Distribution of GOPC:ROS1 and other ROS1 fusions in glioma types

The ROS proto-oncogene 1 (ROS1) gene is rearranged in various cancers. The translated fusion protein presents an attractive therapeutic target, since specific inhibitors have been approved for several tumor types. In glioma, ROS1 fusions are frequent within infantile hemispheric glioma, and single case reports on occurrences in other glioma types exist. However, a comprehensive analysis spanning the full width of glioma types and subtypes is lacking. We here assessed the spectrum and distribution of ROS1 fusions by screening >20,000 glioma cases for typical chromosomal alterations, with subsequent RNA-sequencing for confirmation of candidate cases. ROS1 fusions were identified in 16 cases, from low grade pilocytic astrocytoma WHO grade 1 to glioblastoma, IDH wildtype WHO grade 4. Thus, despite being enriched in some tumor types, ROS1 fusions are not pathognomonic for specific glioma types and may constitute a relevant target in a variety of cases.

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Glioblastoma multiforme as a secondary malignancy following stereotactic radiosurgery of a meningioma: case report

Neurosurgical FOCUS ◽

10.3171/2019.3.focus1948 ◽

2019 ◽

Vol 46 (6) ◽

pp. E11 ◽

Cited By ~ 1

Author(s):

Jason J. Labuschagne ◽

Dinoshan Chetty

Keyword(s):

Glioblastoma Multiforme ◽

Stereotactic Radiosurgery ◽

Single Case ◽

Case Reports ◽

Rare Complication ◽

Secondary Malignancy ◽

Surgical Removal ◽

Who Grade ◽

Grade Ii ◽

Who Grade Ii Meningioma

The documentation and exact incidence of stereotactic radiosurgery (SRS)–induced neoplasia is not well understood, with most literature restricted to single case reports and single-center retrospective reviews. The authors present a rare case of radiosurgery-induced glioblastoma multiforme (GBM) following radiosurgical treatment of a meningioma. A 74-year-old patient with a sporadic meningioma underwent radiosurgery following surgical removal of a WHO grade II meningioma. Eighteen months later she presented with seizures, and MRI revealed an intraaxial tumor, which was resected and proven to be a glioblastoma. As far as the authors are aware, this case represents the third case of GBM following SRS for a meningioma. This report serves to increase the awareness of this possible complication following SRS. The possibility of this rare complication should be explained to patients when obtaining their consent for radiosurgery.

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Supracerebellar infratentorial endoscopically controlled resection of pineal lesions: case series and operative technique

Journal of Neurosurgery Pediatrics ◽

10.3171/2011.8.peds1157 ◽

2011 ◽

Vol 8 (6) ◽

pp. 554-564 ◽

Cited By ~ 22

Author(s):

Timothy Uschold ◽

Adib A. Abla ◽

David Fusco ◽

Ruth E. Bristol ◽

Peter Nakaji

Keyword(s):

Single Case ◽

Clinical Manifestations ◽

Case Series ◽

Pineal Region ◽

Third Ventriculostomy ◽

Low Grade ◽

Who Grade ◽

Estimated Blood Loss ◽

The Mean

Object The heterogeneous clinical manifestations and operative characteristics of pathological entities in the pineal region represent a significant challenge in terms of patient selection and surgical approach. Traditional surgical options have included endoscopic transventricular resection; open supratentorial microsurgical approaches through the midline, choroidal fissure, lateral ventricle, and tentorium; and supracerebellar infratentorial (SCIT) approaches through the posterior fossa. The object of the current study was to review the preoperative characteristics and outcomes for a cohort of patients treated purely via the novel endoscopically controlled SCIT approach. Methods A single-institution series of 9 consecutive patients (4 male and 5 female patients [10 total cases]; mean age 21 years, range 6–37 years) treated via the endoscopically controlled SCIT approach for a pathological entity in the pineal region was retrospectively reviewed. The mean follow-up time was 13.2 months. Results The endoscopically controlled SCIT approach was successfully used to approach a variety of pineal lesions, including pineal cysts (6 patients), epidermoid tumor, WHO Grade II astrocytoma (initial biopsy and recurrence), and malignant mixed germ cell tumor (1 patient each). Gross-total resection and/or adequate cyst fenestration was achieved in 8 cases. Biopsy with conservative debulking was performed for the single case of low-grade astrocytoma and again at the time of recurrence. The mean preoperative tumor and cyst volumes were 9.9 ± 4.4 and 3.7 ± 3.2 cm3, respectively. The mean operating times were 212 ± 71 minutes for tumor cases and 177 ± 72 minutes for cysts. Estimated blood loss was less than 150 ml for all cases. A single case (pineal cyst) was converted to an open microsurgical approach to enhance visualization. There were no operative complications, as well as no documented CSF leaks, additional CSF diversion procedures, or air emboli. Seven patients underwent concomitant third ventriculostomy into the quadrigeminal cistern. At the time of the last follow-up evaluation, all patients had a stable or improved modified Rankin Scale score. Conclusions The endoscopically controlled SCIT approach may be used for the biopsy and resection of appropriately selected solid tumors of the pineal region, in addition to the fenestration and/or resection of pineal cysts. Preoperative considerations include patient presentation, anticipated disease and vascularity, degree of local venous anatomical distortion, and selection of optimal paramedian trajectory.

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MODL-11. COMPARISON OF HUMAN & MURINE PA/PXA CHARACTERISTICS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.585 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii413-iii413

Author(s):

Alexander C Sommerkamp ◽

Pengbo Sun ◽

Annika K Wefers ◽

Britta Ismer ◽

Kathrin Schramm ◽

...

Keyword(s):

Immune Cell ◽

Pleomorphic Xanthoastrocytoma ◽

Braf V600e ◽

Cell Infiltration ◽

Low Grade ◽

Immune Cell Infiltration ◽

Preclinical Research ◽

Who Grade ◽

Pediatric Tumor ◽

Tumor Types

Abstract Pediatric low-grade gliomas (pLGGs) are the most common brain tumors in children. Despite recent advances in the molecular characterization of this heterogeneous set of tumors, the separation of specific tumor types is still not fully established. Pilocytic astrocytoma (PA; WHO grade I) and pleomorphic xanthoastrocytoma (PXA; WHO grade II) are two pLGG types that can be difficult to distinguish based on histology alone. Even though their clinical course is different, they are often grouped as ‘pLGG’ in clinical trials (and therefore treated similarly). Based on a cohort of 89 human pediatric tumor samples, we show that PAs and PXAs have clearly distinct methylation and transcriptome profiles. The difference in gene expression is mainly caused by cell cycle- and development-associated genes, suggesting a key difference in the regulatory circuits involved in tumor growth. In addition to BRAF V600E, we found NTRK fusions and a previously unknown EGFR:BRAF fusion as mutually exclusive driving events in PXAs. Both tumor types show marked signs of immune cell infiltration, but with significant qualitative differences, which might represent therapeutic vulnerabilities. To pave the way for further research on PA and PXA, we developed corresponding mouse models using the virus-based RCAS system, which allows introduction of an oncogenic driver into immunocompetent mice for molecular and preclinical research. The murine tumors do not only histologically resemble their human counterparts but also show a similar growth behavior. Expression analysis revealed that the murine PXAs have a stronger gene signature of proliferation and immune cell infiltration compared to PAs.

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Rosette-forming glioneuronal tumor: an illustrative case and a systematic review

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa116 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Caleb P Wilson ◽

Arpan R Chakraborty ◽

Panayiotis E Pelargos ◽

Helen H Shi ◽

Camille K Milton ◽

...

Keyword(s):

Systematic Review ◽

Aggressive Behavior ◽

Case Reports ◽

World Health ◽

Glioneuronal Tumor ◽

Illustrative Case ◽

Low Grade ◽

Search Term ◽

Who Grade ◽

Mri Features

Abstract Background Rosette-forming glioneuronal tumors (RGNTs) are rare, low-grade, primary CNS tumors first described in 2002 by Komori et al. RGNTs were initially characterized as a World Health Organization (WHO) grade I tumors typically localized to the fourth ventricle. Although commonly associated with an indolent course, RGNTs have the potential for aggressive behavior. Methods A comprehensive search of PubMed and Web of Science was performed through November 2019 using the search term “rosette-forming glioneuronal tumor.” Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. English, full-text case reports and series with histopathological confirmation were included. Patient demographics, presentations, MRI features, tumor location, treatment, and follow-up of all 130 cases were extracted. Results A 19-year-old man with a history of epilepsy and autism presented with acute hydrocephalus. MRI scans from 2013 to 2016 demonstrated unchanged abnormal areas of cortex in the left temporal lobe with extension into the deep gray-white matter. On presentation to our clinic in 2019, the lesion demonstrated significant progression. The patient’s tumor was identified as RGNT, WHO grade I. One hundred thirty patients were identified across 80 studies. Conclusion RGNT has potential to transform from an indolent tumor to a tumor with more aggressive behavior. The results of our systematic review provide insight into the natural history and treatment outcomes of these rare tumors.

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Testis Sparing Surgery in Pediatric Testicular Tumors

Cancers ◽

10.3390/cancers12102867 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2867

Author(s):

Cezanne D. Kooij ◽

Caroline C.C. Hulsker ◽

Mariëtte E.G. Kranendonk ◽

József Zsiros ◽

Annemieke S. Littooij ◽

...

Keyword(s):

Treatment Option ◽

Pediatric Patients ◽

Single Case ◽

Case Reports ◽

Germ Cell Tumors ◽

Testicular Atrophy ◽

Low Grade ◽

Testicular Tumors ◽

Safe Treatment ◽

Safe Treatment Option

Objective: The purpose of this review is to evaluate the outcomes of testis sparing surgery (TSS) and to investigate under which circumstances TSS can be considered a safe treatment option in pediatric patients with testicular tumors. Methods: A database search was performed in Cochrane, Pubmed, and Embase for studies that focused on TSS as treatment for testicular tumors in the pediatric population, excluding reviews and single case reports. Results: Twenty studies, describing the surgical treatment of 777 patients with testicular tumors, were included in the analysis. The majority of pediatric patients with benign germ cell tumors (GCTs) (mean age: 3.7 years) and sex cord-stromal tumors (SCSTs) (mean age: 6.6 years) were treated with TSS, 61.9% and 61.2%, respectively. No cases of testicular atrophy occurred. Four of the benign GCTs, i.e., three teratomas and one epidermoid cyst, recurred. No cases of recurrence were reported in patients with SCSTs. Of the 243 malignant GCTs (mean age: 4.2 years), only one patient had TSS (0.4%). Conclusion: TSS is a safe treatment option for prepubertal patients less than 12 years of age with benign GCTs and low grade SCSTs.

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Challenges in the Intraoperative Consultation of Low-Grade Epilepsy-Associated Neuroepithelial Tumors by Cytomorphology in Squash Preparations

Acta Cytologica ◽

10.1159/000521249 ◽

2022 ◽

pp. 1-7

Author(s):

Olcay Kurtulan ◽

Burçak Bilginer ◽

Figen Soylemezoglu

Keyword(s):

Ganglion Cells ◽

Case Reports ◽

Daily Practice ◽

Individual Case ◽

Glioneuronal Tumor ◽

Dysembryoplastic Neuroepithelial Tumor ◽

Low Grade ◽

Diagnostic Challenge ◽

Neuroepithelial Tumors ◽

Tumor Types

Introduction: Low-grade epilepsy-associated neuroepithelial tumors (LEATs) create a diagnostic challenge in daily practice and intraoperative pathological consultation (IC) in particular. Squash smears are extremely useful in IC for accurate diagnosis; however, the knowledge on cytopathologic features of LEATs is based on individual case reports. Here, we discuss the 3 most common and well-established entities of LEATs: ganglioglioma (GG), dysembryoplastic neuroepithelial tumor (DNT), and papillary glioneuronal tumor (PGNT). Methods: Thirty patients who underwent surgery for GG, DNT, and PGNT between 2001 and 2021 were collected. Squash smears prepared during intraoperative consultation were reviewed by 1 cytopathologist and an experienced neuropathologist. Results: Among the 30 tumors, 16 (53.3%) were GG, 11 (36.6%) DNT, and 3 (10%) PGNT. Cytomorphologically, all of the 3 tumor types share 2 common features such as dual cell population and vasculocentric pattern. GG smears were characteristically composed of dysplastic ganglion cells and piloid-like astrocytes on a complex architectural background of thin- to thick-walled vessels. DNT, on the other hand, showed oligodendroglial-like cells in a myxoid thin fibrillary background associated with a delicate capillary network. Common cytological features of PGNT were hyperchromatic cells with narrow cytoplasm surrounding hyalinized vessels forming a pseudopapillary pattern and bland cells with neuroendocrine nuclei dispersed in a neuropil background. Conclusion: A higher diagnostic accuracy can be obtained when squash smears are applied with frozen sections. However, it is important to integrate clinical and radiologic features of the patient as well as to know the cytopathologic features of the LEAT spectrum in the context of differential diagnosis to prevent misinterpretation in the IC.

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Comparison of diagnostic accuracy of 18F-FDG PET, 123I-IMT- and 99mTc-MIBI SPECT

Nuklearmedizin ◽

10.1055/s-0038-1623934 ◽

2006 ◽

Vol 45 (01) ◽

pp. 49-56 ◽

Cited By ~ 2

Author(s):

N. Özdemir-Sahin ◽

P. Hipp ◽

W. Mier ◽

M. Eisenhut ◽

J. Debus ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Fdg Pet ◽

Tumour Progression ◽

Roc Curves ◽

Low Grade ◽

Who Grade ◽

Pet Tracer ◽

Patient Groups ◽

99Mtc Mibi ◽

Mibi Spect

Summary Aim was to evaluates the diagnostic accuracy of the SPECTtracers 3-123I-α-methyl-L-tyrosine (IMT) and 99mTc(I)- hexakis(2-methoxyisobutylisonitrile) (MIBI) as well as the PET-tracer 2-18F-2-deoxyglucose (FDG) for detecting tumour progression in irradiated low grade astrocytomas (LGA). Patients, methods: We examined 91 patients (56 males; 35 females; 44.7 ± 11.5 years), initially suffering from histologically proven LGAs (mean WHO grade II) and treated by stereotactic radiotherapy (59.0 ± 4.6 Gy). On average 21.9 ± 11.2 months after radiotherapy, patients presented new Gd-DTPA enhancing lesions on MRI, which did not allow a differentiation between progressive tumour (PT) and non-PT (nPT) at this point of time. PET scans (n=82) were acquired 45 min after injection of 208 ± 32 MBq FDG. SPECT scans started 10 min after injection of 269 ± 73 MBq IMT (n=68) and 15 min after injection of 706 ± 63 MBq MIBI (n=34). Lesions were classified as PT and nPT based on prospective follow-up (clinically, MRI) for 17.2 ± 9.9 months after PET/SPECT. Lesion-to-normal ratios (L/N) were calculated using contra lateraly mirrored reference regions for the SPECT examinations and reference regions in the contra lateral grey (GM) and white matter (WM) for FDG PET. Ratios were evaluated by Receiver Operating Characteristic (ROC) analysis. Results: In the patient groups nPT and PT, L/N ratios for FDG (GS) were 0.6 ± 0.3 vs. 1.2 ± 0.5 (p = 0.003), for FDG (WS) 1.2 ± 0.4 vs. 2.6 ± 0.4 (p <0.001), for IMT 1.1 ± 0.1 vs. 1.8 ± 0.4 (p <0.001) and for MIBI 1.6 ± 0.7 vs. 2.6 ± 2.2 (p = 0.554). Areas under the non-parametric ROC-curves were: 0.738 ± 0.059 for FDG (GS), 0.790 ± 0.057 for FDG (WS), 0.937 ± 0.037 for IMT and 0.564 ± 0.105 for MIBI. Conclusion: MIBI-SPECT examinations resulted in a low accuracy and especially in a poor sensitivity even at modest specificity values. A satisfying diagnostic accuracy was reached with FDG PET. Using WM as reference region for FDG PET, a slightly higher AUC as compared to GM was calculated. IMT yielded the best ROC characteristics and the highest diagnostic accuracy for differentiating between PT and nPT in irradiated LGA.

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Prognostic histopathologic features of canine glial tumors

Veterinary Pathology ◽

10.1177/03009858211025795 ◽

2021 ◽

pp. 030098582110257

Author(s):

Joshua L. Merickel ◽

G. Elizabeth Pluhar ◽

Aaron Rendahl ◽

M. Gerard O’Sullivan

Keyword(s):

Brain Tumor ◽

Median Survival ◽

Low Grade ◽

Astrocytic Tumors ◽

Translational Model ◽

Poor Survival ◽

Whole Brain ◽

Tumor Types ◽

Tumor Biopsies ◽

Prognostic Data

Gliomas are relatively common tumors in aged dogs (especially brachycephalic breeds), and the dog is proving to be useful as a translational model for humans with brain tumors. Hitherto, there is relatively little prognostic data for canine gliomas and none on outcome related to specific histological features. Histologic sections of tumor biopsies from 33 dogs with glioma treated with surgical resection and immunotherapy and 21 whole brains obtained postmortem were reviewed. Tumors were diagnosed as astrocytic, oligodendroglial, or undefined glioma using Comparative Brain Tumor Consortium criteria. Putative features of malignancy were evaluated, namely, mitotic counts, glomeruloid vascularization, and necrosis. For biopsies, dogs with astrocytic tumors lived longer than those with oligodendroglial or undefined tumor types (median survival 743, 205, and 144 days, respectively). Dogs with low-grade gliomas lived longer than those with high-grade gliomas (median survival 734 and 194 days, respectively). Based on analysis of tumor biopsies, low mitotic counts, absence of glomeruloid vascularization, and absence of necrosis correlated with increased survival (median 293, 223, and 220 days, respectively), whereas high mitotic counts, glomeruloid vascularization, and necrosis correlated with poor survival (median 190, 170, and 154 days, respectively). Mitotic count was the only histological feature in biopsy samples that significantly correlated with survival ( P < .05). Whole-brain analyses for those same histologic features had similar and more robust correlations, and were statistically significant for all features ( P < .05). The small size of biopsy samples may explain differences between biopsy and whole-brain tumor data. These findings will allow more accurate prognosis for gliomas.

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Post-Infectious Guillain–Barré Syndrome Related to SARS-CoV-2 Infection: A Systematic Review

Life ◽

10.3390/life11020167 ◽

2021 ◽

Vol 11 (2) ◽

pp. 167

Author(s):

Pasquale Sansone ◽

Luca Gregorio Giaccari ◽

Caterina Aurilio ◽

Francesco Coppolino ◽

Valentina Esposito ◽

...

Keyword(s):

Single Case ◽

Case Reports ◽

Case Series ◽

Guillain Barre Syndrome ◽

Response To Treatment ◽

Comprehensive Overview ◽

Fisher Syndrome ◽

Immunomodulating Therapy ◽

Guillain Barré Syndrome ◽

Guillain Barré

Background. Guillain-Barré syndrome (GBS) is the most common cause of flaccid paralysis, with about 100,000 people developing the disorder every year worldwide. Recently, the incidence of GBS has increased during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemics. We reviewed the literature to give a comprehensive overview of the demographic characteristics, clinical features, diagnostic investigations, and outcome of SARS-CoV-2-related GBS patients. Methods. Embase, MEDLINE, Google Scholar, and Cochrane Central Trials Register were systematically searched on 24 September 2020 for studies reporting on GBS secondary to COVID-19. Results. We identified 63 articles; we included 32 studies in our review. A total of 41 GBS cases with a confirmed or probable COVID-19 infection were reported: 26 of them were single case reports and 6 case series. Published studies on SARS-CoV-2-related GBS typically report a classic sensorimotor type of GBS often with a demyelinating electrophysiological subtype. Miller Fisher syndrome was reported in a quarter of the cases. In 78.1% of the cases, the response to immunomodulating therapy is favourable. The disease course is frequently severe and about one-third of the patients with SARS-CoV-2-associated GBS requires mechanical ventilation and Intensive Care Unit (ICU) admission. Rarely the outcome is poor or even fatal (10.8% of the cases). Conclusion. Clinical presentation, course, response to treatment, and outcome are similar in SARS-CoV-2-associated GBS and GBS due to other triggers.

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Analysis of Clinical, Imaging, and Pathologic Features of 36 Patients with Primary Intraspinal Primitive Neuroectodermal Tumors: A Case Series and Literature Review

Journal of Neurological Surgery Part A Central European Neurosurgery ◽

10.1055/s-0041-1723810 ◽

2021 ◽

Author(s):

Xuefeng Wei ◽

Xu Zhang ◽

Zimu Song ◽

Feng Wang

Keyword(s):

Literature Review ◽

Single Case ◽

Case Reports ◽

Case Series ◽

Subtotal Resection ◽

Study Cohort ◽

Primitive Neuroectodermal Tumors ◽

Pathologic Features ◽

Neuroectodermal Tumors ◽

The Mean

Abstract Background and Study Aims Primary intraspinal primitive neuroectodermal tumors (PNETs) account for ∼0.4% of all intraspinal tumors, but information about these tumors in the medical literature is limited to single case reports. We report four cases of primary intraspinal PNETs and present a systematic literature review of the reported cases. Materials and Methods We retrospectively reviewed and analyzed the clinical data of 4 patients with primary intraspinal PNETs who underwent neurosurgical treatment at our clinic between January 2013 and January 2020, and of 32 cases reported in the literature. Results The female-to-male ratio was 2.6:1. The mean patient age was 21.42 ± 15.76 years (range: 1–60 years), and patients <36 years of age accounted for 83.30% of the study cohort. Progressive limb weakness and numbness were the chief symptoms (accounting for ∼55.6%). The mean complaint duration was 0.89 ± 0.66 months for males and 2.72 ± 3.82 months for females (p = 0.028). Epidural (41.7%) was the most common site, and thoracic (47.3%) was the most frequent location. Most PNETs were peripheral, and magnetic resonance imaging (MRI) appearance was isointense or mildly hypointense on T1-weighted images and hyperintense on T2-weighted images. Homogeneous contrast enhancement was observed. The 1-year survival rate of patients who underwent chemoradiation after total or subtotal lesion resection was better compared with patients who did not undergo chemotherapy, radiotherapy, or total or subtotal resection. The modality of treatment was associated with survival time (p = 0.007). Conclusion Primary intraspinal PNETs mainly occur in young people with a female preponderance. In patients with a rapid loss of lower limb muscle strength and large intraspinal lesions on MRI, PNETs should be considered. Surgical resection and adjuvant radio chemotherapy are key prognostic factors.

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