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Background: Craniovertebral junction (CVJ) tumors are challenging due to their unique anatomical location. This study aimed to evaluate the complexities in dealing with such precarious CVJ extradural lesions over the decade., Methods: Twenty-seven patients of extradural CVJ tumors operated between 2009 and 2018 were included. The demographic details, neurological status, surgical approach, extent of resection, type of fixation, complications, and outcome at final follow-up were recorded for each patient., Results: The mean age of the patients was 39.5 ± 20 years. Most (17/27) of the patients had involvement of a single level. Clivus was the most common (9/17) involved region followed by atlas (7/17) vertebrae. Majority of the patients (13/27) were operated through the posterior-only approach. About 15 patients (55.5%) had instability or extensive lesions that necessitated posterior fixation. None of the patients underwent anterior fixation. Gross and near total excision were achieved in 10 patients (37%) and 3 patients (11%) respectively while 14 patients underwent subtotal excision of tumor. On histopathological analysis, clival chordoma (8/27) was found to be the most common pathology followed by giant cell tumor (6/27), plasmacytoma (4/27), and multiple myeloma (2/27). Most patients (13 out of 27) had the same neurological status after the surgery. Six patients (22%) improved post-operatively with decreased weakness and spasticity. Thirteen (48%) patients underwent adjuvant radiotherapy., Conclusions: This retrospective study provides valuable insights into managing extradural CVJ tumors and highlights the importance of individualized approaches for optimal outcome., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Head and neck and base of skull malignancies are challenging for surgical and radiotherapy treatment due to the density of sensitive tissues. Carbon ion radiotherapy (CIRT) is a form of heavy particle therapy that uses accelerated carbon ions to treat malignancies that may be radioresistant or in challenging anatomic locations. CIRT has an increased biological effectiveness (ie, increased cell killing) at the end of the range of the carbon beam (ie, within the target tissue) but not in the entrance dose. This increased biological effectiveness can overcome the effects of radioresistant tumors, tissue hypoxia, and the need for radiotherapy fractionation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The regimen of prophylactic antibiotic for endoscopic endonasal skull base surgery (EE-SBS) varies considerably depending on surgeons and their institutes. The purpose of the present meta-analysis is to assess the effect of antibiotic regimens on EE-SBS surgery for anterior skull base tumor., Methods: The PubMed, Embase, Web of Science, and Cochrane clinical trial databases were systematically searched through October 15, 2022., Results: The 20 included studies were all retrospective. The studies included a total of 10,735 patients who underwent EE-SBS for skull base tumor. The proportion of patients with postoperative intracranial infection across all 20 studies was 0.9% (95% confidence interval [CI] 0.5%-1.3%). The proportion of postoperative intracranial infection in the multiple antibiotics group did not show statistically significant difference to that of the single antibiotic agent group (proportion: 0.6%, 95% CI 0%-1.4% vs. proportion: 1%, 95% CI 0.6%-1.5%, respectively, P = 0.39). The ultra-short duration maintenance group showed lower incidence of postoperative intracranial infection, although it did not reach statistical significance (ultra-short group: 0.7%, 95% CI 0.5%-0.9%; short duration: 1.8%, 95% CI 0.5%-3%; and long duration: 1%, 95% CI 0.2%-1.9%, P = 0.22) The combination of the multiple antibiotics group did not show meaningful low incidence of postoperative intracranial infection (antibiotics combination group: 0.6%, 95% CI 0%-1.4%; cefazolin single group: 0.8%, 95% CI 0%-1.6%; and single antibiotics other than cefazolin: 1.2%, 95% CI 0.7%-1.7%, P = 0.22)., Conclusions: Multiple antibiotics did not show superiority compared with single antibiotic agent. Also, long maintenance duration of antibiotics did not reduce the incidence of postoperative intracranial infection., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: This study aimed to compare the results of irradiation with protons versus irradiation with carbon ions in a raster scan technique in patients with skull base chordomas and to identify risk factors that may compromise treatment results., Methods: A total of 147 patients (85 men, 62 women) were irradiated with carbon ions (111 patients) or protons (36 patients) with a median dose of 66 Gy (RBE (Relative biological effectiveness); carbon ions) in 4 weeks or 74 Gy (RBE; protons) in 7 weeks at the Heidelberg Ion Beam Therapy Center (HIT) in Heidelberg, Germany. The median follow-up time was 49.3 months. All patients had gross residual disease at the beginning of RT. Compression of the brainstem was present in 38%, contact without compression in 18%, and no contact but less than 3 mm distance in 16%. Local control and overall survival were evaluated using the Kaplan-Meier Method based on scheduled treatment (protons vs. carbon ions) and compared via the log rank test. Subgroup analyses were performed to identify possible prognostic factors., Results: During the follow-up, 41 patients (27.9%) developed a local recurrence. The median follow-up time was 49.3 months (95% CI: 40.8-53.8; reverse Kaplan-Meier median follow-up time 56.3 months, 95% CI: 51.9-60.7). No significant differences between protons and carbon ions were observed regarding LC, OS, or overall toxicity. The 1‑year, 3‑year, and 5‑year LC rates were 97%, 80%, and 61% (protons) and 96%, 80%, and 65% (carbon ions), respectively. The corresponding OS rates were 100%, 92%, and 92% (protons) and 99%, 91%, and 83% (carbon ions). No significant prognostic factors for LC or OS could be determined regarding the whole cohort; however, a significantly improved LC could be observed if the tumor was > 3 mm distant from the brainstem in patients presenting in a primary situation., Conclusion: Outcomes of proton and carbon ion treatment of skull base chordomas seem similar regarding tumor control, survival, and toxicity. Close proximity to the brainstem might be a negative prognostic factor, at least in patients presenting in a primary situation., (© 2022. The Author(s).)

Giant cell tumors (GCTs) of the skull base are rare entities. Although considered histologically benign, GCTs are locally aggressive with a high rate of local recurrence. The present case describes a 14-year-old girl with a clival GCT who underwent long-term therapy with denosumab after local relapse. To our knowledge, it is the second case described with a follow-up term >2 years from the start of denosumab and who did not receive any other adjuvant treatment besides denosumab. The patient achieved a local control of the disease. According to the few available data, radical excision with adjuvant therapy helps in long-term control in uncommon sites, such as the skull. However, the definitive treatment is still controversial because of their rarity and few follow-up data. The present case highlights the benefit of denosumab and its safety as long-term therapy and contributes to the existing literature with analysis and evaluation of the management strategies and prognosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Management of lesions involving Meckel's cave can represent a challenge for neurosurgeons, because of the deep-seated location and the surrounding complex neurovascular structures. Very small lesions arising from MC are generally asymptomatic and radiological follow-up with head MRI and PET-CT is sufficient to control these lesions. In rare cases, the rapid increase in the size of lesions and the alteration of the neurologic status make early histological characterization mandatory in the plethora of lesions arising from Meckel's cave; a very small percentage is represented by central nervous system lymphomas. Primary diffuse large B-cell lymphoma is the most commonly found. Aggressive surgery, in case of suspicious Meckel's cave lesions, is strongly discouraged, because this procedure may increase the risk of postoperative deficit and provides no survival benefit compared with biopsy alone. The aim of the present paper is to report a very rare case of primary Meckel's cave diffuse large B-cell lymphoma (only seven cases were described in literature) and standardize an operative algorithm to avoid the risks of an incorrect surgical conduct., (© 2020. Belgian Neurological Society.)

Chordomas are rare slow growing, malignant bone tumors of the axial skeleton with no approved medical treatment. As the majority of chordomas express cMET and its ligand, HGF, and crosstalks between EGFR and MET-signaling exist, we aimed to explore cMET activity in chordoma cell lines and clinical samples. We investigated nine chordoma patients and four chordoma cell lines for cMET expression. Two clival and two sacral chordoma cell lines were tested for chromosomal abnormalities of the MET gene locus; we studied the influence of HGF on the autocrine secretion and migration behavior, as well as protein expression and phosphorylation. Two MET/ALK inhibitors were investigated for their effects on cell viability, cell cycle, cyclin alterations, apoptosis, and downstream signaling pathways. Moderate and strong expression of membrane and cytoplasmic cMET in chordoma patients and cell lines used, as well as concentration-dependent increase in phospho cMET expression after HGF stimulation in all four chordoma cell lines was shown. U-CH2, MUG-Chor1, and UM-Chor1 are polysomic for MET. Chordoma cell lines secreted EGF, VEGF, IL-6, and MMP9 upon HGF-stimulation. Sacral cell lines showed a distinct HGF-induced migration. Both inhibitors dose-dependently inhibited cell growth, induce apoptosis and cell-cycle arrest, and suppress downstream pathways. Heterogeneous responses obtained in our in vitro setting indicate that cMET inhibitors alone or in combination with other drugs might particularly benefit patients with sacral chordomas.

Background: Pneumatosis intestinalis (PI) is a rare entity which refers to the presence of gas within the wall of the small bowel or colon which is a radiographic sign. The etiology and clinical presentation are variable. Patients with PI may present either with chronic mild non-specific symptoms or with acute abdominal pain with peritonitis. Some cases of intestinal pneumatosis have been reported as adverse events of new oncological treatments such as targeted therapies that are widely used in multiple tumors., Case Presentation: A 59-year-old caucasian female with radioactive iodine-refractory metastatic thyroid papillary carcinoma with BRAF V600E mutation was treated with dabrafenib and trametinib as a compassionate use. After 4 months treatment, positron emission tomography-computed tomography (PET-CT) showed PI. At the time of diagnosis, the patient was asymptomatic without signs of peritonitis. The initial treatment was conservative and no specific treatment for PI was needed. Unfortunately, after dabrafenib-trametinib withdrawal, the patient developed tumor progression with significant clinical worsening., Conclusions: This case report is, in our knowledge, the first description of PI in a patient treated with dabrafenib-trametinib. Conservative treatment is feasible if there are no abdominal symptoms.

Alveolar soft part sarcoma (ASPS) is a rare malignancy that typically arises in the trunk or extremities and preferentially metastasises to the brain. Radical resection is generally recommended for cranial metastatic ASPS, but stereotactic radiosurgery (SRS) is a recognised alternative for tumours in surgically challenging locations. Here, we present the case of a 22-year-old female, who underwent SRS and systemic therapy with pazopanib for a metastatic ASPS in the left temporal bone. The tumour was successfully controlled without further intervention over 23 months following SRS, which should be considered for metastatic ASPS when surgical resection is not appropriate.

In this case report, we present a rare and previously unreported case of spontaneous regression of a histologically consistent clival chordoma. At the time of diagnosis, imaging demonstrated a T2 hyperintense and T1 isointense midline skull base mass, centered in the nasopharynx, with scalloping of the ventral clivus consistent with a chordoma measuring 3.1 × 1.9 × 3.0 cm (8.84 cm 3 ). On pre-operative imaging 2 months later, with no intervening therapy, the mass had regressed by 61.7% to a size of 2.3 × 2.1 × 1.4 cm (3.38 cm 3 ). The patient self-administered several herbal supplements and animal oils which may have contributed to tumor regression. The purpose of this report is to document this rare occurrence and provide a comprehensive description of the case details and list of the various medications, herbs, and supplements used prior to this rare event.

Malignancies of the anterior skull base are rare and recur in 40-80% of treated cases, varying with substantial variance according to histology, stage at primary diagnosis, and other factors. Most recurrences manifest within 2-5 years after primary treatment, but some histologies can relapse even decades after the first presentation. Management of recurrent anterior skull base tumors is challenging and a wide variety of treatment options are available. Similar to the primary setting, surgery is the mainstay of treatment. However, only few patients are likely to be suitable for salvage surgery after restaging. In this scenario, non-surgical options such as re-irradiation with photon or heavy particles may play a role, although the potential toxicity and benefits of treatment needs to be considered on a case-by-case basis. Moreover, stereotactic technologies are emerging as an adjunct valuable tool to minimize side effects. Chemotherapy is acquiring a relevant role in the primary treatment of sinonasal malignant lesions involving the anterior skull base in the neoadjuvant setting or in combination with radiotherapy, but evidence of its efficacy in the treatment of the recurrent/metastatic disease is very limited. The specific drugs employed vary considerably and need to be paralleled with the biology of the different histologies., (© 2020 S. Karger AG, Basel.)

Cancer treatment has changed dramatically with the development of oral targeted therapies. Pazopanib, an oral VEGF tyrosine kinase inhibitor, is currently approved for advanced renal cell carcinoma, advanced soft tissue sarcoma, and is being studied for various tumor types. Due to the potential of increased exposure to pazopanib when crushed, pazopanib should be given as an intact whole tablet. Thus, in patients with difficulty swallowing medications or feeding tubes, pazopanib is usually not considered to be an option. Here, we describe two cases which show the administration of crushed pazopanib was feasible and had apparent clinical activity.

Recognition of new cutaneous side effects of combination chemotherapy can help prevent unnecessary cessation or reduction of cancer therapy. Periorbital rash has not been found with docetaxel alone, but here, we report it as a result of combination chemotherapy. A series of three patients who received docetaxel in combination with other chemotherapies developed clinically near-identical, distinctive periorbital rashes. Rashes resolved by resolving underlying docetaxel-induced epiphora in conjunction with ophthalmological consultation, topical skin-directed care, and in some cases, chemotherapy dose reduction. It is important for dermatologists and oncologists to recognise the increased severity of cutaneous reactions when docetaxel is used in combination chemotherapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Giant cell tumors (GCTs) are benign tumors with a predilection for the epimetaphyseal region of the long bones. GCTs involving the skull base are rare, and only a few available cases have been reported. Surgical gross total resection is the recommended method of treatment for GCTs. In the case of skull base tumors, it is very difficult to achieve such a result by direct surgical resection alone without any morbidities. Denosumab is a fully humanized monoclonal anti-receptor activator of nuclear factor-κB ligand antibody that has been recently approved by the Food and Drug Administration for the treatment of GCTs that are surgically unresectable, metastatic, and have a high risk of progression and recurrence. Denosumab has been used in many cases involving the long bones. However, in cases of skull base GCTs, only a limited number of cases have been reported. In addition, in such cases, it was used as postoperative chemotherapy owing to subtotal resection., Case Description: For the present patient, we adopted a unique approach in which denosumab was administered as neoadjuvant chemotherapy to reduce the size of the tumor to a resectable level. Subsequently, surgical resection was performed with good functional and histopathological outcomes., Conclusions: Our findings emphasize the use of denosumab as a neoadjuvant treatment routinely for all cases of skull base GCTs to achieve safe and complete excision of the tumor., (Copyright © 2018. Published by Elsevier Inc.)

Background: We present the results of an academic phase 2 study on imatinib plus everolimus in patients who have progressive advanced chordoma., Methods: In January 2011, 43 adult chordoma patients were enrolled in the study and received imatinib 400 mg/day and everolimus 2.5 mg/day until progression or limiting toxicity. Eligible patients had progressed in the 6 months before study entry. PDGFRB, S6, and 4EBP1 expression and phosphorylation were evaluated by way of immunohistochemistry and/or western blotting. The primary endpoint was the overall response rate (ORR) according to Choi criteria. Secondary endpoints were RECIST 1.1 response, progression-free survival (PFS), overall survival (OS), correlation between S6/4EBP1 phosphorylation and response., Results: Thirteen of 43 patients were pretreated with imatinib. Among 40 of the 43 patients who were evaluable by Choi criteria, the best responses were 9 with partial response (ORR, 20.9%), 24 with stable disease (SD) (ORR, 55.8%), and 7 with progressive disease (ORR, 16.3%). Forty-two patients were evaluable by RECIST criteria, with 1 partial response (ORR, 2.3%), 37 stable disease (ORR, 86%), and 4 progressive disease (ORR, 9.3%). The median PFS according to Choi criteria was 11.5 months (range, 4.6-17.6 months), and 58.8% and 48.1% of patients were progression-free at 9 and 12 months, respectively. The median PFS by RECIST criteria was 14 months; the median OS was 47.1 months. When assessable, S6/4EBP1 was phosphorylated in a high and moderate/low proportion of tumor cells in responsive and nonresponsive patients, respectively. Toxicity caused a temporary and definitive treatment discontinuation in 60.5% and 30.2% of patients, respectively., Conclusions: Imatinib plus everolimus showed a limited activity in progressing advanced chordoma. Interestingly, the amount of tumor cells activated for mammalian target of rapamycin effectors correlated with the response. Toxicity was not negligible., (© 2018 American Cancer Society.)

Background: Chordoma is a rare malignant tumor of the skull base and axial skeleton, with an incidence of less than 0.1/100,000 per year. Patients with advanced chordoma have a poor prognosis due to locoregional recurrence with infiltration and destruction of surrounding bone and soft tissue. Cytotoxic chemotherapy or other systemic therapies have not been proven to be effective for these diseases. Therefore, several molecularly targeted therapies have been proposed as potentially beneficial, including tyrosine kinase inhibitors such as imatinib, sorafenib, lapatinib, and others., Case Presentation: We present three cases of advanced chordoma treated with molecular targeted therapies: a 52-year-old Caucasian man, a 72-year-old Caucasian woman, and a 38-year-old Caucasian woman., Conclusions: Chordoma has few systemic treatment options and they have limited benefit. Randomized trials with large patient numbers are unfeasible in this rare disease. Targeted therapy might be a reasonable alternative treatment for chordoma. Still, new treatment strategies are needed for this rare disease.

Background: Cerebrospinal fluid (CSF) rhinorrhea after medical therapy for pituitary prolactinoma is a rare but well-described phenomenon. To our knowledge, no CSF leaks have been reported after targeted medical treatment of pituitary or anterior skull base metastases. We report this unusual case to raise awareness of spontaneous CSF leaks in the setting of skull base metastatic disease., Case Presentation: A 66-year-old woman presented with epidermal growth factor receptor-mutant stage IV adenocarcinoma of the lung. Headache workup revealed a large sellar and clival lesion consistent with metastatic disease. Systemic erlotinib chemotherapy was initiated with a robust positive response. Approximately 1 week after chemotherapy initiation, the patient noted clear discharge from the right nostril. Her oncologist first diagnosed her with allergic rhinitis, but she presented with meningitis 4 days after diagnosis of CSF leak and was admitted for intravenous antibiotics and definitive repair of a CSF leak via an endoscopic endonasal approach. An erosion of bone and dura was found at the dorsum sellae where tumor had regressed due to the chemotherapy. A multilayer skull base repair was made uneventfully, and she recovered fully with no leakage seen at 2-month follow-up., Conclusions: All members of the treatment team should be aware of this possibility of CSF leak after initiation of systemic chemotherapy and tumor regression and urgently refer patients for repair if a leak should develop before the development of meningitis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Chordomas and chondrosarcomas can occur in the skull base. Currently, 45% of chordomas and 56% of chondrosarcomas recur within 5 years of surgery. The role of adjuvant therapy is highly debated. No pharmacotherapies have been approved by the U.S. Food and Drug Administration for chordomas or chondrosarcomas. High propensity for recurrence and lack of definitive adjuvant therapy necessitate additional basic science research to identify molecular anomalies associated with recurrent disease., Methods: We pooled tumor lysates from patients based on clinical criteria into 4 groups: primary chordomas, primary chordomas that recurred, primary chondrosarcomas, and primary chondrosarcomas that recurred. We used a peptide labeling method, isobaric tags for relative and absolute quantitation, to uniquely identify each tumor group. Phosphorylated peptides were identified and quantified via mass spectroscopy to determine and predict active kinases., Results: Six groups of phosphorylated peptides were associated with primary tumors that later recurred. Specific kinases associated with primary chordomas that recurred were FES and FER. Specific kinases associated with primary chondrosarcomas that recurred were FES, FER, SRC family kinases, PKC, ROCK, and mitogen-activated protein kinase signaling (JNK, ERK1, p38)., Conclusions: These data provide clinicians with a means to screen skull base chordomas and chondrosarcomas to help identify tumors with a propensity to recur. Many of these kinases can be efficaciously inhibited by Food and Drug Administration-approved drugs that have not yet been used in clinical trials for treatment of skull base chordomas or chondrosarcomas. Validation of kinases identified in this study may advance treatment options for patients with these tumors., (Copyright © 2017. Published by Elsevier Inc.)

Background: The treatment of clival chordomas remains challenging. Total tumour resection is often impossible without hampering adjacent anatomical structures and causing functional sequelae. On the other hand, chordomas show limited response to non-surgical treatment modalities. Up to now, no well-established interdisciplinary treatment algorithms for clival chordomas exist. In this regard, we analysed the data from all patients that underwent interdisciplinary treatment for clival chordoma in our institution over the last 10 years., Method: Retrospective report of all patients treated at the authors' institution from 2005 to 2015., Results: Thirteen patients underwent 24 surgeries, of which 2 (8%) were gross total resections and 22 (92%) incomplete resections. Neurological deterioration, endocrinological disturbances and other surgical complications were observed in six (25%), three (13%) and nine (38%) cases, respectively. Three surgeries (13%) led to an improvement of the initial preoperative neurological condition. All patients were discussed on the interdisciplinary tumour board and all underwent one type of radiotherapy following initial surgery: proton beam in 11 cases (85%) and photon beam in two (15%) cases. In the course of their recurrent disease, three patients (23%) received systemic therapy (imatinib, pazopanib and nivolumab). One patient received a personalised cellular immunotherapy. One patient (8%) was lost to follow-up. Of the remaining 12 patients, four patients (33%) died in the period of analysis; all deaths were chordoma-related. The 5-year cumulative survival rate was 83% (52-97%, CI 95%), 5-year progression-free survival rate was 53% (26-79%, CI 95%). The eight patients (66%) still alive had favourable outcome (KPS, 90 ± 10.7%). SF36 analysis among the survivors revealed 43 points for the Physical Component Summary (12% above, 38% at and 50% below the general population norm) and 47 points for the Mental Component Summary (25% above, 38% at and 38% below)., Conclusions: Our patients show a low rate of gross total resection but an outcome well comparable to other published results. This emphasises the importance of interdispiplinary treatment strategies, with surgery supplying maximal safe resection and avoiding severe neurological deficit, allowing patients to undergo adjusted radiotherapy and other treatment options in a good condition.

Background: To assess the role of first-line Molecular Targeted Therapies (MTTs) in Advanced chordoma (AC) patients., Methods: Retrospective study of 80 patients treated between January 2004 and December 2015 at 15 major French Sarcoma or Neurooncology Centres., Results: The sex ratio M/F was 46/34. The median age was 59 (6-86) years. The primary sites were the sacrum (50, 62.5%), mobile spine (12, 15.0%), and skull base (18, 22.5%). Metastases were present in 28 patients (36.0%). The first line of MTTs consisted of imatinib (62, 77.5%), sorafenib (11, 13.7%), erlotinib (5, 6.3%), sunitinib (1, 1.2%) and temsirolimus (1, 1.2%). The reported responses were: partial response (5, 6.3%), stable disease (58, 72.5%), or progressive disease (10, 12.5%). Symptomatic improvement was seen in 28/66 assessable patients (42.4%) and was associated with an objective response occurrence (p = 0.005), imatinib (p = 0.020) or erlotinib use (p = 0.028). The median progression-free survival (PFS) was 9.4°months (95% CI, [6.8-16.1]). Two independent factors of poor prognosis for PFS were identified: a skull-based primary location (HR = 2.5, p = 0.019), and the interval between diagnosis and MTT of <52months (HR = 2.8, p < 0.001). The median overall survival (OS) was 4.4°years (95% CI, [3.8-5.6]). Four independent factors of poor prognosis for OS were identified: the presence of liver metastases (HR = 13.2, p < 0.001), pain requiring opioids (HR = 2.9, p = 0.012), skull-based primary location (HR = 19.7, p < 0.001), and prior radiotherapy (photon alone) (HR = 2.5, p = 0.024). The PFS and OS did not significantly differ between the MTT., Conclusions: The prognostic factors identified require validation in an independent database but are potently useful to guide treatment decisions and design further clinical trials., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Giant cell tumors (GCTs) are histologically benign bone neoplasms with a locally aggressive nature that primarily occur in the epiphyses of the long bones. A small proportion of these tumors, however, occur in the pelvis, spine, or skull bones. Among these, GCTs of the skull base cannot be completely resected and require adjuvant therapy. We report a juvenile case of clival GCT that was successfully treated by endoscopic endonasal transsphenoidal surgery and subsequent adjuvant therapy with denosumab, a monoclonal antibody to receptor activator of nuclear factor-κB ligand., Case Description: A 16-year-old boy was admitted to our hospital with progressively intolerable headache and right oculomotor nerve palsy. Computed tomography and magnetic resonance imaging showed a large tumor mass in the sphenoid sinus with extensive erosion of the clivus and compression of the right cavernous sinus. The tumor was resected by endonasal transsphenoidal surgery and histologically diagnosed as GCT. The giant cells showed positive immunostaining for CD68 and Mib-1 labeling index was less than 1.0%. Postoperative course was uneventful and the oculomotor disturbance was markedly improved. However, magnetic resonance imaging 2 weeks after surgery revealed marked enlargement of the tumor. Adjuvant therapy with denosumab was therefore initiated, resulting in marked reductions in tumor size., Conclusions: This is the first report to describe beneficial effects of denosumab in the treatment of GCT of the skull base., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background/aim: For advanced paranasal sinus cancer, intra-arterial (I-A) chemotherapy has been applied for improving prognosis and organ preservation. While computed tomographic angiography (CTA) is useful for identifying the tumor-feeding artery, CTA cannot always detect the precise artery. The aim of this study was to assess the feasibility of endoscopic ICG (indocyanine green) fluorescence technique during I-A chemotherapy for recurrent skull-base cancer., Patients and Methods: Seven patients with recurrent skull-base cancer were included in this study. Conventional CTA followed by ICG was administered. Additional information regarding tumor-feeding arteries attained via ICG was evaluated., Results: Out of seven cases, the blood supply to the cancer was detected in three by CTA alone. By adding the endoscopic evaluation, the blood supply to the tumor was confirmed without difficulty in all cases. The information from endoscopic fluorescence imaging was helpful in making decisions concerning the administration of drugs for skull-base cancer., Conclusion: Endoscopic ICG fluorescence imaging combined with I-A chemotherapy compensated for deficiencies of CTA and generated more useful information about the feeders to tumors than was previously available., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: To report our experience with the Extended endoscopic endonasal approach (EEEA) for clival and paraclival tumors., Design: Retrospective analysis of a consecutive series of patients., Results: Eleven patients were considered: 3 chordomas, 3 meningiomas, 3 metastatic lesions, one chondroma and one chondrosarcoma. Gross total resection (GTR) was achieved in all chordomas and in chondromas with patients free of disease at the last follow-up. The chondrosarcoma was first operated on using a transfacial approach and endoscopy was performed for local progression with subtotal resection. The meningiomas were treated by a combination of transcranial and endoscopic approach due to their extension. The resection was subtotal and the residue treated by radiosurgery. Two patients with rhinopharyngeal carcinoma underwent palliative debulking. One metastatic melanoma that underwent GTR experienced remission. Two patients had postoperative cranial nerve palsy. No other complications were observed., Conclusions: EEEA allows a direct access to the skull base. Through a minimal access, it limits the incidence of neurological morbidities. For midline epidural clival tumors, EEEA allows a total excision. It also offers an excellent access to the clival component of intradural lesions. A combined approach permits good tumor control with minimal complications., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

OBJECT Adenoid cystic carcinoma (ACC) is a locally aggressive tumor of salivary gland origin. Little data exist to guide treatment when this tumor extends to involve the structures of the skull base. METHODS Fifty-one patients with a diagnosis of ACC affecting the skull base were identified from a prospective database at MD Anderson Cancer Center (from 1992 to 2010). RESULTS Median follow-up for study patients was 6.75 years. The 5- and 10-year overall survival (OS) rates were 78% and 50%, respectively. Sixty-six percent of patients had progression of their disease. The 5- and 10-year progression-free survival (PFS) rates were 46.7% and 21.0%, respectively. Gross-total resection was achieved in 75% of patients, with 49% having microscopically negative margins at the time of first operation. On univariate analysis, resections with microscopically negative margins were associated with a significant OS advantage (20.1 ± 3.3 years) compared with resections that left residual disease, even if microscopic (10.3 ± 1.6 years, p = 0.035). In patients who underwent reoperation, the effect persisted, with improved OS in those with negative margins (21.4 ± 0.0 vs 16.7 ± 4.0 years, p = 0.06). The use of adjuvant radiotherapy was associated with an OS advantage (16.2 ± 2.5 vs 5.5 ± 2.2 years, p = 0.03) at initial diagnosis and improved PFS (7.8 ± 1.0 vs 2.1 ± 0.62 years, p = 0.005), whereas repeat irradiation provided no benefit. The use of adjuvant chemotherapy at diagnosis or at recurrence was not associated with any significant advantage. Multivariate analysis revealed margin-negative resection at initial operation and at recurrence retained OS significance, even after controlling for age, radiation therapy, and T stage. CONCLUSIONS ACC of the skull base is best treated with a multidisciplinary approach aimed at maximal, safe resection. Adjuvant radiotherapy should be offered, whereas chemotherapy does not confer benefit.

Background: Although several reports have shown that proton beam therapy (PBT) offers promise for patients with skull base cancer, little is known about the frequency of late toxicity in clinical practice when PBT is used for these patients. Here, we conducted a retrospective analysis to clarify the late toxicity profile of PBT in patients with malignancies of the nasal cavity, para-nasal sinuses, or involving the skull base., Methods: Entry to this retrospective study was restricted to patients with (1) malignant tumors of the nasal cavity, para-nasal sinuses, or involving the skull base; (2) definitive or postoperative PBT (>50 GyE) from January 1999 through December 2008; and (3) more than 1 year of follow-up. Late toxicities were graded according to the common terminology criteria for adverse events v4.0 (CTCAE v4.0)., Results: From January 1999 through December 2008, 90 patients satisfied all criteria. Median observation period was 57.5 months (range, 12.4-162.7 months), median time to onset of grade 2 or greater late toxicity except cataract was 39.2 months (range, 2.7-99.8 months), and 3 patients had toxicities that occurred more than 5 years after PBT. Grade 3 late toxicities occurred in 17 patients (19%), with 19 events, and grade 4 late toxicities in 6 patients (7%), with 6 events (encephalomyelitis infection 2, optic nerve disorder 4)., Conclusions: In conclusion, the late toxicity profile of PBT in patients with malignancy involving the nasal cavity, para-nasal sinuses, or skull base malignancy was partly clarified. Because late toxicity can still occur at 5 years after treatment, long-term follow-up is necessary.

We describe a case of giant bilateral skull vault haemangiomas in a patient with diffuse skeletal haemangiomatosis. The clinical details, histological and radiographic findings and surgical management are reviewed. This is the first described case of radical surgical management of bilateral giant haemangiomas with relief of intractable headache.

Paragangliomas are rare, slow-growing tumors that frequently arise in the head and neck, with the carotid bodies and temporal bone of the skull base being the most common sites. These neoplasms are histologically similar to pheochromocytomas that form in the adrenal medulla and are divided into sympathetic and parasympathetic subtypes based on functionality. Skull base and head and neck region paragangliomas (SHN-PGs) are almost always derived from parasympathetic tissue and rarely secrete catecholamines. However, they can cause significant morbidity by mass effect on various cranial nerves and major blood vessels. While surgery for SHN-PG can be curative, postoperative deficits and recurrences make these lesions challenging to manage. Multiple familial syndromes predisposing individuals to development of paragangliomas have been identified, all involving mutations in the succinate dehydrogenase complex of mitochondria. Mutations in this enzyme lead to a state of "pseudohypoxia" that upregulates various angiogenic, survival, and proliferation factors. Moreover, familial paraganglioma syndromes are among the rare inherited diseases in which genomic imprinting occurs. Recent advances in gene arrays and transcriptome/exome sequencing have identified an alternate mutation in sporadic SHN-PG, which regulates proto-oncogenic pathways independent of pseudohypoxia-induced factors. Collectively these findings demonstrate that paragangliomas of the skull base and head and neck region have a distinct genetic signature from sympathetic-based paragangliomas occurring below the neck, such as pheochromocytomas. Paragangliomas serve as a unique model of primarily surgically treated neoplasms whose future will be altered by the elucidation of their genomic complexities. In this review, the authors present an analysis of the molecular genetics of SHN-PG and provide future directions in patient care and the development of novel therapies.

Skull base chordomas are challenging tumors due to their deep surgical location and resistance to conventional radiotherapy. Chemotherapy plays a marginal role in the treatment of chordoma resulting from lack of preclinical models due to the difficulty in establishing tumor cell lines and valuable in vivo models. Here, we established a cell line from a recurrent clival chordoma. Cells were cultured for more than 30 passages and the expression of the chordoma cell marker brachyury was monitored using both immunohistochemistry and Western blot. Sensitivity of chordoma cells to the inhibition of specific signaling pathways was assessed through testing of a commercially available small molecule kinase inhibitor library. In vivo tumorigenicity was evaluated by grafting chordoma cells onto immunocompromised mice and established tumor xenografts were treated with rapamycin. Rapamycin was administered to the donor patient and its efficacy was assessed on follow-up neuroimaging. Chordoma cells maintained brachyury expression at late passages and generated xenografts closely mimicking the histology and phenotype of the parental tumor. Rapamycin was identified as an inhibitor of chordoma cell proliferation. Molecular analyses on tumor cells showed activation of the mammalian target of rapamycin signaling pathway and mutation of KRAS gene. Rapamycin was also effective in reducing the growth of chordoma xenografts. On the basis of these results, our patient received rapamycin therapy with about six-fold reduction of the tumor growth rate upon 10-month follow-up neuroimaging. This is the first case of chordoma in whom chemotherapy was tailored on the basis of the sensitivity of patient-derived tumor cells.

Chordomas are rare bone tumors of notochord remnants that may occur anywhere within the axial skeleton. The standard of care is complete surgical removal. Proton beam irradiation is commonly used when the tumor is inaccessible or has recurred. Chemotherapy has been used in the treatment of patients at relapse but it has been generally proven ineffective. We report a 7-month-old infant with a clival chordoma who responded to combination chemotherapy consisting of cycles of vincristine/cyclophosphamide/doxorubicin alternating with etoposide/ifosfamide. She has been off chemotherapy for 2 years and is well at age 5., (Copyright © 2011 Wiley Periodicals, Inc.)

A 43-year-old man with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), including long-standing optic disc swelling, had sudden painless vision loss in the left eye. Brain MRI revealed an intracranial mass adjacent to the left optic nerve and enhancement of the optic nerve. The mass decreased in size following chemotherapy for myeloma with some recovery of vision. This represents a unique case of optic neuropathy due to presumed plasmacytoma in osteosclerotic IgA myeloma and POEMS syndrome.

Purpose: To present a case of Haemangiopericytoma (HPC), a rare neopalsm which originates from the vascular pericytes. HPC occurs most commonly in adults. Only 5-10% of cases occur in children. Congenital orbital HPC is generally unknown in the field of ophthalmology., Material and Methods: A case of congenital, large exophthalmus is reported in a 1 day old male neonate. Imaging studies demonstrated a vascular, orbital mass involving skull base and cranial fossa., Results: The diagnosis of HPC was established after histological exmination. Lesion did not qualify to surgical resection. The child was treated with chemotherapy for 10 months and a great regression of tumor was noted. There was no tumor recurrence during 4 years of a follow up., Conclusions: Chemotherapy may have a significant role in the treatment of infants with nonoperative malignant hemangiopericytoma.

Medulloepithelioma of the central nervous system (CNS) is an uncommon primitive neuroectodermal tumor (PNET) usually occurring in early childhood. It is characterized by highly malignant behavior with a propensity for progression, recurrence, and dissemination despite intensive therapy. Due to its rarity, the optimal management is still unknown. However, gross total resection (GTR) has been considered crucial to achieve cure. In this article, the authors report on 2 cases of CNS medulloepithelioma in which long-term survival (more than 6 years) could be achieved despite evidence of, or suspected postoperative residual disease with an otherwise dismal prognosis.The patients were treated according to different strata of the protocol for primitive neuroectodermal tumors (PNET) of the German-Austrian multicenter trial of the German Society for Pediatric Oncology and Hematology (GPOH) for childhood brain tumors (HIT 2000). Treatment included postoperative hyperfractionated radiotherapy of the craniospinal axis followed by a boost to the tumor site in combination with chemotherapy. A review of the 2 reported and 37 previously published cases confirmed GTR and older age as positive prognostic factors.

Introduction: Chordoma is a rare and a slow-growing tumor originating from the notochord and commonly localized in the skull base. Surgery and occasionally radiotherapy have emerged as the treatments of choice. In the relapsed situations available treatment options are strictly limited; however, recently molecularly targeted agents have been proposed to be of potential beneficial value., The Case: A 63-year-old male presenting with seizures and an extradural mass in the left brain hemisphere. An attempt to resect the tumor was followed by severe bradycardia when manipulating with the dura and therefore discontinued. It was considered too hazardous even to take a biopsy specimen. The tumor was considered radiologically and macroscopically as a chordoma. As the tumor progressed after radiotherapy, chemotherapy with erlotinib in combination with cetuximab was initiated. This treatment was interrupted due to progressive disease and toxicity. However, combination treatment with erlotinib and bevacizumab normalized the uptake of [11C]methionine PET signal and resulted in a slight tumor shrinkage on MRI. The patient is still (March 2011) free of symptoms, without cranial nerve deficits or seizures., Discussion: This report shows that erlotinib and bevacizumab in combination may completely quench the transport of the essential amino acid methionine to a treatment refractory intracranial tumor bearing radiological and clinical characteristics of a chordoma. Further studies are necessary to establish this strategy as a treatment option for this indication.

Object: Pediatric cerebellar astrocytomas with pilomyxoid features include classic pilomyxoid astrocytomas (PMAs) and intermediate pilomyxoid tumors (IPTs). Since the original description of PMA in 1999, most reports in the literature have described PMAs arising from the hypothalamic/chiasmatic region. To the authors' knowledge, PMAs arising from the posterior fossa have not been discussed in the neurosurgical literature. Intermediate pilomyxoid tumors, or tumors with pathological features of both pilocytic astrocytoma (PA) and PMA, have only recently been described. In this article, the authors present 2 cases that fall within the spectrum of pediatric cerebellar PMA-including a classic PMA and an intermediate pilomyxoid tumor. The authors compare the radiological presentation, surgical results, and postoperative course to findings in a cohort of 15 patients with cerebellar PAs., Methods: Between 2003 and 2010, 2 patients with pilomyxoid-spectrum astrocytomas underwent treatment at Vanderbilt Children's Hospital. One was a 22-month-old girl who presented with progressive gait disturbance and falls. The other was a 4-year-old girl who presented with ataxia and generalized weakness. In a retrospective review of pediatric cerebellar neoplasms resected by the senior author during this period, these tumors comprised 4% of cerebellar neoplasms and approximately 10% of cerebellar glial neoplasms., Results: Both patients were treated with midline suboccipital craniotomy for resection. In both cases, tumor invasion anteriorly into the brainstem prevented gross-total resection. the patient in Case 1 was placed on chemotherapy following pathological diagnosis and later developed definitive evidence of leptomeningeal dissemination (LD) 3 years after the operation. The patient in Case 2 was placed on chemotherapy after exhibiting progressive evidence of local recurrence (findings were negative for LD) 12 months following resection., Conclusions: Pediatric patients with cerebellar pilomyxoid-spectrum astrocytomas appear to suffer higher rates of local recurrence and LD than pediatric patients with cerebellar PAs.

Object: The standard surgical treatment for meningiomas is total resection, but the complete removal of skull base meningiomas can be difficult for several reasons. Thus, the management of certain meningiomas of the skull base--for example, those involving basal vessels and cranial nerves--remains a challenge. In recent reports it has been suggested that somatostatin (SST) administration can cause growth inhibition of unresectable and recurrent meningiomas. The application of SST and its analogs is not routinely integrated into standard treatment strategies for meningiomas, and clinical studies proving growth-inhibiting effects do not exist. The authors report on their experience using octreotide in patients with recurrent or unresectable meningiomas of the skull base., Methods: Between January 1996 and December 2010, 13 patients harboring a progressive residual meningioma (as indicated by MR imaging criteria) following operative therapy were treated with a monthly injection of the SST analog octreotide (Sandostatin LAR [long-acting repeatable] 30 mg, Novartis). Eight of 13 patients had a meningioma of the skull base and were analyzed in the present study. Postoperative tumor enlargement was documented in all patients on MR images obtained before the initiation of SST therapy. All tumors were benign. No patient received radiation or chemotherapy before treatment with SST. The growth of residual tumor was monitored by MR imaging every 12 months., Results: Three of the 8 patients had undergone surgical treatment once; 3, 2 times; and 2, 3 times. The mean time after the last meningioma operation (before starting SST treatment) and tumor enlargement as indicated by MR imaging criteria was 24 months. A total of 643 monthly cycles of Sandostatin LAR were administered. Five of the 8 patients were on SST continuously and stabilized disease was documented on MR images obtained in these patients during treatment (median 115 months, range 48-180 months). Three of the 8 patients interrupted treatment: after 60 months in 1 case because of tumor progression, after 36 months in 1 case because of side effects, and after 36 months in 1 case because the health insurance company denied cost absorption., Conclusions: Although no case of tumor regression was detected on MR imaging, the study results indicated that SST analogs can arrest the progression of unresectable or recurrent benign meningiomas of the skull base in some patients. It remains to be determined whether a controlled prospective clinical trial would be useful.

Pathologic proliferation of the plasma cell population can produce a wide spectrum of disorders, ranging from benign solitary plasmacytoma to malignant multiple myeloma. The presentation of the resulting disease can be either localized or systemic, depending on the affected area. Multiple myeloma typically presents with systemic symptoms secondary to skeletal lytic lesions, anemia, renal failure, infection, and hyperviscosity syndrome; a diagnosis of multiple myeloma is not suspected in the absence of these features. Multiple myeloma of the skull base is very rare. We present the case of a 66-year-old man who came to us with a 2-year history of disequilibrium and who was found to have multiple myeloma with extensive involvement of the skull base.

Trabectedin therapy was prescribed for a patient with radiation-induced sarcoma. Two doses of trabectedin were given before therapy was discontinued with the patient experiencing renal and liver failure. Despite discontinuing trabectedin the patient continued to experience increases in liver transaminases, bilirubin, blood urea nitrogen, and serum creatinine. Hemodialysis was initiated with no improvement. With all other causes being ruled out, trabectedin likely caused hepatic and renal failure leading to death in this patient. Recent literature suggests that patients may benefit from prophylactic dexamethasone as a means of reducing hepatic toxicity.

Introduction: Squamous cell carcinoma of the temporal bone is a rare entity. Only a few cases have been reported in the literature and even fewer describe bilateral tumours. Because its clinical presentation resembles chronic otitis media or otitis externa, diagnosis could be delayed., Case Report: A case is presented of bilateral squamous cell carcinoma of the temporal bone in a 66 year old woman. The patient underwent a left subtotal petrosectomy followed by a right subtotal petrosectomy a month later., Conclusions: Early diagnosis is directly related to patient prognosis. However, prognosis remains poor and the surgical treatment is a challenge for the experienced skull base surgeon., (Copyright 2009 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: We report a rare case of small cell carcinoma originating from the right cavernous sinus in a 55-year-old male. The patient had sudden onset of right abducens palsy following right oculomotor palsy., Methods: Post-contrast T1-weighted MRI revealed a mass lesion of 3-cm maximum size occupying the right cavernous sinus and extending to the right middle cranial fossa. After biopsy via the frontozygomatic approach, one radiosurgery treatment was followed by four cycles of chemotherapy (cisplatin together with VP-16 therapy), after which the lesion diminished dramatically in size., Results: Complete remission has currently been achieved. The patient recovered from the extraocular muscle paresis and returned to his previous work. Although it is considered possible that small cell carcinoma can occur wherever neuroendocrine cells exist, a lesion originating in the cranium is extremely rare. To the best of our knowledge, this is the first report of small cell carcinoma of intracranial origin.

Angiosarcoma is a rare tumour of endothelial cell origin whilst malignant skull base tumours are highly unusual in paediatric patients. This case reports an angiosarcoma involving the clivus and basi-sphenoid region of the skull base, in a 1-year-old boy. This tumour is extremely rare in childhood, particularly in this site. The histological features were consistent with a high-grade haemangioendothelioma, categorised as an angiosarcoma. The characteristics of this rare malignancy and the challenges in its management are discussed. This is the youngest reported patient, to our knowledge, with an angiosarcoma of the skull base.

Background: Imatinib (IM) is active in advanced chordoma. The evidence of upstream and/or downstream mammalian target of rapamycin (mTOR) pathway activation prompted us to combine an mTOR inhibitor, sirolimus, to IM in IM-resistant advanced chordoma., Patients and Methods: Since July 2007, 10 progressive advanced chordoma patients with secondary resistance to IM, and biochemical and/or immunohistochemical evidence of upstream and/or downstream mTOR effector activation, started IM (400 mg/day) plus sirolimus (2 mg/day) on a named basis., Results: The mean treatment duration was 9 months. Of nine patients assessable for response, at 3 months, we had one RECIST partial response (PR), seven stable disease (SD) and one progressive disease (PD). According to Choi criteria applied even to magnetic resonance imaging, we had seven PR (> or =10% decrease in size in four cases), one SD and one PD. Seven patients had a positron emission tomography response. The clinical benefit [RECIST complete response + PR + SD > or =6 months] was 89%. Pretreatment mTOR effectors analysis carried out in nine cases was positive in all patients (AKT activation in six patients, S6Sp6 expression/activation in seven). Post-treatment biopsy in one responsive patient confirmed S6 switch off., Conclusion: In addition to PDGFRB, mTOR pathway can be activated in chordomas and the combination of IM plus rapalogs may be effective in IM-resistant chordomas.

Introduction: Cranio-cervical instability is, in some cases, the main surgical concern in posterior skull base tumors. We report on a case in which a solitary plasmacytoma of the skull base presented with cranio-cervical instability. Vertebral artery was injured during surgery. The surgical anatomy is reviewed, with emphasis in vascular complications avoidance., Case Report: A 66 year-old woman was diagnosed of a cranial base solitary plasmacytoma and treated with radio and chemotherapy with complete remission. After receiving that treatment, she presented with tetraparesis and a cranio-cervical instability was diagnosed. She was operated on, under cranial traction, of posterior occipito-cervical instrumentation with C1 to C2 transarticular Magerl screws. The right vertebral artery was injured during surgery without additional neurological deficit. Two years after the operation she remains independent for daily activities., Conclusions: Transarticular screws at the C1 to C2 level of the cervical spine may provide rigid fixation in posterior cranio-cervical instrumentation for osteolytic lesions, but there is a risk of injury to the vertebral artery, specially when some variations in the surgical anatomy exist.

Purpose: To analyze the long-term outcomes in patients with skull base meningiomas (SBMNGs) treated with Gamma Knife radiosurgery (GKRS)., Methods and Materials: Of the 98 consecutive patients with SBMNGs treated with GKRS between 1998 and 2002, 63 were followed up for more than 48 months. The mean (+/-SD) age of the patients was 50 +/- 12 years, the mean tumor volume was 6.5 cm(3) (range, 0.5-18.4 cm(3)), the mean marginal dose was 12.6 Gy (range, 7.0-20.0 Gy), and the mean follow-up duration was 77 +/- 18 months. The mean number of shots was 13.7 +/- 3.8. The tumor volume was decreased at the last follow-up in 28 patients (44.4%) and increased in 6 (9.6%). The actuarial tumor control rate was 90.2% at 5 years. No notable prognostic factor related to tumor control was identified. Ten patients (15.9%) with a cranial neuropathy showed unfavorable outcomes. The rate of improvement in patients with a cranial neuropathy was 45.1%. Age >70 years was likely correlated with an unfavorable outcome in patients with cranial neuropathy (odds ratio = 0.027; p = 0.025; 95% confidence interval 0.001-0.632). Cavernous sinus location was significantly associated with improvement of a cranial neuropathy (odds ratio = 7.314; p = 0.007; 95% confidence interval 1.707-31.34)., Conclusions: Gamma Knife radiosurgery is an effective modality for the treatment of SBMNGs and provides favorable outcomes in patients with cranial neuropathy, even in the long-term follow-up period. However, radiosurgery for patients with no or only mild symptoms should be performed cautiously because neither complication rate is low enough to be negligible, especially in elderly patients. A cranial neuropathy by MNGs involving the cavernous sinus seems to have a higher chance of improvement after radiosurgery than other SBMNGs.

Lymphomas can occur throughout the body, but are relatively rare in the sphenoid region. The clinical presentations are atypical, ranging from nasal symptoms, pituitary hormone dysfunction and neurological impairment. We report a 63-year-old female patient who suffered nasal discharge, retro-ocular pain and left lateral gaze palsy for 3 months. Cranial MRI revealed sellar and suprasellar lesions involving the clivus, cavernous sinus and sphenoid sinus. The patient was treated for chronic sphenoid sinusitis. Histopathological review for possible misdiagnosis was arranged owing to treatment failure 1 month later. The final diagnosis was primary large B-cell lymphoma, which was confirmed by immunohistochemical study and systemic survey. The symptoms of sellar lymphoma resemble those of chronic sphenoid sinusitis. MRI and hematoxylin and eosin histological examination can accurately diagnose most cases. Immunohistochemistry assay is recommended in equivocal cases and provides a more detailed tumor classification.

We describe an extremely rare example of Ewing's sarcoma (ES)/peripheral primitive neuroectodermal tumour (pPNET) originating from the jugular foramen. The patient was a 10-year-old boy who presented with progressive symptoms due to right lower cranial nerve palsies. Computed tomographic (CT) scan and magnetic resonance imaging (MRI) revealed a tumour at the right jugular foramen which showed extra-cranial extension. Open biopsy of the extra-cranial lesion was performed, and diagnosis of ES/pPNET was made by histopathological, immunohistochemical and genetic investigations. The patient received a combination of multi-drug chemotherapy and irradiation. By 12 months after the diagnosis, MRI showed complete remission of the lesion, and the patient has been well apart from slight dysphagia. Previously, there was only one report of a jugular foramen ES/pPNET and in which treatment had failed. To our best knowledge, this is the first patient treated successfully with chemoradiotherapy.

Background: Malignant melanoma of the rhinobasal mucosa is very rare and makes up less than one percent of all malignant melanomas. Symptoms are unspecific in most cases, and patients often present with large tumours. During the past two decades, a variety of therapeutic modalities has been proposed., Materials and Methods: In a retrospective quality assessment, we analysed the charts of fifteen consecutive patients suffering from malignant melanoma of the skull base who where treated in our department since 1993. The influence of specific surgical and adjuvant therapy on recurrence and outcome was evaluated., Results: Initial symptoms were unspecific in all patients. Thus, melanoma was an accidental finding of a biopsy or sinus surgery in most patients, including all cases with amelanotic melanoma. All patients underwent surgery as the initial treatment, in 8 cases followed by adjuvant therapy. In these patients the disease specific survival was slightly better than in patients treated with surgery only. When recurrence was treated by radical mutilating surgery, this did not influence the overall prognosis., Conclusion: We conclude from our data and analysis of literature that the prognosis of MM has not developed favourably during the past two decades. Radiation therapy and adjuvant immuno- or chemotherapy seems to have a positive impact. Mutilating surgery is usually not indicated nor is it associated with an improvement of outcome.

Burkitt lymphoma (BL) is a rapidly dividing tumor that commonly presents itself in the jaw in its endemic form and the abdomen in the sporadic type. Central nervous system involvement at diagnosis is not uncommon, but there have been no previously published reports of BL involving the clivus. Increased tumor burden is associated with complications such as tumor lysis syndrome, and recognition of unusual presentations is important for timely management. We report 3 patients with BL involving the clivus at diagnosis.

Meningioma tumor growth involves the subarachnoid space that contains the cerebrospinal fluid. Modeling tumor growth in this microenvironment has been associated with widespread leptomeningeal dissemination, which is uncharacteristic of human meningiomas. Consequently, survival times and tumor properties are varied, limiting their utility in testing experimental therapies. We report the development and characterization of a reproducible orthotopic skull-base meningioma model in athymic mice using the IOMM-Lee cell line. Localized tumor growth was obtained by using optimal cell densities and matrigel as the implantation medium. Survival times were within a narrow range of 17-21 days. The xenografts grew locally compressing surrounding brain tissue. These tumors had histopathologic characteristics of anaplastic meningiomas including high cellularity, nuclear pleomorphism, cellular pattern loss, necrosis and conspicuous mitosis. Similar to human meningiomas, considerable invasion of the dura and skull and some invasion of adjacent brain along perivascular tracts were observed. The pattern of hypoxia was also similar to human malignant meningiomas. We use bioluminescent imaging to non-invasively monitor the growth of the xenografts and determine the survival benefit from temozolomide treatment. Thus, we describe a malignant meningioma model system that will be useful for investigating the biology of meningiomas and for preclinical assessment of therapeutic agents.