RESUMEN
Introduction: Malignant peripheral nerve sheath tumors (MPNST) pose a significant therapeutic challenge due to high recurrence rates after surgical resection and a largely ineffective response to traditional chemotherapy. An alternative treatment strategy is oncolytic viroimmunotherapy, which can elicit a durable and systemic antitumor immune response and is Food and Drug Administration (FDA)-approved for the treatment of melanoma. Unfortunately, only a subset of patients responds completely, underscoring the need to address barriers hindering viroimmunotherapy effectiveness. Methods: Here we investigated the therapeutic utility of targeting key components of the MPNST immunosuppressive microenvironment to enhance viroimmunotherapy's antitumor efficacy in three murine models, one of which showed more immunogenic characteristics than the others. Results: Myelomodulatory therapy with pexidartinib, a small molecule inhibitor of CSF1R tyrosine kinase, and the oncolytic herpes simplex virus T-VEC exhibited the most significant increase in median survival time in the highly immunogenic model. Additionally, targeting myeloid cells with the myelomodulatory therapy trabectedin, a small molecule activator of caspase-8 dependent apoptosis, augmented the survival benefit of T-VEC in a less immunogenic MPNST model. However, tumor regressions or shrinkages were not observed. Depletion experiments confirmed that the enhanced survival benefit relied on a T cell response. Furthermore, flow cytometry analysis following combination viroimmunotherapy revealed decreased M2 macrophages and myeloid-derived suppressor cells and increased tumor-specific gp70+ CD8 T cells within the tumor microenvironment. Discussion: In summary, our findings provide compelling evidence for the potential to leverage viroimmunotherapy with myeloid cell targeting against MPNST and warrant further investigation.
Asunto(s)
Modelos Animales de Enfermedad , Viroterapia Oncolítica , Microambiente Tumoral , Animales , Viroterapia Oncolítica/métodos , Ratones , Microambiente Tumoral/inmunología , Virus Oncolíticos/inmunología , Virus Oncolíticos/genética , Línea Celular Tumoral , Inmunoterapia/métodos , Humanos , Terapia Combinada , Femenino , Ratones Endogámicos C57BL , Neoplasias de la Vaina del Nervio/terapia , Neoplasias de la Vaina del Nervio/inmunología , Neoplasias de la Vaina del Nervio/genética , Aminopiridinas , PirrolesRESUMEN
Most malignant peripheral nerve sheath tumors (MPNSTs) are clinically aggressive high-grade sarcomas, arising in individuals with neurofibromatosis type 1 (NF1) at a significantly elevated estimated lifetime frequency of 8%-13%. In the setting of NF1, MPNSTs arise from malignant transformation of benign plexiform neurofibroma and borderline atypical neurofibromas. Composed of neoplastic cells from the Schwannian lineage, these cancers recur in approximately 50% of individuals, and most patients die within five years of diagnosis, despite surgical resection, radiation, and chemotherapy. Treatment for metastatic disease is limited to cytotoxic chemotherapy and investigational clinical trials. In this article, we review the pathophysiology of this aggressive cancer and current approaches to surveillance and treatment.
Asunto(s)
Neoplasias de la Vaina del Nervio , Neurofibromatosis 1 , Humanos , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/terapia , Neurofibromatosis 1/patología , Neoplasias de la Vaina del Nervio/terapia , Neoplasias de la Vaina del Nervio/patologíaRESUMEN
Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene that encodes neurofibromin, a RAS GTPase-activating protein. Inactivating NF1 mutations cause hyperactivation of RAS-mediated signaling, resulting in the development of multiple neoplasms, including malignant peripheral nerve sheath tumors (MPNSTs). MPNSTs are an aggressive tumor and the main cause of mortality in patients with NF1. MPNSTs are difficult to resect and refractory to chemo- and radiotherapy, and no molecular therapies currently exist. Immune checkpoint blockade (ICB) is an approach to treat inoperable, undruggable cancers like MPNST, but successful outcomes require an immune cell-rich tumor microenvironment. While MPNSTs are noninflamed "cold" tumors, here, we converted MPNSTs into T cell-inflamed "hot" tumors by activating stimulator of IFN genes (STING) signaling. Mouse genetic and human xenograft MPNST models treated with a STING agonist plus ICB exhibited growth delay via increased apoptotic cell death. This strategy offers a potential treatment regimen for MPNSTs.
Asunto(s)
Inmunoterapia , Proteínas de la Membrana , Neurofibromatosis 1 , Neurofibromina 1 , Microambiente Tumoral , Animales , Microambiente Tumoral/inmunología , Humanos , Ratones , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/inmunología , Neurofibromatosis 1/genética , Neurofibromatosis 1/patología , Neurofibromatosis 1/inmunología , Neurofibromatosis 1/terapia , Neurofibromatosis 1/metabolismo , Neurofibromina 1/genética , Inhibidores de Puntos de Control Inmunológico/farmacología , Neoplasias de la Vaina del Nervio/genética , Neoplasias de la Vaina del Nervio/patología , Neoplasias de la Vaina del Nervio/terapia , Neoplasias de la Vaina del Nervio/inmunología , Neoplasias de la Vaina del Nervio/metabolismo , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Transducción de Señal/inmunologíaRESUMEN
This article reviews the pathology and management of peripheral nerve tumours, including a framework for investigation and decision-making. Most tumours are benign, including schwannomas and neurofibromas, but malignant peripheral nerve sheath tumours can occur. The risk of malignant change is remote for schwannomas but higher for neurofibromas, particularly in neurofibromatosis type 1. Magnetic resonance imaging is useful for defining the relationship of a swelling with adjacent nerves but is not definitive for tissue diagnosis. Increasing size, pain and neurological deficit suggest malignant change and TruCut needle biopsy is indicated, although there is a risk of sampling error. Excision biopsy preserving nerve function may be carried out for benign tumours to relieve symptoms. Malignant tumours require a multidisciplinary approach. Complete surgical excision with clear margins is the only curative treatment and may be supplemented with radiotherapy and chemotherapy. However, prognosis remains poor, particularly for patients with neurofibromatosis.
Asunto(s)
Algoritmos , Neoplasias del Sistema Nervioso Periférico , Humanos , Imagen por Resonancia Magnética , Neoplasias de la Vaina del Nervio/diagnóstico , Neoplasias de la Vaina del Nervio/patología , Neoplasias de la Vaina del Nervio/cirugía , Neoplasias de la Vaina del Nervio/terapia , Neurilemoma/diagnóstico , Neurilemoma/patología , Neurilemoma/cirugía , Neurilemoma/terapia , Neurofibroma/diagnóstico , Neurofibroma/patología , Neurofibroma/cirugía , Neurofibroma/terapia , Neoplasias del Sistema Nervioso Periférico/diagnóstico , Neoplasias del Sistema Nervioso Periférico/patología , Neoplasias del Sistema Nervioso Periférico/cirugía , Neoplasias del Sistema Nervioso Periférico/terapiaRESUMEN
PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that arise from peripheral nerves and are the leading cause of mortality in Neurofibromatosis Type 1 (NF1). In this study, we characterized whether transcriptomic signatures of T-cell dysfunction (TCD) and exclusion (TCE) that inversely correlate with response to immune checkpoint blockade (ICB) immunotherapy exist in MPNSTs. METHODS: MPNST transcriptomes were pooled from Gene Expression Omnibus (GEO). For each sample, a tumor immune dysfunction and exclusion (TIDE) score, TCD and TCE subscores, and cytotoxic T-cell(CTL) level were calculated. In the TIDE predictive algorithm, tumors are predicted to have an ICB response if they are either immunologically hot (CTL-high) without TCD or immunologically cold (CTL-low) without TCE. TIDE scores greater than zero correspond with ICB nonresponse. RESULTS: 73 MPNST samples met inclusion criteria, including 50 NF1-associated MPNSTs (68.5%). The average TIDE score was + 0.41 (SD = 1.16) with 22 (30.1%) predicted ICB responders. 11 samples were CTL-high (15.1%) with an average TCD score of + 0.99 (SD = 0.63). Among 62 CTL-low tumors, 21 were predicted to have ICB response with an average TCE score of + 0.31(SD = 1.20). Age(p = 0.18), sex(p = 0.41), NF1 diagnosis (p = 0.17), and PRC2 loss(p = 0.29) were not associated with ICB responder status. CONCLUSIONS: Transcriptomic analysis of TCD and TCE signatures in MPNST samples reveals that a select subset of patients with MPNSTs may benefit from ICB immunotherapy.
Asunto(s)
Neoplasias de la Vaina del Nervio , Neurofibromatosis 1 , Neurofibrosarcoma , Humanos , Neoplasias de la Vaina del Nervio/genética , Neoplasias de la Vaina del Nervio/terapia , Neoplasias de la Vaina del Nervio/diagnóstico , Neurofibromatosis 1/genética , Neurofibromatosis 1/terapia , Neurofibromatosis 1/complicaciones , Inmunoterapia , Linfocitos T/metabolismoRESUMEN
Schwann cell-derived neoplasms known as malignant peripheral nerve sheath tumors (MPNSTs) are the most common malignancy and the leading cause of death in individuals with neurofibromatosis Type 1. Using genome-scale shRNA screens, we have previously found evidence suggesting that lysophosphatidic acid receptors (LPARs) are essential for MPNST proliferation and/or survival. Here, we examine the expression and mutational status of all six LPA receptors in MPNSTs, assess the role that individual LPA receptors play in MPNST physiology and examine their ability to activate key neurofibromin-regulated signaling cascades. We found that human Schwann cells express LPAR1 and LPAR6, while MPNST cells express predominantly LPAR1 and LPAR3. Whole exome sequencing of 16 MPNST cell lines showed no evidence of mutations in any LPAR genes or ENPP2, a gene encoding a major LPA biosynthetic enzyme. Oleoyl-LPA, an LPA variant with an unsaturated side chain, promoted MPNST cell proliferation and migration. LPAR1 knockdown ablated the promigratory effect of LPA, while LPAR3 knockdown decreased proliferation. Inhibition of R-Ras signaling with a doxycycline-inducible dominant negative (DN) R-Ras mutant, which inhibits both R-Ras and R-Ras2, blocked LPA's promigratory effect. In contrast, DN R-Ras did not affect migration induced by neuregulin-1ß (NRG1ß), suggesting that LPA and NRG1ß promote MPNST migration via distinct pathways. LPA-induced migration was also inhibited by Y27632, an inhibitor of the ROCK1/2 kinases that mediate R-Ras effects in MPNSTs. Thus, LPAR1 and aberrantly expressed LPAR3 mediate distinct effects in MPNSTs. These receptors and the signaling pathways that they regulate are potentially useful therapeutic targets in MPNSTs.
Asunto(s)
Neoplasias de la Vaina del Nervio , Neurofibrosarcoma , Receptores del Ácido Lisofosfatídico , Humanos , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias de la Vaina del Nervio/genética , Neoplasias de la Vaina del Nervio/patología , Neoplasias de la Vaina del Nervio/terapia , Receptores del Ácido Lisofosfatídico/genética , Quinasas Asociadas a rhoRESUMEN
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, invasive cancer that comprise around 10% of all soft tissue sarcomas and develop in about 8-13% of patients with Neurofibromatosis Type 1. They are associated with poor prognosis and are the leading cause of mortality in NF1 patients. MPNSTs can also develop sporadically or following exposure to radiation. There is currently no effective targeted therapy to treat MPNSTs and surgical removal remains the mainstay treatment. Unfortunately, surgery is not always possible due to the size and location of the tumor, thus, a better understanding of MPNST initiation and development is required to design novel therapeutics. Here, we provide an overview of MPNST biology and genetics, discuss findings regarding the developmental origin of MPNST, and summarize the various model systems employed to study MPNST. Finally, we discuss current management strategies for MPNST, as well as recent developments in translating basic research findings into potential therapies.
Asunto(s)
Neoplasias de la Vaina del Nervio , Neurofibromatosis 1 , Neurofibrosarcoma , Sarcoma , Biología , Humanos , Neoplasias de la Vaina del Nervio/genética , Neoplasias de la Vaina del Nervio/terapia , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/genética , Neurofibromatosis 1/terapia , Neurofibrosarcoma/complicaciones , Neurofibrosarcoma/genética , Neurofibrosarcoma/terapiaRESUMEN
Neurofibromatosis type 1, the most common phakomatoses, can present with a host of signs and symptoms, usually involving the skin and the peripheral nervous system. It is characterized by a mutation in the neurofibromatosis type 1 gene on chromosome 17q11.2 that codes for the protein neurofibromin. Neurofibromin acts as a tumor suppressor gene by inhibiting rat sarcoma (Ras) activity and its deficiency leads to increased Ras activity, cellular proliferation and tumor formation. This review was conducted to analyze the various targeted therapies at the genetic and molecular level employed to manage the tumors and other clinical presentations associated with neurofibromatosis type 1. Twenty-eight studies of treatment modalities for the conditions associated with neurofibromatosis and which involved either targeted gene therapy or molecular level therapies, including the latest advances, were included in this review. Mitogen-activated protein kinase kinase inhibition, mammalian target of Rapamycin inhibition and Tyrosine kinase inhibition, represent some of the newer treatment options in this category. Although there are a number of trials for providing therapeutic options at the genetic and molecular level for the various physical and psychological morbidities associated with neurofibromatosis type 1, most of them are in the preclinical stage. Increased clinical trials of the molecules and gene therapies could significantly help in managing the various chronic and sometimes, life-threatening conditions associated with neurofibromatosis 1 and these will probably represent the preferred treatment direction of the future.
Asunto(s)
Terapia Molecular Dirigida , Neurofibromatosis 1/terapia , Disfunción Cognitiva/etiología , Curación de Fractura/genética , Humanos , Neoplasias de la Vaina del Nervio/etiología , Neoplasias de la Vaina del Nervio/terapia , Neurofibroma Plexiforme/etiología , Neurofibroma Plexiforme/terapia , Neurofibromatosis 1/complicaciones , Glioma del Nervio Óptico/etiología , Glioma del Nervio Óptico/terapiaRESUMEN
BACKGROUND: Malignant triton tumor (MTT) is a rare subtype of malignant peripheral nerve sheath tumor with additional rhabdomyolysis differentiation that shows rapid progression and poor clinical outcomes. CASE REPORT: We report the case of an adult male with a metastatic MTT. Despite extensive counseling, the patient initially refused recommended treatment. Upon disease progression, the patient was admitted to our institution and multiple distant organ metastases were found. The patient underwent an above-knee amputation followed by palliative chemotherapy. The patient died a few months later due to rapid disease progression. CONCLUSION: To our knowledge, this is the first report of a case of MTT with multiple splenic metastases. We also describe the first finding of a frame-shift mutation in the tuberous sclerosis complex 2 (TSC2) gene in a patient with MTT. Because of limited clinical experience and the lack of clinical trials, the effects of chemotherapy and radiation therapy for MTT remain controversial. However, given the aggressive nature of these tumors and the tendency for early recurrence and metastasis, prompt diagnosis and early surgical treatment are crucial for the best outcomes.
Asunto(s)
Mutación , Neoplasias de la Vaina del Nervio/genética , Neoplasias del Bazo/secundario , Proteína 2 del Complejo de la Esclerosis Tuberosa/genética , Resultado Fatal , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Vaina del Nervio/patología , Neoplasias de la Vaina del Nervio/terapia , Rabdomiólisis , Tomografía Computarizada por Rayos XRESUMEN
OPINION STATEMENT: Malignant peripheral nerve sheath tumors (MPNSTs) are rare mesenchymal neoplasms that represent a profound therapeutic challenge due to their high proclivity for recurrence and metastasis and relatively poor response to systemic therapy regimens. While our understanding of the pathophysiology of MPNST is growing, including loss of the tumor suppressor gene neurofibromin and subsequent activation of the Ras pathway, targeted therapy to modify the poor prognosis seen in MPNST patients has thus far been without success. Correspondingly, MPNST patients are treated as per soft tissue sarcoma treatment algorithms with anthracycline-based therapy as the front-line therapy of choice for patients with unresectable, locally advanced, or metastatic MPNST. Beyond first-line anthracycline-based therapy, other standard cytotoxic chemotherapy agents used in advanced MPNST include the alkylating agent ifosfamide and the topoisomerase II inhibitor etoposide. Notably, soft tissue sarcoma regimens are used in MPNST despite distinct systemic therapy sensitivity and prognosis. This is particularly notable for neurofibromatosis type 1 (NF1)-associated MPNST, which is associated with poorer response to systemic therapy and prognosis than sporadic MPNST. As such, NF1-associated MPNST is a particular area in need of novel therapeutic strategies. Given the lack of benefit in the targeting of unique aspects of MPNST disease biology thus far, pre-clinical studies to identify novel rational therapies are critical to inform future clinical trials.
Asunto(s)
Neoplasias de la Vaina del Nervio/diagnóstico , Neoplasias de la Vaina del Nervio/terapia , Biomarcadores de Tumor , Toma de Decisiones Clínicas , Terapia Combinada , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Predisposición Genética a la Enfermedad , Humanos , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias de la Vaina del Nervio/etiología , Neoplasias de la Vaina del Nervio/mortalidad , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: No available meta-analysis was printed to systematically introduce the MPNST clinic outcome and risk factors based on largely pooled data. This systematic review and meta-analysis aimed to investigate 5-year OS rate, 5-year EFS rate, and LR rate for MPNST, and to assess potential risk factors for prognosis. METHODS: Electronic articles published between January 1, 1966 and February 29, 2020 were searched and critically evaluated. The authors independently reviewed the abstracts and extracted data for 5-year OS rate, 5-year EFS rate, LR rate, and potential risk factors for prognosis. RESULTS: Twenty-eight literatures were finally included for meta-analysis. The pooled 5-year OS rate, 5-year EFS rate, and LR rate were 49%, 37%, and 38%, respectively. The significant prognostic factors for survival were NF1 status, tumor size, depth, location, malignant grade, margin status, chemotherapy, and radiotherapy. Age and sex were not associated with survival. CONCLUSION: Survival and local recurrence of MPNST are poor. Worse prognosis is mainly associated with NF 1, large size, deep to fascia, high grade, metastases, and location (trunk and head and neck). Complete resection with adequate surgical margins is the mainstay protective factor of MPNST patients, following necessary adjuvant therapies.
Asunto(s)
Neoplasias de la Vaina del Nervio , Neurofibrosarcoma , Humanos , Recurrencia Local de Neoplasia , Neoplasias de la Vaina del Nervio/terapia , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND: We sought to analyze the clinical data and imaging features from a rare case presenting an intravertebral mobile nerve sheath tumor of the lumbar spine, review the relevant literature, discuss the imaging features and possible causes of the tumor, and propose preventive measures and solutions. CASE DESCRIPTION: The clinical data and imaging data of a patient with a lumbar spinal canal mobile nerve sheath tumor were retrospectively analyzed in conjunction with the relevant literature. The first preoperative lumbar spine magnetic resonance imaging (MRI) showed the tumor located at level L1-2. Further lumbar spine MRI, which was performed 5 days later, showed the tumor was at level L3-4, with a range of motion of 8 cm. End spinal resection of the tumor was performed under general anesthesia, and a tumor, which was cystic solid, was found to be located at level L3-4. The tumor originated from a distinctly twisted and elongated posterior root of the spinal cord, with complete fusion of the tumor-bearing nerve. Both the tumor and tumor-carrying nerve were removed. Postoperative pathologic examination confirmed that the tumor was a nerve sheath tumor. Lumbar MRI on postoperative day 10 showed complete resection of the tumor in the L3-4 spinal canal. The patient was discharged with normal urination and defecation, normal sensation in both lower extremities, grade 5 muscle strength, normal muscle tone, and normal reflexes in both knee and Achilles tendons. CONCLUSIONS: Intravertebral mobile nerve sheath tumors are rare, and the marked distortion and elongation of the carrier nerve seen on MRI are important imaging features of this disease. The possible causes of tumor movement include tumor texture, location, positional changes, and altered cerebrospinal fluid dynamics. Acute changes in intraabdominal pressure caused by forceful defecation may be a high-risk factor for tumor migration. Multiple preoperative MRIs to localize the tumor are particularly important.
Asunto(s)
Neoplasias de la Vaina del Nervio/terapia , Neoplasias de la Médula Espinal/terapia , Anciano , Humanos , Región Lumbosacra/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Neoplasias de la Vaina del Nervio/diagnóstico , Neoplasias de la Vaina del Nervio/etiología , Procedimientos Neuroquirúrgicos , Cuidados Preoperatorios , Neoplasias de la Médula Espinal/diagnóstico , Neoplasias de la Médula Espinal/etiología , Nervios Espinales/diagnóstico por imagen , Nervios Espinales/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that present as large, invasive tumors. Our aim was to assess outcomes, identify prognostic factors, and analyze treatment strategies in a prospectively collected pediatric cohort. METHODS: Patients less than 21 years with MPNST treated in the consecutive prospective European Cooperative Weichteilsarkom Studiengruppe (CWS)-trials (1981-2009) and the CWS-SoTiSaR registry (2009-2015) were analyzed. RESULTS: A total of 159 patients were analyzed. Neurofibromatosis type I (NF1) was reported in thirty-eight patients (24%). Most were adolescents (67%) with large (>10 cm, 65%) tumors located at extremities (42%). Nodal involvement was documented in 15 (9%) and distant metastases in 15 (9%) upon diagnosis. Overall, event-free survival (EFS) was 40.5% at 5 and 36.3% at 10 years, and overall survival (OS) was 54.6% at 5 and 47.1% at 10 years. Age, NF1 status, tumor site, tumor size, Intergroup Rhabdomyosarcoma Study (IRS) group, metastatic disease, and achieving first complete remission (CR1) were identified as prognostic factors for EFS and/or OS in the univariate analysis. CONCLUSIONS: Prognostic factors were identified and research questions for future clinical trials were addressed.
Asunto(s)
Neoplasias de la Vaina del Nervio/terapia , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Metástasis de la Neoplasia , Neoplasias de la Vaina del Nervio/mortalidad , Neoplasias de la Vaina del Nervio/patología , Neurofibromatosis 1/terapia , Pronóstico , Estudios Prospectivos , Sistema de Registros , Adulto JovenRESUMEN
BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive soft tissue sarcomas. Children with neurofibromatosis type 1 (NF1) have a 10% lifetime risk for development of MPNST. Prognosis remains poor and survival seems worse for NF1 patients. METHODS: This narrative review highlights current practices and pitfalls in the management of MPNST in pediatric NF1 patients. RESULTS: Preoperative diagnostics can be challenging, but PET scans have shown to be useful tools. More recently, functional MRI holds promise as well. Surgery remains the mainstay treatment for these patients, but careful planning is needed to minimize postoperative morbidity. Functional reconstructions can play a role in improving functional status. Radiotherapy can be administered to enhance local control in selected cases, but care should be taken to minimize radiation effects as well as reduce the risk of secondary malignancies. The exact role of chemotherapy has yet to be determined. Reports on the efficacy of chemotherapy vary as some report lower effects in NF1 populations. Promisingly, survival seems to ameliorate in the last few decades and response rates of chemotherapy may increase in NF1 populations when administering it as part of standard of care. However, in metastasized disease, response rates remain poor. New systemic therapies are therefore desperately warranted and multiple trials are currently investigating the role of drugs. Targeted drugs are nevertheless not yet included in first line treatment. CONCLUSION: Both research and clinical efforts benefit from multidisciplinary approaches with international collaborations in this rare malignancy.
Asunto(s)
Neoplasias de la Vaina del Nervio , Neurofibromatosis 1 , Neurofibrosarcoma , Sarcoma , Neoplasias de los Tejidos Blandos , Niño , Humanos , Neoplasias de la Vaina del Nervio/diagnóstico por imagen , Neoplasias de la Vaina del Nervio/terapia , Neurofibromatosis 1/terapia , Neurofibrosarcoma/terapia , PronósticoRESUMEN
Malignant peripheral nerve sheath tumours of thyroid are rare entities that can present a diagnostic dilemma. We present the case of a patient who presented with neck mass with a history of multiple neck surgeries and airway compression. The patient's previous histopathology was mistaken for Riedel's thyroiditis in an outside hospital, which delayed appropriate treatment leading to suffering on part of the patient and frustration on part of the physician. We emphasise that rare malignancies should be considered in rapidly growing neck masses that are causing airway compression, and histopathology of such tumours should be reported by expert pathologists.
Asunto(s)
Neoplasias de la Vaina del Nervio/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Adulto , Obstrucción de las Vías Aéreas/etiología , Medios de Contraste , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias de la Vaina del Nervio/patología , Neoplasias de la Vaina del Nervio/terapia , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapia , Tiroidectomía , Tomografía Computarizada por Rayos X , TraqueostomíaRESUMEN
BACKGROUND: Despite curative intents of treatment in localized malignant peripheral nerve sheath tumours (MPNSTs), prognosis remains poor. This study investigated survival and prognostic factors for overall survival in non-retroperitoneal and retroperitoneal MPNSTs in the Netherlands. METHODS: Data were obtained from the Netherlands Cancer Registry and the Dutch Pathology Database. All primary MPNSTs were collected. Paediatric cases (age ≤18 years) and synchronous metastases were excluded from analyses. Separate Cox proportional hazard models were made for retroperitoneal and non-retroperitoneal MPNSTs. RESULTS: A total of 629 localized adult MPNSTs (35 retroperitoneal cases, 5.5%) were included for analysis. In surgically resected patients (88.1%), radiotherapy and chemotherapy were administered in 44.2% and 6.7%, respectively. In retroperitoneal cases, significantly less radiotherapy and more chemotherapy were applied. In non-retroperitoneal MPNSTs, older age (60+), presence of NF1, size >5 cm, and deep-seated tumours were independently associated with worse survival. In retroperitoneal MPNSTs, male sex and age of 60+ years were independently associated with worse survival. Survival of R1 and that of R0 resections were similar for any location, whereas R2 resections were associated with worse outcomes. Radiotherapy and chemotherapy administrations were not associated with survival. CONCLUSION: In localized MPNSTs, risk stratification for survival can be done using several patient- and tumour-specific characteristics. Resectability is the most important predictor for survival in MPNSTs. No difference is present between R1 and R0 resections in both retroperitoneal and non-retroperitoneal MPNSTs. The added value of radiotherapy and chemotherapy is unclear.
Asunto(s)
Neoplasias de la Vaina del Nervio/terapia , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Neoplasias de la Vaina del Nervio/mortalidad , Análisis de Supervivencia , Adulto JovenRESUMEN
Malignant peripheral nerve sheath tumors (MPNST) are a rare and aggressive group of tumors that are challenging to treat. Neurofibromatosis type 1 (NF-1)-associated MPNSTs have been associated with poorer clinical outcomes. The treatment options for NF-1-associated MPNSTs broadly include surgery (SG), chemotherapy (CT), and adjuvant radiotherapy (RT). Overall, the role and efficacy of CT and RT are unclear. Examination of existing literature for studies reporting on NF-1-associated MPNSTs and respective treatment-related outcomes was conducted. We conducted a systematic review according to PRISMA guidelines in PubMed/Medline and Cochrane databases of studies which reported treatment-specific outcomes in NF-1-associated MPNSTs. The literature search found 444 records after removal of duplicates. The present study included 50 patients across 12 observational studies. All of the included studies reported data on overall survival (OS 52%, n = 26/50) but mean follow-up in months among the studies and among patients varied widely, between 10.85 (SD, ± 10.38) and 192 (SD, ± 98.22). From the included studies, patients underwent either SG alone (n = 21), SG + CT (n = 10), SG + RT (n = 7), or SG + CT + RT (n = 12). The quality of evidence in the literature regarding optimal treatment options for NF-1-associated MPNSTs remains tenuous. Future retrospective and prospective comparative trials should consider adherence to a set of reporting guidelines to improve the quality of evidence in the literature with respect to individual treatment-related outcomes. The need for prospective multi-institutional efforts cannot be overstated.
Asunto(s)
Neoplasias de la Vaina del Nervio/etiología , Neoplasias de la Vaina del Nervio/terapia , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/terapia , Humanos , Neoplasias de la Vaina del Nervio/cirugía , Procedimientos NeuroquirúrgicosRESUMEN
Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from peripheral nerve fibers and primarily occur in the setting of neurofibromatosis (NF1). MPNST arising from the penis is very rare and may require mutilating surgery to achieve surgical cure. We previously reported a case of MPNST involving the penis in a 14-month-old boy treated with neoadjuvant chemotherapy, total penectomy, and adjuvant radiation. Here we report intermediate follow-up of the same patient, describe his subsequent genitourinary reconstruction, and discuss management dilemmas that arise following treatment of penile MPNST.
Asunto(s)
Cuidados Posteriores/métodos , Neoplasias de la Vaina del Nervio/terapia , Neoplasias del Pene/terapia , Procedimientos de Cirugía Plástica/métodos , Procedimientos Quirúrgicos Urológicos Masculinos/métodos , Niño , Humanos , Masculino , Terapia Neoadyuvante , Neoplasias de la Vaina del Nervio/patología , Neoplasias del Pene/patología , Pene/patología , Pene/cirugía , Escroto/cirugía , Resultado del Tratamiento , Uretra/cirugíaRESUMEN
A neurofibromatose tipo 1 é uma doença autossômica dominante rara, com manifestações clínicas diversas. Sua apresentação mais marcante é a presença de neurofibromas (tumores da bainha neural) cutâneos ou internos, que também podem ocorrer de forma esporádica, associados a outras manifestações sistêmicas, como manchas café com leite e lesões oculares. Por serem tumores da bainha de mielina, os neurofibromas podem acometer diversos nervos periféricos, incluindo nervos da face. Apresentamos o caso de um paciente de 1 ano, portador de neurofibromatose tipo 1, com neurofibroma em nervo infraorbital direito, com o acesso proposto para tratamento cirúrgico que fornecesse ampla visualização e acesso a lesão, sem comprometimento estético importante, permitindo preservação de partes moles e adequado crescimento facial.
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease with multiple clinical manifestations. Its most significant presentation is cutaneous or subcutaneous neurofibromas (myelin sheath tumors), which may be associated with other systemic manifestations such as caféau- lait spots and eye involvement. Neurofibromas can affect several peripheral nerves, including the facial nerves. This report presents a case of a 1-year-old patient with NF1 with right infraorbital nerve neurofibroma in which the proposed access for surgical treatment allowed adequate visualization of the tumor with good aesthetic results, preservation of the soft tissues, and normal facial growth.