A Case of Primary Intracranial Sarcoma, DICER1-Mutant, in a Child with a Germline DICER1 Mutation.

DICER1 syndrome is a tumor predisposition syndrome caused by abnormal micro-RNA processing which leads to a variety of benign and malignant neoplasms in many organ systems, including the central nervous system. This paper reports the case of a primary intracranial sarcoma, DICER1-mutant, in a patient with a germline DICER1 variant thought most likely to be de novo. The patient is a ten-year-old boy who presented acutely with altered level of consciousness, emesis, and left-sided weakness. Imaging revealed a large right frontal hemorrhagic lesion, which was urgently debulked. Histology demonstrated a high-grade sarcomatous lesion. Molecular studies revealed compound heterozygous DICER1 variants (a frame shift insertion and a missense mutation), and a KRAS missense mutation. The final pathologic diagnosis was rendered to be "primary intracranial sarcoma, DICER1-mutant". Germline genetic testing revealed that the patient possessed a germline DICER1 variant (parental testing was negative). A dramatic reduction in tumor size was precipitated via chemotherapy (ifosfamide, carboplatin, and etoposide) and radiotherapy (focal proton beam therapy). There was no evidence of residual disease at the primary site at the end of the therapy.

Early and isolated breast cancer metastasis to the pituitary: A case report and systematic review.

Background: Pituitary metastases (PMs) arising from breast cancer tend to occur many years following initial diagnosis, and after other systemic metastasis have been identified. Survival is generally considered to be poor. However, there are cases where patients present with an isolated metastatic lesion in the pituitary. Survival in this subset of patients has not been evaluated. We present a case of isolated PM that presented two years after initial diagnosis of breast cancer. We performed a systematic review of 38 breast cancer patients with PM. We report presentation, treatment strategy, and outcomes of breast cancer metastasis to the pituitary and highlight cases of isolated PM. Case Description: A 39 year old female presented with complaints of headache and polydipsia two years after diagnosis with breast cancer. Systemic workup was unremarkable, but brain imaging identified an isolated PM. Transsphenoidal debulking was performed with adjuvant radiation therapy (RT) targeted to the sellar region. Unfortunately, she passed away 9 months later from systemic progression. Conclusion: A total of 38 patients were included systematic review. Of these, 13 had isolated PM. Prevalent signs/ symptoms included visual disturbance, diabetes insipidus (DI), and hypothalamic dysfunction. Patients treated with surgical resection and adjuvant chemotherapy (ChT), or RT had better survival than those treated with resection alone. Patients that receive treatment for isolated PM may survive for many years without progression or recurrence.

Radiology reporting of low-grade glioma growth underestimates tumor expansion.

BACKGROUND: An important aspect in the management of patients with diffuse low-grade gliomas (LGGs) involves monitoring the lesions via serial magnetic resonance imaging (MRI). However, radiological interpretations of LGG interval scans are often qualitative and thus difficult to use clinically. METHODS: To contextualize these assessments, we retrospectively compared radiological interpretations of LGG growth or stability to volume change measured by manual segmentation. Tumor diameter was also measured in one, two, and three dimensions to evaluate reported methods for assessment of glioma progression, including RECIST criteria, Macdonald/RANO criteria, and mean tumor diameter/ellipsoid method. RESULTS: Tumors evaluated as stable by radiologists grew a median volume of 5.1 mL (11.1%) relative to the comparison scan, and those evaluated as having grown had a median volume increase of 13.3 mL (23.7%). Diameter-based measurements corresponded well but tended to overestimate gold standard segmented volumes. In addition, agreement with segmented volume measurements improved from 17.6 ± 8.0 to 4.5 ± 5.8 to 3.9 ± 3.6 mm for diameter and from 104.0 ± 96.6 to 25.3 ± 36.8 to 15.9 ± 21.3 mL for volume with radiological measurements in one, two, and three dimensions, respectively. Measurement overestimation increased with tumor size. CONCLUSIONS: Given accumulating evidence that LGG volume and growth are prognostic factors, there is a need for objective lesion measurement. Current radiological reporting workflows fail to appreciate and communicate the true expansion of LGGs. While volumetric analysis remains the gold standard for assessment of growth, careful diametric measurements in three dimensions may be an acceptable alternative.

Operative Complications with and without Image Guidance: A Systematic Review and Meta-Analysis of the Ommaya Reservoir Literature.

BACKGROUND: The use of image guidance (IG) in neurosurgery is ubiquitous, even though evidence from patient outcome data has remained limited to smaller, mostly observational, studies. Ommaya reservoir insertion (ORI) has been available as a treatment option for targeted intraventricular pharmacotherapy since the 1960s, far preceding the modern neuronavigation era. We conducted a systematic review and meta-analysis investigating the impact of IG on surgical outcome from ORI. METHODS: A systematic database search of MEDLINE and EMBASE was performed to identify studies on operative outcomes from ORI. Only studies reporting patient demographics and perioperative outcomes (hemorrhage, infection, malposition, malfunction, and mortality) were included. Study quality was assessed via MINORS criteria. RESULTS: Of the 3560 records screened, 43 studies met study inclusion criteria, for a total of 1995 ORI procedures. Pooled rates of outcome for IG compared with non-IG were 6.4% versus 14.1% for overall complications; 2.0% compared with 2.8% for catheter malfunction; 2.3% compared with 3.3% for catheter malposition; 0.7% compared with 4.5% for early infection; and 0.6% compared with 1.4% for mortality. Postoperative hemorrhage was increased at 3.4% compared with 2.4%. Subgroup analysis revealed a difference in early infection rate between frameless and frame-based IG at 0.0% versus 1.9%. Meta-regression revealed a relationship between publication date and all operative outcomes except for catheter malposition and hemorrhage. CONCLUSIONS: This study offers a historical context on the evolution of the practice of ORI and comprises the largest observational analysis of operative outcomes providing objective support for the use of IG in neurosurgery.

Impact of Functional Magnetic Resonance Imaging on Clinical Outcomes in a Propensity-Matched Low Grade Glioma Cohort.

BACKGROUND: This study aims to evaluate the impact of preoperative functional magnetic resonance imaging (fMRI) on clinical outcomes in patients with low grade glioma (LGG). METHODS: In a retrospective propensity-matched cohort study, we compared patients with LGG based on whether they underwent fMRI as part of preoperative assessment. Twelve patients with LGG who underwent preoperative fMRI were selected, and a contemporaneous group of 12 control patients with LGG who did not undergo fMRI were matched to the fMRI group based on age, sex, and 1p/19q status. RESULTS: fMRI group subjects tended to have more aggressive surgeries (67% resection, 33% biopsy) than the control group (33% resection, 67% biopsy). There were no significant differences in outcomes between the 2 groups. Time between clinical assessment and surgery tended to be longer in the fMRI group (6.3 ± 4.2 weeks) than in the control group (2.7 ± 2.2 weeks). Extent of resection was similar between the 2 cohorts. fMRI group subjects had lower preoperative functional status and tended to have a greater postoperative functional status improvement than control group subjects. Mean survival was not significantly different (fMRI group 5-year survival: 88.9%, control group 5-year survival: 61.1%). CONCLUSIONS: We evaluated the impact of preoperative fMRI in patients with LGG in this propensity-matched cohort study. This study has not demonstrated any significant difference in outcomes between the fMRI and control groups; however, there were nonsignificant trends for patients who underwent fMRI to undergo more aggressive surgical interventions and have a greater postoperative functional status improvement.

Tumor growth dynamics in serially-imaged low-grade glioma patients.

BACKGROUND: Diffuse low-grade gliomas (LGGs) are infiltrative, slow-growing primary brain tumors that remain relatively asymptomatic for long periods of time before progressing into aggressive and fatal high-grade gliomas. METHODS: We retrospectively identified LGG patients with numerous (≥ 8) serial magnetic resonance imaging (MRI) studies. Tumor volumes were measured by manual segmentation on serial imaging to study the natural history and growth of the lesion. Patient demographic information, tumor characteristics, and histological data were collected from electronic medical records and paper charts. RESULTS: Out of 74 LGG patients, 10 patients (13.5%) were identified to meet the study criteria with number of MRIs acquired ranging from 8 to 18 (median, 11.5) over a median of 79.7 months (range 39.8-113.8 months). Tumor diameter increased at a median of 2.17 mm/year in a linear trajectory. Cox regression analysis revealed that initial tumor volume was an independent predictor of time to clinical intervention, and Mann-Whitney U test found that patients younger than 50 years old had significantly slower-growing tumors. Clinical intervention was more likely for tumors above a volume threshold of 73.6 mL. CONCLUSION: We retrospectively analyzed the natural history of LGGs of patients managed at a single institution with numerous serial MRI scans. Comparisons of our cohort to the literature suggest that this is a subset of particularly slow-growing and low-risk tumors.

Image-guided Ommaya reservoir insertion for intraventricular chemotherapy: a retrospective series.

BACKGROUND: Ayub Ommaya proposed a surgical technique for subcutaneous reservoir and pump placement in 1963 to allow access to intraventricular cerebrospinal fluid (CSF). Currently, the most common indication for Ommaya reservoir insertion (ORI) in adults is for patients with hematologic or leptomeningeal disorders requiring repeated injection of chemotherapy into the CSF space. Historically, the intraventricular catheter has been inserted blindly based on anatomical landmarks. The purpose of this study was to examine short-term complication rates with ORI with image guidance (IG) and without image guidance (non-IG). METHODS: We retrospectively evaluated all operative cases of ORI from 2000 to 2014 by the senior author. Patient demographic data, surgical outcomes, and peri-operative complications were collected. Accurate placement and early (30-day) morbidity or mortality were considered primary outcomes. RESULTS: Fifty-five consecutive patients underwent ORI by the senior author over the study period (43.5 ± 16.6 years; 40.0% female). Indications for placement included acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and leptomeningeal carcinomatosis. There were seven (12.7%) total complications: three (37.5%) with no-IG versus four (8.5%) with IG. Catheter malpositions were significantly higher in the non-IG group at 37.5% compared to 2.1%. Catheters were also more likely to require multiple passes with non-IG at 25% compare to 0% with IG. There were no early infections in either group. CONCLUSIONS: We demonstrate improved accuracy and decreased complications using an image-guided approach compared with a traditional approach. Our results support routine use of intra-operative image guidance for proximal catheter insertion in elective ORI for intraventricular chemotherapy.

Functional Magnetic Resonance Imaging for Preoperative Planning in Brain Tumour Surgery.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is being increasingly used for the preoperative evaluation of patients with brain tumours. METHODS: The study is a retrospective chart review investigating the use of clinical fMRI from 2002 through 2013 in the preoperative evaluation of brain tumour patients. Baseline demographic and clinical data were collected. The specific fMRI protocols used for each patient were recorded. RESULTS: Sixty patients were identified over the 12-year period. The tumour types most commonly investigated were high-grade glioma (World Health Organization grade III or IV), low-grade glioma (World Health Organization grade II), and meningioma. Most common presenting symptoms were seizures (69.6%), language deficits (23.2%), and headache (19.6%). There was a predominance of left hemispheric lesions investigated with fMRI (76.8% vs 23.2% for right). The most commonly involved lobes were frontal (64.3%), temporal (33.9%), parietal (21.4%), and insular (7.1%). The most common fMRI paradigms were language (83.9%), motor (75.0%), sensory (16.1%), and memory (10.7%). The majority of patients ultimately underwent a craniotomy (75.0%), whereas smaller groups underwent stereotactic biopsy (8.9%) and nonsurgical management (16.1%). Time from request for fMRI to actual fMRI acquisition was 3.1±2.3 weeks. Time from fMRI acquisition to intervention was 4.9±5.5 weeks. CONCLUSIONS: We have characterized patient demographics in a retrospective single-surgeon cohort undergoing preoperative clinical fMRI at a Canadian centre. Our experience suggests an acceptable wait time from scan request to scan completion/analysis and from scan to intervention.