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Feng Chun Yang - One of the best experts on this subject based on the ideXlab platform.
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The Plexiform Neurofibroma Microenvironment
Cancer Microenvironment, 2012Co-Authors: Feng Chun Yang, Karl Staser, D. Wade ClappAbstract: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.
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pathogenesis of Plexiform Neurofibroma tumor stromal hematopoietic interactions in tumor progression
Annual Review of Pathology-mechanisms of Disease, 2012Co-Authors: Karl Staser, Feng Chun Yang, Wade D ClappAbstract:Neurofibromatosis type 1 (NF1) is a genetic disease that results from either heritable or spontaneous autosomal dominant mutations in the NF1 gene. A second-hit mutation precedes the predominant NF1 neoplasms, which include myeloid leukemia, optic glioma, and Plexiform Neurofibroma. Despite this requisite NF1 loss of heterozygosity in the tumor cell of origin, nontumorigenic cells contribute to both generalized and specific disease manifestations. In mouse models of Plexiform Neurofibroma formation, Nf1 haploinsufficient mast cells promote inflammation, accelerating tumor formation and growth. These recruited mast cells, hematopoietic effector cells long known to permeate Neurofibroma tissue, mediate key mitogenic signals that contribute to vascular ingrowth, collagen deposition, and tumor growth. Thus, the Plexiform Neurofibroma microenvironment involves a tumor/stromal interaction with the hematopoietic system that depends, at the molecular level, on a stem cell factor/c-kit-mediated signaling axis. These observations parallel findings in other NF1 disease manifestations and are clearly relevant to medical management of these Neurofibromas.
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Plexiform Neurofibroma genesis questions of nf1 gene dose and hyperactive mast cells
Current Opinion in Hematology, 2010Co-Authors: Karl Staser, Feng Chun Yang, David Wade ClappAbstract:Purpose of review Tumorigenic cells can co-opt normal functions of non-malignant hematopoietic cells, promoting tumor progression. Recent mouse and human studies indicate that mast cells underpin inflammation in the Plexiform Neurofibroma microenvironment of Neurofibromatosis type 1. In this model, Nf1 homozygous deficient Schwann cells recruit hyperactive mast cells, promoting tumorigenesis. Here, we discuss the importance of Nf1 gene dosage, delineate hematopoietic contributions to the Plexiform Neurofibroma microenvironment, and highlight applications to human treatment.
Karl Staser - One of the best experts on this subject based on the ideXlab platform.
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The Plexiform Neurofibroma Microenvironment
Cancer Microenvironment, 2012Co-Authors: Feng Chun Yang, Karl Staser, D. Wade ClappAbstract: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.
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pathogenesis of Plexiform Neurofibroma tumor stromal hematopoietic interactions in tumor progression
Annual Review of Pathology-mechanisms of Disease, 2012Co-Authors: Karl Staser, Feng Chun Yang, Wade D ClappAbstract:Neurofibromatosis type 1 (NF1) is a genetic disease that results from either heritable or spontaneous autosomal dominant mutations in the NF1 gene. A second-hit mutation precedes the predominant NF1 neoplasms, which include myeloid leukemia, optic glioma, and Plexiform Neurofibroma. Despite this requisite NF1 loss of heterozygosity in the tumor cell of origin, nontumorigenic cells contribute to both generalized and specific disease manifestations. In mouse models of Plexiform Neurofibroma formation, Nf1 haploinsufficient mast cells promote inflammation, accelerating tumor formation and growth. These recruited mast cells, hematopoietic effector cells long known to permeate Neurofibroma tissue, mediate key mitogenic signals that contribute to vascular ingrowth, collagen deposition, and tumor growth. Thus, the Plexiform Neurofibroma microenvironment involves a tumor/stromal interaction with the hematopoietic system that depends, at the molecular level, on a stem cell factor/c-kit-mediated signaling axis. These observations parallel findings in other NF1 disease manifestations and are clearly relevant to medical management of these Neurofibromas.
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Plexiform Neurofibroma genesis questions of nf1 gene dose and hyperactive mast cells
Current Opinion in Hematology, 2010Co-Authors: Karl Staser, Feng Chun Yang, David Wade ClappAbstract:Purpose of review Tumorigenic cells can co-opt normal functions of non-malignant hematopoietic cells, promoting tumor progression. Recent mouse and human studies indicate that mast cells underpin inflammation in the Plexiform Neurofibroma microenvironment of Neurofibromatosis type 1. In this model, Nf1 homozygous deficient Schwann cells recruit hyperactive mast cells, promoting tumorigenesis. Here, we discuss the importance of Nf1 gene dosage, delineate hematopoietic contributions to the Plexiform Neurofibroma microenvironment, and highlight applications to human treatment.
Reinhard E Friedrich - One of the best experts on this subject based on the ideXlab platform.
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microdont developing outside the alveolar process and within oral diffuse and Plexiform Neurofibroma in Neurofibromatosis type 1
Anticancer Research, 2021Co-Authors: Reinhard E Friedrich, Christian Hagel, Hannah T Scheuer, Jozef Zustin, Andreas M Luebke, Hanna A ScheuerAbstract:Background/aim Numerical aberrations of permanent dentition and dystopic tooth eruption are part of the phenotype of the tumor predisposition syndrome Neurofibromatosis type 1 (NF1). In these cases, surplus tooth germs usually develop in the alveolar processes of the jaw. This report attests to the dystopic development of a dysplastic supernumerary tooth in NF1 arising outside the jaw. Case report The 8-year-old male patient developed a microdont outside the bone and above the occlusal plane of the retained maxillary right second molar. The supernumerary tooth was completely embedded in oral soft tissue. Hyperplastic oral soft tissue in the molar region and microdont were excised. Specimen of the mucosa surrounding the teeth was interspersed with diffuse and Plexiform Neurofibroma. The retained upper right first molar emerged spontaneously within a few months after surgery. The upper right second molar did not change position. Conclusion Odontogenesis can take place within tumorous oral mucosa in NF1. Surgical removal of the tumorous mucous membrane facilitates tooth eruption in some cases.
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Size of Tooth Crowns and Position of Teeth Concerning the Extension of Facial Plexiform Neurofibroma in Patients with Neurofibromatosis Type 1
Anticancer research, 2012Co-Authors: Reinhard E Friedrich, M. Giese, Claudia Stelljes, Christine Froeder, Hanna A ScheuerAbstract:Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited tumour syndrome. NF1 is also a disorder of bone in terms of altered bone metabolism and bone dysplasia. Facial Plexiform Neurofibroma (PNF) is frequently associated with osseous alterations and may cause severe disfigurement. These PNFs regularly affect the oral cavity and teeth. PNF pose many problems in reconstructive and oral surgery. This study was undertaken to describe oral findings related to PNFs and to investigate the size and position of teeth in these tumours. Materials and Methods: Forty-eight patients with NF1 were investigated. Tumour type was histologically proven in all patients with PNF following aesthetic/functional orofacial surgery. Twenty-four patients were affected with a PNF and 24 had disseminated cutaneous Neurofibroma (DCNF). In the PNF group, the side of the PNF was registered; PNF was unilateral in all cases. DCNF patients were 15 females and 9 males (mean age: 23.92±10.48 years, minimum: 6, maximum 45 years). Patients with PNF were 17 males and 7 females (mean age: 23.92±13.76 years, minimum 6, maximum 61 years). The right side was affected in 16 and the left in 8 PNF patients. All patients were orally investigated and dental casts were obtained. Distances of the alveolar processes and of the teeth were measured in transverse and sagittal planes. In order to evaluate the possible impact of the tumour localisation inside the trigeminal nerve, the topography of the affected facial areas was assigned to the trigeminal nerve branches. Radiographs were taken to asses the formation of dental roots, to reveal retained teeth and to estimate dysplastic areas of the jaws. Results: The size of tooth crowns did not differ from published standards on tooth parameters of Caucasian individuals. The dental arches were symmetrically arranged in all patients of the DCNF group. However, the position of teeth showed some relevant differences in the PNF group. We observed spacing between teeth, probably due to interdental invasion of Plexiform Neurofibroma or interference of tumour tissue with the mesial drift of teeth. Maxilla and mandible showed characteristic alterations in the PNF group that were confined to the side and extension of a PNF. Conclusion: Oral inspection should be carried out in all patients with NF1. Unilateral alterations of the position of teeth and asymmetries of the jaws should alert the investigator to search for an ipsilateral PNF of the second or third trigeminal branch. The size and dimensions of tooth crowns appear not to be affected by the disease.
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dysplasia of the orbit and adjacent bone associated with Plexiform Neurofibroma and ocular disease in 42 nf 1 patients
Anticancer Research, 2010Co-Authors: Reinhard E Friedrich, Christian Hagel, M. Giese, Claudia Stelljes, Hanna A ScheuerAbstract:Neurofibromas are the hallmark of Neurofibromatosis type 1 (NF1). Interestingly, generalised and localised interference or dysfunction of bone is also a key element of the NF1 phenotype. In the skull, NF1-associated orbital dysplasia often results in a severe disfigurement of affected individuals. However, the underlying pathology of orbital dysplasia is a complex phenomenon and up to now poorly understood. This study was performed to describe the orbit in 42 NF1 patients with large, disfiguring soft-tissue tumour of the orbital/eyelid region (Plexiform Neurofibroma (PNF)). A dysplastic orbit on the affected side was diagnosed in 80.9%. Orbital PNF extension to adjacent regions revealed a significant correlation of orbit and temporal region (0.33, p 0.011), oral cavity and nose (0.35, p<0.026), and temporal region and cheek (0.46, p<0.003). Alterations of the optic nerve and adjacent structures were identified on MRI or CT in 14 patients. On plain skull radiographs, only sphenoid wing dysplasia and ipsilateral orbital enlargement were significantly correlated (0.528, p<0.01). This study reveals PNF as the main component of soft tissue affecting eyelids and orbit in those cases, which show a soft tissue mass in the affected orbital region. The oval-shaped orbital rim, typically seen on plain skull radiographs in sagittal projections, seems to be strongly associated with the (lateral and caudal) extension of a PNF and independent from sphenoid wing dysplasia. Several factors constitute the individual orbital dysplasia, including the growth of the invasive PNF.
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clinical relevance of positron emission tomography and magnetic resonance imaging in the progression of internal Plexiform Neurofibroma in nf1
Anticancer Research, 2007Co-Authors: V F Mautner, Winfried Brenner, Carsten Funsterer, Christian Hagel, K A Gawad, Reinhard E FriedrichAbstract:Neurofibromatosis type 1 (NF1) is a frequent and inherited disease with a predisposition for malignant peripheral nerve sheath tumor (MPNST) development. MPNST are soft tissue sarcomas that arise from peripheral nerves, being one of the most aggressive malignancies in humans with extremely poor prognosis. MPNST frequently arise from a previously undetected Plexiform Neurofibroma (PNF). The malignant transformation of an internal PNF to an MPNST is difficult to assess and requires advanced imaging techniques like magnetic resonance imaging or positron emission tomography. Despite the high quality of current diagnostics, the changing tumor biology inside a Plexiform Neurofibroma cannot currently be visualized accurately. We report 4 cases of NF1 patients with PNF who showed imaging findings suspicious for malignant degeneration, but proved to have MPNST in only one case. Three tumors might represent an intermediate type between PNF and MPNST. Ablative surgery and complete histological work-up of specimens is the only way to clarify tumor status, thereby enabling provision of adequate local treatment.
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malignant peripheral nerve sheath tumours in Neurofibromatosis type 1 mri supports the diagnosis of malignant Plexiform Neurofibroma
Neuroradiology, 2003Co-Authors: V F Mautner, Bruce R Korf, Christian Hagel, Reinhard E Friedrich, A Von Deimling, M T Knofel, R Wenzel, C FunstererAbstract:Plexiform Neurofibroma (PNF) is a typical feature of Neurofibromatosis 1 (NF1). About 10% of patients with NF1 develop malignant peripheral nerve-sheath tumours (MPNST), usually arising from PNF, and this is the major cause of poor survival. A better prognosis can be achieved if the tumours are diagnosed at an early stage. Our objective was to establish MRI criteria for MPNST and to test their usefulness in detecting early malignant change in PNF. MRI was performed on 50 patients with NF1 and nerve-sheath tumours, of whom seven had atypical pain, tumour growth or neurological deficits indicative of malignancy; the other 43 were asymptomatic. On MRI all seven symptomatic patients had inhomogeneous lesions, due to necrosis and haemorrhage and patchy contrast enhancement. In one patient, the multiplicity of confluent tumours with inhomogeneous areas in addition to central lesions did not allow exclusion of malignancy. Only three of the 43 asymptomatic patients had comparable changes; the other 40 patients had tumours being of relatively homogeneous structure on T1- and T2-weighted images before and after contrast enhancement. All three asymptomatic patients with inhomogeneous lesions were shown to have MPNST.
C Funsterer - One of the best experts on this subject based on the ideXlab platform.
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malignant peripheral nerve sheath tumours in Neurofibromatosis type 1 mri supports the diagnosis of malignant Plexiform Neurofibroma
Neuroradiology, 2003Co-Authors: V F Mautner, Bruce R Korf, Christian Hagel, Reinhard E Friedrich, A Von Deimling, M T Knofel, R Wenzel, C FunstererAbstract:Plexiform Neurofibroma (PNF) is a typical feature of Neurofibromatosis 1 (NF1). About 10% of patients with NF1 develop malignant peripheral nerve-sheath tumours (MPNST), usually arising from PNF, and this is the major cause of poor survival. A better prognosis can be achieved if the tumours are diagnosed at an early stage. Our objective was to establish MRI criteria for MPNST and to test their usefulness in detecting early malignant change in PNF. MRI was performed on 50 patients with NF1 and nerve-sheath tumours, of whom seven had atypical pain, tumour growth or neurological deficits indicative of malignancy; the other 43 were asymptomatic. On MRI all seven symptomatic patients had inhomogeneous lesions, due to necrosis and haemorrhage and patchy contrast enhancement. In one patient, the multiplicity of confluent tumours with inhomogeneous areas in addition to central lesions did not allow exclusion of malignancy. Only three of the 43 asymptomatic patients had comparable changes; the other 40 patients had tumours being of relatively homogeneous structure on T1- and T2-weighted images before and after contrast enhancement. All three asymptomatic patients with inhomogeneous lesions were shown to have MPNST.
Richard Bendorsamuel - One of the best experts on this subject based on the ideXlab platform.
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massive intratumor hemorrhage in facial Plexiform Neurofibroma
Head and Neck-journal for The Sciences and Specialties of The Head and Neck, 1997Co-Authors: Tungchain Tung, Yuray Chen, Kuoting Chen, Chientzung Chen, Richard BendorsamuelAbstract:Background Plexiform Neurofibromatosis is a feature of von Recklinghausen's disease. Head and neck lesions may produce varying degrees of cosmetic and functional deformity. However, life-threatening hemorrhage into facial Plexiform Neurofibromas has not been previously reported. Method We report two patients with von Recklinghausen's disease who experienced massive hemorrhage into facial Neurofibromas, one following a blunt injury and the other without a known initiating event. Results Conservative management did not stop the hemorrhage into facial Neurofibromas in either instance. Surgical exploration was mandated for hemorrhage control and evacuation of blood clots. Hemostasis was attained by a combination of hypotensive anesthesia and chromic catgut suture ligatures. Conclusions These case reports demonstrate a potentially lethal complication in patients with facial Plexiform Neurofibroma. Where a competent and experienced interventional neuroradiologist is not available, surgical exploration should be undertaken to control bleeding. © 1997 John Wiley & Sons, Inc. Head Neck19: 158–162, 1997.