Diagnosis and Treatment of Pineal Region Tumors in Adults: A EURACAN Overview

Pineal region tumors are rare intracranial tumors, accounting for less than 1% of all adult intracranial tumor lesions. These lesions represent a histologically heterogeneous group of tumors. Among these tumors, pineal parenchymal tumors and germ cell tumors (GCT) represent the most frequent types of lesions. According to the new WHO 2021 classification, pineal parenchymal tumors include five distinct histotypes: pineocytoma (PC), pineal parenchymal tumors of intermediate differentiation (PPTID), papillary tumor of the pineal region (PTPR), pinealoblastoma (PB), and desmoplastic myxoid tumor of the pineal region, SMARCB1-mutant; GCTs include germinoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, mixed GCTs. Neuroradiological assessment has a pivotal role in the diagnostic work-up, surgical planning, and follow-up of patients with pineal masses. Surgery can represent the mainstay of treatment, ranging from biopsy to gross total resection, yet pineal region tumors associated with obstructive hydrocephalus may be surgically managed via ventricular internal shunt or endoscopic third ventriculostomy. Radiotherapy remains an essential component of the multidisciplinary treatment approach for most pineal region tumors; however, treatment volumes depend on the histological subtypes, grading, extent of disease, and the combination with chemotherapy. For localized germinoma, the current standard of care is chemotherapy followed by reduced-dose whole ventricular irradiation plus a boost to the primary tumor. For pinealoblastoma patients, postoperative radiation has been associated with higher overall survival. For the other pineal tumors, the role of radiotherapy remains poorly studied and it is usually reserved for aggressive (grade 3) or recurrent tumors. The use of systemic treatments mainly depends on histology and prognostic factors such as residual disease and metastases. For pinealoblastoma patients, chemotherapy protocols are based on various alkylating or platinum-based agents, vincristine, etoposide, cyclophosphamide and are used in association with radiotherapy. About GCTs, their chemosensitivity is well known and is based on cisplatin or carboplatin and may include etoposide, cyclophosphamide, or ifosfamide prior to irradiation. Similar regimens containing platinum derivatives are also used for non-germinomatous GCTs with very encouraging results. However, due to a greater understanding of the biology of the disease's various molecular subtypes, new agents based on targeted therapy are expected in the future. On behalf of the EURACAN domain 10 group, we reviewed the most important and recent developments in histopathological characteristics, neuro-radiological assessments, and treatments for pineal region tumors

Surgical treatment of symptomatic pineal cysts without hydrocephalus-meta-analysis of the published literature

Background To examine published data and assess evidence relating to safety and efficacy of surgical management of symptomatic pineal cysts without hydrocephalus (nhSPC), we performed a systematic review of the literature and meta-analysis. Methods Following the PRISMA guidelines, we searched Pubmed and SCOPUS for all reports with the query 'Pineal Cyst' AND 'Surgery' as of March 2021, without constraints on study design, publication year or status (PROSPERO_CRD:42,021,242,517). Assessment of 1537 hits identified 26 reports that met inclusion and exclusion criteria. Results All 26 input studies were either case reports or single-centre retrospective cohorts. The majority of outcome data were derived from routine physician-recorded notes. A total of 294 patients with surgically managed nhSPC were identified. Demographics: Mean age was 29 (range: 4-63) with 77% females. Mean cyst size was 15 mm (5-35). Supracerebellar-infratentorial approach was adopted in 90% of cases, occipital-transtentorial in 9%, and was not reported in 1%. Most patients were managed by cyst resection (96%), and the remainder by fenestration. Mean post-operative follow-up was 35 months (0-228). Presentation: Headache was the commonest symptom (87%), followed by visual (54%), nausea/vomit (34%) and vertigo/dizziness (31%). Other symptoms included focal neurology (25%), sleep disturbance (17%), cognitive impairment (16%), loss of consciousness (11%), gait disturbance (11%), fatigue (10%), 'psychiatric' (2%) and seizures (1%). Mean number of symptoms reported at presentation was 3 (0-9). Outcomes: Improvement rate was 93% (to minimise reporting bias only consecutive cases from cohort studies were considered, N= 280) and was independent of presentation. Predictors of better outcomes were large cyst size (OR= 5.76; 95% CI: 1.74-19.02) and resection over fenestration (OR= 12.64; 3.07-52.01). Age predicted worse outcomes (OR= 0.95; 0.91-0.99). Overall complication rate was 17% and this was independent of any patient characteristics. Complications with long-term consequences occurred in 10 cases (3.6%): visual disturbance (3), chronic incisional pain (2), sensory disturbance (1), fatigue (1), cervicalgia (1), cerebellar stroke (1) and mortality due to myocardial infarction (1). Conclusions Although the results support the role of surgery in the management of nhSPCs, they have to be interpreted with a great deal of caution as the current evidence is limited, consisting only of case reports and retrospective surgical series. Inherent to such studies are inhomogeneity and incompleteness of data, selection bias and bias related to assessment of outcome carried out by the treating surgeon in the majority of cases. Prospective studies with patient-reported and objective outcome assessment are needed to provide higher level of evidence.Peer reviewe

HyperProbe consortium: innovate tumour neurosurgery with innovative photonic solutions

Recent advancements in imaging technologies (MRI, PET, CT, among others) have significantly improved clinical localisation of lesions of the central nervous system (CNS) before surgery, making possible for neurosurgeons to plan and navigate away from functional brain locations when removing tumours, such as gliomas. However, neuronavigation in the surgical management of brain tumours remains a significant challenge, due to the inability to maintain accurate spatial information of pathological and healthy locations intraoperatively. To answer this challenge, the HyperProbe consortium have been put together, consisting of a team of engineers, physicists, data scientists and neurosurgeons, to develop an innovative, all-optical, intraoperative imaging system based on (i) hyperspectral imaging (HSI) for rapid, multiwavelength spectral acquisition, and (ii) artificial intelligence (AI) for image reconstruction, morpho-chemical characterisation and molecular fingerprint recognition. Our HyperProbe system will (1) map, monitor and quantify biomolecules of interest in cerebral physiology; (2) be handheld, cost-effective and user-friendly; (3) apply AI-based methods for the reconstruction of the hyperspectral images, the analysis of the spatio-spectral data and the development and quantification of novel biomarkers for identification of glioma and differentiation from functional brain tissue. HyperProbe will be validated and optimised with studies in optical phantoms, in vivo against gold standard modalities in neuronavigational imaging, and finally we will provide proof of principle of its performances during routine brain tumour surgery on patients. HyperProbe aims at providing functional and structural information on biomarkers of interest that is currently missing during neuro-oncological interventions

Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations

Background Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations. Methods Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required. Results Only two changes were made to clinical diagnostic criteria reported in 2013: “multiple cortical tubers and/or radial migration lines” replaced the more general term “cortical dysplasias,” and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals. Conclusions Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families

Imagerie de la microcirculation cérébrale par vidéomicroscopie Sidestream Dark Field : application à l’étude de l’oedème péritumoral dans les méningiomes intracrâniens

Cerebral microcirculation represents a primordial network embedded between the arterial and venous beds, and is mainly involved in the coupling of neuronal activity and cerebral blood flow regulation, as well as in some pathological conditions such as subarachnoid hemorrhage and in the peritumoral environment of brain tumors. Imaging of cerebral microcirculation mainly relies on pre-operative macroscopic technologies (MRI, CT-Scan, PET…). A more accurate microscopic and intraoperative technology for microcirculation imaging may help better understanding the pathogenesis of specific pathological conditions (peritumoral edema…) or assist for the monitoring of local cerebral blood flow during specific neurosurgical procedures (vascular malformations…). Several technologies have been developed for the intraoperative microcirculation imaging but remain limited by their temporal/spatial resolution, cost, ability to provide quantitative measurements or their integration in the surgical workflow. Among these technologies, only videomicroscopy provides a morphological imaging of microcirculation as well as semi-quantitative measurements. After a reminder of the key notions of cerebral microcirculation and available imaging technologies, we present an application of videomicroscopy in the peritumoral edema in meningiomas and we discuss the perspectives of use in neurosurgery.Constituant un réseau vasculaire primordial situé entre les versants artériel et veineux, la microcirculation cérébrale est impliquée principalement dans le couplage entre l’activité neuronale et la régulation du débit sanguin cérébral, mais intervient également dans diverses situations pathologiques telles l’hémorragie sous-arachnoïdienne ou au sein de l’environnement immédiat des tumeurs cérébrales. L’imagerie de la microcirculation cérébrale repose essentiellement sur des techniques macroscopiques pré-opératoires (IRM, TDM, PET…). Une étude plus fine à l’échelle microscopique et surtout per-opératoire pourrait permettre de mieux comprendre la physiopathologie de certaines situations cliniques (œdème péritumoral par exemple) et de monitorer le débit sanguin cérébral local lors de certaines interventions neurochirurgicales (malformations vasculaires…). Diverses technologies ont été développées pour une utilisation per-opératoire mais beaucoup restent limitées par leur résolution temporelle et/ou spatiale, leur coût, leur possibilité ou non de proposer une évaluation quantitative et enfin leur intégration dans le processus chirurgical. Parmi ces technologies, seule la vidéomicroscopie permet une étude à la fois morphologique et semi-quantitative de la microcirculation. Après avoir rappelé les notions fondamentales de la microcirculation cérébrale et les méthodes actuelles de son imagerie, nous avons appliqué la vidéomicroscopie per-opératoire à l’étude de l’œdème péri-tumoral dans les méningiomes intracrâniens afin d’essayer de mieux en comprendre la pathogénie. Nous conclurons sur les perspectives qu’ouvre cette technique d’imagerie per-opératoire en neurochirurgie

Imagerie de la microcirculation cérébrale par vidéomicroscopie Sidestream Dark Field : application à l’étude de l’oedème péritumoral dans les méningiomes intracrâniens

Cerebral microcirculation represents a primordial network embedded between the arterial and venous beds, and is mainly involved in the coupling of neuronal activity and cerebral blood flow regulation, as well as in some pathological conditions such as subarachnoid hemorrhage and in the peritumoral environment of brain tumors. Imaging of cerebral microcirculation mainly relies on pre-operative macroscopic technologies (MRI, CT-Scan, PET…). A more accurate microscopic and intraoperative technology for microcirculation imaging may help better understanding the pathogenesis of specific pathological conditions (peritumoral edema…) or assist for the monitoring of local cerebral blood flow during specific neurosurgical procedures (vascular malformations…). Several technologies have been developed for the intraoperative microcirculation imaging but remain limited by their temporal/spatial resolution, cost, ability to provide quantitative measurements or their integration in the surgical workflow. Among these technologies, only videomicroscopy provides a morphological imaging of microcirculation as well as semi-quantitative measurements. After a reminder of the key notions of cerebral microcirculation and available imaging technologies, we present an application of videomicroscopy in the peritumoral edema in meningiomas and we discuss the perspectives of use in neurosurgery.Constituant un réseau vasculaire primordial situé entre les versants artériel et veineux, la microcirculation cérébrale est impliquée principalement dans le couplage entre l’activité neuronale et la régulation du débit sanguin cérébral, mais intervient également dans diverses situations pathologiques telles l’hémorragie sous-arachnoïdienne ou au sein de l’environnement immédiat des tumeurs cérébrales. L’imagerie de la microcirculation cérébrale repose essentiellement sur des techniques macroscopiques pré-opératoires (IRM, TDM, PET…). Une étude plus fine à l’échelle microscopique et surtout per-opératoire pourrait permettre de mieux comprendre la physiopathologie de certaines situations cliniques (œdème péritumoral par exemple) et de monitorer le débit sanguin cérébral local lors de certaines interventions neurochirurgicales (malformations vasculaires…). Diverses technologies ont été développées pour une utilisation per-opératoire mais beaucoup restent limitées par leur résolution temporelle et/ou spatiale, leur coût, leur possibilité ou non de proposer une évaluation quantitative et enfin leur intégration dans le processus chirurgical. Parmi ces technologies, seule la vidéomicroscopie permet une étude à la fois morphologique et semi-quantitative de la microcirculation. Après avoir rappelé les notions fondamentales de la microcirculation cérébrale et les méthodes actuelles de son imagerie, nous avons appliqué la vidéomicroscopie per-opératoire à l’étude de l’œdème péri-tumoral dans les méningiomes intracrâniens afin d’essayer de mieux en comprendre la pathogénie. Nous conclurons sur les perspectives qu’ouvre cette technique d’imagerie per-opératoire en neurochirurgie

Sidestream dark field imaging of cerebral microcirculation : Sidestream dark field imaging of cerebral microcirculation

Constituant un réseau vasculaire primordial situé entre les versants artériel et veineux, la microcirculation cérébrale est impliquée principalement dans le couplage entre l’activité neuronale et la régulation du débit sanguin cérébral, mais intervient également dans diverses situations pathologiques telles l’hémorragie sous-arachnoïdienne ou au sein de l’environnement immédiat des tumeurs cérébrales. L’imagerie de la microcirculation cérébrale repose essentiellement sur des techniques macroscopiques pré-opératoires (IRM, TDM, PET…). Une étude plus fine à l’échelle microscopique et surtout per-opératoire pourrait permettre de mieux comprendre la physiopathologie de certaines situations cliniques (œdème péritumoral par exemple) et de monitorer le débit sanguin cérébral local lors de certaines interventions neurochirurgicales (malformations vasculaires…). Diverses technologies ont été développées pour une utilisation per-opératoire mais beaucoup restent limitées par leur résolution temporelle et/ou spatiale, leur coût, leur possibilité ou non de proposer une évaluation quantitative et enfin leur intégration dans le processus chirurgical. Parmi ces technologies, seule la vidéomicroscopie permet une étude à la fois morphologique et semi-quantitative de la microcirculation. Après avoir rappelé les notions fondamentales de la microcirculation cérébrale et les méthodes actuelles de son imagerie, nous avons appliqué la vidéomicroscopie per-opératoire à l’étude de l’œdème péri-tumoral dans les méningiomes intracrâniens afin d’essayer de mieux en comprendre la pathogénie. Nous conclurons sur les perspectives qu’ouvre cette technique d’imagerie per-opératoire en neurochirurgie.Cerebral microcirculation represents a primordial network embedded between the arterial and venous beds, and is mainly involved in the coupling of neuronal activity and cerebral blood flow regulation, as well as in some pathological conditions such as subarachnoid hemorrhage and in the peritumoral environment of brain tumors. Imaging of cerebral microcirculation mainly relies on pre-operative macroscopic technologies (MRI, CT-Scan, PET…). A more accurate microscopic and intraoperative technology for microcirculation imaging may help better understanding the pathogenesis of specific pathological conditions (peritumoral edema…) or assist for the monitoring of local cerebral blood flow during specific neurosurgical procedures (vascular malformations…). Several technologies have been developed for the intraoperative microcirculation imaging but remain limited by their temporal/spatial resolution, cost, ability to provide quantitative measurements or their integration in the surgical workflow. Among these technologies, only videomicroscopy provides a morphological imaging of microcirculation as well as semi-quantitative measurements. After a reminder of the key notions of cerebral microcirculation and available imaging technologies, we present an application of videomicroscopy in the peritumoral edema in meningiomas and we discuss the perspectives of use in neurosurgery

Pathogenesis of peri-tumoral edema in intracranial meningiomas

International audienc