel concepts of MPNST precancerous lesions, which revealed sequential mutations in MPNST development. This review summarized the current understanding of MPNST and the latest consensus from its diagnosis to treatment, with highlights on molecular biomarkers and targeted therapies. Additionally, we discussed the current challenges and prospects for MPNST management. [ABSTRACT FROM AUTHOR]

The perineal presentation of plexiform neurofibroma is exceptional, with only two cases reported to date. We present an 8-year-old African male with a large perineal tumor of years of evolution. He had no associated symptoms. Café au lait stains were observed on examination, without other findings of relevance. The patient had no preoperative radiological studies. Partial excision of the lesion was performed. Histopathological study of the specimen revealed a plexiform neurofibroma. The lack of diagnostic suspicion due to the atypical nature of the location, the anatomical complexity of surgical resection and the potential urological and rectal involvement make this lesion a diagnostic-therapeutic challenge. Among the differential diagnoses, schwannoma, congenital lipoma, hamartoma and lipoblastoma should be considered. [ABSTRACT FROM AUTHOR]

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disease caused by mutations in neurofibromin -NF1- which are decisive in the development of tumors such as plexiform neurofibromas. CLINICAL CASE: A 12-year-old male patient was diagnosed with neurofibromatosis type 1 with a plexiform neurofibroma in the preauricular region associated with moderate to severe pain. A decrease in size and complete remission of pain was obtained with topical sirolimus. CONCLUSIONS: The treatment of plexiform neurofibromas is surgical resection; however, this is not always possible. Sirolimus is a mTOR pathway inhibitor that has shown efficacy in managing pain associated with plexiform neurofibromas and, to a lesser extent, in reducing their size. This case supports the use of topical sirolimus as a palliative therapeutic option in patients with unresectable plexiform neurofibromas. [ABSTRACT FROM AUTHOR]

Plexiform neurofibromas (PNFs) are a prevalent and severe phenotype associated with NF1, characterized by a high teratogenic rate and potential for malignant transformation. The growth and recurrence of PNFs are attributed to aberrant proliferation and migration of Nf1 -deficient Schwann cells. Protein tyrosine phosphatase receptor S (PTPRS) is believed to modulate cell migration and invasion by inhibiting the EMT process in NF1-derived malignant peripheral nerve sheath tumors. Nevertheless, the specific role of PTPRS in NF1-derived PNFs remains to be elucidated. The study utilized the GEO database and tissue microarray to illustrate a decrease in PTPRS expression in PNF tissues, linked to tumor recurrence. Furthermore, the down- and over-expression of PTPRS in Nf1 -deficient Schwann cell lines resulted in the changes of cell migration and EMT processes. Additionally, RTK assay and WB showed that PTPRS knockdown can promote EGFR expression and phosphorylation. The restoration of EMT processes disrupted by alterations in PTPRS levels in Schwann cells can be achieved through EGFR knockdown and EGFR inhibitor. Moreover, high EGFR expression has been significantly correlated with poor prognosis. These findings underscore the potential role of PTPRS as a tumor suppressor in the recurrence of PNF via the regulation of EGFR-mediated EMT processes, suggesting potential targets for future clinical interventions. • Reduced PTPRS expression in PNF tissues, which links to tumor recurrence. • PTPRS knockdown in Schwann cells reduces cell migration and weakens EMT processes. • Restoring disrupted EMT processes in Schwann cells can be done with EGFR knockdown or EGFR inhibitor. • High levels of EGFR expression are linked to a worse prognosis in PNFs. [ABSTRACT FROM AUTHOR]

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive soft tissue sarcomas that can occur sporadically or in the setting of the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. These tumors carry a dismal overall survival. Previous work in our lab had identified ATRX chromatin remodeler (ATRX), previously termed, Alpha Thalassemia/Mental Retardation Syndrome X Linked as a gene mutated in a subset of MPNSTs. Given the great need for novel biomarkers and therapeutic targets for MPNSTs, we sought to determine the expression of ATRX in a larger subset of sporadic and NF1 associated MPNSTs (NF1-MPNSTs). We performed immunohistochemistry (IHC) on 74 MPNSTs (43 NF1-associated and 31 sporadic), 21 plexiform neurofibromas, and 9 atypical neurofibromas. Using this approach, we have demonstrated that 58% (43/74) of MPNSTs have aberrant ATRX expression (120 months) for intact expression, p = 0.0276). In summary, we demonstrate that ATRX is aberrantly expressed in the majority of NF1-MPNSTs, but not plexiform or atypical neurofibromas. Additionally, aberrant ATRX expression is associated with decreased overall survival in NF1-MPNST, but not sporadic MPNST and may serve as a prognostic marker for patients with NF1-MPNST.

Plexiform neurofibroma represents an uncommon variant of neurofibromatosis type 1, constituting only 5%–30% of all cases. Plexiform neurofibroma is usually diagnosed during childhood and arises from multiple nerves, manifesting as bulging and deforming masses that can also involve connective tissue and skin folds. We report a case of a two-year-old girl who presented with worsening stridor since birth and later exhibited progressively increasing left neck swelling at the age of 10 months old. Ultrasound and magnetic resonance imaging (MRI) showed a lobulated solid mass in the left deep neck space extending to the midline and having a mass effect on the airway with involvement of the supraglottic region. Tracheostomy was done, and a biopsy of the supraglottic lesion revealed a plexiform neurofibroma. The patient was conservatively managed after a discussion with her parents concerning the associated potential of operative morbidity. The patient’s parents had learned about tracheostomy care, and the patient was scheduled for yearly MRI surveillance. MRI was performed again three months after the initial diagnosis and showed stable lesion. Plexiform neurofibroma is a slow-growing tumor. A treatment decision must consider the benefits of surgery and the morbidity of the progressing disease. Hence, airway management is crucial prior to the final decision of such cases.