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Cancer Microenvironment : Official... Dec 2012Dynamic interactions between tumorigenic cells and surrounding cells, including immunomodulatory hematopoietic cells, can dictate tumor initiation, progression, and...
Dynamic interactions between tumorigenic cells and surrounding cells, including immunomodulatory hematopoietic cells, can dictate tumor initiation, progression, and transformation. Hematopoietic-stromal interactions underpin the plexiform neurofibroma, a debilitating tumor arising in individuals afflicted with Neurofibromatosis type 1 (NF1), a common genetic disorder resulting from mutations in the NF1 tumor suppressor gene. At the tissue level, plexiform neurofibromas demonstrate a complex microenvironment composed of Schwann cells, fibroblasts, perineural cells, mast cells, secreted collagen, and blood vessels. At the cellular level, specific interactions between these cells engender tumor initiation and progression. In this microenvironment hypothesis, tumorigenic Schwann cells secrete pathological concentrations of stem cell factor, which recruit c-kit expressing mast cells. In turn, activated mast cells release inflammatory effectors stimulating the tumorigenic Schwann cells and their supporting fibroblasts and blood vessels, thus promoting tumor expansion in a feed-forward loop. Bone marrow transplantation experiments in plexiform neurofibroma mouse models have shown that tumorigenesis requires Nf1 haploinsufficiency in the hematopoietic compartment, suggesting that tumor microenvironments can depend on intricate interactions at both cellular and genetic levels. Overall, our continued understanding of critical tumor-stromal interactions will illuminate novel therapeutic targets, as shown by the first-ever successful medical treatment of a plexiform neurofibroma by targeted inhibition of the stem cell factor/c-kit axis.
PubMed: 22821631
DOI: 10.1007/s12307-012-0115-x -
Open Access Macedonian Journal of... Apr 2019Neurofibromatosis is a genetic disease with an autosomal dominant type of inheritance. It is a multisystem disease in which, besides skin manifestations, there is a...
BACKGROUND
Neurofibromatosis is a genetic disease with an autosomal dominant type of inheritance. It is a multisystem disease in which, besides skin manifestations, there is a possibility for the involvement of other organs and systems, and an atypical variant of neurofibromatosis type 1 can also be observed- the so-called plexiform neurofibroma. In patients with this inherited disease, mortality is higher due to the existing risk for malignant transformation and development of malignant peripheral nerve sheath tumours (MPNSTs) or neurofibrosarcoma.
CASE REPORT
We present a 25-year-old woman with neurofibromatosis type 1 and a family history of the disease-father and grandmother with NF-1, with fatal outcome in the grandmother as a result of malignant transformation to neurofibrosarcoma. The patient has clinical data for multiple cafés- au- lait spots on the skin of the trunk, upper and lower limbs, and plexiform tumour formation in the seating area. From the performed imaging diagnostic there are available MRT data for 1) giant pelvic neurofibroma, 2) plexiform giant neurofibroma in the subcutaneous fat on the right thigh and gluteal fat tissue to the right, passing through the midline in the area of the external genitalia, leading to deformation of the front wall of the sacrum with bilateral meningoceles and 3) diffuse involvement of the bladder wall from the process in the area of the trigonum vesicae felleae/the two urethral ostium, as well as 4) the presence of neurofibromas in the course of the iliac vessels on the right. Surgical removal of the oval pelvic formation, identified as neurofibroma was planned, as well as the initiation of systemic therapy with Sirolimus for the plexiform sciatic formation, infiltrating the bladder.
CONCLUSION
Neurofibromatosis type-1 is a problematic disease due to the parallel systemic involvement of different organs and systems, which can be both limited and diffuse. Limited tumour lesions in the form of neurofibromas with diverse localisation (as in the patient we describe) could be surgically removed without difficulty. On the other hand, the diffuse involvement of internal organs within a giant, network-3spreading plexiform neurofibromas (as in the described patient) makes interdisciplinary interventions impossible, and therefore therapeutic alternatives should be considered.
PubMed: 31110582
DOI: 10.3889/oamjms.2019.304 -
PloS One 2020Patients with Neurofibromatosis type 1 (NF1) develop plexiform neurofibromas (PNF) and cutaneous neurofibromas. These tumors are a major cause of the patient's morbidity...
INTRODUCTION
Patients with Neurofibromatosis type 1 (NF1) develop plexiform neurofibromas (PNF) and cutaneous neurofibromas. These tumors are a major cause of the patient's morbidity and mortality. An influence of estrogen and progesterone on tumor growth has been suggested but reports on growth or malignant transformation of tumors during pregnancy remain anecdotal. The purpose of this study was to quantify growth of cutaneous and plexiform neurofibromas in NF1 patients during pregnancy, and to assess the onset of NF1 related symptoms.
MATERIAL AND METHODS
Retrospectively, 13 mothers with NF1 were included and compared to nullipara, nulligravida, age-matched women with NF1. All women received whole-body magnetic resonance imaging (MRI) before and after pregnancy or after a matched time period. Presence of plexiform and cutaneous neurofibromas was evaluated. PNF were subjected to semi-automated volumetry (MedX). The sum of the longest diameters (SLD) of representative cutaneous neurofibromas was determined for both groups. Clinical symptoms and subjective tumor growth were assessed.
RESULTS
PNF were identified in 12/26 women (46.2%). Follow up showed neither new PNF nor a significant difference in growth rate (median tumor-growth/year: pregnant group-0.38% (IQR -1.1-5.4%) vs control group 3.59% (IQR -2.1-5.5%; P = 0.69). Malignant transformation of PNF was not observed. There was a significant growth of cutaneous neurofibromas in both groups (median SLD increase: pregnant group 17mm; P = 0.0026 / control group 12mm; P = 0.0004) The difference in increase of SLD was not significant (P = 0.48). Singular cutaneous neurofibromas in the pregnant group displayed high levels of tumor growth (>20%/year). NF1-associated symptoms and subjective tumor growth were not significantly increased in pregnant patients.
CONCLUSIONS
Growth of plexiform and cutaneous neurofibromas in pregnant patients is not significantly different compared to non-pregnant patients. Cutaneous neurofibromas show a significant increase in growth over time in both, pregnant and non-pregnant patients and NF1 related clinical symptoms do not significantly aggravate during the course of pregnancy.
Topics: Adolescent; Adult; Case-Control Studies; Disease Progression; Female; Humans; Magnetic Resonance Imaging; Neurofibroma, Plexiform; Neurofibromatosis 1; Pregnancy; Pregnancy Complications, Neoplastic; Retrospective Studies; Skin Neoplasms; Tumor Burden; Young Adult
PubMed: 32343738
DOI: 10.1371/journal.pone.0232031 -
British Journal of Cancer Jul 2020Neurofibromatosis type 1 (NF1) is a hereditary tumour syndrome that predisposes to benign and malignant tumours originating from neural crest cells. Biallelic... (Review)
Review
Neurofibromatosis type 1 (NF1) is a hereditary tumour syndrome that predisposes to benign and malignant tumours originating from neural crest cells. Biallelic inactivation of the tumour-suppressor gene NF1 in glial cells in the skin, along a nerve plexus or in the brain results in the development of benign tumours: cutaneous neurofibroma, plexiform neurofibroma and glioma, respectively. Despite more than 40 years of research, only one medication was recently approved for treatment of plexiform neurofibroma and no drugs have been specifically approved for the management of other tumours. Work carried out over the past several years indicates that inhibiting different cellular signalling pathways (such as Hippo, Janus kinase/signal transducer and activator of transcription, mitogen-activated protein kinase and those mediated by sex hormones) in tumour cells or targeting cells in the microenvironment (nerve cells, macrophages, mast cells and T cells) might benefit NF1 patients. In this review, we outline previous strategies aimed at targeting these signalling pathways or cells in the microenvironment, agents that are currently in clinical trials, and the latest advances in basic research that could culminate in the development of novel therapeutics for patients with NF1.
Topics: Genes, Tumor Suppressor; Humans; Molecular Targeted Therapy; Mutation; Neurofibroma, Plexiform; Neurofibromatosis 1; Neurofibromin 1; Signal Transduction; Translational Research, Biomedical; Tumor Microenvironment
PubMed: 32439933
DOI: 10.1038/s41416-020-0903-x -
JPGN Reports Aug 2021Mesenteric plexiform neurofibroma is a subtype of plexiform neurofibroma that involves the mesentery and causes a variety of gastrointestinal complaints. Plexiform...
Mesenteric plexiform neurofibroma is a subtype of plexiform neurofibroma that involves the mesentery and causes a variety of gastrointestinal complaints. Plexiform neurofibroma is classically found in patients with neurofibromatosis type 1, although genetic contributions to plexiform neurofibroma pathogenesis are heterogeneous. We report the first case of mesenteric plexiform neurofibroma in a patient with a pathogenic variant. This patient presented with growth failure, generalized abdominal pain and chronic diarrhea. She was confirmed to have mesenteric plexiform neurofibroma on histopathology and targeted sequencing on affected tissue confirmed that there were no neurofibromatosis type 1 variants present. Given that this patient's mesenteric plexiform neurofibroma is associated with dysfunction, she is unlikely to benefit from MEK inhibitors, which are the newly approved treatment for inoperable plexiform neurofibroma in patients with neurofibromatosis type 1.
PubMed: 37205972
DOI: 10.1097/PG9.0000000000000098 -
Journal of Pediatric Neurosciences 2016Plexiform neurofibroma (PNF) of the scalp is an extremely rare lesion reported in association with neurofibromatosis (NF). Occipital location of PNF is even more... (Review)
Review
Congenital extra calvarial plexiform neurofibroma in occipito-cervical region with Occipital bone defect with neurofibromatosis type 1 and segmental neurofibromatosis: Case report and review of literature.
Plexiform neurofibroma (PNF) of the scalp is an extremely rare lesion reported in association with neurofibromatosis (NF). Occipital location of PNF is even more infrequent; we reported one pediatric case of PNF in occipito-cervical region with multiple small occipital bone defects and associated with NF-1.
PubMed: 28217149
DOI: 10.4103/1817-1745.199469 -
International Archives of... Oct 2015Introduction Laryngeal neurofibromas are extremely rare, accounting for only 0.03 to 0.1% of benign tumors of the larynx. Objectives To report the first case of...
Introduction Laryngeal neurofibromas are extremely rare, accounting for only 0.03 to 0.1% of benign tumors of the larynx. Objectives To report the first case of massive neck plexiform neurofibroma with intralaryngeal (supraglottic) extension in a 5-year-old boy with neurofibromatosis type 1 and to describe its treatment. Resumed Report This massive plexiform neurofibroma was surgically removed, relieving its significant respiratory obstructive symptoms without recurrence to date. Conclusion Massive neck plexiform neurofibroma with supraglottic part was found in a child with neurofibromatosis type 1; it should be included in differential diagnosis of stridor and neck mass in children. It was diagnosed and removed in early in childhood without recurrence.
PubMed: 26491483
DOI: 10.1055/s-0034-1396793 -
Plexiform neurofibromas, trial design, and the definitions of "progression" and "treatment failure".Neuro-oncology May 2014
Topics: Antineoplastic Agents; Enzyme Inhibitors; Farnesyltranstransferase; Female; Humans; Male; Neurofibroma, Plexiform; Neurofibromatosis 1; Quinolones
PubMed: 24714524
DOI: 10.1093/neuonc/nou050 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Jun 2022Neurofibromatosis type 1(NF1) is an autosomal dominant genetic disease in which a mutation in the NF1 gene on chromosome 17q11.2 results in inactivation or... (Review)
Review
Neurofibromatosis type 1(NF1) is an autosomal dominant genetic disease in which a mutation in the NF1 gene on chromosome 17q11.2 results in inactivation or down-regulation of neurofibromin. This results in a series of neurocutaneous lesions characterized by neurofibromatosis. Patients with plexiform neurofibromas(PN), as one of the main manifestations of NF1, often experience pain, dysfunction, skeletal deformities, changes in appearance and other symptoms. In severe cases, compression of the airways and vital organs occurs, and the PN is at risk of malignancy progression. At present, its treatment is still challenging. Surgery is the primary treatment for PN, but complete resection is often difficult. In recent years, chemotherapy for PN has become a hot topic. This article reviews the research progress in the pathogenesis, diagnosis and treatment of PN in recent years.
Topics: Child; Genes, Neurofibromatosis 1; Humans; Mutation; Neurofibroma, Plexiform; Neurofibromatosis 1
PubMed: 35822370
DOI: 10.13201/j.issn.2096-7993.2022.06.015 -
Diagnostics (Basel, Switzerland) Feb 2021We present a case demonstrating the performance of different radiographical imaging modalities in the diagnostic work-up of a patient with neurofibromatosis type 1 (NF1)...
We present a case demonstrating the performance of different radiographical imaging modalities in the diagnostic work-up of a patient with neurofibromatosis type 1 (NF1) and plexiform neurofibroma (PN). The newborn boy showed an expansive-infiltrative cervical and facial mass presented with macrocrania, craniofacial disfigurement, exophthalmos and glaucoma. A computer tomography (CT) and a magnetic resonance imaging (MRI) were performed. The CT was fundamental to evaluate the bone dysmorphisms and the MRI was crucial to estimate the mass extension. The biopsy of the lesion confirmed the suspicion of PN, thus allowing the diagnosis of NF1. PN is a variant of neurofibromas, a peripheral nerves sheath tumor typically associated with NF1. Even through currently available improved detection techniques, NF1 diagnosis at birth remains a challenge due to a lack of pathognomonic signs; therefore congenital PN are recognized in 20% of cases. This case highlights the importance of using different radiological methods both for the correct diagnosis and the follow-up of the patient with PN. Thanks to MRI evaluation, it was possible to identify earlier the progressive increasing size of the PN and the possible life threatening evolution in order to perform a tracheostomy to avoid airways compression.
PubMed: 33540839
DOI: 10.3390/diagnostics11020218