Benign peripheral nerve tumors.

Benign peripheral nerve tumors encompass a wide range of neoplasms and non-neoplastic tumor like lesions. Some of these lesions if not encountered in the setting of genetic syndromes, are occurring sporadically. The principles of oncology should be respectfully followed in every step of diagnostic approach and surgical management. Albeit, classified as benign, some of them do have different level of malignant potential, thus the treating physicians should be aware of that to avoid possible pitfalls with devastating outcomes. This article reviews the most common benign peripheral nerve tumors discussing the clinicopathological findings, imaging appearance and the current trend in their approach.

The subparaneurial compartment: A new concept in the clinicoanatomic classification of peripheral nerve lesions.

Based on our experience in treating peripheral non-neural sheath derived pathology, we have identified a novel pattern of lesion progression along the anatomic course of nerves. This report highlights the existence of a subparaneurial compartment around peripheral nerves. We first applied an anatomic framework to review MR images and intraoperative photographs of patients treated by the senior author in the last 10 years. After identifying a pattern that was consistent with subparaneurial lesion progression, we searched for other examples of cases that might exhibit this pattern. Four examples of subparaneurial pathology were identified, a hemangioma of the ulnar nerve, a ganglion cyst of the common fibular nerve, a lymphoma of the sciatic nerve and a lipoma of the ulnar nerve. All four patients were operated on and had intraoperative photographs; three had high resolution MR imaging. This report highlights the existence of pathology contained within a subparaneurial compartment, outside of the epineurium, that follows the course of the nerve and surrounds it circumferentially. The subparaneurial localization of peripheral nerve lesions has hitherto received little attention. Identification of this new pattern on preoperative MRI may have implications for surgical management.

Clinical Neuropathology practice guide 6-2013: morphology and an appropriate immunohistochemical screening panel aid in the identification of synovial sarcoma by neuropathologists.

AIMS: Pathologists are under increasing pressure to accurately subclassify sarcomas, yet neuropathologists have limited collective experience with rare sarcoma types such as synovial sarcoma. We reviewed 9 synovial sarcomas affecting peripheral nerve diagnosed by neuropathologists and explored the morphologic and immunohistochemical differences between these and MPNST. Our goal was to make practical recommendations for neuropathologists regarding which spindle cell tumors affecting nerve should be sent for SYT-SSX testing. METHODS: Clinical records and genetics were reviewed retrospectively and central pathology review of 9 synovial sarcomas and 6 MPNST included immunohistochemistry for SOX10, S100, BAF47, CK (lmw, pan, CK7, CK19), EMA, CD34, bcl2, CD99, and neurofilament. RESULTS: Common synovial sarcoma sites were brachial plexus, spinal and femoral nerve, none were "intra-neural", all had the SYTSSX1 translocation, and 6/9 were monophasic with myxoid stroma and distinct collagen. Half of the monophasic synovial sarcomas expressed CK7, CK19 or panCK in a "rare positive cells pattern", 8/9 (89%) expressed EMA, and all were SOX10 immunonegative with reduced but variable BAF47 expression. CONCLUSIONS: We recommend that upon encountering a cellular spindle cell tumor affecting nerve neuropathologists consider the following: 1) SYT-SSX testing should be performed on any case with morphology suspicious for monophasic synovial sarcoma including wiry or thick bands of collagen and relatively monomorphous nuclei; 2) neuropathologists should employ a screening immunohistochemical panel including one of CK7, panCK or CK19, plus EMA, S100 and SOX10, and 3) SYT-SSX testing should be performed on any spindle cell tumor with CK and/or EMA immunopositivity if SOX10 immunostaining is negative or only labels entrapped nerve elements.

Intradural spinal tumours and their mimics: a review of radiographic features.

Intradural spinal tumours, although relatively uncommon, can be diagnostically challenging, and often result in significant morbidity. They can be subdivided according to their cell of origin and whether they are within the cord (intramedullary) or intradural but extramedullary in location. The differential diagnosis for masses of the cauda equina region is often considered separately. Additionally, some inflammatory processes, cysts, benign tumour-like masses and vascular malformations may mimic intradural tumours. Although in many instances, a precise preoperative diagnosis is not possible as many of the imaging findings overlap, some features may strongly suggest one diagnosis over others. This article reviews the range of intradural spinal tumours in the adult and paediatric populations, with an emphasis on pertinent imaging characteristics. An approach is provided for distinguishing tumours from lesions that mimic tumours and for narrowing the differential diagnosis according to imaging findings.

A study of gata3 and phox2b expression in tumors of the autonomic nervous system.

Autonomic neurons and chromaffin cells, which constitute the autonomic nervous system, are derived from a common progenitor from the neural crest, and its development is controlled by a network of transcription factors, including the master regulator, Phox2b, and its downstream, Gata3. Anti-Phox2b and anti-Gata3 antibodies were applied to a total of 77 autonomic nervous system tumors, including 35 paragangliomas, 21 pheochromocytomas, 9 neuroblastomas, 4 ganglioneuroblastomas, and 8 ganglioneuromas, as well as their potential morphologic mimics, including tumors of the small round cell tumor group, neuroendocrine carcinomas of lung and gastrointestinal tract (carcinoid tumors/neuroendocrine tumors, large cell neuroendocrine carcinomas, and small cell carcinomas), Merkel cell carcinomas, benign and malignant tumors of thyroid, parathyroid, and adrenal cortex, and malignant melanomas. A variety of nonendocrine/neuroendocrine carcinomas were also studied. Gata3 expression was seen in 89% of paragangliomas, 95% of pheochromocytomas, and all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas, as well as in all parathyroid tumors, a majority of urothelial and mammary carcinomas, and a subset of squamous cell carcinomas, but all other tumors were negative. Phox2b expression was seen in all neuroblastomas, ganglioneuroblastomas, and ganglioneuromas and in 40% of paragangliomas, but pheochromocytomas and all other tumors were negative. Gata3 is a highly reliable marker for paragangliomas, pheochromocytomas, and neuroblastic tumors to distinguish from their simulators. This is an additional utility for this marker, which is used for the diagnosis of urothelial and mammary carcinomas. Phox2b is also highly specific, but its low sensitivity to paragangliomas and pheochromocytomas would limit the utility only to neuroblastic tumors.

Adipose lesions of nerve: the need for a modified classification.

OBJECT: Adipose lesions of nerve are rare and poorly understood. Their current classification, although not universally accepted, generally includes lipomatosis of nerve with or without localized macrodactyly, and intra- as well as extraneural lipoma. The authors believe that the spectrum of these lesions and their interrelationships are not currently appreciated. They propose an adaptation to the existing framework to illustrate the expanding spectrum of adipose lesions of nerve by considering lipomatosis and lipoma singly or in combination. METHODS: Fourteen representative cases are presented to demonstrate not only the intraneural and extraneural examples of lipomatosis and lipoma, but also their anatomical combinations. RESULTS: Based on the cases presented and a careful literature review, a conceptual approach to the classification of adipose lesions of nerve is generated. This approach incorporates the 2 essential lesions, lipomatosis of nerve and lipoma, in both their intra- and extraneural forms. This permits expansion to encompass combinations. CONCLUSIONS: To press the concept that adipose tumors of nerve are a broad but interrelated spectrum of lesions, the authors propose modification of the present classification system. This approach provides an orderly platform for progress, reflects understanding of these interrelated lesions, and facilitates optimal treatment by distinguishing resectable from nonresectable components.

A novel classification system for perineural invasion in noncutaneous head and neck squamous cell carcinoma: histologic subcategories and patient outcomes.

OBJECTIVE: The aims of this study were to define a novel classification system of tumor perineural invasion (PNI) with respect to tumor/nerve involvement such as intratumoral (IT), peripheral, or extratumoral (ET) and to determine the prognostic significance of each of these histologic subcategories in patients with noncutaneous head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: This study is a retrospective chart review and histologic analysis of patients with HNSCC in the setting of a tertiary care medical center. METHODS: A clinical chart review of 142 patients with HNSCC who underwent primary surgical treatment from January 2004 through December 2007 was performed. Clinical information collected included patient age, sex, alcohol and tobacco use, tumor location, TNM stage, postoperative adjuvant chemotherapy and/or radiation treatment, and patient outcome. For each case, PNI density, the distance of each PNI focus to the tumor edge, and size of the largest nerve involved were measured. Furthermore, PNI was subcategorized as IT, peripheral, or ET. A Cox regression analysis was performed to determine if PNI was related to regional disease recurrence. Kaplan-Meier survival analysis was also performed. RESULTS: Among the 142 patients, 37 (26%) had disease progression. The maximum extent of PNI was significantly correlated with disease-free survival on multivariate analysis (P = .019) and was also significantly related to disease-free survival when T stage (P = .017), N stage (P = .021), and T and N stages (P = .02) were added to the Cox regression model. Kaplan-Meier analysis demonstrated a trend toward increased disease-free survival of PNI negative and IT/peripheral PNI compared with ET PNI. CONCLUSION: Perineural invasion is correlated with nodal status and T stage and is related to disease-free survival. It can be subcategorized as IT, peripheral, or ET. This novel classification system has important implications with regard to clinical outcome and may help define a cohort of patients that may require more aggressive management.

Primary benign brachial plexus tumors: an experience of 115 operated cases.

Primary benign brachial plexus tumors are rare. They pose a great challenge to the neurosurgeon, because the majority of patients present with minimal or no neurological deficits. Radical to complete excision of the tumor with preservation of neurological function of the involved nerve is an ideal surgical treatment option with benign primary brachial plexus tumor surgery. We present a review article of our 10-year experience with primary benign brachial plexus tumors surgically treated at King Edward Memorial Hospital and P.D. Hinduja National Hospital from 2000 to 2009. The clinical presentations, radiological features, surgical strategies, and the eventual outcome following surgery are analyzed, discussed, and compared with available series in the world literature. Various difficulties and problems faced in the management of primary benign brachial plexus tumors are analyzed. Irrespective of the tumor size, the indications for surgical intervention are also discussed. The goal of our study was to optimize the treatment of patients with benign brachial plexus tumors with minimal neurological deficits. It is of paramount importance that brachial plexus tumors be managed by a peripheral nerve surgeon with expertise and experience in this field to minimize the neurological insult following surgery.

[Correlation between typing of peripheral neuroblastic tumors and prognosis: a clinicopathologic study of 135 cases].

OBJECTIVE: To study the clinicopathologic characteristics of peripheral neuroblastic tumors and to investigate the prognostic significance of International Neuroblastoma Pathology Classification (INPC). METHODS: One hundred and thirty-five cases of peripheral neuroblastic tumors encountered in Shanghai Children's Medical Center were enrolled into the study. All the cases were classified according to INPC and International Neuroblastoma Staging System (INSS). The follow-up data were analyzed. RESULTS: The consensus diagnoses of the 135 cases were as follows: 80 cases (59.2%) of neuroblastoma, 24 cases (17.8%) of ganglioneuroblastoma, intermixed, 17 cases (12.6%) of ganglioneuroma and 14 cases (10.4%) of ganglioneuroblastoma, nodular. The cases were subdivided into 2 subgroups: favorable histology (number = 90, 66.7%) and unfavorable histology (number = 45, 33.3%). According to INSS, the number of cases in stages I, II, III and IV was 22 (16.3%), 24 (17.8%), 34 (25.2%) and 55 (40.7%), respectively. The survival of peripheral neuroblastic tumors correlated with histologic diagnosis, INPC and INSS (P < 0.05). CONCLUSION: Diagnostic categorization of peripheral neuroblastic tumors according to INPC is of prognostic value.

Classification of neural tumors in laboratory rodents, emphasizing the rat.

Neoplasms of the nervous system, whether spontaneous or induced, are infrequent in laboratory rodents and very rare in other laboratory animal species. The morphology of neural tumors depends on the intrinsic functions and properties of the cell type, the interactions between the neoplasm and surrounding normal tissue, and regressive changes. The incidence of neural neoplasms varies with sex, location, and age of tumor onset. Although the onset of spontaneous tumor development cannot be established in routine oncogenicity studies, calculations using the time of diagnosis (day of death) have revealed significant differences in tumor biology among different rat strains. In the central nervous system, granular cell tumors (a meningioma variant), followed by glial tumors, are the most common neoplasms in rats, whereas glial cell tumors are observed most frequently in mice. Central nervous system tumors usually affect the brain rather than the spinal cord. Other than adrenal gland pheochromocytomas, the most common neoplasms of the peripheral nervous system are schwannomas. Neural tumors may develop in the central nervous system and peripheral nervous system from other cell lineages (including extraneural elements like adipose tissue and lymphocytes), but such lesions are very rare in laboratory animals.

[Neurogenic tumors of the mediastinum in adults]. / Tumeurs nerveuses du médiastin de l'adulte.

In adults, mediastinal neurogenic tumours constitute the third group of mediastinal tumours, after thymomas and lymphomas. If the group of neurogenic tumour is frequent, each type of tumour is relatively unusual in everyday's clinic. Among them, nerve sheath tumours are the more frequent, followed by tumour of the autonomic system. Askin tumour remains uncommon. Treatment of this tumour requires complete preoperative work-up, including standard radiography, CT-scan, MRI, and sometimes nuclear imaging. In most cases, the treatment is based on surgical resection, and may be associated with radiotherapy or chemotherapy in case of malignant tumour or incomplete resection. Better understanding of these tumours, including their molecular abnormalities, may lead to new changes in their classifications, and to their management.

[Peripheral nerve tumors]. / Tumeurs des nerfs périphériques.

Peripheral nerve tumors are most often benign tumors of the nerve sheath; uncommonly they come from the nerve cells or are metastatic tumors. A precise diagnosis is required for well-adapted and effective treatment, as is good knowledge of fibromatosis diseases. In some cases, the diagnosis of the nerve tumor will lead to a diagnosis of phakomatosis. Surgical treatment must be clearly discussed, which, in case of schwannomas gives very good functional results. Primitive malignant tumors remain an unsolved therapeutic problem.

Results of surgical treatment of cervical dumbbell tumors: surgical approach and development of an anatomic classification system.

STUDY DESIGN: A retrospective study of a new classification and surgical approach of cervical dumbbell tumors. OBJECTIVE: To evaluate PUTH classification. SUMMARY OF BACKGROUND DATA: The high recurrence rate and postoperative deformity are unsolved problems. Asazuma's landmark classification could not cover all cases and could not provide clear suggestion for the surgical approach. The ideal classification should be comprehensive, easily understood and of practical value. METHODS: PUTH classification for cervical dumbbell tumors includes 7 categories (types 1-7) and 2 foraminal modifiers. Posterior approach is appropriate for type 1, 2 and 5 tumors, anterior and anterolateral approach is an ideal choice for type 4 and 6 tumors. Type 7 tumors need combined anterior and posterior approach. RESULTS: Forty-four consecutive patients with cervical dumbbell tumor were surgically treated. The pathology included schwannoma in 31 cases, neurofibroma in 9 and ganglioneuroma in 4. Based on PUTH classification, type 3 was diagnosed in 13 cases, type 5 in 17, type 6 in 8, and type 7 in 6. Tumors were unilateral in 41 cases, and bilateral in 3 cases. Five were tumor revision cases. Thirty patients underwent posterior approach, 7 had anterior approach, 1 had anterolateral approach, and 6 had combined approach. Gross total resection was achieved in all the patients. Tumors involved nerve roots were transected in 12 cases. Single vertebral artery was ligated in 3. The complications included cerebrospinal fluid leakage in 18 cases, esophagus injury in 1, Horner syndrome in 1, dysphagia in 2, dyspnea in 1 and deep infection in 1. Thirty-six cases (81.1%) had an average 61-month follow-up. Recurrence was found in only one case (2.8%). CONCLUSION: PUTH classification covers all tumor types and is easier to remember. It is practical and useful for determining the surgical approach. The recurrence rate decreases significantly after radial tumor resection. Revision surgeries are associated with more complications.

Malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare variety of soft tissue sarcoma of ectomesenchymal origin. MPNSTs arise from major or minor peripheral nerve branches or sheaths of peripheral nerve fibers and are derived from Schwann cells or pluripotent cells of neural crest origin. Arthur Purdy Stout played a pivotal role in the development of our current understanding of the pathogenesis of peripheral nerve sheath tumors by identifying the Schwann cell as the major contributor to the formation of benign and malignant neoplasms of the nerve sheath. Although this fact remains essentially true, the cell of origin of the MPNST remains elusive and has not yet conclusively been identified. Some have suggested these tumors may have multiple cell line origins. In the present review, MPNSTs and their epidemiology, diagnosis, management, and treatment are discussed.

Prognostic value of the International Neuroblastoma Pathology Classification in Neuroblastoma (Schwannian stroma-poor) and comparison with other prognostic factors: a study of 182 cases from the Spanish Neuroblastoma Registry.

In addition to clinical and biological factors, further valuable prognostic information in neuroblastoma (Schwannian stroma-poor) (NB) patients is provided by the histopathologic analysis and the application of the International Neuroblastoma Pathology Classification (INPC) system. The objective of this study was to assess the prognostic impact of the INPC classification in a series of NB (Schwannian stroma-poor) and its relation with other prognostic factors. One hundred eighty-two cases of NB were collected from the files of the Spanish Neuroblastoma Registry. Slides were reviewed, and NB cases were grouped into favorable and unfavorable categories according to INPC criteria, taking into account morphological features (mitosis-karyorrhexis index, histological subtype) and patient's age at diagnosis. Other pathological [presence of calcifications, tissular components, and number of mitotic cells per 10 high-power field (HPF)], immunohistochemical (P-glycoprotein and Ki-67 protein expression) and genetic (MYCN amplification and chromosome 1p deletion) features were also studied. Statistical analyses of overall survival with Kaplan-Meier curves and a multivariate study using Cox regression were performed (40.3% of NBs were considered favorable and 59.7% unfavorable). Unfavorable NB showed a mean survival time of 57 months compared with 89 months in favorable cases. Advanced stage, more than ten mitoses per 10 HPF, Ki-67 expression in more than 30% of tumor cells, MYCN oncogene amplification and chromosome 1p deletion were observed more frequently in unfavorable NB. The Cox regression analysis demonstrated that clinical stage (International Neuroblastoma Staging System stage 4) and histological subtype (undifferentiated NB) were the most important factors that influence the overall survival (p<0.001). INPC classification results are major prognostic indicators in NB and should be considered in the therapeutic stratification of NB patients.

International neuroblastoma pathology classification adds independent prognostic information beyond the prognostic contribution of age.

Age has been used as a prognostic factor for patients with peripheral neuroblastic tumours (pNTs). The latest analysis disclosed a cut-off around 18 months for the optimal prognostic distinction. The International Neuroblastoma Pathology Classification (INPC) distinguishes favourable and unfavourable histology based on the age-appropriate evaluation of histologic indicators (grade of neuroblastic differentiation, mitosis-karyorrhexis index) in the categories of neuroblastoma and ganglioneuroblastoma, nodular. This study showed that age tested by using 3 different cut-offs (12, 18, 24 months) was prognostically significant. INPC remained prognostically significant regardless of the age group to which it was applied. Prognostic effects of age and histologic indicators were independently significant, i.e., age had prognostic ability beyond that of histologic indicators, and histologic indicators had prognostic ability beyond that of age. Due to the fact that INPC incorporated age factor (18, 60 months) in the system, it served better than age by itself for prognostic distinction of pNT patients.

Is clear cell sarcoma a malignant form of psammomatous melanotic schwannoma? Case report.

The authors present a case of clear cell sarcoma (CCS) in which the tumor originated in the S-1 nerve root and had been previously diagnosed as psammomatous melanotic schwannoma (PMS). This is the third case of a spinal nerve root origin for CCS reported in the English-language literature. The similar histogenesis of CCS and malignant melanoma supports the hypothesis that biological agents or immunotherapy are potentially important areas of investigation. The patient underwent S1-3 laminectomy and gross-total resection of the mass lesion. The border of the resection was extended 1 cm distal to the tumor margin. The postoperative period was uneventful. The new histopathological diagnosis was CCS (malignant melanoma of soft tissue). Despite total resection, the patient returned with disseminated disease at the 18-month follow-up visit. His follow-up magnetic resonance image of the lumbar spine revealed sacral L5-S3 involvement of the vertebral bodies along with disseminated cauda equina seeding. A CCS originating from peripheral nerves is quite rare. The histopathological and immunohistochemical appearance of CCSs resembles those of PMSs. Surgery should be the first choice of treatment.

Classification of benign fatty tumours of the upper limb.

In this paper, the authors offer a classification of benign fatty tumours of the upper limb. There are three histologically distinct types of fat cells: immature fat cells which give rise to lipoblastomas, mature brown fat cells which give rise to hibernomas and mature white fat cells which give rise to lipomas. Lipomas are the most common and they are sub-classified according to the anatomic site of fat cells into dermal, subcutaneous and sub-fascial lipomas; or tumours directly related to muscle, bone, synovium or nerve. Finally, the authors review 67 patients with benign fatty tumours of the upper limb and provide clinical examples of these tumours including their characteristic histological and radiological features.

Comparative genomic hybridization in central and peripheral nervous system tumors of childhood and adolescence.

Brain tumors amount to less than 2% of all malignant neoplasms. However, they account for approximately 20% of all childhood cancers and are the leading cause of cancer mortality among children. Recently, enormous progress has been achieved in the field of pediatric neuro-oncology regarding the classification of children's brain tumors, as well as the understanding of the genetic events involved in their pathogenesis; thus leading to an emerging role of molecular diagnostic approaches using novel tools. Comparative genomic hybridization (CGH) is a technique that has revolutionized cytogenetic knowledge in the past decade. It permits the detection of chromosomal copy number changes without the need for cell culturing and gives a global overview of chromosomal gains and losses throughout the whole genome of a tumor. A survey of CGH-related publications on central and peripheral nervous system tumors in the pediatric and adolescent population revealed 884 cases. The CNS tumor groups most frequently examined by CGH were embryonal tumors (268 cases/30.3%) and ependymomas (241/27.2%), followed by astrocytic (163/18.4%), peripheral nerve (73/8.2%), choroid plexus tumors (56/6.3%), and craniopharyngiomas (38/4.3%). The most common CNS tumor entities were medulloblastomas (238/26.9%), classic ependymomas (160/18.1%), anaplastic ependymomas (70/7.9%), pleomorphic xanthoastrocytomas (53/6.0%), and pilocytic astrocytomas (50/5.6%). This article provides a short review of the CGH technique and its pitfalls, summarizes the current CGH-related data on pediatric brain tumors and muses on the future of CGH.