Salvage rates and prognostic factors after relapse in children and adolescents with malignant peripheral nerve sheath tumors.

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.

Stereotactic radiosurgery for non-vestibular cranial nerve schwanommas.

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.

Malignant peripheral nerve sheath tumor in children: A single-institute retrospective analysis.

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.

The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study.

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.

Loss of H3K27 tri-methylation is a diagnostic marker for malignant peripheral nerve sheath tumors and an indicator for an inferior survival.

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.

Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas.

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.

The effect of surgical margins on outcomes for low grade MPNSTs and atypical neurofibroma.

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.

Neuroblastoma in the adult: the Italian experience with 21 patients.

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.

The clinical features and surgical outcomes of pediatric patients with primary spinal cord tumor.

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.

Extracranial head and neck Schwannomas: a study of the nerve of origin.

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.

Malignant peripheral nerve sheath tumors arising from schwannomas: case series and literature review.

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.

Infantile intracranial neoplasms: characteristics and surgical outcomes of a contemporary series of 21 cases in an Egyptian referral center.

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.

Clinical Characteristics and Surgical Management of Gastrointestinal Schwannomas.

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.

Tumors in the cauda equina: A SEER analysis of tumor types and predictors of outcome.

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.

Stereotactic radiosurgery for trigeminal schwannoma: tumor control and functional preservation Clinical article.

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.

Oncologic Accuracy of Image-guided Percutaneous Core-Needle Biopsy of Peripheral Nerve Sheath Tumors at a High-volume Sarcoma Center.

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.

[Results of surgical management of spinal neurinomas and neurofibromas at Yaounde]. / Resultats du traitement chirurgical des neurinomes et neurofibromes spinaux a Yaounde.

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.

A Clinicopathologic Study of Head and Neck Malignant Peripheral Nerve Sheath Tumors.

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.

Fractionated Radiation Therapy for Benign Nonacoustic Schwannomas.

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.

Stereotactic radiosurgery for jugular foramen schwannomas: an international multicenter study.

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 cm3 (range 0.8-22.6 cm3), 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 cm3 (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.