Luxación de cadera atraumática en paciente con Neurofibromatosis tipo I / Atraumatic hip dislocation in a patient with Neurofibromatosis type I

Introducción: La neurofibromatosis tipo 1 es una enfermedad rara de herencia autosómica dominante. Con frecuencia el sistema esquelético se ve afectado con manifestaciones como escoliosis, pseudoartrosis congénita de tibia y lesiones quísticas intraóseas. Son menos frecuentes las manifestaciones sobre fémur proximal. Objetivo: Exponer las características clínicas y de imagen típicas de esta enfermedad a raíz del caso que se presenta, así como el tratamiento realizado y la evolución de la paciente. Presentación del caso: Se presenta el caso de una luxación atraumática de cadera derecha en una paciente de 14 años. La luxación sucedió en contexto hospitalario mientras consultaba por dolor insidioso en cadera derecha de días de evolución, sin evento traumático identificable. Mediante radiología simple y ampliando el estudio con tomografía axial computerizada se objetivó la luxación posterior femoroacetabular. Mediante sedación se llevo a cabo la reducción cerrada y se colocó una tracción blanda. Se completó el estudio con resonancia magnética, la cual objetivó la existencia de un neurofibroma intraarticular. La paciente ha cumplido 12 meses de seguimiento, encontrándose asíntomática y habiendo reiniciado su actividad en atletismo. Conclusiones: Es poca la bibliografía existente acerca de casos de luxación de cadera en pacientes con NF-1, siendo su tratamiento poco definido y debatido. (AU)

Introduction: Neurofibromatosis type 1 is a rare disease that follows an autosomal dominant inheritance pattern. The skeletal system is frequently affected with manifestations such as scoliosis, congenital pseudarthrosis of the tibia, and intraosseous cystic lesions. Manifestations on the proximal femur are less frequent. Objective: To expose the typical clinical and imaging characteristics of this disease as a result of the case that is presented, as well as the treatment carried out and the evolution of the patient.Case presentation: The case of an atraumatic dislocation of the right hip in a 14-year-old patient is presented. The dislocation happened in a hospital context while consulting for insidious pain in the right hip of days of evolution, without an identifiable traumatic event. Through simple radiology and expanding the study with computerized axial tomography, the posterior femoroacetabular dislocation was observed. Under sedation, closed reduction was performed and soft traction was placed. The study was completed with magnetic resonance imaging, which revealed the existence of an intra-articular neurofibroma. The patient has completed 12 months of follow-up, being asymptomatic and having restarted her athletic activity. Conclusions: There is little existing bibliography on cases of hip dislocation in patients with NF-1, and its treatment is poorly defined and debated. (AU)

MEK inhibition exerts temporal and myeloid cell-specific effects in the pathogenesis of neurofibromatosis type 1 arteriopathy.

Mutations in the NF1 tumor suppressor gene are linked to arteriopathy. Nf1 heterozygosity (Nf1+/-) results in robust neointima formation, similar to humans, and myeloid-restricted Nf1+/- recapitulates this phenotype via MEK-ERK activation. Here we define the contribution of myeloid subpopulations to NF1 arteriopathy. Neutrophils from WT and Nf1+/- mice were functionally assessed in the presence of MEK and farnesylation inhibitors in vitro and neutrophil recruitment to lipopolysaccharide was assessed in WT and Nf1+/- mice. Littermate 12-15 week-old male wildtype and Nf1+/- mice were subjected to carotid artery ligation and provided either a neutrophil depleting antibody (1A8), liposomal clodronate to deplete monocytes/macrophages, or PD0325901 and neointima size was assessed 28 days after injury. Bone marrow transplant experiments assessed monocyte/macrophage mobilization during neointima formation. Nf1+/- neutrophils exhibit enhanced proliferation, migration, and adhesion via p21Ras activation of MEK in vitro and in vivo. Neutrophil depletion suppresses circulating Ly6Clow monocytes and enhances neointima size, while monocyte/macrophage depletion and deletion of CCR2 in bone marrow cells abolish neointima formation in Nf1+/- mice. Taken together, these findings suggest that neurofibromin-MEK-ERK activation in circulating neutrophils and monocytes during arterial remodeling is nuanced and points to important cross-talk between these populations in the pathogenesis of NF1 arteriopathy.

Current Understanding of Neurofibromatosis Type 1, 2, and Schwannomatosis.

Neurofibromatosis (NF) is a neurocutaneous syndrome characterized by the development of tumors of the central or peripheral nervous system including the brain, spinal cord, organs, skin, and bones. There are three types of NF: NF1 accounting for 96% of all cases, NF2 in 3%, and schwannomatosis (SWN) in <1%. The NF1 gene is located on chromosome 17q11.2, which encodes for a tumor suppressor protein, neurofibromin, that functions as a negative regulator of Ras/MAPK and PI3K/mTOR signaling pathways. The NF2 gene is identified on chromosome 22q12, which encodes for merlin, a tumor suppressor protein related to ezrin-radixin-moesin that modulates the activity of PI3K/AKT, Raf/MEK/ERK, and mTOR signaling pathways. In contrast, molecular insights on the different forms of SWN remain unclear. Inactivating mutations in the tumor suppressor genes SMARCB1 and LZTR1 are considered responsible for a majority of cases. Recently, treatment strategies to target specific genetic or molecular events involved in their tumorigenesis are developed. This study discusses molecular pathways and related targeted therapies for NF1, NF2, and SWN and reviews recent clinical trials which involve NF patients.

Exploring associations between constipation, severity of neurofibromatosis type 1 and NF1 mutational spectrum.

Neurofibromatosis type 1 (NF1) is inherited in an autosomal dominant manner and is a rather common rare disease. Until recently, studies on gastrointestinal symptoms in patients with NF1 have been few and mostly described as case reports. In three previously published studies, the frequency of constipation in patients with NF1 has been found to be as high as 30%. In this study, associations between the frequency of constipation and NF1 disease severity and NF1 mutational spectrum were investigated. Among 277 patients with NF1, 49 had constipation. The highest rate of constipation was found among patients with a high perception of NF1 illness burden, and patients with constipation had a significantly higher NF1 illness burden when comparing the "not bothered" and the "very bothered" (p = 0.013). We found no significant association between constipation and the remaining measures on severity of NF1, nor between constipation and genetic variants. When observing the NF1 mutational spectrum, one variant (c.1013A>G (p.Asp338Gly/p.?) was identified in three patients with constipation of which two patients were related. The variant c.2970_2972delAAT (p.Met992del) associated with a mild NF1 phenotype was identified in two related patients with constipation. This study is the first to explore the association between symptoms of constipation, NF1 severity, and NF1 mutational spectrum. The results suggest an association between constipation and a high degree of illness burden. Awareness of this association among physicians could lead to more patients with NF1 being diagnosed with constipation. Constipation impacts on quality of life, hence a timely diagnosis and treatment will improve quality of life.

MEKK2 mediates aberrant ERK activation in neurofibromatosis type I.

Neurofibromatosis type I (NF1) is characterized by prominent skeletal manifestations caused by NF1 loss. While inhibitors of the ERK activating kinases MEK1/2 are promising as a means to treat NF1, the broad blockade of the ERK pathway produced by this strategy is potentially associated with therapy limiting toxicities. Here, we have sought targets offering a more narrow inhibition of ERK activation downstream of NF1 loss in the skeleton, finding that MEKK2 is a novel component of a noncanonical ERK pathway in osteoblasts that mediates aberrant ERK activation after NF1 loss. Accordingly, despite mice with conditional deletion of Nf1 in mature osteoblasts (Nf1fl/fl;Dmp1-Cre) and Mekk2-/- each displaying skeletal defects, Nf1fl/fl;Mekk2-/-;Dmp1-Cre mice show an amelioration of NF1-associated phenotypes. We also provide proof-of-principle that FDA-approved inhibitors with activity against MEKK2 can ameliorate NF1 skeletal pathology. Thus, MEKK2 functions as a MAP3K in the ERK pathway in osteoblasts, offering a potential new therapeutic strategy for the treatment of NF1.

Phenotypic heterogeneity of neurofibromatosis type 1 in a large international registry.

Neurofibromatosis type 1 (NF1) is a rare genetic disorder, characterized by the development of benign and malignant nerve tumors. Although all individuals with NF1 harbor genetic alterations in the same gene, the clinical manifestations of NF1 are extremely heterogeneous even among individuals who carry identical genetic defects. In order to deepen the understanding of phenotypic manifestations in NF1, we comprehensively characterized the prevalence of 18 phenotypic traits in 2051 adults with NF1 from the Children's Tumor Foundation's NF1 registry. We further investigated the coassociation of traits and found positive correlations between spinal neurofibromas and pain, spinal neurofibromas and scoliosis, spinal neurofibromas and optic gliomas, and optic gliomas and sphenoid wing dysplasia. Furthermore, with increasing numbers of cutaneous neurofibromas, the odds ratio of malignant peripheral nerve sheath tumor increased. Phenotypic clustering revealed 6 phenotypic patient cluster subtypes: mild, freckling predominant, neurofibroma predominant, skeletal predominant, late-onset neural severe, and early-onset neural severe, highlighting potential phenotypic subtypes within NF1. Together, our results support potential shared molecular pathogenesis for certain clinical manifestations and illustrate the utility of disease registries for understanding rare diseases.

Clinical characteristics and quality of life, depression, and anxiety in adults with neurofibromatosis type 1: A nationwide study.

Neurofibromatosis type 1 (NF1) is a genetic condition characterized by numerous somatic manifestations. The psychosocial burden in adults has rarely been studied. We examined the prevalence of self-reported impairment of quality of life (QoL), symptoms of anxiety and depression and need for support, associated with disease severity and visibility. We conducted a nationwide cross-sectional study of all 467 adults with NF1 diagnosed between 1977 and 2016 at one of the two national centers for rare diseases in Denmark. A total of 244 (56% response rate) completed a questionnaire that included standard measures of QoL, symptoms of depression and anxiety, indicators of disease-related severity, visibility, and need for professional support. Associations between disease severity and visibility and psychosocial burden were analyzed in descriptive and multivariate models. We observed impaired QoL (mean = 81.3; 95% CI, 76.2; 86.4); 19% reported symptoms of depression (mean = 5.7; SD = 5.4), and 15% reported anxiety (mean = 5.1; SD = 5.2) at a clinical level. Adults with NF1 also reported requiring professional support for physical, psychological, and work-related problems. Disease severity and (partly) visibility were significantly (p < .0001) associated with psychosocial well-being and a requirement for support. This study provides new understanding of the factors associated with impaired QoL, indicating that follow-up care should be optimized into adult life.

Clinical and neuroradiological characterisation of spinal lesions in adults with Neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) manifests itself in many ways in the spine. This study aims to report the types of spinal lesions, clinical and demographic data in a large cohort from a complex NF1 centre. The characteristics of those with spinal neurofibromatosis, where neurofibromas are present on every spinal nerve root, were sought for comparison with the wider group of NF1 patients. This is a retrospective review of MDT minutes of 303 patients from a UK NF1 centre and the largest reported series of NF1 patients based on radiological data. Prevalence of each symptom and lesion was calculated and statistically significant associations were established. The most reported findings were cutaneous lesions (44.9%) and neurological deficit (27.4%). 28.4% had dural ectasia, 52.5% had some form of spinal deformity. 57.8% had spinal nerve root tumours, the most common of which were at C2. The most progressive lesions were spinal nerve root tumours (29.1%). The only statistically significant association found was between dural ectasia and spinal deformity (P < 0.003), where dural ectasia is associated with a 32.6% increase in spinal deformity incidence. This is the largest descriptive study of spinal lesions in NF1. Spinal tumours and spinal deformity are prevalent in NF1. The predilection of spinal tumours for flexible spinal regions suggests that repetitive movement might be an important factor in pathogenesis. Physicians and patients should be alert to the observation that although many spinal neurofibromatosis patients display no neurological deficit, they often have significant lesions which require monitoring and sometimes surgery.

Evaluation and Factors of Quality of Life Among Patients With Neurofibromatosis Type 1-Associated Craniofacial Plexiform Neurofibromas.

OBJECTIVES: The aim was to evaluate overall quality of life (QOL) and investigate impact factors in Chinese neurofibromatosis type 1 (NF1) patients, particularly in those with craniofacial plexiform neurofibromas (pNFs). METHODS: The Impact of NF1 on quality of life (INF1-QOL) Questionnaire were completed from a department of plastic and reconstructive surgery by 27 patients. Patients were 3 to 49 years of age. The correlation between subdomains were calculated using Pearson correlation. The difference between groups were evaluated using Fisher exact t-test. P value <0.05 were considered significant. RESULTS: In age group of craniofacial pNFs, significant difference presented in cosmetic appearance, role and outlook on life and general QOL. Higher impact on general QOL in adults (6/8) than children (1/7) pointed to more impaired QOL in adults, as well as 2 subdomains including appearance, role and outlook on life. The patients who have more than 50 cutaneous neurofibromas (cNFs) (6/7) presented a significantly greater negative impact on the role and outlook of life. No statistically significant difference of QOL were detected between craniofacial and non-craniofacial pNFs patients. CONCLUSIONS: Age and cNFs were 2 main factors that have a negative impact on QOL in craniofacial pNFs patients. Adults reported lower QOL in cosmetic appearance, the role and outlook of life and general QOL. Patients with more than 50 cNFs reported more negative impact on the role and outlook of life. A multidiscipline management for these patients is required, including psychosocial intervention.

Neurofibromatosis tipos 1 y 2 / Neurofibromatosis type 1 and 2

La neurofibromatosis (NF) comprende un grupo de enfermedades genéticas de herencia autosómica dominante, que se clasifican de la siguiente manera: neurofibromatosis tipo 1 (NF1), neurofibromatosis tipo 2 (NF2) y schwannomatosis (también conocida como neurofibromatosis tipo 3). Esta última es una enfermedad muy infrecuente, con una prevalencia aproximada de 1/126 000 personas, por lo que solo profundizaremos las dos primeras. La NF1, también conocida como la enfermedad de Von Recklinghausen, es la más frecuente de las tres y afecta principalmente la piel y el sistema nervioso periférico. Se caracteriza por la presencia de máculas "café con leche", pecas axilares o inguinales, nódulos de Lisch (hamartomas en el iris) y neurofibromas (tumores de la vaina de nervios periféricos). Otras manifestaciones menos frecuentes, aunque de mayor gravedad, incluyen gliomas del nervio óptico, meningiomas, neurofibromas malignos, escoliosis y displasia de la tibia. Su diagnóstico se suele realizar al nacimiento o durante los primeros años de vida, y se estima que un 50% de quienes la padecen presenta dificultades cognitivas. No hay datos concluyentes sobre la mortalidad en los pacientes con NF1, aunque se sabe que la expectativa de vida es menor que en la población general. La NF2 tiene una prevalencia considerablemente menor que la NF1 y su inicio es más tardío, afectando principalmente a adultos jóvenes. La presentación clínica típica se caracteriza por acúfenos, hipoacusia y ataxia en contexto de la presencia de schwannomas vestibulares bilaterales. Otros hallazgos menos frecuentes incluyen schwannomas de nervios periféricos, meningiomas, ependimomas o astrocitomas. La esperanza de vida es de unos 36 años, con una supervivencia media desde el momento del diagnóstico de 15 años. (AU)

Neurofibromatosis (NF) includes a group of genetic diseases with an autosomal-dominant inheritance pattern, and they are classified as follows: Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and Schwannomatosis (also known as neurofibromatosis type 3). This last one is a very rare disease, with an approximate prevalence of 1/126000, so we will only deepen in the first two. NF1, also known as von Recklinghausen disease, is the most frequent, and mainly affects the skin and peripheral nervous system. Its typical manifestations are the presence of café-au-lait macules, axillary or inguinal freckles, Lisch nodules (hamartomas in the iris) and neurofibromas (peripheral nerve sheath tumors). Less frequent manifestations, although more serious, include optic nerve gliomas, meningiomas, malignant neurofibromas, scoliosis and tibial dysplasia. The diagnosis is usually made at birth or during the first years of life, and approximately 50% of patients present cognitive difficulties. There is no conclusive data on mortality in patients with NF1, although it is known that life expectancy is lower than in general population. NF2 has a considerably lower prevalence than NF1, and its onset is later in life, mainly affecting young adults. Its typical clinical presentation is characterized by tinnitus, hearing loss and ataxia in the context in the presence of bilateral vestibular schwannomas. Less frequent findings include peripheral nerve schwannomas, meningiomas, ependymomas or astrocytomas. Life expectancy is about 36 years old, with a median survival from the moment of diagnosis of 15 years. (AU)

Neurofibromatosis 1 y cavernomatosis múltiple familiar en un lactante con sialorrea profusa episódica / Neurofibromatosis 1 and multiple familial cavernomatosis in an infant with episodic profuse sialorrhoea

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Gastrointestinal Stromal Tumor in a Patient with Neurofibromatosis Type 1 That Was Successfully Treated with Regorafenib.

An unconscious 55-year-old man with a history of neurofibromatosis type 1 (NF1) was transported to the emergency department and was diagnosed with acute renal failure owing to a large bladder tumor. A submucosal tumor was also identified in the duodenum. The patient was diagnosed with a primary gastrointestinal stromal tumor (GIST) of the bladder and duodenum. After six cycles of regorafenib therapy, 18F-fluorodeoxyglucose accumulation in the duodenal GIST on positron emission tomography-computed tomography (PET-CT) showed a partial metabolic response. Currently, no standard drug therapy for unresectable or relapsed NF1-associated GIST has been established. Regorafenib may thus be considered as and appropriate initial therapy.

From process to progress-2017 International Conference on Neurofibromatosis 1, Neurofibromatosis 2 and Schwannomatosis.

The neurofibromatoses are inherited, tumor suppressor disorders that are characterized by multiple, benign peripheral nerve sheath tumors and other nervous system tumors. Each disease is associated with a distinct genetic mutation and with a different pathogenesis and clinical course. Neurofibromatosis 1 (NF1) is common and epitomized by multiple neurofibromas with widespread complications. NF2 and schwannomatosis are rare diseases that are typified by multiple schwannomas that are particularly painful in people with schwannomatosis. Since 1985, the Children's Tumor Foundation (formerly the National Neurofibromatosis Foundation) has hosted an international Neurofibromatosis Conference, bringing together international participants who are focused on NF research and clinical care. The 2017 Conference, held in Washington, DC, was among the largest gatherings of NF researchers to date and included presentations from clinicians and basic scientists, highlighting new data regarding the molecular and cellular mechanisms underlying each of these diseases as well as results from clinical studies and clinical trials. This article summarizes the findings presented at the meeting and represents the current state-of-the art for NF research.

Neurofibromatosis tipo I. Presentación de un caso / Neurofibromatose tipo I. Apresentação de um caso / Neurofibromatosis type I. Case report

Se presentó un paciente masculino de 25 años de edad con tumoraciones subcutáneas en miembros, región dorsovertebral y dificultad en la marcha. Por este cuadro se ingresó en el Hospital General Docente Dr Agostinho Neto para estudio y tratamiento. Al realizar examen neurológico se constató presencia de marcha antiálgica, atrofia muscular supra e infraclavicular, espinosa, interósea, tenar e hipotenar bilateral, tumoraciones subcutáneas a nivel del cuello, extremidades y tronco, varias manchas color café con leche multiformes, así como disminución de fuerza muscular 4/5 próximo distal de extremidades. Los estudios radiológicos evidenciaron paquete tumoral en área paravertebral e inguinal, se realizó extracción y biopsia, informándose presencia de neurofibromas, diagnosticándose neurofibromatosis tipo I. Por ser una de las enfermedades hereditarias más frecuentes, pero menos estudiadas en nuestro medio se decidió la realización de este estudio(AU)

A 25-year-old male patient presented with subcutaneous tumors in the limbs, dorso-vertebral region and difficulty walking. For this picture, he was admitted to the General Teaching Hospital Dr Agostinho Neto for study and treatment. When the neurological examination was performed, there was presence of antalgic gait, supra and infraclavicular muscular atrophy, spinous, interosseous, tenar and bilateral hypothenar, subcutaneous tumors at the level of the neck, extremities and trunk, several coffee with milk spots, as well as a decrease of muscular strength 4/5 proximal distal of extremities. The radiological studies evidenced tumor bundle in the paravertebral and inguinal area, extraction and biopsy were performed, and neurofibromas were reported, diagnosing neurofibromatosis type I. Because it is one of the most frequent hereditary diseases, but less studied in our environment, it was decided to carry out this study(AU)

Paciente do sexo masculino, 25 anos, apresentava tumores subcutâneos nos membros, região dorso-vertebral e dificuldade para deambular. Para esta foto, ele foi internado no Hospital Geral de Ensino Dr Agostinho Neto para estudo e tratamento. Ao realizar presença exame neurológico da marcha antálgica, supra atrofia muscular e infraclaviculares, espinhosa, interósseo, tenar e hipotenar bilateral, tumores subcutâneos na região do pescoço, tronco e membros, vários pontos coloridos café com leite multiforme foi encontrado, bem como a diminuição de força muscular 4/5 proximal distal de extremidades. Estudos radiológicos mostraram tumores no pacote paravertebral e região da virilha, a remoção e a biópsia, informando a presença de neurofibromas, diagnosticándose neurofibromatosis tipo I. Tal comouma das doenças hereditárias mais comuns, mas pouco estudada no nosso hospital por este motivo decidiu-se realizar este estudo(AU)

2016 Children's Tumor Foundation conference on neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis.

Organized and hosted by the Children's Tumor Foundation (CTF), the Neurofibromatosis (NF) conference is the premier annual gathering for clinicians and researchers interested in neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). The 2016 edition constituted a blend of clinical and basic aspects of NF research that helped in clarifying different advances in the field. The incorporation of next generation sequencing is changing the way genetic diagnostics is performed for NF and related disorders, providing solutions to problems like genetic heterogeneity, overlapping clinical manifestations, or the presence of mosaicism. The transformation from plexiform neurofibroma (PNF) to malignant peripheral nerve sheath tumor (MPNST) is being clarified, along with new management and treatments for benign and premalignant tumors. Promising new cellular and in vivo models for understanding the musculoskeletal abnormalities in NF1, the development of NF2 or SWN associated schwannomas, and clarifying the cells that give rise to NF1-associated optic pathway glioma were presented. The interaction of neurofibromin and SPRED1 was described comprehensively, providing functional insight that will help in the interpretation of pathogenicity of certain missense variants identified in NF1 and Legius syndrome patients. Novel promising imaging techniques are being developed, as well as new integrative and holistic management models for patients that take into account psychological, social, and biological factors. Importantly, new therapeutic approaches for schwannomas, meningiomas, ependymomas, PNF, and MPNST are being pursued. This report highlights the major advances that were presented at the 2016 CTF NF conference.

The characteristics of 76 atypical neurofibromas as precursors to neurofibromatosis 1 associated malignant peripheral nerve sheath tumors.

Background: Neurofibromatosis 1 (NF1) leads to the development of benign and malignant peripheral nerve sheath tumors (MPNST). MPNST have been described to develop in preexisting benign plexiform neurofibromas (PN) and have a poor prognosis. Atypical neurofibromas (ANF) were recently described as precursor lesions for MPNST, making early detection and management of ANF a possible strategy to prevent MPNST. We aimed to clinically characterize ANF and identify management approaches. Methods: We analyzed clinical, imaging, and pathology findings of all patients with NF1 and ANF at 3 institutions. Results: Sixty-three patients had 76 ANF (32M/31F; median age 27.1 y). On MRI, most ANF appeared as distinct nodular lesions and were 18F-fluorodeoxyglucose (FDG) avid. Forty-six ANF were associated with pain, 19 with motor weakness, 45 were palpable or visible, and 13 had no clinical signs. Completely resected ANF (N = 57) have not recurred (median follow-up, 4.1 y; range, 0-14 y). Four ANF transformed into MPNST and 17 patients had a history of MPNST in a different location than was their ANF. Conclusions: Growth of distinct nodular lesions, pain, and FDG-PET avidity should raise concern for ANF in NF1. Patients with ANF are at greater risk for development of MPNST. Complete resection of ANF may prevent development of MPNST.

Liponeurofibroma: Clinicopathological features and histogenesis.

A neurofibroma is a common cutaneous benign tumor of neural origin. Various histological variants have been reported. Recently, sporadic reports of fatty variants have been reported but their clinicopathological features have not been well studied. The purpose of this study was to examine liponeurofibroma, and to report the distinctive clinicopathological features and histogenesis in comparison with the classic form. A retrospective study was performed on 130 cases. Immunohistochemical staining was performed for S100, factor VIIIa, perilipin and vascular endothelial growth factor. Masson's trichrome stain was also used. Intratumoral adipocytes were examined with transmission electron microscopy. Thirty-two (24.6%) cases were classified as liponeurofibroma on microscopic examination. This variant was more common in patients with neurofibromatosis type 1, older age and female sex. The most prevalent location was the head and neck. Intratumoral fat deposits showed differences in morphology and size compared with subcutaneous fat on light microscopy. Neurofibromatosis type 1 had the highest odds of fatty change in liponeurofibroma. In sporadic cases, fatty change can be caused by senescence, chronic injury, or tissue hypoxia secondary to internal or external stimuli. Further investigation is needed to identify the pathomechanism of fatty change in various cutaneous neoplasms, including neurofibroma.

Florid cemento-osseous dysplasia and peripheral giant cell granuloma in a patient with neurofibromatosis 1.

We report a 35-year-old mulatto female patient with neurofibromatosis Type 1 who presented with facial asymmetry. The patient had two lesions: florid cemento-osseous dysplasia associated with peripheral giant cell granuloma. She was referred for surgical treatment of the peripheral giant cell granuloma and the florid cemento-osseous dysplasia was treated conservatively by a multidisciplinary team. So far, no changes have been observed in the patient's clinical status. We observed no recurrence of peripheral giant cell granuloma. To the best of our knowledge, the present case is the first report of a patient with neurofibromatosis Type 1 associated with a giant cell lesion and florid cemento-osseous dysplasia.