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Abstract This study compared the thickness of each intraretinal layer in patients with neurofibromatosis 1 (NF1) and controls to analyze the association between intraretinal layer thickness and visual function. The macular spectral-domain optical coherence tomography volumetric dataset obtained from 68 eyes (25 adult eyes, 43 pediatric eyes) with NF1 without optic glioma and 143 control eyes (100 adult eyes, 43 pediatric eyes) was used for image auto-segmentation. The intraretinal layers segmented from the volumetric data included the macular retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor layer. Cases and controls were compared after adjusting for age, sex, refractive error, and binocular use. The association between retinal layer thickness and visual acuity was also analyzed. The GCIPL was significantly thinner in both adult and pediatric patients with NF1 compared with healthy controls. Average RNFL and GCIPL thicknesses were associated with visual acuity in adult patients with NF1. In pediatric patients, average GCIPL thickness was associated with visual acuity. These results suggest that changes in the inner retinal layer could be a biomarker of the structural and functional status of patients with NF1.

ABSTRACT Objectives: This study aims to report and analyze two cases of tension hemothorax in patients with neurofibromatosis type 1 (NF1) undergoing scoliosis surgery, highlighting the incidence, etiology, and optimal treatment strategies. Methods: We present two detailed cases of tension hemothorax in NF1 patients who underwent scoliosis surgery. Clinical presentations, diagnostic findings, treatment interventions, and outcomes were meticulously documented. A literature review was conducted to contextualize these cases within the broader spectrum of tension hemothorax in NF1 patients undergoing similar surgeries. Results: Both cases involved severe complications requiring immediate surgical interventions. The first patient experienced arterial bleeding necessitating endovascular embolization, while the second patient required open thoracotomy. Postoperative management included intensive monitoring and multidisciplinary care. The literature review supported these findings, indicating that surgical interventions such as chest tube insertion, thoracoscopy, and angiography with endovascular embolization are common in such cases. Conclusion: These cases underscore the critical need for vigilance and prompt intervention in managing tension hemothorax in NF1 patients undergoing scoliosis surgery. A multidisciplinary approach is essential for optimizing treatment outcomes and improving understanding of this rare but life-threatening complication in this specific surgical context. Level of Evidence IV; Case Report.

A 28-year-old female, a known case of neurofibromatosis 1, presented to the respiratory medicine department with complaints of breathlessness and cough for 2 weeks’ duration. Clinical examination revealed right-sided moderate pleural effusion. Computed tomography (CT) chest revealed a large anterior mediastinal mass with chest wall infiltration. Histopathology showed neoplasm with epithelioid cells, arranged as sheets and interlacing spindle cells with a moderate amount of eosinophilic cytoplasm and inconspicuous nucleoli. Histopathological examination of excised specimen showed a malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation also known as malignant triton tumor. After palliative chemotherapy, later on follow-up, CT-guided biopsy from right side chest wall lesion also showed the same. Because of this rare presentation, we are reporting this case.

Abstract Background Neurofibromatosis type 1 is a genetic disease that affects multiple organs and systems, leading to various clinical manifestations. In Neurofibromatosis type 1, rare intrathoracic meningoceles often occur alongside bone dysplasia. These meningoceles contain cerebrospinal fluid and can be mistakenly diagnosed as ‘pleural effusion’. Case presentation In this case report, we mistakenly identified ‘cerebrospinal fluid’ as ‘pleural effusion’ and proceeded with drainage. This error posed significant risks to the patient and holds valuable implications for the future diagnosis and treatment of similar patients. Conclusions In patients with Neurofibromatosis type 1 complicated by spinal deformity, there is a high incidence of intrathoracic meningoceles. Treatment strategies may differ based on the specific features of the lesions, and collaboration among multiple disciplines can significantly improve patient outcomes.

Study Design A retrospective cohort study. Purpose To determine outcomes following all-posterior surgery using computed tomography navigation, hybrid stabilization, and multiple anchor point techniques in patients with neurofibromatosis type 1 (NF-1) and dystrophic scoliosis. Overview of Literature Previous studies favored antero-posterior fusion as the most reliable method; however, approaching the spine anteriorly was fraught with significant complications. With the advent of computer assisted navigation and multiple anchor point method, posterior only approach is reporting successful outcomes. Methods This study included patients who underwent all-posterior surgical deformity correction for dystrophic NF-1 curves. Coronal and sagittal Cobbs angles, apical rotation, and the presence of dystrophic features were evaluated before surgery. Postoperatively, sagittal, coronal, and axial correction, implant position, and implant densities were evaluated. The decline in curve correction and implant-related complications were evaluated at follow-up. Clinical outcomes were evaluated using the Scoliosis Research Society-22 revised index. Results This study involved 50 patients with a mean age of 13.6 years and a mean follow-up duration of 5.52 years. With a mean coronal flexibility of 18.7%, the mean apical vertebral rotation (AVR), preoperative coronal Cobb angle, and sagittal kyphosis were 27.4°, 64.01°, and 47.70°, respectively. The postoperative mean coronal Cobb angle was 30.17° (p

This case presents a 35-year-old male with spinal predominant neurofibromatosis-1 who developed an incomplete spinal cord injury (C3 Asia C) which did not improve despite urgent decompressive surgery for multiple cervical neurofibromas. This report outlines a novel indication for intrathecal baclofen. The patient suffered from lower limb weakness with severe spasticity and required assistance of at least two for all activities. The aim of rehabilitation was to improve overall tone while focusing on independence, mobility and quality of life. After a successful trial of intrathecal baclofen, he underwent implantation of an intrathecal baclofen pump. The dose was gradually increased while he received a progressive programme of stretching and functional rehabilitation therapy. After 6 weeks, his MAS had improved to 1–2/4 and he had progressed to independent transfers, independence for most activities of daily living and was able to discharge to his family home with minimal support.

Abstract Background Neurofibromatosis type 1 (NF1) is one of the most common RASopathies predisposing affected patients to melanic lesions and benign tumors. NF1 is associated with considerable esthetic and functional burden negatively affecting the patient’s quality of life (QoL). This study aims to assess the clinical features of NF1 patients and evaluate their impact on QoL. We identified NF1 patients from a public health database of a region in Spain. All patients underwent clinical and ophthalmological evaluation for NF1 features. We measured QoL using the Spanish version of the Skindex-29. Results Forty patients fulfilled the NF1 National Institute of Health criteria when we recruited patients. The median age was 42.00 years (IQR 26.5 -53.75). The median total Skindex-29 score was 12.3 (IQR 5.9–22.4); (emotion: 15.0, IQR 5.0-37.5; symptoms 8.9, IQR 0.0-17.9 and functioning 8.3; IQR 0.5–18.3). Women and NF1 patients with lower educational levels were associated with poorer QoL scores. We identified itching and sleep troubles to influence NF1 patients’ QoL negatively. Conclusion NF1 considerably influences the psychological well-being of NF1 patients. We observed that female and low-educated patients scored higher on the emotional dimension of the Skindex-29 and could, therefore, be more at risk of depression. We also pointed out some “minor symptoms” that negatively impact NF1 patients’ QoL such, as itching and sleep troubles which doctors could treat if sought by doctors.

Introduction: Multiple sclerosis (MS) is an autoimmune neurodegenerative disease which can rarely co-exist with neurofibromatosis 1 (NF1), a neurocutaneous inherited disorder that predisposes to oncogenesis. Patients who suffer from both conditions can be challenging cases for clinicians, as clinical symptoms and radiological findings may overlap, while MS immune-modifying treatments could further increase the risk of oncogenesis. Case Presentation: In this study, we describe the case of a 27-year-old woman who presented with signs and symptoms of optic neuritis and was then diagnosed with both MS and NF1. As the patient continued to experience MS relapses despite initial interferon-beta treatment, she was subsequently switched to natalizumab and responded well. Conclusion: This case illustrates how MRI lesion differentiation with the co-existence of MS and NF1 can be difficult due to overlaps in lesion characteristics, while treatment decisions can be challenging mainly due to scarce data on the oncogenic risk of MS immunomodulary therapies. Therefore, clinicians need to balance out the risk of malignancy development with the risk of progressive neurological disability when treating such patients.

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.

BackgroundNeurofibromatosis type 1 (NF1) is an autosomal dominant disease that can give rise to the formation of vascular lesions in affected individuals. These lesions, whether occurring spontaneously or as a result of trauma, have the potential to cause severe and even fatal hemorrhage.Case descriptionWe presented a case demonstrating the most extensive hematoma ever documented in a patient with NF1, resulting from a minor trauma. He experienced hemodynamic instability due to severe anemia. Arteriography revealed a rupture in the intercostal artery, which was successfully treated through interventional embolization to stop the hemorrhage. Additionally, we implemented a refined surgical approach, beginning with suturing, followed by the meticulous resection of necrotic and aberrant tissues, thereby markedly diminishing bleeding.ConclusionMinor trauma may cause severe bleeding in patients with NF1, which can be life-threatening. Timely diagnosis of NF1 and effective hemostatic techniques are key to successful treatment.

Purpose: To examine whether image processing of non-mydriatic DRI Triton SS-OCT (Topcon Corporation, Tokyo, Japan) using the red free filter could assess the presence of choroidal nodules and thus include their detection as a diagnostic criterion in neurofibromatosis type 1 (NF1). Material and methods: We included 417 eyes from 210 patients, 377 - from 190 patients diagnosed with NF1 according to the criteria established by the National Institutes of Health Consensus Development Conference (NIH) and 40 from 20 healthy patients as a control group. The mean age was 9.4 years (range 2 years–18 years). All patients had their visual acuity measured by a test according to age, were examined for the presence of lisch nodules and an Optical Coherence Tomography (OCT) of the macular area was performed. All the OCT images were analysed to check if visible nodules could be identified. Results: Ages 14 (95% CI=(9.7,18.3)) and 12 years (95% CI=(9.1,14)) are the cut-off points that best separate those with choroidal nodules with Triton OCT and lisch with slit lamp, respectively, from those without. lisch nodules were detected in 50% of cases of NF1 patients. The presence of choroidal nodules did not present a statistically significant correlation with the occurrence of optic pathway glioma (p = 0.96) nor with the patient's visual worsening (p = 0.072). A statistically significant correlation was observed between the presence of choroidal nodules and the presence of lisch nodules (p

Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous disorder in which tumors form in the nervous system (neurofibromas). Neurofibromas are the most common benign tumors in NF1. The type, size, number, and location of the neurofibromas should be considered for the choice of treatment. We present a case of NF1, in which a wide scalp resection was performed due to the presence of multiple neurofibromas. Associated with this, reconstruction was performed with advancement flaps plus partial skin autograft with favorable results and good coverage of the areas where the tumors were removed.

Abstract Background Little is known about employment status, occupation, and disposable income in adults with NF1. Methods From the Danish National Patient Registry and database of two national Centers for Rare Diseases, we identified 1469 adults with NF1, who were matched to 11,991 randomly selected population comparisons on sex and birth year and month. Annual information on employment, occupation and disposable income was ascertained from national registries in 1980–2019. Results Adults with NF1 had a lower odds ratio (OR) for employment [OR 0.71, 95% confidence interval (CI) 0.61–0.83] and higher OR for health-related unemployment (OR 2.94, 95% CI 2.16–3.96) at age 30 years than population comparisons, which persisted at age 40 and 50 years. Somatic diagnoses were associated with a higher OR for health-related unemployment in adults with NF1 than in the population comparisons. Adults with NF1 had a slightly lower disposable income, with a 14% (0.82–0.89) reduction observed among the youngest birth cohort. Furthermore, adults with NF1 were less likely to be in a high skilled occupation at ages 30, 40 and 50 years. Conclusion Adults with NF1 have a lower employment rate, which was mainly due to health-related reasons and a slightly lower disposable income than adults without NF1. Thus, anticipation guidance for employment should be part of the management of NF1 families.

Abstract Objective To obtain updated estimates of the incidence and prevalence of neurofibromatosis type 1 (NF1) and type 2 (NF2). Study design We conducted a systematic search of NF1 and NF2 incidence or prevalence studies, in OVID Medline, OVID Embase, Web of Science, and Cinahl. Studies were appraised with the Joanna Briggs Institute Prevalence Critical Appraisal tool. Pooled incidence and prevalence rates were estimated through random-effects meta-analysis. Results From 1,939 abstracts, 20 studies were fully appraised and 12 were included in the final review. Pooled NF1 prevalence was 1 in 3,164 (95%CI: 1 in 2,132-1 in 4,712). This was higher in studies that screened for NF1, compared to identification of NF1 through medical records (1 in 2,020 and 1 in 4,329, respectively). NF1 pooled birth incidence was 1 in 2,662 (95%CI: 1 in 1,968-1 in 3,601). There were only 2 studies on NF2 prevalence, so data were not pooled. Pooled NF2 birth incidence was 1.08 per 50,000 births (95%CI: 1 in 32,829-1 in 65,019). Conclusion We present updated estimates of the incidence and prevalence of NF1 and NF2, to help plan for healthcare access and allocation. The prevalence of NF1 from screening studies is higher than from medical record studies, suggesting that the disease may be under recognized. More studies are needed regarding the prevalence of NF2.

Purpose The aim of this study was to investigate the clinical efficacy of near-infrared reflectance (NIR) imaging and optical coherence tomography (OCT) in identifying ocular manifestations of neurofibromatosis type 1 (NF1) in Korean children. Methods This retrospective chart review study included five Korean children with NF1 aged under 18 years who had undergone ophthalmic procedures, including slit-lamp examinations, NIR imaging, and OCT scanning. Results Multiple patchy bright lesions were observed on NIR imaging in all eyes (10 eyes in five patients). Further NIR imaging and OCT scans showed that these lesions, confined to the choroid, were choroidal nodules. Lisch nodules, contrastingly, were found in only four of 10 eyes by slit-lamp examinations on the same day as the NIR imaging. One of those four eyes had only one Lisch nodule, which did not meet the NF1 diagnostic criteria. Conclusion NIR imaging enabled the detection of choroidal nodules in Korean children with NF1. Moreover, for Korean children with NF1, choroidal nodules were earlier-detected ocular manifestations relative to Lisch nodules. NIR imaging, along with OCT, is a useful protocol for localizing NF1 nodules in children.

Neurofibromatosis (NF) is a heterogeneous group of tumor predisposition syndromes that lead to malignancy in the central and peripheral nervous systems. Neurofibromatosis type 1 (NF1), along with neurofibromatosis type 2 (NF2) and schwannomatosis (SCH), are the three main types of NF. As the most common form, NF1 is characterized by neurofibromas and Cafe-au-lait macules (CALMs) in early childhood. Neurofibromatosis type 1 is caused by mutations in the NF1 gene, which codes for neurofibromin, and mutations in NF2 and SMARCB1 gene lead to neurofibromatosis type 2 and schwannomatosis, respectively. In addition, most patients with neurofibromatosis type 2 have vestibular schwannoma, also associated with hearing problems and body imbalance. Recently, schwannomatosis has been proposed as a distinct genetic disorder because it shares many symptoms with neurofibromatosis types one and two, characterized by benign schwannoma around nerves. NF1 and NF2 may show symptoms in childhood, but schwannomatosis is often diagnosed in people in their thirties or older. This article reviews the latest scientific literature according to the keywords of neurofibromatosis, pathogenesis, treatment, NF1, and NF2 in Google Scholar, PubMed, and Web of Science online databases on the types of neurofibromatosis, molecular pathways, diagnostic criteria, clinical symptoms, condition management, treatments and drugs under development.

Abstract Background Neurofibromatosis type 1 is an autosomal dominant disorder with an incidence of 1 in 3000 births. Neurofibromas can occur anywhere in the body. Of all the head and neck tumours parapharyngeal space tumours constitute 0.5%. Neurofibromas can constitute about 9% of all the neurogenic tumours (41%) of the parapharyngeal space. Prevalence of nasal obstruction and obstructive sleep-disordered breathing symptoms due to Plexiform neurofibroma in Neurofibromatosis type 1 is rare amounting to less than 0.5% of cases of parapharyngeal space tumours. Case presentation We present a case report of a 24-year-old female patient of Neurofibromatosis type 1 who presented with obstructive sleep-disordered breathing symptoms due to Plexiform neurofibroma in the parapharyngeal space. She had complaints of progressive nasal obstruction with associated snoring, disturbed sleep, and daytime somnolence without any significantly large external neck swelling. She underwent excision of the right parapharyngeal tumor by combined trans parotid and transcervical approach. After histopathological examination, a diagnosis of Plexiform neurofibroma was made. On 1-year follow-up, she is doing well without any recurrence and her presenting symptoms of obstructive sleep-disordered breathing symptoms had improved. Conclusion The symptoms of obstructive sleep-disordered breathing symptoms need to be kept in mind while evaluating such patients and careful attention needs to be given to the patients who report disturbed sleep. Neurofibromatosis type 1 is a multi-system disease which needs holistic care and approach. Such patients should be offered symptomatic treatment and leading questions on the quality of sleep should be asked. Any treatable cause of disturbed sleep like organic sleep disorder should be treated promptly in such patients.

Introduction: Neurofibromatosis is an autosomal dominant disorder, and type 1 is associated with an increased risk of tumor formation with neurocutaneous involvement. The variable evolution, often with limiting tumors, in addition to the significant incidence of cases requiring treatment, makes it fundamental to discuss procedures already performed in medical practice for early, careful, and individualized recognition of the diagnosis and treatment of the patient. The report aims to present a surgical case of neurofibromatosis, calling attention to the surgical technique, the characteristics of the disease, and the importance of the procedure in the quality of life of patients limited by the condition. Case Report: A 23-year-old male patient with a large mass neurofibroma in the gluteus and posterior surface of the right leg, in addition to café au lait stains in the distal third of the legs. He was treated with surgery to remove the tumor and a flap and graft in the affected region. The procedures were performed by a multidisciplinary team, allowing the total removal of the tumor mass, with subsequent skin grafting in the hip and thigh lesion on the right side and the fasciocutaneous flap in VY in the area. There were no significant complications in the immediate postoperative period. Conclusion: Neurofibromas can become limiting and impair patients’ quality of life with neurofibromatosis type 1; therefore, early management and diagnosis are essential. Although the condition does not present a cure, there is a need for research into less invasive and preventive treatments for injuries.

Background Neurofibromatosis type 1 (NF1) is a genetic disorder with diverse phenotypic manifestations. Cerebral vasculopathy is one of the multisystem involvements often overlooked unless symptomatic. Case Report A 28-year-old male patient with prolonged NF1 complained of right-hand position-specific rhythmic tremor after surviving an ipsilateral cerebellar arteriovenous malformation (AVM) hemorrhagic transformation. Not only did he suffer rupture of the infratentorial vasculopathy but he also endured asymmetric supratentorial occlusive vessel changes in moyamoya syndrome. Due to contralateral limb clumsiness, his right hemispheric vasculature was revascularized by encephaloduroarteriosynangiosis 13 years before the AVM rupture. Conclusion This case report describes exceptional NF1 central nervous system involvement where the cerebral vasculature had concomitant moyamoya syndrome and unilateral cerebellar AVM in a single patient. Cerebral vasculopathy should be surveyed and adequately addressed during the follow-up of chronic NF1, as it can cause irreversible sequelae or can be life-threatening.

Los tumores malignos de la vaina del nervio periférico (TMVNP) son sarcomas de tejidos blandos (STB) agresivos y de mal pronóstico. Su origen exacto es desconocido, no obstante, su ubicación cerca de las raíces nerviosas principales de las extremidades y la pelvis hace suponer un origen neural1. Los TMVNP corresponden al 10 % de los STB, el 50 % son esporádicos y el otro 50 % ocurren en pacientes con neurofibromatosis tipo 1 (NF1), condición que confiere un riesgo 30 veces mayor de desarrollar la enfermedad comparado con la población general2. Su incidencia es similar en ambos sexos y la edad de presentación oscila entre los 20 y 50 años3. Son síntomas frecuentes el dolor y el déficit neurológico4. La cirugía oncológica y la radioterapia adyuvante son el estándar de manejo en pacientes con tumores resecables1. La supervivencia global a 5 años es de sólo 25 %5.

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Introduction: Neurofibromatosis (NF) is a group of multisystem diseases with an autosomal dominant inheritance pattern. It affects the neural crest cells, being able to compromise all tissues. NF type 1 is the most prevalent, also known as the peripheral type. This includes multiple musculoskeletal manifestations, such as severe and difficult-to-manage scoliosis. Including two types: dystrophic and non-dystrophic. Case report: 40-year-old man with a history of NF1, grave spine deformity, extreme back pain, and severe functional limitation. The initial diagnostic images of the spine showed a thoracolumbar kyphoscoliosis over 80 degrees which collapsed the thoracolumbar junction and generated spinal cord compression. He was managed with a Vertebral Column Resection (VCR) at the thoracolumbar junction level, thoracoplasty, and posterior thoracic to lumbosacral arthrodesis. The patient required hospitalization and long rehabilitation therapy. Currently, he has good clinical and diagnostic imaging results after one year of following. Discussion: This patient's case corresponds to dystrophic kyphoscoliosis. This group of patients requires more aggressive surgical management, considering the high risk of progression and deterioration even after surgery.

Abstract Background Neurofibromatosis type 1 and pseudoachondroplasia are both rare autosomal dominant disorders, caused by pathogenic mutations in NF1 and COMP genes, respectively. Both neurofibromin 1 and cartilage oligomeric matrix protein (COMP) play a role in the development of the skeleton. Carrying both germline mutations has not been previously reported; however, it can affect the developing phenotype. Case presentation The index patient, an 8-year-old female presented with several skeletal and dermatologic anomalies resembling the coexistence of multiple syndromes. Her mother had dermatologic symptoms characteristic for neurofibromatosis type 1, and her father presented with distinct skeletal anomalies. NGS-based analysis revealed a heterozygous pathogenic mutation in genes NF1 and COMP in the index patient. A previously unreported heterozygous variant was detected for the NF1 gene. The sequencing of the COMP gene revealed a previously reported, pathogenic heterozygous variant that is responsible for the development of the pseudoachondroplasia phenotype. Conclusions Here, we present the case of a young female carrying pathogenic NF1 and COMP mutations, diagnosed with two distinct heritable disorders, neurofibromatosis type 1 and pseudoachondroplasia. The coincidence of two monogenic autosomal dominant disorders is rare and can pose a differential diagnostic challenge. To the best of our knowledge, this is the first reported co-occurrence of these syndromes.

Neurofibromatosis 1 (NF1) is a multisymptomatic disorder with highly variable presentations, which include short stature, susceptibility to formation of the characteristic benign tumors known as neurofibromas, intense freckling and skin discoloration, and cognitive deficits, which characterize most children with the condition. Attention deficits and Autism Spectrum manifestations augment the compromised learning presented by most patients, leading to behavioral problems and school failure, while fragmented sleep contributes to chronic fatigue and poor quality of life. Neurofibromin (Nf1) is present ubiquitously during human development and postnatally in most neuronal, oligodendrocyte, and Schwann cells. Evidence largely from animal models including Drosophila suggests that the symptomatic variability may reflect distinct cell-type-specific functions of the protein, which emerge upon its loss, or mutations affecting the different functional domains of the protein. This review summarizes the contributions of Drosophila in modeling multiple NF1 manifestations, addressing hypotheses regarding the cell-type-specific functions of the protein and exploring the molecular pathways affected upon loss of the highly conserved fly homolog dNf1. Collectively, work in this model not only has efficiently and expediently modelled multiple aspects of the condition and increased understanding of its behavioral manifestations, but also has led to pharmaceutical strategies towards their amelioration.

Introducción: en los pacientes con neurofibromatosis tipo 1 (NF!) la prevalencia de feocromocitoma es alta. El riesgo de tener feocromocitoma es 10 veces mayor que en la población general. Objetivo: describir el caso de un paciente con patologías poco frecuentes que requiere del concurso de expertos para su manejo previo y para el seguimiento después de la cirugía. Presentación del caso: paciente masculino de 38 años con antecedente de NF1, evaluado por 4 meses de cefalea, dolor abdominal e hipertensión arterial de difícil control. Se hace diagnóstico de feocromocitoma y se define adrenalectomía con hospitalización perioperatoria para control de cifras tensionales con alfa y beta bloqueadores. Discusión: el manejo del feocromocitoma es la resección quirúrgica. Para el procedimiento quirúrgico los pacientes deben recibir bloqueo alfa por lo menos 10 días antes del procedimiento y betabloqueadores 3 días antes. Las crisis de catecolaminas pueden ocurrir en un intraoperatorio por estrés mecánico del tumor al ser manipulado, y estrés psicológico y por medicamentos. Conclusión: el tratamiento quirúrgico es la elección y se debe realizar por un grupo interdisciplinario para garantizar un adecuado control de las cifras tensionales en el perioperatorio y así evitar complicaciones.

Neurofibromatosis type 1 (NF1) is one of the most frequently encountered familial tumor syndromes. NF1 patients are highly prone to have multiple nervous system tumors, and are also at increased risk for various nonnervous mesenchymal or neuroendocrine tumor developments. This is an NF1 patient who developed two different unusual tumors: an intramedullary anaplastic astrocytoma of the thoracic spine and myxoid liposarcoma of the lower limb. The family members were carefully investigated as per the NF1 diagnostic criteria. A strong cutaneous NF1 penetrance was found in 6 of the 14 family members in four successive generations, two of whom had NF1 and developed breast cancer and bilateral optic gliomas. The NF1 tumor syndrome highlights a wide-ranging tumor spectrum, and clinicians should keep an eye on tumor surveillance and encourage medical counseling, and long-term NF1 family follow-up is warranted for prophylactic warning.

Abstract Background Neurofibromatosis 1 (NF1) is a common autosomal dominant syndrome with complete penetrance and highly variable expressivity. The cutaneous neurofibroma (Cnf) and plexiform neurofibroma (Pnf), café-au-lait spots, and freckle-like lesions are common in NF1, but many other manifestations can occur. We aimed to evaluate head circumference, height, weight, body mass index (BMI), head circumference-to-height ratio (HCHR) and waist–hip ratio (WHR) in adult NF1 Brazilian individuals versus a paired control group and investigate their correlation with the presence of clinically visible Pnfs, and number of “skin neurofibromas” (Snf), which include both cutaneous and subcutaneous neurofibromas. Methods A case–control study was conducted with 168 individuals, 84 with NF1 and 84 without NF1, paired by sex and age. Head circumference and anthropometric measurements, Snf quantification, evaluation of clinically visible Pnf and familial inheritance were accessed. Results Prevalence of macrocephaly was significantly higher in NF1 women. Height and weight were significantly lower in both males and females with NF1. HCHR was higher in the NF1 group than in the control group for both sexes. BMI was significantly lower in men with NF1. Waist and hip circumferences were significantly reduced in NF compared with the controls, but the mean WHR was significantly lower only in NF1 women. No correlation was found between the Snf and head circumference and anthropometric measurements, sex or family history. The presence and larger size of clinically visible plexiform neurofibromas were associated with normal stature (p = 0.037 and p = 0.003, respectively). Conclusions NF1 individuals have increased prevalence of macrocephaly, short stature, low BMI, and reduced abdominal fat. There is no relation between head circumference and anthropometric data with family history, or neurofibromas.

Gastric malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare spindle cell sarcomas that arise within the peripheral nerves of the gastrointestinal tract. MPNST can present as a mass that may or may not be accompanied by obstruction or bleeding. Type 1 neurofibromatosis (NF) is an autosomal dominant genetic disorder with an incidence of 1 in 2,500-3,000. Plexiform neurofibromas in Type 1 NF can undergo a malignant transformation to MPNSTs. Approximately half of the incidence of MPNST is associated with the NF-1 gene. MPNST behaves aggressively, and radical excisional surgery is important for treatment. Recurrence and metastasis are significant, even after a radical excision. Despite multidisciplinary treatment, the five-year survival rate is only 30-50%. This paper reports the case of a 47-year-old man with Type 1 NF who presented with hemorrhage of a gastric subepithelial lesion. He underwent surgery under the suspicion of a gastrointestinal stromal tumor, but it was diagnosed as MPNST after confirming the histopathological appearance and immunohistochemical profiles. In addition, the large mass invaded the spleen and diaphragm. Radical surgery was performed, and additional chemotherapy was administered. This paper reports the experience of a patient with NF 1 with advanced MPNST discovered due to a subepithelial lesion.

Introduction: Neurofibromatosis type 1 (NF1) is a progressive multisystem disorder following an autosomal dominant inheritance pattern that presents with multiple neurological manifestations. Methods: We reviewed medical histories of patients with NF1 followed up at our hospital’s paediatric neurology department from May 1990 to 31 December 2018. We collected data on neurological symptoms. Results: A total of 128 patients with NF1 were identified. Mean age (SD) at NF1 diagnosis was 4.43 (3.38) years (range, 0.5-14.5 years). There was a slight female predominance (53.1%). Macrocephaly (head circumference over 2 SDs above average for age) was present in 37.5% of cases. Attention-deficit/hyperactivity disorder was recorded in 28.9% of patients (37): combined type in 20 patients, predominantly inattentive in 15, and predominantly impulsive/hyperactive in 2. Other manifestations included headache (18.6%), cognitive impairment (7.8%), motor deficit (6.2%), and epilepsy (4.68%). Brain MRI was performed in 85 patients, revealing T2-weighted hyperintensities in the basal ganglia and/or cerebellum in 60 patients (70.5%), Chiari malformation type 1 in 4 cases, and arachnoid cysts in 3. Optic nerve gliomas were identified by MRI in 22 patients (25.8%). Other MRI findings included plexiform neurofibromas (9.3%) and central nervous system gliomas (3.1%). Conclusions: The neurological manifestations identified in our sample are consistent with those reported in the literature. Effective transfer strategies from paediatric neurology departments and subsequent clinical follow-up by adult neurology departments are needed to prevent loss to follow-up in adulthood. Resumen: Introducción: La Neurofibromatosis tipo 1 (NF1) es un desorden progresivo multisistémico de herencia autosómica dominante que presenta numerosas manifestaciones neurológicas. Métodos: Revisión de historias clínicas de pacientes afectos de NF1 controlados en una Unidad de Neuropediatría de mayo de 1990 a 31 de diciembre de 2018 y sus manifestaciones neurológicas asociadas. Resultados: Se revisaron 128 pacientes afectos de NF1. Edad media al diagnóstico de NF1, 4,43 años ± 3,38 SDS (Rango 6 meses - 14,5 años) con discreto predominio femenino (53,1%). Se asocia macrocefalia (PC > 2SDS) en el 37,5% de los casos. TDAH en el 28,9% de los casos (37), subtipo combinado 20, inatento 15 casos y predominantemente hiperactivo 2 casos. Otras manifestaciones incluyen; cefalea (18,7%), déficit cognitivo (7,8%), afectación motora (6,2%) y epilepsia (4,68%). Se realizó RM cerebral a 85 pacientes, mostrando 60 (70,5%) hiperseñales en T2 en ganglios basales y/o cerebelo, junto con otras alteraciones como Chiari I (4 casos) y quistes aracnoideos (3 casos). Se identificaron gliomas de nervio óptico en 22 casos (25,8%). Otros hallazgos diagnosticados por RM incluyen neurofibromas plexiformes (9.3%) y otros gliomas localizados en sistema nervioso central (3,1%). Conclusiones: Las manifestaciones neurológicas encontradas concuerdan con lo recogido en la literatura. El seguimiento de estos pacientes se pierde en la edad adulta, siendo necesario establecer adecuadas estrategias de transferencia y posterior seguimiento de pacientes a los servicios de adultos.

The malignant peripheral nerve sheath tumor is one of the rare sarcomas that have a challenging diagnosis. It occurs independently with neurofibromatosis type 1. Some studies referred that malignant peripheral nerve sheath tumor attains a worse prognosis when it occurs in the head and neck region. In the reported case, a male patient with neurofibromatosis type 1 manifestations presented with a large mass in the temporal region. Based on the clinical history, histopathology, and immunohistochemical findings, the lesion was diagnosed as a low-grade malignant peripheral nerve sheath tumor with rhabdoid features. Surgical resection followed by intensity-modulated radiotherapy was the treatment of choice.

Resumen: Introducción: La neurofibromatosis tipo 1 (NF1) es un desorden progresivo multisistémico de herencia autosómica dominante que presenta numerosas manifestaciones neurológicas. Métodos: Revisión de historias clínicas de pacientes afectos de NF1 controlados en una Unidad de Neuropediatría de mayo de 1990 a 31 de diciembre de 2018 y sus manifestaciones neurológicas asociadas. Resultados: Se revisaron 128 pacientes afectos de NF1. Edad media al diagnóstico de NF1, 4,43 años ± 3,38 SDS (rango 6 meses-14,5 años) con discreto predominio femenino (53,1%). Se asocia macrocefalia (PC> 2SDS) en el 37,5% de los casos. TDAH en el 28,9% de los casos (37), subtipo combinado 20, inatento 15 casos y predominantemente hiperactivo 2 casos. Otras manifestaciones incluyen; cefalea (18,7%), déficit cognitivo (7,8%), afectación motora (6,2%) y epilepsia (4,68%). Se realizó RM cerebral a 85 pacientes, mostrando 60 (70,5%) hiperseñales en T2 en ganglios basales y/o cerebelo, junto con otras alteraciones como Chiari I (4 casos) y quistes aracnoideos (3 casos). Se identificaron gliomas de nervio óptico en 22 casos (25,8%). Otros hallazgos diagnosticados por RM incluyen neurofibromas plexiformes (9,3%) y otros gliomas localizados en sistema nervioso central (3,1%). Conclusiones: Las manifestaciones neurológicas encontradas concuerdan con lo recogido en la literatura. El seguimiento de estos pacientes se pierde en la edad adulta, siendo necesario establecer adecuadas estrategias de transferencia y posterior seguimiento de pacientes a los servicios de adultos. Abstract: Introduction: Neurofibromatosis type 1 (NF1) is a progressive multisystem disorder following an autosomal dominant inheritance pattern that presents with multiple neurological manifestations. Methods: We reviewed medical histories of patients with NF1 followed up at our hospital's paediatric neurology department from May 1990 to 31 December 2018. We collected data on neurological symptoms. Results: A total of 128 patients with NF1 were identified. Mean age (SD) at NF1 diagnosis was 4.43 (3.38) years (range, 0.5-14.5 years). There was a slight female predominance (53.1%). Macrocephaly (head circumference over 2 SDs above average for age) was present in 37.5% of cases. Attention-deficit/hyperactivity disorder was recorded in 28.9% of patients (37): combined type in 20 patients, predominantly inattentive in 15, and predominantly impulsive/hyperactive in 2. Other manifestations included headache (18.6%), cognitive impairment (7.8%), motor deficit (6.2%), and epilepsy (4.68%). Brain MRI was performed in 85 patients, revealing T2-weighted hyperintensities in the basal ganglia and/or cerebellum in 60 patients (70.5%), Chiari malformation type 1 in 4 cases, and arachnoid cysts in 3. Optic nerve gliomas were identified by MRI in 22 patients (25.8%). Other MRI findings included plexiform neurofibromas (9.3%) and central nervous system gliomas (3.1%). Conclusions: The neurological manifestations identified in our sample are consistent with those reported in the literature. Effective transfer strategies from paediatric neurology departments and subsequent clinical follow-up by adult neurology departments are needed to prevent loss to follow-up in adulthood.

Introduction: Gastrointestinal stromal tumors (GIST), although relatively rare, account for 80% of mesenchymal tumors of the digestive tract. They manifest in any part of the alimentary tract and are derived from Cajal cells. They may occur sporadically or be associated with familial syndromes such as neurofibromatosis type I. The clinical picture is variable, and they are often diagnosed incidentally. The diagnosis requires imaging tests associated with histopathological and immunohistochemical analysis. The best strategy for treatment is surgical resection and cases should be analyzed individually to verify additional advantages with the association of systemic therapy. This study aims to present an unusual case of GIST associated with neurofibromatosis type I in a patient with incidental diagnosis after semi-intestinal occlusion secondary to an episode of pancreatitis, in addition to performing a literature review on the subject. Case report: A 49-year-old woman with a history of severe pancreatitis presented with intestinal obstruction approximately 8 months after this episode. Abdominal computed tomography revealed a heterogeneous formation in the mesogastric region, measuring 6.6 x 5.1 x 5.3 cm. She underwent surgical resection and histopathological and immunohistochemical studies confirmed the diagnosis of GIST. Six months after diagnosis, the patient is in good general condition and is on systemic therapy. Conclusion: GIST are rare tumors, but their diagnosis should come to mind in patients with neurofibromatosis type 1 with abdominal masses.

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Background and objectives: Diagnosis of neurofibromatosis 1 (NF1) diagnosis is challenging in young children without a family history of NF1. The aims of this study were to estimate diagnostic delays in children without a family history of NF1 and to examine the effects of considering café-au-lait macules and skinfold freckling as a single diagnostic criterion. Patients and methods: Retrospective, descriptive, observational study of all patients diagnosed with NF1 before the age of 18 years who were seen at our hospital. The medical records of those included were reviewed to identify the date on which the diagnostic criteria of NF1 were objectified. The patients were categorized into 2 groups: those with a known parental history of NF1 and those without. Café-au-lait macules and skinfold freckling were assessed as a single diagnostic criterion, and genetic evidence was considered to confirm highly suspicious cases. Results: We studied 108 patients younger than the age of 18 years with a diagnosis of NF1. Mean (SD) age at diagnosis was 3.94 (±3.8) years for the overall group, 1 year for patients with a parental history of NF1, and 4 years and 8 months for those without. Diagnosis was therefore delayed by 3 years and 8 months in patients without a family history. Conclusion: Skin lesions were the first clinical manifestation of NF1 in most patients. We believe that the National Institutes of Health's diagnostic criteria for NF1 should be updated to aid diagnosis in young children. Resumen: Antecedentes y objetivos: El diagnóstico de la neurofibromatosis 1 (NF1) plantea dificultades en niños sin antecedentes familiares durante la primera infancia. En este estudio pretendemos estimar la demora diagnóstica de los pacientes sin antecedentes familiares de NF1 y definir la repercusión de considerar las manchas café con leche y las efélides como un único criterio diagnóstico. Pacientes y métodos: Estudio observacional descriptivo retrospectivo en el que se revisaron los hitos diagnósticos de la NF1 en las historias clínicas de los pacientes menores de 18 años atendidos en nuestro centro. Distribuimos a los pacientes en dos grupos en función de la existencia de antecedentes de NF1 entre sus progenitores, considerando las manchas café con leche y las efélides como un único criterio y aceptando el estudio genético como criterio de confirmación en casos de elevada sospecha. Resultados: Se incluyeron en el estudio 108 menores con diagnóstico de NF1. La edad media de diagnóstico en nuestra serie fue de 3,94 años (desviación estándar: ±3,8 años). En el grupo 1, sin antecedentes, la edad media de diagnóstico fue de 4 años y 8 meses, mientras que en el grupo 2, con antecedentes, fue de 12 meses, siendo la demora en el diagnóstico de 3 años y 8 meses entre ambos grupos. Conclusión: Las lesiones cutáneas representan, en la mayoría de los casos, las primeras manifestaciones clínicas de la enfermedad. Consideramos necesaria la actualización de los criterios diagnósticos del NIH con el fin de facilitar el diagnóstico en los primeros años de vida.

Abstract Background While computed tomography (CT) exams are the major cause of medical exposure to ionising radiation, the radiation-induced risks must be documented. We investigated the impact of the cellular models and individual factor on the deoxyribonucleic acid double-strand breaks (DSB) recognition and repair in human skin fibroblasts and brain astrocytes exposed to current head CT scan conditions. Method Nine human primary fibroblasts and four human astrocyte cell lines with different levels of radiosensitivity/susceptibility were exposed to a standard head CT scan exam using adapted phantoms. Cells were exposed to a single-helical (37.4 mGy) and double-helical (37.4 mGy + 5 min + 37.4 mGy) examination. DSB signalling and repair was assessed through anti-γH2AX and anti-pATM immunofluorescence. Results Head CT scan induced a significant number of γH2AX and pATM foci. The kinetics of both biomarkers were found strongly dependent on the individual factor. Particularly, in cells from radiosensitive/susceptible patients, DSB may be significantly less recognised and/or repaired, whatever the CT scan exposure conditions. Similar conclusions were reached with astrocytes. Conclusions Our results highlight the importance of both individual and tissue factors in the recognition and repair of DSB after current head CT scan exams. Further investigations are needed to better define the radiosensitivity/susceptibility of individual humans.

Abstract Background Neurofibromatosis 1 (NF1) is a rare autosomal dominant disease characterized by increased Schwann cell proliferation in peripheral nerves. Several small studies of brain morphology in children with NF1 have found increased total brain volume, total white matter volume and/or corpus callosum area. Some studies (mostly in children with NF1) also attempted to correlate changes in brain morphology and volume with cognitive or behavioural abnormalities, although the findings were inconsistent. We aimed to characterize alterations in brain volumes by three-dimensional (3D) MRI in adults with NF1 in major intracranial sub-regions. We also aimed to assess the effect of age on these volumes and correlated brain white matter and grey matter volumes with neuropsychometric findings in adults with NF1. Methods We obtained brain volume measurements using 3D magnetic resonance imaging for 351 adults with NF1 and, as a comparison group, 43 adults with neurofibromatosis 2 (NF2) or Schwannomatosis. We assessed a subset of 19 adults with NF1 for clinical severity of NF1 features and neurological problems and conducted psychometric testing for attention deficiencies and intelligence quotient. We compared brain volumes between NF1 patients and controls and correlated volumetric measurements to clinical and psychometric features in the NF1 patients. Results Total brain volume and total and regional white matter volumes were all significantly increased in adults with NF1. Grey matter volume decreased faster with age in adults with NF1 than in controls. Greater total brain volume and white matter volume were correlated with lower attention deficits and higher intelligence quotients in adults with NF1. Conclusion Our findings are consistent with the hypothesis that dysregulation of brain myelin production is a cardinal manifestation of NF1 and that these white matter changes may be functionally important in affected adults.

Abstract Background While computed tomography (CT) exams are the major cause of medical exposure to ionising radiation, there is increasing evidence that the potential radiation-induced risks must be documented. We investigated the impact of cellular models and individual factor on the deoxyribonucleic acid double-strand breaks (DSB) recognition and repair in human fibroblasts and mammary epithelial cells exposed to current chest CT scan conditions. Method Twelve human primary fibroblasts and four primary human mammary epithelial cell lines with different levels of radiosensitivity/susceptibility were exposed to a standard chest CT scan exam using adapted phantoms. Cells were exposed to a single helical irradiation (14.4 mGy) or to a topogram followed, after 1 min, by one single helical examination (1.1 mGy + 14.4 mGy). DSB signalling and repair was assessed through anti-γH2AX and anti-pATM immunofluorescence. Results Chest CT scan induced a significant number of γH2AX and pATM foci. The kinetics of both biomarkers were found strongly dependent on the individual factor. The topogram may also influence the biological response of radiosensitive/susceptible fibroblasts to irradiation. Altogether, our findings show that a chest CT scan exam may result in 2 to 3 times more unrepaired DSB in cells from radiosensitive/susceptible patients. Conclusions Both individual and tissue factors in the recognition and repair of DSB after current CT scan exams are important. Further investigations are needed to better define the radiosensitivity/susceptibility of individual humans.

Abstract Introduction The neurofibromatoses (NF) are a group of rare, genetic diseases sharing a predisposition to develop multiple benign nervous system tumors. Given the wide range of NF symptoms and medical specialties involved in NF care, we sought to evaluate the level of awareness of, and agreement with, published NF clinical guidelines among NF specialists in the United States. Methods An anonymous, cross-sectional, online survey was distributed to U.S.-based NF clinicians. Respondents self-reported demographics, practice characteristics, awareness of seven NF guideline publications, and level of agreement with up to 40 individual recommendations using a 5-point Likert scale. We calculated the proportion of recommendations that each clinician rated “strongly agree”, and assessed for differences in guideline awareness and agreement by respondent characteristics. Results Sixty-three clinicians (49% female; 80% academic practice) across > 8 medical specialties completed the survey. Awareness of each guideline publication ranged from 53%-79% of respondents; specialists had higher awareness of publications endorsed by their medical professional organization (p 0.05 for all). Conclusions We identified wide variability in both awareness of, and agreement with, published NF care guidelines among NF experts. Future quality improvement efforts should focus on evidence-based, consensus-driven methods to update and disseminate guidelines across this multi-specialty group of providers. Patients and caregivers should also be consulted to proactively anticipate barriers to accessing and implementing guideline-driven care. These recommendations for improving guideline knowledge and adoption may also be useful for other rare diseases requiring multi-specialty care coordination.

Abstract Background Neurofibromatosis type 1 (NF1) is a common human genetic disease with age-dependent phenotype progression. The overview of clinical and radiological findings evaluated by whole-body magnetic resonance imaging (WBMRI) in NF1 patients 3 cm in diameter, disfigurement, accompanying pain, bony destruction, or located para-aortic area), brain tumors, nerve root tumors, malignant peripheral nerve sheath tumors, moyamoya disease, and bony dysplasia were included. Results The age at WBMRI was 1.6 ± 0.7 years old, and NF1 mutations were found in 66 patients (94.3%). Focal areas of signal intensity (FASI) were the most common WBMRI finding (66.1%), followed by optic pathway glioma (15.7%), spine dural ectasia (12.9%), and plexiform neurofibromas (10.0%). Plexiform neurofibromas and NF1+ were more prevalent in familial case (28.7% vs 5.7%, p = 0.030; 71.4% vs 30.2%, p = 0.011). Follow-up WBMRI was conducted in 42 patients (23 girls and 19 boys) after 1.21 ± 0.50 years. FASI and radiologic progression were more frequent in patients with mutations involving GTPase activating protein-related domain (77.8% vs 52.4%, p = 0.047; 46.2% vs 7.7%, p = 0.029). Conclusions WBMRI provides important information for the clinical care for young pediatric NF1 patients. As NF1 progresses in even these young patients, and is related to family history and the affected NF1 domains, serial evaluation with WBMRI should be assessed based on the clinical and genetic features for the patients’ best care.

Soft tissue neoplasm is common among patients with neurofibromatosis type 1 (NF-1). We present a case of a middle-aged woman with NF-1 who presented with a painless, insidiously increasing perineal mass for the past eight months. She underwent colonoscopy, computed tomography staging, magnetic resonance imaging of the pelvis, core-needle biopsy, and later wide local excision of left perineum swelling. Histopathological examination showed a high-grade spindle cell sarcoma, which is a rare association among NF-1. Spindle cell sarcoma is a group of malignant soft tissue tumors with locally destructive growth with spindle-shaped neoplastic cells. The solitary spindle cell sarcoma of the perineum is rare, and wide local resection with a clear margin is the only treatment at present—the scarcely available evidence limiting the use of adjuvant chemotherapy, immunotherapy, and radiotherapy.

ABSTRACT BACKGROUND: Plexiform neurofibromas represent a common neoplasia of type 1 neurofibromatosis in which neurofibromas arise from multiple nerves involving connective tissue and skin and rarely affect the colon and rectum. Co-occurrence of plexiform neurofibromas, neuroendocrine tumors with primary involvement of the rectum, and medullary thyroid carcinoma in patients with neurofibromatosis type 1 is a previously undescribed condition. The aim of this manuscript was to present a case of primary plexiform neurofibroma and neuroendocrine tumors of the upper rectum in a patient with neurofibromatosis type 1 whose genetic sequencing found a novel mutation in the neurofibromatosis type 1 gene and to review the literature. CASE REPORT: A 49-year-old woman with a familial history of neurofibromatosis type 1 complained of abdominal cramps for 6 months. She had previously been submitted for a total thyroidectomy due to medullary thyroid carcinoma. She was submitted to a colonoscopy, which identified a submucosa lesion located in the upper rectum. The patient was referred for a laparoscopic rectosigmoidectomy, and the histopathological study of the surgical specimen identified two different tumors. An immunohistochemical panel was done for histopathological confirmation of the etiology of both lesions. The results of the panel showed intense immunoexpression of S100 protein in the largest and superficial lesion, as well as positivity for chromogranin and synaptophysin in the minor and deep lesion confirming the diagnosis of rectal plexiform neurofibromas concomitant with neuroendocrine tumors. The proliferative activity rate using Ki-67 antibodies showed that both tumors had a low rate of mitotic activity (

Background: Neurofibromatosis type 1 (NF-1) is a genetic disorder. A heterogeneous group of benign and malignant neoplasms are associated with NF-1. Adrenocortical carcinoma (ACC) is an extremely rare invasive malignancy. The association of ACC with NF1 is not well understood. Case Presentation: We report a case of ACC in the context of NF1 in a 39- year-old woman who referred with the chief complaint of a mass in left abdomen. A left adrenal lesion was diagnosed by CT scan. Biochemical tests showed no abnormality. Adrenalectomy was done and histological and immunohistochemical findings confirmed ACC. Due to the absence of metastasis, clinical stage II was considered for the tumor. On follow-up after six months, she was still alive and well and with no evidence of metastasis. The age of patient and lack of secretion of adrenal cortical hormones in this case were unlike most ACCs. Conclusion: Also, modified Weiss score for malignancy of adrenocortical neoplasms, clinical staging system and different modality of treatment is discussed.

Resumen: Antecedentes: El diagnóstico de la neurofibromatosis tipo 1 (NF1) habitualmente se demora en niños sin antecedentes familiares. Nuestro objetivo fue definir la prevalencia y características de las manifestaciones cutáneas prevalentes en la NF1, en comparación con la población general, que siguen siendo excluidas de los criterios diagnósticos para NF1. Pacientes y métodos: Estudio de casos y controles, pareado por grupos de edad, en el que se incluyó a 108 pacientes diagnosticados de NF1 y 137 controles sanos. Resultados: La prevalencia de nevus anemicus (NA) (p < 0,001) y xantogranuloma juvenil (XJ) (p < 0,001) fue significativamente superior en la población afectada de NF1, en comparación con el grupo control. Se estimaron una especificidad del 99,27% (intervalo de confianza: 95,4-99,96%) y un valor predictivo positivo (VPP) del 98,80% (92,54-99,94%) para NA, y una especificidad del 99,27% (95,4-99,96%) y VPP del 92,86% (64,17-99,63%) para XJ en el diagnóstico de NF1 en niños que presentan 6 o más manchas café con leche. También se evidenciaron diferencias estadísticamente significativas en la distribución por fototipos (p = 0,025) y con el generalizado sin otra causa conocida (p

The induced membrane technique is an innovative approach for repairing critical bone defects and has been applied recently in patients with congenital pseudarthrosis of the tibia (CPT). CPT is frequently associated with neurofibromatosis type 1 (NF1). Here, we briefly describe the clinical results of the induced membrane technique in NF1-deficient patients with CPT and in an animal model of CPT. Furthermore, we discuss the hypotheses used to explain inconsistent outcomes for the induced membrane technique in CPT–especially when associated with NF1.

Abstract Background Neurofibromatosis type 1 (NF1), which is caused by heterozygous inactivating pathogenic variants in the NF1, has poor phenotypic expressivity in the early years of life and there are numerous conditions, including many other tumor predisposition syndromes, that can mimic its appearance. These are collectively termed NF1-like syndromes and are also connected by their genetic background. Therefore, the NF1’s clinical diagnostic efficiency in childhood could be difficult and commonly should be completed with genetic testing. Methods To estimate the number of syndromes/conditions that could mimic NF1, we compiled them through an extensive search of the scientific literature. To test the utility of NF1’s National Institutes of Health (NIH) clinical diagnostic criteria, which have been in use for a long time, we analyzed the data of a 40-member pediatric cohort with symptoms of the NF1-like syndromes’ overlapping phenotype and performed NF1 genetic test, and established the average age when diagnostic suspicion arises. To facilitate timely identification, we compiled strongly suggestive phenotypic features and anamnestic data. Results In our cohort the utility of NF1’s clinical diagnostic criteria were very limited (sensitivity: 80%, specificity: 30%). Only 53% of children with clinically diagnosed NF1 had a detectable NF1 pathogenic variation, whereas 40% of patients without fulfilled clinical criteria tested positive. The average age at first genetic counseling was 9 years, and 40% of children were referred after at least one tumor had already been diagnosed. These results highlight the need to improve NF1-like syndromes’ diagnostic efficiency in childhood. We collected the most extensive spectrum of NF1-like syndromes to help the physicians in differential diagnosis. We recommend the detailed, non-invasive clinical evaluation of patients before referring them to a clinical geneticist. Conclusions Early diagnosis of NF1-like syndromes can help to prevent severe complications by appropriate monitoring and management. We propose a potential screening, diagnostic and management strategy based on our findings and recent scientific knowledge.

Abstract Neurofibromatosis 1 (NF1) is an inherited, autosomal-dominant, tumor predisposition syndrome with a birth incidence as high as 1:2000. A patient with NF1 is four to five times more likely to develop a malignancy as compared to the general population. The number of epidemiologic studies on lymphoproliferative malignancies in patients with NF1 is limited. The aim of this study was to determine the incidence rate of lymphoproliferative malignancies (lymphoma and leukemia) in NF1 patients followed in our referral center for neurofibromatoses. We used the Informatics for Integrated Biology and the Bedside (i2b2) platform to extract information from the hospital’s electronic health records. We performed a keyword search on clinical notes generated between Jan/01/2014 and May/11/2020 for patients aged 18 years or older. A total of 1507 patients with confirmed NF1 patients aged 18 years and above were identified (mean age 39.2 years; 57% women). The total number of person-years in follow-up was 57,736 (men, 24,327 years; women, 33,409 years). Mean length of follow-up was 38.3 years (median, 36 years). A total of 13 patients had a medical history of either lymphoma or leukemia, yielding an overall incidence rate of 22.5 per 100,000 (0.000225, 95% confidence interval (CI) 0.000223–0.000227). This incidence is similar to that of the general population in France (standardized incidence ratio 1.07, 95% CI 0.60–1.79). Four patients had a medical history leukemia and 9 patients had a medical history of lymphoma of which 7 had non-Hodgkin lymphoma, and 2 had Hodgkin lymphoma. Our results show that adults with NF1 do not have an increased tendency to develop lymphoproliferative malignancies, in contrast to the general increased risk of malignancy. While our results are consistent with the recent population-based study in Finland, they are in contrast with the larger population-based study in England whereby NF1 individuals were found to be 3 times more likely to develop both non-Hodgkin lymphoma and lymphocytic leukemia. Large-scale epidemiological studies based on nationwide data sets are thus needed to confirm our findings.

Abstract Introduction Neurofibromin, a protein encoded by the NF1 gene, is mutated in neurofibromatosis 1, one of the most common genetic diseases. Oral manifestations are common and a high prevalence of hyposalivation was recently described in individuals with neurofibromatosis 1. Although neurofibromin is ubiquitously expressed, its expression levels vary depending on the tissue type and developmental stage of the organism. The role of neurofibromin in the development, morphology, and physiology of salivary glands is unknown and a detailed expression of neurofibromin in human normal salivary glands has never been investigated. Aim To investigate the expression levels and distribution of neurofibromin in acinar and ductal cells of major and minor salivary glands of adult individuals without NF1. Material and method Ten samples of morphologically normal major and minor salivary glands (three samples of each gland: parotid, submandibular and minor salivary; and one sample of sublingual gland) from individuals without neurofibromatosis 1 were selected to assess neurofibromin expression through immunohistochemistry. Immunoquantification was performed by a digital method. Results Neurofibromin was expressed in the cytoplasm of both serous and mucous acinar cells, as well as in ducts from all the samples of salivary glands. Staining intensity varied from mild to strong depending on the type of salivary gland and region (acini or ducts). Ducts had higher neurofibromin expression than acinar cells (p = 0.003). There was no statistical association between the expression of neurofibromin and the type of the salivary gland, considering acini (p = 0.09) or ducts (p = 0.50) of the four salivary glands (parotid, submandibular, minor salivary, and sublingual gland). Similar results were obtained comparing the acini (p = 0.35) and ducts (p = 0.50) of minor and major salivary glands. Besides, there was no correlation between the expression of neurofibromin and age (p = 0.08), and sex (p = 0.79) of the individuals, considering simultaneously the neurofibromin levels of acini and duct (n = 34). Conclusion Neurofibromin is expressed in the cytoplasm of serous and mucous acinar cells, and ductal cells of salivary glands, suggesting that this protein is important for salivary gland function.

Abstract Background Diffuse interstitial lung disease have been described in Neurofibromatosis type 1 (NF1), but its diversity and prevalence remain unknown. The aim of this study was to assess the prevalence and characteristics of (NF1)-associated lung manifestations in a large single-center study using multidetector computed tomography (MDCT) and to evaluate the smoking history, patients’ age, genetics, and the presence of malignant peripheral nerve sheath tumors (MPNST) as potential influencing factors for lung pathologies. Methods In this retrospective study, 71 patients with NF1 were evaluated for the presence of distinctive lung manifestations like reticulations, consolidations, type of emphysema, pulmonary nodules and cysts. All patients underwent F-18-FDG PET/CT scans, which were reviewed by two experienced radiologists in consensus. Patients’ subgroups were formed based on their smoking history (current smokers/previous smokers/never smokers), age ( 18 years), and presence of MPNST (MPNST/no MPNST). In 57 patients (80%), genetic analysis of sequences coding for the neurofibromin on chromosome 17 was performed, which was correlated with different lung pathologies. Results Among all NF1 patients (33 ± 14 years, 56% females), 17 patients (24%) were current smokers and 62 patients (87%) were > 18 years old. Pulmonary cysts, nodules, and paraseptal emphysema were the most common pulmonary findings (35%, 32%, 30%). The presence of pulmonary metastases, MPNST and centrilobular emphysema was associated with smoking. Cysts were observed only in adults, whereas no significant correlation between age and all other pulmonary findings was found (p > 0.05). Presence of MPNST was accompanied by higher rates of intrapulmonary nodules and pulmonary metastasis. Neither the presence nor absence of any of the specific gene mutations was associated with any particular lung pathology (p > 0.05). Conclusions All pulmonary findings in NF1 patients occurred independently from specific mutation subtypes, suggesting that many NF1 mutations can cause various pulmonary pathologies. The presence of pulmonary metastases, MPNST and centrilobular emphysema was associated with smoking, indicating the value of smoking secession or the advice not to start smoking in NF1 patients as preventive strategy for clinicians. For screening of pulmonary manifestations in NF1 patients, an MDCT besides medical history and physical examination is mandatory in clinical routine.