Malignant Neurofibroma Research Articles

Nerve Sheath Tumours In and Around Spine—A Series of 50 Cases

Abstract Background: Nerve sheath tumours in and around the spine, especially in the junctional zones, are a challenging endeavour for the surgeon, because of the difficulty in approaching these structures as well as their close proximity to the major vessels and nerves. Most of these tumours are benign in nature. They are usually very slow growing, and hence the tumour may be detected very late in its clinical course unless it compresses or encircles any of the major neurovascular structures early in its course. The surgical results after the excision of these tumours are excellent. Most of the patients get completely cured by prompt treatment. Here we present a series of 50 nerve sheath tumours in and around the spine operated over a period of 21 years. Materials and Methods: A retrospective study was done for 50 patients who underwent an operation for nerve sheath tumours in and around the spine, over a period of 21 years. Patient’s clinical and radiological data were extracted from the Medical Record Department (MRD) of our hospital and analysed. Results: Out of the 50 cases of nerve sheath tumours, 40 patients (80%) were of schwannoma and 10 patients (20%) were of neurofibroma. Overall, 10 patients had dumbbell tumours (neurofibroma+schwannoma). The mean age group was between 4th and 6th decade. Patients were followed up for a minimum of 1 year and a maximum of 20 years period. All of these tumours were benign except one patient who had a malignant neurofibroma of the C-8 nerve root. 15 out of 50 patients presented with paraparesis, 5 with paraplegia and another 5 with quadriparesis. All these patients had complete neurological recovery after surgical removal of the tumours. Conclusion: This case series brings out the nuances in the management of nerve sheath tumours in and around the spine and their results.

RECURRENCE OF MALIGNANT PERIPHERAL NERVE SHEATH TUMOR

Peripheral nerve sheath tumor (PNST) is known as a benign tumor called Schwannomas, developed from the Schwann cells that produce myelin and collagen, and can occur in a wide variety of locations. In some cases, it can take a malignant turn and grow as a pelvic mass known as malignant peripheral nerve sheath tumor (MPNST), malignant schwannoma, malignant neurofibroma, malignant mesenchynoma and neurogenic sarcoma. Our case report presents a female patient presenting dysuria and pelvic pain. The clinical examination revealed a palpable mass in the lower abdomen. The computer tomography (CT) scan of the abdomen and pelvic region showed a tumor mass that was in contact with the nearby organs, but not infiltrating them. After the surgery, histopathology confirmed the MPNST proliferation. A month after, the patient returned for a follow-up and presenting pelvic pain. The CT scan of the abdomen and pelvic region showed a tumoral mass compressing the nearby organs, but not infiltrating them. The patient was referred to oncology board for palliative treatment. The particularity of this case report is the short period of time recurrence of the MPNST, rather than metastases. The most important treatment for MPNSTs remains surgery, trying to achieve negative margins. However, there have been reported two cases of unresectable MPSNT with partial remission to chemo- and radiotherapy.

Case report and immunohistochemical study of a malignant peripheral nerve sheath tumor in a dog

Malignant peripheral nerve sheath tumor is rare and rarely reported in dogs. The term neurofibroma/sarcoma is classically used when the tumor is composed of Schawann and perineural cells. This work describes the clinical, histopathological, and immunohistochemical case of a subcutaneous malignant peripheral nerve sheath tumor, most likely a malignant neurofibroma located in the pelvic member of a Rottweiler dog. Histopathological features and immunohistochemical analysis corroborated the diagnosis, showing positivity for S-100 protein, vimentin, and CD57, and was useful to distinguish this type of neoplasm from other malignancies of similar morphologies.

Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors.

Benign neurofibromas, the main phenotypic manifestations of the rare neurological disorder neurofibromatosis type 1, degenerate to malignant tumors associated to poor prognosis in about 10% of patients. Despite efforts in the field of (epi)genomics, the lack of prognostic biomarkers with which to predict disease evolution frustrates the adoption of appropriate early therapeutic measures. To identify potential biomarkers of malignant neurofibroma transformation, we integrated four human experimental studies and one for mouse, using a gene score-based meta-analysis method, from which we obtained a score-ranked signature of 579 genes. Genes with the highest absolute scores were classified as promising disease biomarkers. By grouping genes with similar neurofibromatosis-related profiles, we derived panels of potential biomarkers. The addition of promoter methylation data to gene profiles indicated a panel of genes probably silenced by hypermethylation. To identify possible therapeutic treatments, we used the gene signature to query drug expression databases. Trichostatin A and other histone deacetylase inhibitors, as well as cantharidin and tamoxifen, were retrieved as putative therapeutic means to reverse the aberrant regulation that drives to malignant cell proliferation and metastasis. This in silico prediction corroborated reported experimental results that suggested the inclusion of these compounds in clinical trials. This experimental validation supported the suitability of the meta-analysis method used to integrate several sources of public genomic information, and the reliability of the gene signature associated to the malignant evolution of neurofibromas to generate working hypotheses for prognostic and drug-responsive biomarkers or therapeutic measures, thus showing the potential of this in silico approach for biomarker discovery.

Retraction Note: Ulnar malignant peripheral nerve sheath tumour diagnosis in a mixed-breed dog as a model to study human: histologic, immunohistochemical, and clinicopathologic study.

Canine Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are uncommonly reported in the ulnar, since they are underestimated relative to the more common spindle cell tumours of soft tissue. In dogs, MPNST accounts for 27% of nervous system tumours. In man, MPNST represents 5-10% of all soft tissue sarcomas and is often associated with neurofibromatosis type 1 (NF-1).An 8-year-old, 9 kg, female mixed-breed dog with a subcutaneous mass on the upper right side of the ulnar region was presented to the small animal research and teaching hospital of Tehran University. The dog was anorexic with general weakness. The mass (7 × 4 cm) was removed surgically and processed routinely. Microscopically, the mass was composed of highly cellular areas with a homogeneous population of round or spindle cells, high cellular pleomorphism, high mitotic index and various morphologic patterns. Furthermore, spindle cells arranged in densely or loosely sweeping fascicles, interlacing whorls, or storiform patterns together with wavy cytoplasm, nuclear palisades, and round cells were arranged in sheets or cords with a meshwork of intratumoral nerve fibers. In addition, in this case the presence of neoplastic cells within the blood vessels was observed. Immunohistochemically, tumor was positive for vimentin and S-100 protein. The histopathologic features coupled with the S-100 and vimentin immunoreactivity led to a diagnosis of malignant neurofibroma.

RETRACTED ARTICLE: Ulnar malignant peripheral nerve sheath tumour diagnosis in a mixed-breed dog as a model to study human: histologic, immunohistochemical, and clinicopathologic study

Canine Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are uncommonly reported in the ulnar, since they are underestimated relative to the more common spindle cell tumours of soft tissue. In dogs, MPNST accounts for 27% of nervous system tumours. In man, MPNST represents 5-10% of all soft tissue sarcomas and is often associated with neurofibromatosis type 1 (NF-1).An 8-year-old, 9 kg, female mixed-breed dog with a subcutaneous mass on the upper right side of the ulnar region was presented to the small animal research and teaching hospital of Tehran University. The dog was anorexic with general weakness. The mass (7 × 4 cm) was removed surgically and processed routinely. Microscopically, the mass was composed of highly cellular areas with a homogeneous population of round or spindle cells, high cellular pleomorphism, high mitotic index and various morphologic patterns. Furthermore, spindle cells arranged in densely or loosely sweeping fascicles, interlacing whorls, or storiform patterns together with wavy cytoplasm, nuclear palisades, and round cells were arranged in sheets or cords with a meshwork of intratumoral nerve fibers. In addition, in this case the presence of neoplastic cells within the blood vessels was observed. Immunohistochemically, tumor was positive for vimentin and S-100 protein. The histopathologic features coupled with the S-100 and vimentin immunoreactivity led to a diagnosis of malignant neurofibroma.To the best of our knowledge, primary ulnar MPNST has not been reported in animals. This is the first documentation of an ulnar malignant peripheral nerve sheath tumour in a dog.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1310907815984587

Comparison of whole body diffusion weighted magnetic resonance imaging and somatostatin receptor scintigraphy for oncogenic osteomalacia.

To compare the accuracy of whole body diffusion weighted magnetic resonance imaging (WB-DWI) with that of somatostatin receptor scintigraphy (SRS) in the detection and localization of the lesions in patients with oncogenic osteomalacia (OOM). Totally 6 patients with clinically suspected oncogenic osteomalacia were enrolled. All of them underwent WB-DWI and SRS within 2 weeks to evaluate the possible presence of tumors that lead to osteomalacia. Surgical and pathological findings were considered as the gold standard. The sensitivity, specificity, and accuracy were calculated. Pathology confirmed the diagnosis of two soft tissue tumors (including 1 angiolipoma and 1 mesenchymal tumor) and one bone tumor of malignant neurofibroma. The sensitivity, specificity, and accuracy in the identification of lesions in patients with oncogenic osteomalacia were 33.33%, 100%, 66.67% for WB-DWI and 33.33%, 66.67%, 50% for SRS (P>0.05). For adult patients with osteomalacia, WB-DWI and SRS can provide mutually supportive data and be used for identifying potential oncogenic osteomalacia.

Imaging manifestations and its clinical significance in patients with oncogenic osteomalacia

目的 探讨不同影像方法在瘤源性骨质软化病变的影像学表现.方法8例瘤源性骨质软化患者年龄28～69岁,平均44.1岁,其中男5例,女3例.所有患者的骨质软化诊断依据临床检查和X线表现.主要实验室检查包括血清钙、磷、碱性磷酸酶活性、甲状旁腺激素、尿磷和肝肾功能.根据临床寻找瘤源性骨质软化病变的需求,所有患者均先行99mTC-生长抑素核素扫描检查.MR检查8例,螺旋CT检查4例,对MR、CT发现的4例骨内病变又进一步行常规X线检查4例.所有局部病变均行手术切除并得取病理诊断.结果所有患者实验室检查均示血磷降低(0.29～0.65 mmol·L-1),碱性磷酸酶(36.6～310.6μmol·s-1·L-1)和尿磷增高(11.5～40.9 mmol·L-1),但甲状旁腺水平和肝、肾功能均正常.术后病理结果为:软组织肿瘤4例(血管瘤、腱鞘巨细胞瘤、血管外皮细胞瘤和间叶细胞瘤各1例);骨肿瘤4例(恶性神经纤维瘤1例,间叶细胞瘤2例和纤维母细胞瘤1例).所有病变区的奥曲肽显像均示异常浓聚,但不足以区分病变是源于骨还是软组织,而MR影像可进行这种区分.所有病变的T1WI示低或等强度信号,T2WI示高强度信号;病变的边界均清晰;信号强度不均匀者6例,均匀者2例;4例病理证实的骨肿瘤中有2例CT和X线显示恶性的骨质破坏征象,如边界不清等.结论对年长、血钙和甲旁状腺激素正常且低血磷的骨质软化,应首选奥曲肽显像检查用以寻找瘤源性骨质软化病变,进一步结合MR、CT或X线所见有助于病变性质的分析。

Malignant peripheral nerve sheath tumor presenting as a massive intra-abdominal mass

Malignant peripheral nerve sheath tumours (MPNST) have been designated by various names in the past including malignant schwannoma, malignant neurilemmoma, malignant neurofibroma, malignant neurofibrosarcoma, malignant mesenchymoma and neurogenic sarcoma. They usually present as large painful masses, are locally invasive, highly metastatic and obstruct the gut, ureters, blood vessels and so on. Criteria for diagnosis include demonstration of origin from a nerve, presence of Schwann cells, presence of neurofibromata, nuclear palisading on microscopy and immunohistochemical findings of S-100 protein. Resection and combination chemotherapy are the accepted modes of treatment [1]. There are many histological variants namely melanotic, epithelioid and a divergent variant with epithelial, glandular and mesenchymal differentiation. However, the cellular variant is considered benign [2].

Neurofibromatosis of the cervical spine. A report of eight cases.

Eight patients with neurofibromatosis presented with symptoms of cervical spine involvement over a period of 17 years, five of them within the second decade of life. The symptoms included neurological deficit in five, a neck mass in four, and deformity in three; only two complained of pain. Osteolysis of vertebral bodies with kyphosis of more than 90 degrees was the most common radiological feature. Posterior fusion failed in the one patient in whom it was performed. Good results were achieved by anterior fusion, alone, or combined with posterior fusion. Surgical complications included one death in a patient with a malignant neurofibroma, and one case of transient neurological deterioration.

CT morphology of malignant schwannoma

Thirty patients with histologically confirmed malignant schwannomas were examined. In five patients the lesions were malignant neurofibromas, as part of von Recklinghausen's disease, the others were solitary malignant schwannomas. CT appearances of malignant schwannomas are variable. Shape, structure and attenuation vary considerably. Most malignant schwannomas present with the CT criteria of benign tumours. Altogether neither the solitary schwannomas, nor those associated with von Recklinghausen's disease show specific diagnostic features, whether for the primary tumour or for recurrences. Reliable information on the nature of these lesions is possible in a few cases only.

当院における脊髄腫よう例の検討

37 cases of spinal cord tumors were treated in our clinic. Seven cases were malignant tumors: astrocytoma, glioblastoma, malignant neurofibroma, reticulosarcoma, germinoma and malignant melanoma. 30 cases were benign tumors: 17 neurinomas, 4 meningiomas, 4 hemangiomas, 2 ependymomas, 2 epidermoid cysts and lipoma.Prognosis of these tumors were not good, so that early diagnosis and atraumatic extirpation were necessary.

Neurofibromatosis and childhood tumors.

Although tumors are a known complication of von Recklinghausen's neurofibromatosis (NF), they often develop after the second decade and their characteristics in the pediatric population are unclear. To define the frequency and distribution of tumor types in children with NF, the authors reviewed the experience at Children's Hospital of Pittsburgh between 1953 and 1984. During that time, 121 children younger than 18 years with documented NF were seen. Three patients (2.5%) developed locally extensive, unresectable sarcomas, two of which were clearly neural in origin. Two other children died from complications of highly cellular but not histologically malignant neurofibromas. Seventeen patients (14%) had brain tumors, of which 3 (2.5%) were malignant astrocytomas and 9 were optic gliomas. Two children had acute myelogenous leukemia. Although it has been said that patients with NF are particularly susceptible to the oncogenic effects of radiation, 12 children were treated with a median of 5000 rad to their tumor bed. Follow-up after radiation in that small cohort of patients ranged from 6 months to 12 years (mean, 6 years). Eleven of 12 patients experienced adequate local control. During the follow-up period, none developed a second tumor outside or within the radiation port that could be related to radiation. The authors conclude that clinically significant tumors in children with NF, not all of which are histologically malignant, are not rare. Although more prospective information is needed on response to and sequelae from therapy, the data in this report suggest no contraindication to aggressive therapy.

Neurofibromatosis associated with malignant neurofibromas

Neurofibromatosis associated with malignant neurofibromas

The Malignant Tumors of the Peripheral Nerves

There are two groups of malignant tumors which develop in peripheral nerves: those which have the morphological characteristics of malignant fibroblastic tumors and those which are epithelial in type and reproduce in a more or less recognizable form embryonal or adult neuro-ectodermal structures. Both classes develop from structures in the nerve sheaths but not from the nerve fibers themselves. Of the first group, which is by far the more common, the great majority develop in individuals suffering from von Recklinghausen's disease. It will be shown that most of these tumors may properly be called fibrosarcomas, while a few with slightly different morphology are better termed malignant neurofibromas. All of these tumors are characterized by persistent growth, with a marked tendency to reappear after attempts at removal, and a great many have proved fatal, although metastases are uncommon. The second group of tumors is represented by a very few cases, each one of which differs from the others. The only features which are common to all of them are a probable common origin from neuroectoderm and the fact that all are malignant. It is the purpose of this communication to present the evidence which seems to support the above statements, derived from an analysis of published cases and from 8 new cases which have come to the writer's attention. For the purposes of this discussion the term “peripheral nerves” includes not only the derivatives of the spinal nerve roots but also the extradural portions of the cranial nerves, excluding the optic nervc. They are extremely radioresistant. The second group of tumors is represented by a very few cases, each one of which differs from the others. The only features which are common to all of them are a probable common origin from neuroectoderm and the fact that all are malignant.