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A malignant peripheral nerve sheath tumor (MPNST) arising from a schwannoma is extremely rare, with limited literature on its clinicopathologic features. Here, we present a case series and literature review on patients with MPNSTs arising from schwannomas. We performed a retrospective review of patients from our institution's records to identify those with MPNSTs arising from schwannomas. We conducted a search for additional cases from the literature utilizing PubMed. 20 patients (including 2 at our institution and 18 from 16 prior publications) were identified. The patients aged 22-93 (mean 52) years, and 63% were females. Histologically, while most MPNSTs arising from schwannomas were of epithelioid-type, 7 tumors (including 2 at our institution) were of conventional spindle-cell type. All 20 patients underwent surgical excision, while a subset received additional radiotherapy and/or chemotherapy. In 17 patients with available follow-up, the overall survival was 2-72 (median 12) months. MPNSTs rarely arise from schwannomas and should be considered in patients with a clinical diagnosis of schwannoma, however, with atypical radiologic or clinical features. MPNSTs arising from schwannomas can show epithelioid or spindle-cell histology and harbor an aggressive course, even with surgical excision and adjuvant treatment., (© 2021 Scandinavian Societies for Medical Microbiology and Pathology.)

Caudaequinatumors are histologically diverse. International Classification of Diseases for Oncology (ICD-O3) confers dedicated site code (C72. 1) for cauda equina. This code is excluded during analyses of other primary spinal cord tumors. In this retrospective study, the Surveillance, Epidemiology and End Results (SEER) data for primary cauda equina tumors (PCET, C72. 1) excluding the tumors of spinal meninges (C70. 1) from 1992 to 2015 were reviewed. Demographic characteristics, tumor types, and clinical outcomes were analyzed using univariable analysis. Overall survival was estimated using Kaplan-Meier methods and compared for age, histology and treatment type. 293 patients with PCET met inclusion criteria. The most common tumors comprised schwannoma (32%), myxopapillary ependymoma (21%), malignant ependymoma (22%). The median age at diagnosis was 50 years (range < 1 year to 98 years), 57% of patients were males. 77% of the patients underwent surgery. Median follow up time for these patients was 70 months. Of the 293 patients, 250 (85%) were living at the end of 2015. The cause of death was tumor or CNS related in 15 patients. 136 patients were followed for <5 years, of which 102 were censored and 34 died (11.6%) before 5 years. Using univariable analysis, age at diagnosis (Hazard Ratio, HR 1.05; confidence interval, CI 1.03-1.07; p < 0.001), malignant tumor type (HR 2.88, CI 1.15-7.19, p = 0.0239) and absence of surgical intervention (HR 2.54, CI1.26-5.11, p = 0.0092) were predictors of increased mortality. Although most patients did well, older age and lack of surgical intervention were associated with worse survival., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Schwannomas are tumors arising from Schwan cells of the neural sheath. Gastrointestinal schwannomas (GS) are rare and easily confused with a heterogeneous group of neuroectodermal or mesenchymal neoplasms. The aim of the present study is to analyze the clinicopathological features, surgical management methods, and long-term prognoses of GS patients., Methods: Between August 2004 and July 2019, 51 patients with GS were treated at the Peking Union Medical College Hospital. The medical records were reviewed retrospectively. A database containing demographic characteristics, clinical symptoms, imaging tests, operation details, pathological results, and prognoses was constructed and analyzed., Results: GS accounted for 2.0% of all schwannomas. The cohort comprised 19 men (37.3%) and 32 women (62.7%). The mean age was 55.7 ± 11.4 years. The most common symptom was abdominal pain (29.4%). Twenty-seven patients (52.9%) were asymptomatic and diagnosed incidentally. The most common tumor location of GS was the stomach (90.2%). S-100 had the highest positive rate (100%) in immunohistochemical staining. Forty-six patients (90.2%) were followed-up at a mean period of 49.5 ± 41.4 months. Forty-four patients (95.7%) survived without tumor, 1 patient survived with tumor, and 1 patient died. The 5-year cumulative overall survival rate and cumulative disease-free survival rate were 97.5% and 95.2%, respectively., Conclusion: GS are rare gastrointestinal tumors with favorable prognoses after surgical resection. Stomach is the most common site. Definitive diagnosis is determined by postoperative pathology. S-100 expression has diagnostic significance., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Xin Wu et al.)

Objectives: Peripheral nerve sheath tumors (PNSTs) are clinically heterogenous, comprising benign (BPNST) and malignant (MPNST) variants. BPNSTs can be managed with nerve-sparing excision or observation. MPNSTs require radical resection and multidisciplinary oncologic management (1, 15). Image-guided core-needle biopsy (IGCNBx) is the well-established standard to obtain preoperative tissue diagnosis of soft tissue tumors. However, there has been resistance to performing IGCNBx of PNSTs because of the presumed risk of nerve injury and unknown accuracy in determining malignancy. We sought to define the accuracy and safety of IGCNBx in PNSTs., Materials and Methods: All patients that underwent both IGCNBx and surgical resection of a PNST at our institution between 2002 and 2016 were analyzed. The accuracy of IGCNBx in determining malignancy was calculated, including subgroup analyses by histologic subtype and neurofibromatosis 1 status. Complication data were collected and analyzed., Results: Among the 78 PNSTs with IGCNBx and postresection surgical pathology, 76% (n=59) had BPNST and 24% (n=19) had MPNST on postresection surgical pathology. IGCNBx accurately determined malignancy in 94% of cases. IGCNBx demonstrating schwannoma or MPNST were 100% accurate in determining malignancy. IGCNBx demonstrating neurofibroma or indeterminate results were 33% and 57% malignant on postresection surgical pathology, respectively. There were no long-term complications, including sensory or motor deficits, from IGCNBx., Conclusions: Percutaneous IGCNBx demonstrates 94% accuracy in differentiating benign from malignant PNSTs. IGCNBx demonstrating neurofibroma or indeterminate pathology should be interpreted with caution because of risk of malignant reclassification on surgical pathology. Our results reaffirm the safety of IGCNBx, as no patients experienced long-term complications.

Objective: For some jugular foramen schwannomas (JFSs), complete resection is possible but may be associated with significant morbidity. Stereotactic radiosurgery (SRS) is a minimally invasive alternative or adjunct to microsurgery for JFSs. The authors reviewed clinical and imaging outcomes of SRS for patients with these tumors., Methods: Nine participating centers of the International Gamma Knife Research Foundation identified 92 patients who underwent SRS between 1990 and 2013. Forty-one patients had prior subtotal microsurgical resection. The median interval between previous surgery and SRS was 15 months (range 0.5-144 months). Eighty-four patients had preexisting cranial nerve (CN) symptoms and signs. The median tumor volume was 4.1 cm 3 (range 0.8-22.6 cm 3 ), and the median margin dose was 12.5 Gy (range 10-18 Gy). Patients with neurofibromatosis were excluded from this study., Results: The median follow-up was 51 months (range 6-266 months). Tumors regressed in 47 patients, remained stable in 33, and progressed in 12. The progression-free survival (PFS) was 93% at 3 years, 87% at 5 years, and 82% at 10 years. In the entire series, only a dumbbell shape (extension extracranially via the jugular foramen) was significantly associated with worse PFS. In the group of patients without prior microsurgery (n = 51), factors associated with better PFS included tumor volume < 6 cm 3 (p = 0.037) and non-dumbbell-shaped tumors (p = 0.015). Preexisting cranial neuropathies improved in 27 patients, remained stable in 51, and worsened in 14. The CN function improved after SRS in 12% of patients at 1 year, 24% at 2 years, 27% at 3 years, and 32% at 5 years. Symptomatic adverse radiation effects occurred in 7 patients at a median of 7 months after SRS (range 5-38 months). Six patients underwent repeat SRS at a median of 64 months (range 44-134 months). Four patients underwent resection at a median of 14 months after SRS (range 8-30 months)., Conclusions: Stereotactic radiosurgery proved to be a safe and effective primary or adjuvant management approach for JFSs. Long-term tumor control rates and stability or improvement in CN function were confirmed.

Head and neck high grade malignant peripheral nerve sheath tumors (HN-MPNSTs) are rare highly aggressive soft tissue sarcomas that show overlapping morphologic and immunophenotypic features with melanoma and other high grade sarcomas, resulting in diagnostic challenges, particularly in sporadic settings. Recent discoveries have implicated loss of function mutations in the polycomb repressive complex 2 (PRC2) components, including EED or SUZ12 genes, as one of the leading pathogenetic mechanisms in high grade MPNST. MPNSTs with PRC2 loss are associated with complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3), which emerged as a reliable immunohistochemical marker in the diagnosis of sporadic and radiation induced MPNST. As the diagnosis of MPNST in the HN is particularly challenging to distinguish from melanoma and other sarcoma types, we carried out a clinicopathologic analysis on HN-MPNST patients managed at our institution over a 20-year period (1997-2016), using the latest diagnostic criteria including H3K27me3 staining and other molecular investigations. The overall survival of HN-MPNST was compared with other HN soft tissue sarcomas. The diagnosis of HN-MPNST was confirmed in 13 patients (seven males and six females), with a mean age of 31 years; with 3 (23%) patients being of pediatric age. The most common site was the neck soft tissue (77%). Two-thirds of patients (n = 9) had stigmata of NF1, three had prior radiotherapy and only one developed a de novo MPNST. All except one tumor (86%) tested showed loss of H3K27me3 expression, including all non-NF1 patients. The 2 and 5-year DSS rates were 50 and 30%. The 2-year DFS rate was 21%. Adverse predictors on DSS included adult age (p = 0.011), prior-history of RT (p = 0.003) and recurrence (p = 0.003). Compared to other molecularly confirmed subsets of HN sarcomas (Ewing and Ewing-like sarcoma, rhabdomyosarcoma and synovial sarcoma), HN-MPNST had the worst overall survival (p < 0.0001). We conclude that HN-MPNSTs are highly aggressive sarcomas associated with an unfavorable outcome and the utility of H3K27me3 IHC stains in the evaluation of MPNST is a reliable ancillary diagnostic adjunct.

Background: Malignant peripheral nerve sheath tumor (MPNST) is one of the most common nonrhabdomyosarcoma soft tissue sarcomas encountered in pediatric age, and it is generally characterized by poor outcome, particularly for relapsing patients., Materials and Methods: This study considered 73 patients <21 years of age with relapsing MPNST observed among 120 patients enrolled in Italian pediatric protocols from 1979 to 2004. With the aim of possibly establishing a risk-adapted stratification, patients' outcome was examined using univariate and multivariate analysis based on clinical features at onset, first-line treatments, clinical findings at the time of first relapse, and second-line treatments., Results: The time to relapse ranged from 1 to 204 months after first diagnosis (median 7 months). The first relapse event was mainly local. At the time of our analysis, nine patients were alive in remission. The median overall survival after first relapse was 11 months, and the survival rates were 39.2% at 1 year and 15.8% at 5 years. The factors revealing the greatest impact on prognosis were as follows: initial tumor invasiveness, time of relapse, and achievement of a secondary complete remission (which was related to the feasibility of radical surgery)., Conclusions: Our study confirmed the unsatisfactory prognosis for pediatric patients with relapsing MPNST and pointed to a risk-adapted stratification model for the purposes of deciding second-line treatments. For the time being, an aggressive surgical approach seems to be the only effective salvage treatment and should be recommended. New therapeutic approaches are under evaluation with a view to improving current outcomes., (© 2017 Wiley Periodicals, Inc.)

Objectives: We analyzed the outcomes of patients with benign nonacoustic schwannomas treated with fractionated radiation therapy (RT)., Methods: Between October 1987 and March 2013, 11 patients with benign nonacoustic schwannomas diagnosed radiographically (n=3) or pathologically (n=8) were treated with fractionated RT with curative intent at the University of Florida. We reviewed patients' medical records to assess outcomes and toxicities from treatment., Results: The median follow-up for all patients was 8.2 years (range, 2.2 to 22.7 y) and 8 years for all living patients (range, 2.2 to 22.7 y). Of the 11 patients included in the analysis, 8 (73%) were treated solely with RT, 1 (9%) was treated with postoperative RT after subtotal resection, and 2 (18%) were treated with postoperative RT after recurrence following initial surgical resection. The 5-year overall survival, disease-free survival, and local control rates were 100%. There were no grade 2 to 5 treatment toxicities., Conclusions: RT for benign nonacoustic schwannoma may be effective when used alone or in addition to surgery. Irradiation should be considered in patients for whom resection is likely to result in one or more neurological deficits. Fractionated RT to a total dose of 50 Gy provides excellent local control and minimal morbidity.

Malignant peripheral nerve sheath tumors are rare tumors that originate from Schwann cells. Patients with neurofibromatosis type 1 are prone to develop these tumors. Due to their rarity and lack of established treatment, the prognosis of malignant peripheral nerve sheath tumors is poor. A retrospective study was conducted on children treated for malignant peripheral nerve sheath tumors at the Seoul National University Children's Hospital between 2007 and 2016. Eleven patients were diagnosed with malignant nerve sheath tumors at a median age of 12 years, eight of whom had neurofibromatosis type 1. All the patients underwent chemotherapy and received surgical resection, and 5 patients relapsed. The 2-year overall survival rate was 72.7%, and the 2-year event-free survival rate was 58.2%. Univariate analysis was performed to assess the correlations between the clinical factors. There was no statistically significant difference in the overall survival rate according to the patients' clinical factors. However, there was a decreasing trend in the relationship between the event-free survival rate and the prevalence of neurofibromatosis type 1. Regular follow up of neurofibromatosis type 1. Regular follow-up of neurofibromatosis type 1 patients may identify detection of early relapse of malignant peripheral nerve sheath tumors. Genetic studies of these patients and tumors may identify opportunities for targeted therapy.

Objective: Radiation-induced malignant peripheral nerve sheath tumors (MPNSTs) are an uncommon late risk of irradiation. We conducted the largest systematic review to date of individual patient data for patients with these tumors., Methods: We conducted a systematic search using the PubMed database, and compiled a systematic literature review. We used Kaplan-Meier analysis and a log-rank test to estimate survival., Results: We analyzed 65 radiation-induced and 26 radiation-associated MPNSTs in patients with neurofibromatosis. The mean ages of onset for primary lesions of the 2 types were 31.7 ± 18.2 and 17.1 ± 12.4 years, respectively (P = 0.0008). The latency periods between radiotherapy and onset of the 2 types of MPNSTs were 13.5 ± 7.8 and 11.8 ± 7.5 years, respectively (P = 0.3101). The median overall survival and 5-year survival were 11 months (6.8%) and 23 months (5.8%), respectively (P = 0.2168). Negative surgical margin and patient sex were variables retained for the prognosis of radiation-induced and radiation-associated MPNSTs., Conclusions: The prognosis of radiation-induced and radiation-associated MPNST was worse than that reported for de novo MPNSTs. Surgical complete resection is the mainstay for treatment of radiation-induced and radiation-associated MPNSTs. The risk of incidence of secondary MPNSTs in patients treated with radiotherapy warrants longer follow-up periods., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Radiation-induced benign peripheral nerve sheath tumors are uncommon late complications of irradiation. We conducted the largest systematic review of individual patient data., Methods: We performed a systematic search of PubMed databases and compiled a comprehensive literature review. Kaplan-Meier analysis was used to investigate survival, and statistical significance was assessed with a log-rank test., Results: We analyzed 40 cases of radiation-induced benign peripheral nerve sheath tumors. The histologic distributions were 28 schwannomas, 11 neurofibromas, and 1 ganglioneuroma. The average age of radiation exposure for development of primary lesions was 14.9 ± 15.5 years, and the latency period between radiotherapy to the onset of secondary tumors was 24.5 ± 12.7 years. The average irradiation dose delivered was 26.3 ± 20.3 Gy. The median overall survival for all cases was not reached (95% confidence interval, 22-not reached) months, with 10-year survival rates of 65.2%. Surgical negative margin was a positive prognostic factor for radiation-induced benign peripheral nerve sheath tumors., Conclusions: The risk of incidence of secondary benign peripheral nerve sheath tumors in patients treated with radiotherapy should be considered in long-term follow-up periods. At present, complete surgical resection is the main stay for the treatment of radiation-induced benign peripheral nerve sheath tumors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Non-vestibular cranial nerve schwannomas (NVCNS) are rare lesions, representing <10 % of cranial nerve schwannomas. The optimal treatment for NVCNS is often derived from vestibular schwannomas experience. Surgical resection has been referred to as the first line treatment for those benign tumors, but significant complication rates are reported. Stereotactic radiosurgery (SRS) has arisen as a mainstay of treatment for many benign tumors, including schwanommas. We retrospectively reviewed the outcomes of NVCNS treated by SRS to characterize tumor control, symptom relief, toxicity, and the role of hypo-fractionation of SRS dose. Eighty-eight (88) patients, with ninety-five (95) NVCNS were treated with either single or multi-session SRS from 2001 to 2014. Local control was achieved in 94 % of patients treated (median follow-up of 33 months, range 1-155). Complications were seen in 7.4 % of cases treated with SRS. At 1-year, 57 % of patients had improvement or resolution of their symptoms, while 35 % were stable and 8 % had worsening or increased symptoms. While 42 % received only one session, results on local control were similar for one or multiple sessions (p = 0.424). SRS for NVCNS is a treatment modality that provides excellent local control with minimal complication risk compared to traditional neurosurgical techniques. Tumor control obtained with a multi-session treatment was not significantly different from single session treatment. Safety profile was also comparable for uni or multi-session treatments. We concluded that, as seen in VS treated with CK SRS, radiosurgery treatment can be safely delivered in cases of NVCNS.

Communicating hydrocephalus (HCP) in vestibular schwannomas (VS) after gamma knife radiosurgery (GKRS) has been reported in the literature. However, little information about its incidence and risk factors after GKRS for intracranial schwannomas is yet available. The objective of this study was to identify the incidence and risk factors for developing communicating HCP after GKRS for intracranial schwannomas. We retrospectively reviewed a total of 702 patients with intracranial schwannomas who were treated with GKRS between January 2002 and December 2015. We investigated patients' age, gender, tumor origin, previous surgery history, tumor volume, marginal radiation dose, and presence of tumor control to identify associations with communicating HCP following GKRS. To make predictive models of communicating HCP, we performed Cox regression analyses and constructed a decision tree for risk factors. In total, 29 of the 702 patients (4.1%) developed communicating HCP following GKRS, which required ventriculo-peritoneal (VP) shunt surgery. Multivariate analyses indicated that age (P = 0.0011), tumor origin (P = 0.0438), and tumor volume (P < 0.0001) were significant predictors of communicating HCP in patients with intracranial schwannoma after GKRS. Using machine-learning methods, we fit an optimal predictive model. We found that developing communicating HCP following GKRS was most likely if the tumor was vestibular origin and had a volume ≥13.65 cm 3 . Communicating HCP is not a rare complication of GKRS for intracranial schwannomas. Under specific conditions, communicating HCP following GKRS is warranted for this patient group, and this patient group should be closely followed up., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with few treatment options. Tumor immune state has not been characterized in MPNST, and is important in determining response to immune checkpoint blockade. Our aim was to evaluate the expression of programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and presence of CD8+ tumor infiltrating lymphocytes (TILs) in MPNST, and correlate these findings with clinical behavior and outcome., Results: PD-L1 staining of at least 1% was seen in 0/20 nerves, 2/68 benign lesions and 9/53 MPNST. Two of 68 benign lesions and 7/53 (13%) MPNST had at least 5% PD-L1 staining. CD8 staining of at least 5% was seen in 1/20 (5%) nerves, 45/68 (66%) benign lesions and 30/53 (57%) MPNST. PD-L1 was statistically more prevalent in MPNST than both nerves and benign lesions (p=0.049 and p=0.008, respectively). Expression of PD-1 was absent in all tissue specimens. There was no correlation of PD-L1 or CD8 expression with disease state (primary versus metastatic) or patient survival., Methods: A comprehensive PNST tissue microarray was created from 141 surgical specimens including primary, recurrent, and metastatic MPNST (n=53), neurofibromas (n=57), schwannoma (n=11), and normal nerve (n=20). Cores were stained in triplicate for PD-L1, PD-1, and CD8, and expression compared between tumor types. These data were then examined for survival correlates in 35 patients with primary MPNST., Conclusions: MPNST is characterized by low PD-L1 and absent PD-1 expression with significant CD8+ TIL presence. MPNST immune microenvironment does not correlate with patient outcome.

An accurate histopathologic diagnosis is essential for an adequate treatment of soft tissue sarcomas. The diagnosis of malignant peripheral nerve sheath tumor (MPNST) can be complex, particularly outside the neurofibromatosis type 1 (NF1) context. MPNST is a rare malignancy, and due to the lack of specific histologic criteria, several differential diagnoses must be considered. A total of 350 patients diagnosed with MPNST (from 1990 to 2013) were retrieved from the French sarcoma network (RRePS) and the Conticabase (Connective Tissue Cancer Network database). Tumor samples were available for 160 cases (45.2%). Pathology review, immunohistochemistry (IHC), and molecular analysis (when dealing with a monomorphic sarcoma) were systematically performed. Patient, tumor, and treatment characteristics were evaluated to identify prognostic factors for the definitive primary MPNST (n=106) cohort. Twenty-nine tumors (18.1%) initially diagnosed as MPNST were reclassified on the basis of histologic review, IHC, and molecular analysis. Patients with NF1 disease comprised 64% of the remaining cohort. The 5-year overall survival for patients from the entire cohort was 47%, 34.8% for NF1 patients, and 68.5% for patients without NF1 disease, making NF1 syndrome an independent poor prognostic factor of survival. Positive margins and lack of radiation therapy were independent predictors of local recurrence. The Fédération Nationale des Centres de Lutte Contre le Cancer tumor grade was an independent prognostic indicator of metastasis. Given the therapeutic implications of a misdiagnosis, the systematic pathology review, IHC, and molecular analysis (when dealing with monomorphic sarcoma) strategy allowed reclassification of 20% of cases, mainly the sporadic MPNSTs.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that can show overlapping features with benign neurofibromas as well as high-grade sarcomas. Additional diagnostic markers are needed to aid in this often challenging differential diagnosis. Recently mutations in two critical components of the polycomb repressor 2 (PRC2) complex, SUZ12 and EED, were reported to occur specifically in MPNSTs while such mutations are absent in neurofibromas, both in the setting of neurofibromatosis (NF) and sporadic cases. Furthermore, both SUZ12 and EED mutations in MPNSTs were associated with loss of H3K27 tri-methylation, a downstream target of PRC2. Therefore, we tested whether H3K27me3 immunohistochemistry is useful as a diagnostic and prognostic marker for MPNSTs. We performed H3K27me3 immunohistochemistry in 162 primary MPNSTs, 97 neurofibromas and 341 other tumors using tissue microarray. We observed loss of H3K27me3 in 34% (55/162) of all MPNSTs while expression was retained in all neurofibromas including atypical (n=8) and plexiform subtypes (n=24). Within other tumors we detected loss of H3K27me3 in only 7% (24/341). Surprisingly, 60% (9/15) of synovial sarcomas and 38% (3/8) of fibrosarcomatous dermatofibrosarcoma protuberans (DFSP) showed loss of H3K27 trimethylation. Only 1 out of 44 schwannomas showed loss of H3K27me3 and all 4 perineuriomas showed intact H3K27me3. Furthermore, MPNSTs with loss of H3K27 tri-methylation showed inferior survival compared with MPNSTs with intact H3K27 tri-methylation, which was validated in two independent cohorts. Our results indicate that H3K27me3 immunohistochemistry is useful as a diagnostic marker, in which loss of H3K27me3 favors MPNST above neurofibroma. However, H3K27me3 immunohistochemistry is not suitable to distinguish MPNST from its morphological mimicker synovial sarcoma or fibrosarcomatous DFSP. Since loss of H3K27 tri-methylation was related to poorer survival in MPNST, chromatin modification mediated by this specific histone seems to orchestrate more aggressive tumour biology.

Background: Because the efficacy and safety of pazopanib in Japanese patients with soft tissue sarcoma (STS) had not been evaluated previously in a large-scale cohort, the authors investigated the efficacy and safety of pazopanib in 156 Japanese patients with relapsed STS. This was a retrospective study based on the collection of real-life, postmarketing surveillance data., Methods: Patients received pazopanib with the objective of treating local recurrence (n = 20), metastasis (n = 104), and both (n = 32). The patient median age was 53.8 years. The primary objective of this study was to clarify the efficacy of pazopanib for patients with STS., Results: The median treatment duration was 28.7 weeks, and the average dose intensity of pazopanib was 609 mg. Adverse events occurred in 127 patients (81.4%). In addition to the main common toxicities, such as hypertension and liver disorder, pneumothorax (n = 11) and thrombocytopenia (n = 16) also were observed. The median progression-free survival for all patients was 15.4 weeks. The median progression-free survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 18.6 weeks, 16.4 weeks, 15.3 weeks, and 8 weeks, respectively. The median survival for all patients was 11.2 months. The median survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 20.1 months, 10.6 months, 9.5 months, and 7.3 months, respectively., Conclusions: There were apparent differences in the efficacy of pazopanib treatment among histologic types of STS. Pazopanib treatment is a new treatment option; however, adverse events like pneumothorax and thrombocytopenia, which did not occur frequently in the PALETTE study (pazopanib for metastatic soft-tissue sarcoma), should be taken into consideration. Cancer 2016;122:1408-16. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society., (© 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Background: Malignant peripheral nerve sheath tumors (MPNST) are rare, highly malignant, and poorly understood sarcomas. The often poor outcome of MPNST highlights the necessity of identifying prognostic predictors for this aggressive sarcoma. Here, we investigate the role of fibroblast growth factor receptor (FGFR) family members in human MPNSTs., Results: aCGH and bioinformatics analysis identified frequent amplification of the FGFR1 gene. FISH analysis revealed that 26.9% MPNST samples had amplification of FGFR1, with both focal and polysomy patterns observed. IHC identified that FGFR1 protein expression was positively correlated with FGFR1 gene amplification. High expression of FGFR1 protein was associated with better overall survival (OS) and was an independent prognostic predictor for OS of MPNST patients. Additionally, combined expression of FGFR1 and FGFR2 protein characterized a subtype of MPNST with better OS. FGFR4 protein was expressed 82.3% of MPNST samples, and was associated with poor disease-free survival., Materials and Methods: We performed microarray-based comparative genomic hybridization (aCGH) profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Medical University Cancer Institute and Hospital. Fluorescence in situ hybridization (FISH) was used to validate the gene amplification detected by aCGH analysis. Another cohort of 63 formalin-fixed paraffin-embedded MPNST samples (including 52 samples for FISH assay) was obtained to explore FGFR1, 2, 3, and 4 protein expression by immunohistochemical (IHC) analysis., Conclusions: Our integrated genomic and molecular studies provide evidence that FGFRs play different prognostic roles in MPNST., Competing Interests: The authors have no potential conflicts of interest to declare.

Background: Malignant peripheral nerve sheath tumors (MPNST) are a rare subtype of soft tissue sarcoma. They can arise in irradiated fields, in patients with type 1 neurofibromatosis (NF1), or sporadically. MPNST exhibit an aggressive behaviour, and their optimal management remains controversial. An unsolved issue is whether NF1-related and sporadic forms of MPNST have a different prognosis, and should be managed differently., Material and Methods: Adult and paediatric patients with histologically confirmed MPNST treated between 1990 and 2013 in French cancer centres of the GSF/GETO network, were included in this retrospective study., Results: A total of 353 patients (37% with NF1 and 59% with sporadic tumours) were analysed. Median age at diagnosis was 42 years (range 1-94). The majority of tumours developed in the limbs, were deep-seated and of high grade. Two hundreds and ninety four patients underwent a curative intent surgery. Among them, 60 patients (21%) had neoadjuvant treatment (mainly chemotherapy), and 173 (59%) had adjuvant treatment (mainly radiotherapy). For operated patients, median progression free and overall survival (OS) were 26.3 months and 95.8 months, respectively. In multivariate analysis, poor-prognosis factors for OS were high grade, deep location, locally advanced stage at diagnosis, and macroscopically incomplete resection (R2). NF1 status was not negatively prognostic, except in the recurrence or metastatic setting, where NF1-related MPNST patients treated with palliative chemotherapy showed worse survival than patients with sporadic forms., Conclusion: To our knowledge, our series is the largest study of patients with MPNST reported to date. For operated patients, we showed a worse prognosis for NF1-related MPNST, due to different clinical features at diagnosis, more than NF1 status itself. The French sarcoma group is now conducting correlative analyses on these patients, using the latest molecular tools., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To investigate the outcomes of jugular foramen schwannomas (JFSs) and to evaluate the risk factors for tumor recurrence and poor final outcomes., Methods: Between 1993 and 2013, 133 patients (68 female patients) with JFSs were surgically treated. Clinical charts were reviewed, and scheduled follow-up examinations were performed., Results: The average preoperative Karnofsky Performance Scale (KPS) score was 79.6. The JFSs were classified as follows: 65 cases, type A; 15 cases, type B; 5 cases, type C; and 48 cases, type D. Gross total resection was achieved in 107 (80.5%) patients. Transient and permanent morbidities affecting cranial nerves IX and X were 19.8% and 11.5%, respectively. After a mean follow-up duration of 108.0 months, 13 (9.9%) patients experienced recurrence. The most recent KPS scores averaged 83.7. Compared with the preoperative KPS score, the most recent KPS score was improved in 87 (65.4%) patients and stabilized in 29 (21.8%) patients. The presence of a solid tumor (hazard ratio [HR] = 5.815, P = 0.010), nontotal resection (HR = 4.613, P = 0.007), and pathologic mitoses (HR = 11.018, P < 0.001) were independent risk factors for tumor recurrence. Decreased preoperative KPS score (per 10 points) (odds ratio [OR] = 2.483, P = 0.027), a less soft tumor consistency (OR = 2.257, P = 0.039), and a solid tumor (OR = 3.755, P = 0.041) were risk factors for poor long-term outcomes., Conclusions: Quality of life and preservation of neurologic function are the goals of surgical treatment of JFSs. Favorable long-term surgical outcomes for JFSs can be achieved. Morbidity of cranial nerves IX and X is significant, and patients with nontotal resection or pathologic mitosis should be followed closely., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Malignant peripheral nerve sheath tumors (MPNSTs) are a group of tumors that arise from peripheral nerves or from the various elements of the nerve sheath, including Schwann cells and perineural fibroblasts. Head and neck MPNSTs (HN-MPNSTs) are rare, accounting for 8% to 16% of all soft tissue sarcomas. This study analyzes the demographic, clinicopathologic, and survival characteristics of HN-MPNSTs and establishes comparisons with MPNSTs at other body sites (other-MPNSTs)., Study Design: Analysis of population-based tumor registry., Setting: Academic medical center., Subjects and Methods: The SEER database (Surveillance, Epidemiology, and End Results; 1973-2012) was queried for HN-MPNSTs (324 cases) and other-MPNSTs (1680 cases). Data were analyzed comparatively with respect to various demographic and clinicopathologic factors. Disease-specific survival was analyzed with the Kaplan-Meier model., Results: Mean age at diagnosis for HN-MPNST was 49.1 years, compared with 46.1 years for other-MPNSTs (P = .0169). There was a sex predilection for males in HN-MPNSTs (60.2%) versus a female predilection for other-MPNSTs (54.2%; P < .0001). Average tumor size for HN-MPNSTs was 4.9 cm, compared with 8.7 cm for other-MPNSTs (P < .0001). HN-MPNSTs were more commonly of low histologic grade types, whereas other-MPNSTs were mostly of high histologic grade (P = .0073). HN-MPNSTs had a higher 5-year disease-specific survival than other-MPNSTs (65.1% vs 57.4%; P = .0209)., Conclusions: HN-MPNSTs are rare entities. This study represents the largest series of HN-MPNSTs to date. Although HN-MPNSTs and other-MPNSTs share a common histology, there are important clinical differences between the 2 groups., (© American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.)

Objectives: To determine the epidemiology and prognostic indicators in patients with malignant peripheral nerve sheath tumors (MPNST) of the head and neck., Materials and Methods: The surveillance, epidemiology, and end results registry was reviewed for patients with head and neck MPNST from 1973 to 2011. Study variables included age, sex, race, tumor size, stage at presentation, and treatment modality., Results: There were 374 cases of head and neck MPNST identified. Mean age at diagnosis was 50.7 y ears; 60.2% of patients were male and 82.6% were white. After diagnosis, 38.8% of patients underwent surgery and radiation therapy and 48.1% underwent surgery alone. Kaplan-Meier analysis demonstrated overall (OS) and disease-specific survival (DSS) of 51% and 67% at 5 years. Multivariate Cox regression analysis showed that age (p=0.030), stage (p=0.002), surgery (p=0.037), and size (p<0.001) were predictors of OS, while stage (p<0.001) and size (p<0.001) were predictors of DSS. For stage I/II cancers, surgery (p=0.011) and size (p=0.010) were predictors of OS, and size (p=0.001) predicted DSS. For stage III/IV cancers, both radiotherapy (p=0.024, p=0.009) and size (p=0.001, p=0.001) predicted OS and DSS. For tumors ⩽5 cm, stage (p=0.031) predicted DSS. For tumors >5 cm, male gender (p=0.005), stage (p=0.001), surgery (p=0.003), and radiotherapy (p=0.050) were determinants of OS, and male gender (p=0.022), stage (p<0.001), and radiotherapy (p=0.002) were determinants of DSS., Conclusion: Surgical resection confers survival benefit in patients with early stage MPNST, while radiotherapy improves survival in cases with metastatic disease. Surgery and radiotherapy are prognostically important in patients with tumors >5 cm., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Diffuse-type neurofibroma, an uncommon variant of neurofibroma, is associated with neurofibromatosis type 1 in ∼60% of cases. Typically presenting in young adults as ill-defined plaque-like dermal/subcutaneous thickening, most cases are located on the trunk or the head and neck region. Malignant transformation is extremely rare. Nine cases of malignant peripheral nerve sheath tumor (MPNST) arising in diffuse-type neurofibroma (identified in consult files) are described, including clinicopathologic features and follow-up. Five patients were male and 4 female, aged 31 to 59 years (median 49 y). All diffuse-type neurofibromas contained Meissner corpuscles, with tumor sizes ranging between 3.6 and 45 cm (median, 7.4 cm). Five patients had a clinical history of neurofibromatosis type 1, and 1 had Klippel-Trénaunay-Weber syndrome. Six tumors arose on the trunk and 1 each on the leg, arm, and scalp. Increased cellularity, nuclear atypia, and mitoses (range, 1 to 63/50 high-power fields) indicated transition to MPNST, classified as low grade in 5, intermediate to high grade in 1, and high grade in 3 cases, 1 of which exhibited heterologous angiosarcomatous differentiation. S-100 expression was quite strong and diffuse in the neurofibroma components and less extensive or weaker in MPNST. Follow-up, available for all patients (median, 80.5 mo, except 1 recent case), revealed that 1 patient developed local recurrence after 9 months; 1 with metastases at the time of initial diagnosis died 1 month after tumor resection. All other patients were alive without evidence of disease at 15 to 145 months (median, 83 mo). Diffuse-type neurofibroma may show transformation to MPNST in very rare instances. It is important to be aware of possible malignant change, requiring thorough sampling of resection specimens and long-term clinical follow-up of patients with unexcised lesions.

No consensus treatment regime exists beyond surgery for malignant peripheral nerve sheath tumours (MPNST), and the purpose of the present study was to find new approaches to stratify patients with good and poor prognosis and to better guide therapeutic intervention for this aggressive soft tissue cancer. From a total of 67 MPNSTs from Scandinavian patients with and without neurofibromatosis type 1, 30 MPNSTs were investigated by genome-wide RNA expression profiling and 63 MPNSTs by immunohistochemical (IHC) analysis, and selected genes were submitted to analyses of disease-specific survival. The potential drug target genes survivin (BIRC5), thymidine kinase 1 (TK1), and topoisomerase 2-alpha (TOP2A), all encoded on chromosome arm 17q, were up-regulated in MPNST as compared to benign neurofibromas. Each of them was found to be independent prognostic markers on the gene expression level, as well as on the protein level. A prognostic profile was identified by combining the nuclear expression scores of the three proteins. For patients with completely resected tumours only 15% in the high risk group were alive after two years, as compared to 78% in the low risk group. In conclusion, we found a novel protein expression profile which identifies MPNST patients with inferior prognosis even after assumed curative surgery. The tested proteins are drug targets; therefore the expression profile may provide predictive information guiding the design of future clinical trials. Importantly, as the effect is seen on the protein level using IHC, the biomarker panel can be readily implemented in routine clinical testing., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: To report our early experience with carbon ion irradiation in the treatment of gross residual or unresectable malignant peripheral nerve sheath tumors (MPNST)., Methods: We retrospectively analysed 11 patients (pts) with MPNST, who have been treated with carbon ion irradiation (C12) at our institution between 2010 and 2013. All pts had measurable gross disease at the initiation of radiation treatment. Median age was 47 years (29-79). Tumors were mainly located in the pelvic/sacral (5 pts) and sinunasal/orbital region (5 pts). 5 pts presented already in recurrent situation, 3 pts had been previously irradiated, and in 3 pts MPNST were neurofibromatosis type 1 (NF1) associated. Median cumulative dose was 60 GyE. Treatment was carried out either as a combination of IMRT plus C12 boost (4 pts) or C12 only (7 pts)., Results: Median follow-up was 17 months (3-31 months). We observed 3 local progressions, translating into estimated 1- and 2-year local control rates of 65%. One patient developed distant failure, resulting in estimated 1- and 2-year PFS rates of 56%. Two patients have died, therefore the estimated 1- and 2-year OS rates are 75%. Acute radiation related toxicities were generally mild, no grade 3 side effects were observed. Severe late toxicity (grade 3) was scored in 2 patients (trismus, wound healing delays)., Conclusion: Carbon ion irradiation yields very promising short term local control and overall survival rates with low morbidity in patients suffering from gross residual or unresectable malignant peripheral nerve sheath tumors and should be further investigated in a prospective trial.

Cellular schwannoma is an uncommon, but well-recognized, benign peripheral nerve sheath tumor, which can be misdiagnosed as malignant peripheral nerve sheath tumor. To develop consensus diagnostic criteria for cellular schwannoma, we reviewed 115 malignant peripheral nerve sheath tumor and 26 cellular schwannoma cases from two institutions. Clinical data were retrieved from the electronic medical records, and morphologic features, maximal mitotic counts, Ki67 labeling indices, and immunohistochemical profiles (SOX10, SOX2, p75NTR, p16, p53, EGFR, and neurofibromin) were assessed. Several features distinguish cellular schwannoma from malignant peripheral nerve sheath tumor. First, in contrast to patients with malignant peripheral nerve sheath tumor, no metastases or disease-specific deaths were found in patients with cellular schwannoma. More specifically, 5-year progression-free survival rates were 100 and 18%, and 5-year disease-specific survival rates were 100 and 32% for cellular schwannoma and malignant peripheral nerve sheath tumor, respectively. Second, the presence of Schwannian whorls, a peritumoral capsule, subcapsular lymphocytes, macrophage-rich infiltrates, and the absence of fascicles favored the diagnosis of cellular schwannoma, while the presence of perivascular hypercellularity, tumor herniation into vascular lumens, and necrosis favor malignant peripheral nerve sheath tumor. Third, complete loss of SOX10, neurofibromin or p16 expression, or the presence of EGFR immunoreactivity was specific for malignant peripheral nerve sheath tumor (P<0.001 for each). Expression of p75NTR was observed in 80% of malignant peripheral nerve sheath tumors compared with 31% of cellular schwannomas (P<0.001). Fourth, Ki-67 labeling indices ≥20% were highly predictive of malignant peripheral nerve sheath tumor (87% sensitivity and 96% specificity). Taken together, the combinations of these histopathological and immunohistochemical features provide useful criteria to distinguish between malignant peripheral nerve sheath tumor and cellular schwannoma with high sensitivity and specificity. Additional retrospective and prospective multicenter studies with larger data sets will be required to validate these findings.

Objective: This review examined the diagnostic approach, surgical treatment, and outcomes of cervical sympathetic chain schwannomas (CSCS) to guide clinical decision making., Data Sources: Medline, EMBASE, and Cochrane databases., Review Methods: A literature review from 1998 to 2013 identified 156 articles of which 51 representing 89 CSCS cases were evaluated in detail. Demographic, clinical, and outcomes data were extracted by 2 independent reviewers with high interrater reliability (κ = .79). Cases were mostly international (82%), predominantly from Asia (50%) and Europe (27%)., Conclusions: On average, patients were 42.6 years old (SD = 13.3) and had a neck mass ranging between 2 to 4 cm (52.7%) or >4 cm (43.2%). Nearly 70% of cases were asymptomatic at presentation. Presurgical diagnosis relied on CT (63.4%), MRI (59.8%), or both (19.5%), supplemented by cytology (33.7%), which was nearly always inconclusive (96.7%). US-treated cases were significantly more likely to receive presurgical MRI than internationally treated cases but less likely to have cytology (P < .05). Presurgical diagnosis was challenging, with only 11% confirmatory accuracy postsurgically. Irrespective of mass size, extracapsular resection (ie, complete resection with nerve sacrifice) was the most frequently (87.6%) performed surgical procedure. Common postsurgical adverse events included Horner's syndrome (91.1%), first bite syndrome (21.1%), or both (15.7%), with higher prevalence when mass size was >4 cm. Adverse events persisted in 82.3% of cases at an average 30.0 months (SD = 30.1) follow-up time., Implications for Practice: Given the typical CSCS patient is young and asymptomatic and the likelihood of persistent morbidity is high with standard surgical approaches, less invasive treatment options warrant consideration., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.)

Background and Objectives: While convention defines atypical neurofibroma as benign and low-grade malignant peripheral nerve sheath tumors (MPNSTs) as malignant, sparse outcomes data exist for these tumors. This study reviews clinical outcomes of surgically resected low-grade MPNST and atypical neurofibroma, focusing on the effect of surgical margins on outcome., Methods: This study is a retrospective review of 23 patients who underwent surgical resection of a low-grade MPNST or atypical neurofibroma. Treatment characteristics of adjuvant therapy and surgical margin were noted. Endpoints of local recurrence, presence of metastatic disease, disease-specific survival, and overall survival were reviewed., Results: Eighteen of 23 patients (78%) had microscopically positive margins on the resection. Disease-specific survival was 100% for both atypical neurofibroma patients and those with low-grade MPNST, regardless of surgical margin. Local recurrence in terms of recurrence of measureable disease occurred in 2/12 (16.7%) of LGMPNST patients and 1/11 (9.1%) of atypical NF patients, all of whom had microscopically positive surgical margins., Conclusions: In a study dedicated exclusively to "intermediate" nerve sheath tumors, no patients developed metastatic disease nor died of disease despite a high rate of microscopically positive surgical margins (78%). While positive margins did lead to increased rates of local recurrence, these data suggest that surgeons potentially can temper their zeal for negative surgical margins in the setting of low-grade MPNST and atypical neurofibroma, as surgical morbidity may be more important than a presumed survival benefit of wide resection., (© 2014 Wiley Periodicals, Inc.)

Background: Neuroblastoma in the adult is rare. No established therapeutic guidelines exist for these patients and the literature on this issue is scant and contradictory., Materials and Methods: Between 1986 and 2011, 21 adults (18 to 38 y; median, 23) diagnosed with neuroblastoma were referred to our hospital. Three of the 21 were classified as neuroblastoma, not otherwise specified, 13 as neuroblastoma, schwannian stroma-poor, and 5 as ganglioneuroblastoma, nodular. Nine patients had a resectable (stage 1/2) and 6 an unresectable primary tumor (stage 3); 6 had disseminated disease (stage 4)., Results: Of 9 stage 1/2 patients, 6 underwent surgery alone (2 survive, 4 died), 2 received adjuvant chemotherapy (both survive), and 1 received radiation therapy (alive). Four of the 6 stage 3 patients received chemotherapy and died, 1 underwent partial tumor resection only and died, and 1 received radiation therapy after partial tumor resection and is alive. The 6 stage 4 patients received chemotherapy with/without radiotherapy, and all died. Event-free survival at 10 years was 33.3% for stage 1/2, 16.7% for stage 3, and 0% for stage 4 patients. The 10-year overall and event-free survival rates were 39.8% and 19.1%, respectively., Conclusions: The outcome of neuroblastoma in adults is poorer than in younger patients at all stages. The clinical course seems modestly influenced by therapy.

Melanotic schwannomas (MSs), variably associated with the Carney complex, are rare tumors that usually involve spinal nerve roots but may occur in other locations. Clinicopathologic evaluation poorly predicts the behavior of MS. Fewer than 200 cases have been reported. We report a series of 40 well-characterized MSs, one of the largest series to date. The tumors were comprehensively evaluated, and clinical follow-up was obtained. Immunohistochemistry for S100 protein, Melan-A, HMB45, tyrosinase, glial fibrillary acidic protein (GFAP), EMA, SMARCB1, Ki-67 antigen, ASMTL, and the Carney complex-associated PRKAR1A gene product was performed using commercially available antibodies and the Ventana Ultraview detection system. Gene microarray study was conducted on formalin-fixed, paraffin-embedded blocks from 10 MSs and the results compared with previous data from melanoma and schwannoma. Differentially expressed genes were selected at >3-fold and P<0.001. The Fisher exact test was used for statistical analysis. The tumors occurred in 18 male and 22 female patients (mean age 41 y; range, 11 to 84 y) and involved the paravertebral nerve roots (N=31), mediastinum (N=3), sacrum, cauda equina, para-aortic region, fifth cranial nerve, buttock, and cerebellum (N=1 each). Two patients had known Carney complex, and 1 patient also had a cutaneous myxoma, suggestive of Carney complex. The tumors expressed S100 protein (21/25, 84%), Melan-A (23/25, 92%), HMB45 (25/25, 100%), tyrosinase (25/25, 100%), GFAP (0/24, 0%), EMA (0/9, 0%), SMARCB1 (retained in 25/25, 100%), and ASMTL (5/19, 26%); PRKAR1A expression was lost in 7/20 cases (35%). Ki-67-labeling index was <5% in 23/25 cases (92%) and 5% to 10% in 2/25 cases (8%). Gene expression profiling showed significant differences between MS, melanoma, and conventional schwannoma. Clinical follow-up (26/40, 65%; mean 55 mo; range, 1 to 300 mo) showed local recurrences in 9/26 (35%) and metastases in 11/26 (44%) patients. Fourteen patients were alive without disease, 5 were alive with disease, and 7 had died of disease. Only a mitotic rate >2/10 HPF correlated with metastases (P=0.008). The clinicopathologic features of tumors with and without psammoma bodies were identical. We conclude that MSs are distinctive malignant tumors, rather than benign neoplasms with occasionally unpredictable behavior, and propose their reclassification as "malignant melanotic schwannian tumors." Loss of PRKAR1A expression suggests a link to Carney complex, even when this history is absent.

Background: Primary spinal cord tumors (PSCTs) in pediatric patients are rare, with a reported overall incidence rate of 1-2.6 per one million children. We reviewed our experience of surgically treated 27 pediatric patients with PSCT and discussed the clinical features, radiological findings, surgical outcomes, and prognostic factors., Methods: Between March 1999 and March 2010, a total of 27 pediatric patients with PSCT were surgically treated in a single institution. We retrospectively analyzed their data., Results: There were 13 females and 14 males, and their ages ranged from 6 months to 19 years (mean age, 12.1 years). The most common presenting symptom was motor weakness, and the histologic type of the tumors were mainly schwannoma, astrocytoma, and ependymoma. The tumor was completely resected in 17 patients, subtotally resected in 7 patients, and partial resection or biopsy was performed in 3 patients. Adjuvant chemotherapy was performed in 9 patients, and radiotherapy in 12 patients, respectively. The average follow-up period was 33.5 months (1.17-129). Five patients experienced the progression of disease, and three of them expired. The mean time for disease progression was 19.0 months (4.5-48.7)., Conclusions: PSCT in pediatric patients can be surgically removed with an acceptable low surgical morbidity. Progression-free survival was found to be related to the grade of tumor and the extent of tumor resection. Early diagnosis and treatment anticipate good functional neurologic outcome.

Purpose: To report early clinical outcomes of helical tomotherapy (HT)-based image-guided intensity-modulated radiation therapy (IMRT) in brain tumors of varying shape, size, and location., Materials and Methods: Patients with residual, recurrent, and/or progressive low-grade intracranial and skull-base tumors were treated on a prospective protocol of HT-based IMRT and followed clinicoradiologically. Standardized metrics were used for plan evaluation and outcome analysis., Results: Twenty-seven patients with 30 lesions were treated to a median radiotherapy dose of 54 Gy in 30 fractions. All HT plans resulted in excellent target volume coverage with steep dose-gradients. The mean (standard deviation) dose homogeneity index and conformity index was 0.07 (0.05) and 0.71 (0.08) respectively. At first response assessment, 20 of 30 lesions were stable, whereas 9 showed partial regression. One patient with a recurrent clival chordoma though neurologically stable showed imaging-defined progression, whereas another patient with stable disease on serial imaging had sustained neurologic worsening. With a median follow-up of 19 months (interquartile range, 11-26 months), the 2-year clinicoradiological progression-free survival and overall survival was 93.3% and 100% respectively., Conclusions: Careful selection of radiotherapy technique is warranted for benign/low-grade brain tumors to achieve durable local control with minimum long-term morbidity. Large or complex-shaped tumors benefit most from IMRT. Our early clinical experience of HT-based IMRT for brain tumors has been encouraging., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Schwannoma is a type of benign nerve sheath tumour arising from the Schwann cell. Because of the close relationship between the tumour and the nerve of origin (NOO), the operation of extracranial head and neck schwannoma may lead to palsy of major nerve. For this reason, an accurate diagnosis of schwannoma with the identification of the NOO is crucial to the management. The aim of this review was to find out the distribution of the NOO and the usefulness of the investigations in the diagnosis of schwannoma. Medical records of the patients who underwent operation of the extracranial head and neck schwannoma in our division were reviewed. Between January 2000 and December 2009, 30 cases of extracranial head and neck schwannoma were operated. Sympathetic trunk (10, 33%) and vagus nerve (6, 20%) were the two most common NOOs. In five (17%) cases, the NOO was not found to be arising from any major nerve. For these 30 patients, 20 received fine needle aspiration cytology (FNAC) and 26 underwent imaging studies (computed tomography or magnetic resonance imaging) before operation. The specificity of FNAC and imaging studies in making the diagnosis of schwannoma was 20 and 38%, respectively. For the patients who had nerve palsies on presentation, their deficits remained after operation. The rate of nerve palsy after tumour excision with division of NOO and intracapsular enucleation was 100 and 67%, respectively. The diagnosis of schwannoma is suggested by clinical features and supported by investigations. Most of the time, the diagnosis can only be confirmed on the histological study of the surgical specimen. Sympathetic trunk and vagus nerve are the two common NOOs. MRI is the investigation of choice in the diagnosis of schwannoma and the identification of NOO.

Objective: To investigate the demographic, clinical, radiological, pathological and surgical features and outcomes of infantile intracranial neoplasms, the second most common neoplasm in infants., Patients and Methods: We conducted a retrospective study in the Department of Pediatric Neurosurgery at the Abo El-Reish Children's Hospital from 2005 to 2008., Results: Out of 451 patients with primary intracranial neoplasms (age 0-14 years), 21 infants (<1 year) underwent surgery, representing 4.7% of total cases. The most common tumor was choroid plexus papilloma (23.8%), followed by teratoma (19%) then astrocytoma and ependymoma (14.3% each). Of the 21 surgical cases, 90% were intra-axial, 80% were in the supratentorial region, and 57% were intraventricular. There was only 1 case of intraoperative mortality (4.8%). Gross total excision was achieved in 65%, debulking in 30%, and biopsy in 5%. Three patients received chemotherapy, but none received radiotherapy. The statistically significant predictors of prognosis were the extent of resection and tumor grade., Conclusion: Although the prognosis for infantile intracranial neoplasms is worse than for older children, an overall promising outcome with low operative morbidity and mortality was achieved using gross total excision and appropriate adjuvant chemotherapy as part of a multidisciplinary approach., (Copyright © 2010 S. Karger AG, Basel.)

Purpose: Stereotactic radiotherapy using the CyberKnife has become a key treatment in the multidisciplinary management of secondary tumours, as well as primary benign or malignant tumours located within or adjacent to vertebral bodies and the spinal cord. The aim of this treatment is to improve local control and clinical response, including previously irradiated cases., Patients and Methods: In this study, we present the first patients treated with CyberKnife between December 2006 and December 2007 for spinal or paraspinal tumours. The primary aim was to assess the feasibility and tolerance of stereotactic radiotherapy using the CyberKnife. Secondary aims were to establish the short-term local control, to calculate the local progression-free survival and overall survival. Clinical examination and imaging procedures were performed every three months. Response was assessed according to RECIST criteria., Results: During that period, 16 patients were treated with CyberKnife. Thirteen patients had been pre-treated, three of whom had received spinal cord doses considered to be maximal. Three patients did not receive previous irradiation. The median age was 59 (36-74). The most frequent symptoms were pain (n = 8) and motor weakness (n = 4). The median dose was 30 Gy (16-50). The median number of fractions was 3 (1-5). No patient developed acute myelitis. Three patients developed acute reaction. Overall survival at 18 months was 72.4%, with a mean survival of 18.2 months (95% CI: 15.4-20.9). Local progression-free survival at 18 months was 58.4%, with a mean value of 16.9 months (95% CI: 13.6-20.2)., Conclusion: The use of stereotactic radiotherapy with CyberKnife represents a major progress in the management of paraspinal tumours. The main advantages are better sparing of the spinal cord and the possibility of increasing the dose to the tumour target volume., (2009 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Object: To evaluate outcome predictors after stereotactic radiosurgery (SRS) in patients with trigeminal schwannomas, the authors compared tumor control, functional preservation, and complications with tumor grade, tumor volume, patient age, and tumor imaging characteristics., Methods: The records of 33 consecutive patients with trigeminal schwannoma treated via Gamma Knife surgery were retrospectively reviewed. The median patient age was 49.5 years (range 15.1-82.5 years). Eleven patients had undergone prior tumor resection. Two patients had neurofibromatosis Type 2. Lesions were classified as root type (6 tumors), ganglion type (17 tumors), and dumbbell type (10 tumors) based on their location. The median radiosurgery target volume was 4.2 cm3 (range 0.5-18.0 cm3), and the median dose to the tumor margin was 15.0 Gy (range 12-20 Gy)., Results: At an average of 6 years (range 7.2-147.9 months), the rate of progression-free survival (PFS) at 1, 5, and 10 years after SRS was 97.0, 82.0, and 82.0%, respectively. Factors associated with improved PFS included female sex, smaller tumor volume, and a root or ganglion tumor type. Neurological symptoms or signs improved in 11 (33.3%) of 33 patients and were unchanged in 19 (57.6%). Three patients (9.1%) had symptomatic disease progression. Patients who had not undergone a prior tumor resection were significantly more likely to show improvement in neurological symptoms or signs., Conclusions: Stereotactic radiosurgery is an effective and minimally invasive management option in patients with residual or newly diagnosed trigeminal schwannomas. Predictors of a better treatment response included female sex, smaller tumor volume, root or ganglion tumor type, and the application of SRS as the primary treatment.

Background: Spinal neurinomas and neurofibromas are poorly studied in Sub-Saharan Africa., Aim: The objective of this study was to report the results of the surgical management of these tumours in Yaoundé., Methods: This was a retrospective study done at the Yaoundé General and Yaoundé Central Hospitals from the 1st of January 1995 to the 1st of January 2005. The inclusion criteria: medical files which had the results of pre and post operatory clinical examinations, neuroradiologic and histopathologic examinations, the post operatory report. The follows up of at least six months. The functional outcome was evaluated using the Karnofsky scale., Results: Of the 62 patients operated for an intraspinal tumor, 12 (19.35%) were selected (nine neurinomas, two neurofibromas, one neurofibrosarcoma). The mean age was 40.66 years +/- 13.20 with a sex ratio of 0.71. The average duration of symptoms before the diagnosis was 17.83 months +/- 5.81; the most frequent symptom was radicular pain (six cases). Five patients were paraplegic. The average Karnofsky score was 50.00 +/- 12.79 before surgery and 70.83 +/- 23.53 after. The situation of the tumor was cervical (four cases), dorsal (six cases) and lumbar (two cases). The tumor was extradural, intradural, intra and extradural in six, four and two cases respectively. Tumor excision was macroscopically complete in nine cases and partial in three. Five patients were well enough after treatment to continue their professional activities., Conclusion: The diagnosis of neurinomas and neurofibromas are late in our environment, resulting to poor surgical results.

Purpose: The most appropriate treatment of laryngeal nonsquamous malignancies is a controversial subject, mainly because of the limited number of cases diagnosed. Surgery, which is an obligatory choice in nearly all cases, is sometimes indiscriminately demolitive despite the relatively low locoregional aggressiveness that characterizes certain histotypes and locations. Even in extremely aggressive tumors, where the prognosis is almost invariably unfavorable because of distant metastasis, the suitability of radical surgery should be carefully assessed, especially considering the patient's remaining life quality. The aim of the present investigation was to evaluate the postsurgical oncological results in a series of consecutive patients with laryngeal nonsquamous primary malignancy., Methods: We analyzed retrospectively 29 consecutive patients with laryngeal nonsquamous malignancies of whom 10 underwent total laryngectomy and 19 conservative surgery (partial laryngectomies)., Results: Of the 29 patients with of laryngeal nonsquamous malignancies, 16 were alive and free from disease after treatment, 5 died of other causes, 1 was lost at follow-up, and 7 died of the disease. Statistical analysis failed in disclosing a significantly different local recurrence rate after conservative surgery vs radical surgery after a mean follow-up period of 5.5 years., Conclusions: From the preliminary data emerging from the study, it seems that in nonsquamous malignancies of the larynx, the surgical approach should be the most conservative surgery possible, tailored to neoplasm extent and patient conditions. Although cervical lymph node metastases are unusual, long-term follow-up is mandatory considering the relatively high incidence of distant metastases even after years.

Context and Objective: Schwannomas are benign neoplasms of the peripheral nerves originating in the Schwann cells. According to their cellularity, they can be subdivided into Antoni A or Antoni B types. They are rare and usually solitary, with clearly delimited capsules. They occur in the head and neck region in only 25% of the cases, and may be associated with Von Recklinghausen's disease. The present study retrospectively analyzed some data on this disease in the head and neck region and reviewed the literature on the subject., Design and Setting: Retrospective study at Head and Neck Service, Universidade Estadual de Campinas., Methods: Data on 21 patients between 1980 and 2003 were reviewed. The sites of cervical schwannomas and the intraoperative, histopathological and postoperative clinical status of these cases were studied. Diagnostic methods, type of surgery and association with neurofibromatosis were evaluated., Results: The patients' ages ranged from 16 to 72 years. Four patients had a positive past history of type I neurofibromatosis or Von Recklinghausen's disease. The nerves affected included the brachial and cervical plexuses, vagus nerve, sympathetic chain and lingual or recurrent laryngeal nerve. The nerve of origin was not identified in six cases. Tumor enucleation was performed in 16 patients; the other five required more extensive surgery., Conclusion: Schwannomas and neurofibromas both derive from Schwann cells, but are different entities. They are solitary lesions, except in Von Recklinghausen's disease. They are generally benign, and rarely recur. The recommended surgical treatment is tumor enucleation.

Background: Melanotic schwannoma is a rare variant of schwannoma composed of melanin-producing cells with ultrastructural features of schwann cells. The description of the course of the tumors differs somewhat, but it is generally considered as a benign lesion. We investigated the clinicopathologic features, immunophenotypes, and ultrastructural features of 13 patients with nonpsammomatous melanotic schwannoma (NPMS)., Methods: Tumor specimens of each patient were sectioned and stained with hematoxylin-eosin, Fontana-Masson, Prussian blue, and periodic acid-Schiff (PAS). Immunohistochemical markers such as S-100, Leu-7, HMB-45, Melan-A, CK, EMA, vimentin, GFAP, laminin, collagen IV and MIB-1 were detected with the Envision immunohistochemical staining method. Four of the cases were observed by electron microscopy., Results: Of the 13 patients, 8 were male and 5 female, aged from 11 to 92 years (mean, 38.6 years). The tumor sites included the spinal nerve root (5 patients), cranial nerve (1), greater omentum (1), subcutaneous tissue (3), mesentery (1), bone (1) and mediastinum (1). Eleven patients were followed up for over 2 years, with a mean of 5.9 years. One patient (9.1%) with a primary tumor in the greater omentum developed another primary tumor of the same type in the subcutaneous tissue of the abdominal wall after the first operation. Local recurrence of the tumor was seen in 2 patients (18.2%). One patient (9.1%) showed the local recurrence and metastasis. Seven patients (63.6%) showed no evidence of the recurrence or metastasis. Grossly, all tumors were well-circumscribed and the gross findings were suggestive of melanin-containing tumors. The tumor was composed of spindled and epithelioid cells with abundant intracytoplasmic melanin pigments. Nuclei were round and contained delicate, evenly distributed chromatins as well as small, distinct nucleoli. In some areas, the nucleoli were large and prominent. Rare mitoses were seen in most lesions except the larger omentum lesion. The pigment was shown to be positive for the Fontana-Masson and negative for Prussian blue and PAS. Immunohistochemical staining for S-100, Leu-7, HMB-45, Melan-A, and vimentin were strongly positive. Linear immunoreactions of both laminin and collagen IV was detected in all patients. Ultrastructurally, numerous elongated tumor-cell processes, duplicated basement membrane and melanosomes were observed in all developmental stages., Conclusions: Histologically, melanotic schwannoma is a rare variant of schwannoma composed of melanin-producing cells with ultrastructural features of schwann cells. Distinguishing between this tumor and malignant melanoma is of paramount importance in planning of management. Immunohistochemically, combined use of laminin and collagen IV is valuable in distinguishing melanotic schwannoma from malignant melanoma. Wide local resection and additional radiotherapy should be advocated. Further studies including cytogenetic or molecular biology are still required to better delineate melanotic schwannoma from malignant melanoma. Appropriate long-term follow-up is needed for all melanotic schwannomas.

Purpose: To determine local control (LC) and complication rates for patients who underwent radiosurgery for radiation-induced intracranial tumors., Methods and Materials: Review of a prospectively maintained database (2,714 patients) identified 16 patients (20 tumors) with radiation-induced tumors treated with radiosurgery between 1990 and 2004. Tumor types included typical meningioma (n=17), atypical meningioma (n=2), and schwannoma (n=1). Median patient age at radiosurgery was 47.5 years (range, 27-70 years). The median tumor margin dose was 16 Gy (range, 12-20 Gy). Median follow-up was 40.2 months (range, 10.8-146.2 months). Time-to-event outcomes were calculated with Kaplan-Meier estimates., Results: Three-year and 5-year LC rates were 100%. Three-year and 5-year overall survival rates were 92% and 80%, respectively. Cause-specific survival rates at 3 and 5 years were 100%. Three patients died: 1 had in-field progression 65.1 months after radiosurgery and later died of the tumor, 1 died of progression of a preexisting brain malignancy, and 1 died of an unrelated cause. One patient had increased seizure activity that correlated with development of edema seen on neuroimaging., Conclusions: LC, survival, and complication rates in our series are comparable to those in previous reports of radiosurgery for intracranial meningiomas. Also, LC rates with radiosurgery are at least comparable to those of surgical series for radiation-induced meningiomas. Radiosurgery is a safe and effective treatment option for radiation-induced intracranial tumors, most of which are typical meningiomas.

Objective: To describe clinical and demographic characteristics of the parapharyngeal space tumors and assess surgical approaches used to treat them at our institution., Methods: A retrospective and descriptive study of the parapharyngeal space tumors, excluding paragangliomas, treated from June 1991 to October 2002 in a cancer center. The study population included 21 patients, 8 men and 13 women, average age of 41 years (range, 20 to 70 years). Fine needle biopsy was done in 5 (24%) patients. Computed tomography (CT) was performed in all patients, and only a few required magnetic resonance image (MRI)., Results: Surgical approaches included transcervical alone or in combination with parotidectomy, transoral, or transmandibular (mandibular swing) approach. Laminectomy and segmentary approaches were also performed in 1 patient each. Sixteen (76%) patients had benign lesions and 5 (24%) had malignant tumors. Neurogenic tumors represented 57% of all tumors. Mean tumor size was of 6.7 cm (range, 3 to 11 cm). Six (29%) patients received adjuvant radiotherapy. Complications occurred in 6 (29%) patients, 4 (19%) of which were nervous injuries associated with peripheral nerve sheath tumors. Median disease-free follow-up survival was 33 months (range, 2 to 184 months) despite being an heterogeneous group of histologies., Conclusion: Parapharyngeal space is a rare location for head and neck tumors. Cervical approach should be the first choice for large tumors; transoral approach is reserved for tumors less than 3 cm. Conversion to mandibular swing approach when the cervical approach is not offering proper exposure for tumor resection is indicated. Preoperative histologic diagnosis is not required. Nevertheless, CT scan should always be performed in order to exclude paragangliomas, distinguish prestyloid from poststyloid lesions, and to assess the extension of the tumor as well as its relationship with adjacent structures.

Malignant schwannomas are uncommon sarcomas that arise from the sheath of Schwann surrounding peripheral nerve fibers. These tumors may arise spontaneously in adult patients or may occur with reportedly increased frequency in patients with neurofibromatosis Type I. The tumors have had a reputation for malignancy with rapid metastasis, especially when they arise in relation to neurofibromatosis. We have reviewed the experience of the connective tissue oncology unit with patients with these tumors during the past 25 years. There were 80 malignant schwannomas identified in 41 females and 39 males with a mean age of 36 +/- 17 years. The largest numbers of tumors were seen in the thigh, shoulder, and pelvis but they also occurred in more central (abdomen and thorax) and distal (forearm, hand and foot) locations. The Musculoskeletal Tumor Society stages showed that the majority of the patients had Stage II (high grade but not metastasized) tumors; however, additionally, 10 of the patients had metastases at outset (Stage III). Patient gender was not a factor but stage was a notable determinant of survival. Anatomic location also had a significant effect. Overall, the entire series of patients had a survival of 85% at 11 +/- 5 years and even more remarkable was the fact that there was no difference between the numbers and outcome statistics for tumors arising spontaneously and those occurring in patients with neurofibromatosis.

Retrorectal tumors (RRT) constitute an anatomical grouping of various tumors of different nature, both benign and malignant. The diversity of their presentation, surgical management, and prognosis are illustrated by five clinical cases. A simple categorization would distinguish vestigial tumors (whether cystic or solid), congenital nonvestigial tumors such as chordoma, and tumors of neural or bony origin. Imaging by CT scan and by MRI will usually determine the nature of the tumor and its relationship to the surrounding anatomical structures. The principle of treatment is complete removal with free margins. The surgical approach may be posterior, anterior or combined depending on the nature and the size of the lesion and on how high it is situated relative to the second sacral vertebra. Complete resection may be both difficult and bloody. Sacral segments may need to be resected either for reasons of surgical approach or to obtain clear margins. Rectal resection is rarely necessary. The prognosis of these lesions depends on the nature of the tumor and particularly on the quality and completeness of the resection.

The rich multidisciplinary environment in which skull base surgery has developed has allowed for significant progress in the field and has improved patient outcomes. More precise and detailed anatomic dissection in the laboratories has provided surgeons with the benefit of undertaking the serious technical challenges encountered in the skull base. Significant work has been done and continues to be developed in the field of adjuvant treatments including radiotherapy, chemotherapy, and hormonal therapy. Using biologic end points and specific genetic targets in the tumors may further expand our management options in the future.

Objective: To study the clinical manifestations, diagnostic methods, surgical management and prognosis of patients with neurogenic tumors of the mediastinum., Method: One hundred and ten patients with neurogenic tumors of the mediastinum were analyzed retrospectively., Results: After operation, 2 patients died in hospitalization and 8 experienced such complications as Horner's syndrome or laryngeal recurrent nerve paralysis. In 102 patients with benign tumors, 2 patients had recurrence, and 4 patients with neurofibrosarcoma or malignant neurilemmoma died within 3 years postoperatively., Conclusions: Most neurogenic tumors of the mediastinum are benign and could be diagnosed by chest X-ray or CT. The clinical manifestations, diagnosis methods, surgical management of the dumbbell tumors differ from others. Minimal invasive surgery and video assist thoracoscopy surgery are of special value in treatment of the selected neurogenic tumors of the mediastinum. Benign neurogenic tumors rarely recur after complete resection, and malignant neurogenic tumors have poor prognosis.

Background: Spinal intradural extramedullary tumors account for 2/3 of all intraspinal neoplasms and are mainly represented by meningiomas and schwannomas, with the former accounting for the 25-46% of all primary intraspinal tumors. Technical advances in imaging technique, magnetic resonance imaging (MRI) and surgical procedures have brought about significant better clinical results in the last 2 decades. Neverthless a small percentage of patients still present poor postoperative outcome mainly related to the duration of clinical history, the severity of preoperative neurological deficits and to some specific anatomo-surgical aspects., Methods: In an effort to clarify the influence of these factors on patient's outcome, the authors analyze the clinical, surgical and prognostic data of 41 patients with intradural extramedullary spinal tumor surgically treated between January 1990 and December 1999. The follow-up period ranged from 1 to 9 years. The clinical history until admission and treatment was 3-48 months for meningiomas and 1-72 months for schwannomas., Results: Morbidity and mortality rate was 5 and 0% for meningiomas and 0 and 6% for schwannomas. Almost all the patients experienced a significant neurological improvement after surgery, with a percentage of Nurick's grade 1 and 2 of 68% among patients with meningiomas and 66% among patients with schwannomas. Removal of the tumor was complete in 90% of meningiomas and 94% of schwannomas., Conclusions: The authors address radical surgery as the ideal goal in these neoplasms, as it gives the patients the best long-terms results, pointing out the importance of systematic early identification of any main radiculomedullary artery during debulking and dissection of the tumor to avoid any risk of severe postoperative neurological worsening of the patients.