Complete and durable regression of leptomeningeal involvement during lorlatinib treatment in a patient with lung cancer.

Metastatic spread to the central nervous system (CNS) is frequent in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) and has an important impact on patient prognosis and quality of life. Leptomeningeal involvement may occur in up to 10% of cases of ALK-positive NSCLC. Lorlatinib is a third-generation ALK inhibitor that has excellent CNS penetrability and demonstrated its efficacy both in pretreated and treatment-naive patients. Herein, we present the case of a 34-year-old patient diagnosed with stage IV ALK-rearranged NSCLC who received two lines of ALK inhibitors (crizotinib followed by alectinib) and several courses of brain stereotactic ablative radiotherapy until leptomeningeal involvement was detected. Third-line lorlatinib was then administered, and 2 months later encephalic MRI documented complete regression of the leptomeningeal involvement that is still maintained after 36 months while treatment with lorlatinib is still ongoing with good tolerability. To the best of our knowledge, this is the longer intracranial response reported in the literature, underlining the importance of the most appropriate choice of systemic treatments and their integration with loco-regional approaches to improve outcomes.

The coming of age of liquid biopsy in neuro-oncology.

The clinical role of liquid biopsy in oncology is growing significantly. In gliomas and other brain tumours, targeted sequencing of cell-free DNA (cfDNA) from CSF may help differential diagnosis when surgery is not recommended and be more representative of tumour heterogeneity than surgical specimens, unveiling targetable genetic alterations. Given the invasive nature of lumbar puncture to obtain CSF, the quantitative analysis of cfDNA in plasma is a lively option for patient follow-up. Confounding factors may be represented by cfDNA variations due to concomitant pathologies (inflammatory diseases, seizures) or clonal haematopoiesis. Pilot studies suggest that methylome analysis of cfDNA from plasma and temporary opening of the blood-brain barrier by ultrasound have the potential to overcome some of these limitations. Together with this, an increased understanding of mechanisms modulating the shedding of cfDNA by the tumour may help to decrypt the meaning of cfDNA kinetics in blood or CSF.

Consensus on criteria for acromegaly diagnosis and remission.

PURPOSE: The 14th Acromegaly Consensus Conference was convened to consider biochemical criteria for acromegaly diagnosis and evaluation of therapeutic efficacy. METHODS: Fifty-six acromegaly experts from 16 countries reviewed and discussed current evidence focused on biochemical assays; criteria for diagnosis and the role of imaging, pathology, and clinical assessments; consequences of diagnostic delay; criteria for remission and recommendations for follow up; and the value of assessment and monitoring in defining disease progression, selecting appropriate treatments, and maximizing patient outcomes. RESULTS: In a patient with typical acromegaly features, insulin-like growth factor (IGF)-I > 1.3 times the upper limit of normal for age confirms the diagnosis. Random growth hormone (GH) measured after overnight fasting may be useful for informing prognosis, but is not required for diagnosis. For patients with equivocal results, IGF-I measurements using the same validated assay can be repeated, and oral glucose tolerance testing might also be useful. Although biochemical remission is the primary assessment of treatment outcome, biochemical findings should be interpreted within the clinical context of acromegaly. Follow up assessments should consider biochemical evaluation of treatment effectiveness, imaging studies evaluating residual/recurrent adenoma mass, and clinical signs and symptoms of acromegaly, its complications, and comorbidities. Referral to a multidisciplinary pituitary center should be considered for patients with equivocal biochemical, pathology, or imaging findings at diagnosis, and for patients insufficiently responsive to standard treatment approaches. CONCLUSION: Consensus recommendations highlight new understandings of disordered GH and IGF-I in patients with acromegaly and the importance of expert management for this rare disease.

High prevalence of morphometric vertebral fractures opportunistically detected on thoracic radiograms in patients with non-functioning pituitary adenoma.

PURPOSE: Vertebral fractures (VFs), the hallmark of skeletal fragility, have been reported as an emerging complication in patients with pituitary diseases associated with hormonal excess and/or deficiency, independently from bone mineral density. Non-functioning pituitary adenoma (NFPA) is amongst the most frequent pituitary adenomas; however, skeletal health in this context has never been investigated. We aimed at assessing the prevalence and the determinants of morphometric VFs in patients with NFPA. METHODS: We enrolled 156 patients (79 M/77F, mean age 55.75 ± 12.94 years) at admission in Neurosurgery Unit before trans-sphenoidal surgery and compared them with an age and sex-matched control group of subjects with neither history/risk factors for secondary osteoporosis nor pituitary disorders. We performed a vertebral morphometric evaluation of the thoracic spine on pre-operative X-ray images (MTRx) and collected biochemical, demographic, and clinical data from the entire cohort. RESULTS: The prevalence of thoracic VFs in patients with NFPA was significantly higher than the control group (26.3% vs. 10.3%; p < 0.001). In the NFPA group, 20 patients (48.8% of the fractured patients) showed multiple VFs, 14 (34.1% of them) showed moderate/severe VFs. Patients with VFs were significantly older and had lower serum free triiodothyronine (fT3) levels than non-fractured ones (p = 0.002 and p = 0.004; respectively). The prevalence of secondary male hypogonadism was higher among men with VFs as compared to those with no VFs (72% vs. 48.1%; p = 0.047). Consistently, total testosterone levels in males were significantly lower in fractured patients than in non-fractured ones (p = 0.02). The prevalence of gonadotroph adenomas was significantly higher among patients with VFs (p = 0.02). In multiple logistic regression analysis, older age and lower serum fT3 levels were independent factors predicting the risk for VFs. CONCLUSIONS: For the first time, we reported a high prevalence of thoracic radiological VFs in patients with NFPAs. Our data should prompt clinicians to proceed with a clinical bone fragility evaluation already during the diagnostic work-up, particularly in those with concomitant hypogonadism, or in those with older age and/or with lower fT3.

Gamma Knife radiosurgery for central neurocytoma: a quantitative systematic review and metanalysis.

Central neurocytomas (CN) are rare tumors within the central nervous system. Originating from the septum pellucidum and subependymal cells, they are typically found in the third and lateral ventricles. For this reason, they may lead to hydrocephalus and increased intracranial pressure. CNs are generally benign lesions that exhibit locally aggressive behavior and a high recurrence rate. Complete surgical resection is the preferred treatment; however, due to their anatomical location, this is often not feasible. Based on these findings, Gamma Knife radiosurgery (GKRS) has been introduced for managing both residual and recurrent tumors and as an initial therapy in selected cases. This study aimed to systematically review the available knowledge regarding GKRS for CN. A systematic investigation of the scientific literature was undertaken through an exhaustive search across prominent databases, including PubMed, Web of Science, and Google Scholar, by employing precise MeSH terms such as "Central neurocytoma," "Radiosurgery," "Gamma Knife," and "Stereotactic Radiosurgery." A comprehensive quantitative systematic review and meta-analysis were meticulously conducted, focusing on cases of CN treated with GKRS for a thorough evaluation of outcomes and efficacy. Seventeen articles, including 289 patients, met the inclusion criteria. Random effects meta-analysis estimates for disease control and local tumor control were 90% (95% CI 87-93%; I2 = 0%, p < 0.74) and 94% (95% CI 92-97%; I2 = 0%, p < 0.98), respectively. When considering only studies with at least 5 years of follow-up, progression-free survival was 89% (95% CI 85-94%; I2 = 0.03%, p < 0.74). The mean clinical control rate was 96%. This systematic review and meta-analysis confirmed the safety and efficacy of GKRS in managing CN.

Surgical management of Glioma Grade 4: technical update from the neuro-oncology section of the Italian Society of Neurosurgery (SINch®): a systematic review.

PURPOSE: The extent of resection (EOR) is an independent prognostic factor for overall survival (OS) in adult patients with Glioma Grade 4 (GG4). The aim of the neuro-oncology section of the Italian Society of Neurosurgery (SINch®) was to provide a general overview of the current trends and technical tools to reach this goal. METHODS: A systematic review was performed. The results were divided and ordered, by an expert team of surgeons, to assess the Class of Evidence (CE) and Strength of Recommendation (SR) of perioperative drugs management, imaging, surgery, intraoperative imaging, estimation of EOR, surgery at tumor progression and surgery in elderly patients. RESULTS: A total of 352 studies were identified, including 299 retrospective studies and 53 reviews/meta-analysis. The use of Dexamethasone and the avoidance of prophylaxis with anti-seizure medications reached a CE I and SR A. A preoperative imaging standard protocol was defined with CE II and SR B and usefulness of an early postoperative MRI, with CE II and SR B. The EOR was defined the strongest independent risk factor for both OS and tumor recurrence with CE II and SR B. For intraoperative imaging only the use of 5-ALA reached a CE II and SR B. The estimation of EOR was established to be fundamental in planning postoperative adjuvant treatments with CE II and SR B and the stereotactic image-guided brain biopsy to be the procedure of choice when an extensive surgical resection is not feasible (CE II and SR B). CONCLUSIONS: A growing number of evidences evidence support the role of maximal safe resection as primary OS predictor in GG4 patients. The ongoing development of intraoperative techniques for a precise real-time identification of peritumoral functional pathways enables surgeons to maximize EOR minimizing the post-operative morbidity.

Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification.

Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-year OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-year progression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.

Efficacy of neoadjuvant stereotactic radiotherapy in brain metastases from solid cancer: a systematic review of literature and meta-analysis.

Neoadjuvant stereotactic radiotherapy (NaSRT) is a novel strategy for brain metastasis (BM) treatment, promising to achieve good local control, improved survival, and low toxicity. This is a systematic review of available literature and meta-analysis of 8 articles eligible for inclusion after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases up to March 2023. A total of 484 patients undergoing NaSRT to treat 507 lesions were included. The median age was 60.9 (IQR 57-63) years, with a median tumor volume of 12.1 (IQR 9-14) cm3. The most frequent histology was non-small-cell lung cancer (41.3%), followed by breast (18.8%), and melanoma (14.3%). Lesions had a preferred supratentorial location (77.4%). Most of the studies used a single fraction schedule (91% of patients, n = 440). Treatment parameters were homogeneous and showed a median dose of 18 (IQR 15.5-20.5) Gy at a median of 80% isodose. Surgery was performed after a median of 1.5 (IQR 1-2.4) days and achieved gross-total extent in 94% of cases. Median follow-up was 12.9 (IQR 10-15.7) months. NaSRT showed an overall mortality rate of 58% (95% CI 43-73) at the last follow-up. Actuarial outcomes rates were 60% (95% CI 55-64) for 1-year overall survival (1y-OS), 38% (95% CI 33-43) for 2y-OS, 29% (95% CI 24-34) for 3y-OS; overall 15% (95% CI 11-19) for local failure, 46% (95% CI 37-55) for distant brain failure, 6% (95% CI 3-8) for radionecrosis, and 5% (95% CI 3-8) for leptomeningeal dissemination. The median local progression-free survival time was 10.4 (IQR 9.5-11.4) months, while the median survival without distant failure was 7.4 (IQR 6.9-8) months. The median OS time for the entire cohort was 17 (IQR 14.9-17.9) months. Existing data suggest that NaSRT is effective and safe in the treatment of BMs, achieving good local control on BMs with and low incidence of radionecrosis and leptomeningeal dissemination. Distant control appears limited compared to other radiation regimens.

Efficacy of radiotherapy and stereotactic radiosurgery as adjuvant or salvage treatment in atypical and anaplastic (WHO grade II and III) meningiomas: a systematic review and meta-analysis.

The role of radiotherapy (RT) and stereotactic radiosurgery (SRS) as adjuvant or salvage treatment in high-grade meningiomas (HGM) is still debated. Despite advances in modern neuro-oncology, HGM (WHO grade II and III) remains refractory to multimodal therapies. Published reports present aggregated data and are extremely varied in population size, exclusion criteria, selection bias, and inclusion of mixed histologic grades, making it extremely difficult to draw conclusions when taken individually. This current work aims to gather the existing evidence on RT and SRS as adjuvants following surgery or salvage treatment at recurrence after multimodality therapy failure and to conduct a systematic comparison between these two modalities. An extensive systematic literature review and meta-analysis were performed. A total of 42 papers were eligible for final analysis (RT n = 27; SRS n = 15) after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases. Adjuvant regimens were addressed in 37 papers (RT n = 26; SRS n = 11); salvage regimens were described in 5 articles (RT n = 1; SRS n = 4). The primary outcomes of the study were the overall recurrence rate and mortality. Other actuarial rates (local and distant control, OS, PFS, and complications) were retrieved and analyzed as secondary outcomes. A total of 2853 patients harboring 3077 HGM were included. The majority were grade II (87%) with a mean pre-radiation volume of 8.7 cc. Adjuvant regimen: 2742 patients (76.4% RT; 23.6% SRS) with an overall grade II/III rate of 6.6/1. Lesions treated adjSRS were more frequently grade III (17 vs 12%, p < 0.001), and received subtotal resection (57 vs 27%, p = 0.001) compared to the RT cohort. AdjSRS cohort had a significantly shorter mean follow-up than adjRT (36.7 vs 50.3 months, p = 0.01). The overall recurrence rate was 38% in adjRT vs 25% in adjSRS (p = 0.01), while mortality did not differ between the groups (20% vs 23%, respectively; p = 0.80). The median time to recurrence was 1.5 times longer in the RT group (p = 0.30). Five-year local control was 55% in adjRT and 26% in adjSRS (p = 0.01), while 5-year OS was 73% and 78% (p = 0.62), and 5-year PFS was 62% and 40% in adjRT and adjSRS (p = 0.008). No difference in the incidence of complications (24% vs 14%, p = 0.53). Salvage regimen: 110 patients (37.3% RT; 62.7% SRS) with a grade II/III rate of 8.6/1. The recurrence rate was 46% in salRT vs 24% in salSRS (p = 0.39), time to recurrence was 1.8 times longer in the salRT group (35 vs 18.5 months, p = 0.74). Mortality was slightly yet not significantly higher in salRT (34% vs 12%, p = 0.54). Data on local and distant control were only available for salSRS. The 5-year OS was 49% and 83% (p = 0.90), and the 5-year PFS was 39% and 50% in salRT and salSRS (p = 0.66), respectively. High-grade meningiomas (WHO grade II and III) receiving adjuvant RT showed a higher overall recurrence rate than meningiomas receiving adjuvant SRS. The adjRT cohort, however, achieved higher 5-year LC and PFS rates, thus suggesting a potentially longer time to recurrence compared to adjSRS patients, who, meanwhile, experienced a significantly shorter follow-up. This result must also consider the higher number of grade III lesions and the smaller extent of resection achieved in the adjSRS group. Overall mortality did not differ between the two groups. No differences in outcome measures were observed in salvage regimens.

Brain and/or Spinal Cord Tumors Accompanied with Other Diseases or Syndromes.

Several medical conditions that interest both the brain and the spinal cord have been described throughout the history of medicine. Formerly grouped under the term Phacomatosis because lesions of the eye were frequently encountered or genodermatosis when typical skin lesions were present, these terms have been progressively discarded. Although originally reported centuries ago, they still represent a challenge for their complexity of cure. Nowadays, with the introduction of advanced genetics and the consequent opportunity of whole-genome sequencing, new single cancer susceptibility genes have been identified or better characterized; although there is evidence that the predisposition to a few specific tumor syndromes should be accounted to a group of mutations in different genes while certain syndromes appeared to be manifestations of different mutations in the same gene adding supplementary problems in their characterization and establishing the diagnosis. Noteworthy, many syndromes have been genetically determined and well-characterized, accordingly in the near future, we expect that new targeted therapies will be available for the definitive cure of these syndromes and other gliomas (Pour-Rashidi et al. in World Neurosurgery, 2021). The most common CNS syndromes that will be discussed in this chapter include neurofibromatosis (NF) types 1 and 2, von Hippel-Lindau (VHL) disease, and tuberous sclerosis complex (TSC), as well as syndromes having mostly extra-neural manifestations such as Cowden, Li-Fraumeni, Turcot, and Gorlin syndromes.

Other Less Prevalent Tumors of the Central Nervous System.

The presented tumors in this chapter are somewhat very rare, and their management is still debated due to the scarcity of information about their cell of origin, behavior, and biology. Treatment options are still limited, but we are confident that in the near future by discovering the genetic and biological mechanisms that drive tumor growth we will be able to offer new target therapies that should be flanked by surgery, radiotherapy, and chemotherapeutic agents actually in use. The purpose of this chapter is to highlight the most important known characteristics of these tumors offering the chance to recognize the disease and then offer the best opportunity for treatment to patients. The 5th WHO Classification Central Nervous System features substantial changes by moving further to advance the role of molecular diagnostics in CNS tumor classification, but remaining rooted in other established approaches to tumor characterization, including histology and immunohistochemistry, and probably, the category of many tumors will change. Here, the most important characteristics of each neoplasm are summarized focusing on genetic mechanisms and molecular pathways, their histopathologic footprints, signs and symptoms, radiologic features, therapeutic approaches, and prognosis as well as follow-up protocols. Schematic classifications are also presented to offer a better understanding of the pathology.

Benign and Malignant Tumors of the Pituitary Gland.

Pituitary gland tumors represent approximately 10-15% of all brain tumors and the most common neoplasms of the sellar region. Among them, pituitary adenomas are the widespread accounting for more than 80%. Recently, the fourth edition of the World Health Organization (WHO) 2017 classified pituitary tumors focusing on histopathologic and molecular genetics features and introduced new entities like pituitary blastoma. Most of pituitary gland neoplasms occur sporadically, whereas 5% are related to familial syndromes. They present with several clinical manifestations including signs and symptoms related to excessive hormone secretion by the tumor, signs of hormone deficits by the normal pituitary gland and others commonly secondary to mass effects, and compression of nearby structures such as the optic chiasm; headache and visual disturbance are the most frequent mass effect symptoms. Some tumors, however, are detected as an incidental finding on magnetic resonance imaging (MRI) or computed tomography (CT) scans performed for some other reasons. A correct evaluation involves the assessment of hypothalamic-pituitary hormonal function and an ophthalmological examination once a pituitary lesion is encountered. Surgery, more specifically transsphenoidal approach, represents the primary treatment chosen for the majority of pituitary tumors (except for prolactinomas where medical treatment is indicated) allowing for pathologic analysis and complete or partial tumor removal. On the contrary, to date, craniotomy is rarely performed. Sometimes, due to the proximity of critical structures and to tumor's location and characteristics, a successful surgical procedure may often not be achievable due to the high risks related to the procedure itself. Therefore, the treatment of pituitary tumors commonly requires a multimodal approach, including surgery, radiosurgery, radiation therapy, and medical therapy. Aggressive pituitary tumors or carcinomas are associated with poor prognosis due to limited therapeutic options. Furthermore, they tend to recur quickly after initial surgical treatment or present metastasis, may be unresponsive to therapy, and are difficult to manage. In this chapter, we provide an overview of the most common pituitary gland tumors focusing on epidemiology, new pathological features, diagnosis, available treatment, and prognosis.

Meningioma and Other Meningeal Tumors.

Meningiomas develop from meningothelial cells and approximately account for more than 30 percent of central nervous system (CNS) tumors. They can occur anywhere in the dura, most often intracranially and at dural reflection sites. Half of the cases are usually at parasagittal/falcine and convexity locations; other common sites are sphenoid ridge, suprasellar, posterior fossa, and olfactory groove. The female-to-male ratio is approximately 2 or 3-1, and the median age at diagnosis is 65 years. Meningiomas are generally extremely slow-growing tumors; many are asymptomatic or paucisymptomatic at diagnosis and are discovered incidentally. Clinical manifestations, when present, are influenced by the tumor site and by the time course over which it develops. Meningiomas are divided into three grades. Grade I represents the vast majority of cases; they are considered typical or benign, although their CNS location can still lead to severe morbidity or mortality, resulting in a reported ten-year net survival of over 80%. Atypical (WHO grade II) meningiomas are considered "intermediate grade" malignancies and represent 5-7% of cases. They show a tendency for recurrence and malignant degeneration with a relevant increase in tumor cell migration and surrounding tissue infiltration; ten-year net survival is reported over 60%. The anaplastic subtype (WHO III) represents only 1-3% of cases, and it is characterized by a poor prognosis (ten-year net survival of 15%). The treatment of choice for these tumors stands on complete microsurgical resection in case the subsequent morbidities are assumed minimal. On the other hand, and in case the tumor is located in critical regions such as the skull base, or the patient may have accompanied comorbidities, or it is aimed to avoid intensive treatment, some other approaches, including stereotactic radiosurgery and radiotherapy, were recommended as safe and effective choices to be considered as a primary treatment option or complementary to surgery. Adjuvant radiosurgery/radiotherapy should be considered in the case of atypical and anaplastic histology, especially when a residual tumor is identifiable in postoperative imaging. A "watchful waiting" strategy appears reasonable for extremely old individuals and those with substantial comorbidities or low-performance status, while there is a reduced threshold for therapeutic intervention for relatively healthy younger individuals due to the expectation that tumor progression will inevitably necessitate proactive treatment. To treat and manage meningioma efficiently, the assessments of both neurosurgeons and radiation oncologists are essential. The possibility of other rarer tumors, including hemangiopericytomas, solitary fibrous tumors, lymphomas, metastases, melanocytic tumors, and fibrous histiocytoma, must be considered when a meningeal lesion is diagnosed, especially because the ideal diagnostic and therapeutic approaches might differ significantly in every tumor type.

Craniopharyngioma in Pediatrics and Adults.

Craniopharyngiomas are rare malignancies of dysembryogenic origin, involving the sellar and parasellar areas. These low-grade, epithelial tumors account for two main histological patterns (adamantinomatous craniopharyngioma and papillary craniopharyngioma), which differ in epidemiology, pathogenesis, and histomorphological appearance. Adamantinomatous craniopharyngiomas typically show a bimodal age distribution (5-15 years and 45-60 years), while papillary craniopharyngiomas are limited to adult patients, especially in the fifth and sixth decades of life. Recently, craniopharyngioma histological subtypes have been demonstrated to harbor distinct biomolecular signatures. Somatic mutations in CTNNB1 gene encoding ß-catenin have been exclusively detected in adamantinomatous craniopharyngiomas, which predominantly manifest as cystic lesions, while papillary craniopharyngiomas are driven by BRAF V600E mutations in up to 95% of cases and are typically solid masses. Despite the benign histological nature (grade I according to the World Health Organization classification), craniopharyngiomas may heavily affect long-term survival and quality of life, due to their growth pattern in a critical region for the presence of eloquent neurovascular structures and possible neurological sequelae following their treatment. Clinical manifestations are mostly related to the involvement of hypothalamic-pituitary axis, optic pathways, ventricular system, and major blood vessels of the circle of Willis. Symptoms and signs referable to intracranial hypertension, visual disturbance, and endocrine deficiencies should promptly raise the clinical suspicion for sellar and suprasellar pathologies, advocating further neuroimaging investigations, especially brain MRI. The optimal therapeutic management of craniopharyngiomas is still a matter of debate. Over the last decades, the surgical strategy for craniopharyngiomas, especially in younger patients, has shifted from the aggressive attempt of radical resection to a more conservative and individualized approach via a planned subtotal resection followed by adjuvant radiotherapy, aimed at preserving functional outcomes and minimizing surgery-related morbidity. Whenever gross total removal is not safely feasible, adjuvant radiotherapy (RT) and stereotactic radiosurgery (SRS) have gained an increasingly important role to manage tumor residual or recurrence. The role of intracavitary therapies, including antineoplastic drugs or sealed radioactive sources, is predominantly limited to monocystic craniopharyngiomas as secondary therapeutic option. Novel findings in genetic profiling of craniopharyngiomas have unfold new scenarios in the development of targeted therapies based on brand-new biomolecular markers, advancing the hypothesis of introducing neoadjuvant chemotherapy regimens in order to reduce tumor burden prior to resection. Indeed, the rarity of these neoplasms requires a multispecialty approach involving an expert team of endocrinologists, neurosurgeons, neuro-ophthalmologists, neuroradiologists, radiotherapists, and neuro-oncologists, in order to pursue a significant impact on postoperative outcomes and long-term prognosis.

Brain Tumors Affecting the Orbit Globe and Orbit Tumors Affecting the Brain.

Brain tumors affecting the orbit and orbital tumors affecting the brain are a heterogeneous group of lesions, with histological features, behaviors, diagnostic criteria, and treatments varying from each other. Dermoid cyst and cavernous hemangiomas are considered the most frequent benign lesions, while non-Hodgkin lymphoma is the most common malignant tumor in this region. Sharing the same anatomical region, clinical manifestations of orbital lesions may be often common to different types of lesions. Imaging studies are useful in the differential diagnosis of orbital lesions and the planning of their management. Lesions can be classified into ocular or extra-ocular ones: the latter can be further differentiated into extraconal or intraconal, based on the relationship with the extraocular muscles. Surgical therapy is the treatment of choice for most orbital lesions; however, based on the degree of removal, their histology and extension, other treatments, such as chemotherapy and radiotherapy, are indicated for the management of orbital lesions. In selected cases, chemotherapy and radiotherapy are the primary treatments. This chapter aimed to discuss the orbital anatomy, the clinical manifestations, the clinical testing and the imaging studies for orbital lesions, and the principal pathological entities affecting the orbit together with the principles of orbital surgery.

MIS removal of extraforaminal lumbar spine schwannoma using MAS-TLIF retractor: technical note.

BACKGROUND: To report the use of Nuvasive MAS-TLIF retractor for the removal of lumbar spine schwannomas. METHODS: A 47-year-old man with 1-year history of back pain with progressive left sciatica underwent surgical resection of a left extraforaminal lumbar schwannoma (type IV according to Eden's classification) using the MAS-TLIF retractor. RESULTS: The patient completely recovered from the preoperative symptoms and was discharged three days after surgery. The MRI acquired 6 months postoperatively showed complete tumour removal, with no signs of instability. The MAS-TLIF retractor allows for an optimal paraspinal tissues retraction, improving the area of exposure and the manoeuverability angle. Moreover, the stability of the retraction is guaranteed by the positioning of the two transpedicular screws. Spinal fusion is not necessary because the posterior tension band is not jeopardised. CONCLUSIONS: MAS-TLIF retractor allows for a minimally invasive and safe surgical removal of LSS maximising surgical exposure and avoiding spinal fusion.

Primary sellar melanocytoma: report of two cases treated at the same institution and their long-term outcome.

Sellar melanocytomas represent a small subgroup of primary melanocytic tumors arising from leptomeningeal melanocytes. They are benign, slow-growing tumors with a high risk of recurrence. We report two cases of sellar melanocytoma treated at the same institute. A 35-year-old woman presented with amenorrhea and an intrasellar mass with suprasellar extension simulating a hemorrhagic pituitary adenoma. The second case is a 51-year-old man with progressive visual loss and a recurrence of primary sellar and suprasellar melanocytoma. The first patient underwent gross total resection and the second patient underwent subtotal resection. Neither of them was treated with postoperative adjuvant therapies. The second patient had tumor regrowth 75 months after surgery; he therefore underwent gamma knife radiosurgery. Both patients are alive and well at the last follow-up (140 and 93 months, respectively).

COVID-19 and hypopituitarism.

Besides the pulmonary manifestations caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), an emerging endocrine phenotype, which can heavily impact on the severity of the syndrome, has been recently associated with coronavirus disease 2019 (COVID-19). Patients with pituitary diseases or the pituitary gland itself may also be involved in COVID-19 clinical presentation and/or severity, causing pituitary apoplexy.Moreover, hypopituitarism is frequently burdened by several metabolic complications, including arterial hypertension, hyperglycemia, obesity and vertebral fractures, which have all been associated with poor outcomes and increased mortality in patients infected by SARS-CoV-2.This review will discuss hypopituitarism as a condition that might have a bidirectional relationship with COVID-19 due to the frequent presence of metabolic comorbidities, to the direct or indirect pituitary damage or being per se a potential risk factor for COVID-19. Finally, we will address the current recommendations for the clinical management of vaccines in patients with hypopituitarism and adrenal insufficiency.

Alterations of brain structural MRI are associated with outcome of surgical treatment in trigeminal neuralgia.

BACKGROUND AND PURPOSE: To assess magnetic resonance imaging (MRI) alterations occurring in patients with trigeminal neuralgia (TN) and to explore the predictive ability of MRI for initial surgical outcome and long-term pain relief/recurrence after Gamma Knife radiosurgery (GKS). METHODS: Thirty patients with idiopathic or classic TN, who underwent GKS and were followed for at least 24 months, were retrospectively included. Pre-treatment structural MRI and pre- and serial, postoperative clinical features were investigated. Fifteen age- and sex-matched healthy controls were also enrolled. Cortical thickness and gray matter (GM) volumes were assessed in TN patients relative to controls, as well as between patient subgroups according to treatment outcomes (initial responders/non-responders, patients with pain recurrence/long-lasting pain relief at the last follow-up). Clinical and MRI predictors of treatment outcomes were explored. RESULTS: Cortical thinning of temporal, prefrontal, cingulate, somatosensory and occipital areas bilaterally was found in TN patients relative to controls. No cortical thickness and GM volume differences were observed when TN initial responders and non-responders were compared. Patients who experienced TN recurrence after initial pain relief were characterized by thicker parahippocampal and temporal cortices bilaterally and greater volume of right amygdala and hippocampus compared to patients with long-lasting pain relief. In TN patients, disease duration and baseline cortical thinning of right parahippocampal, left fusiform and middle temporal cortices were associated with poor outcome after GKS at the last follow-up (R2 =0.57, p<0.001). CONCLUSION: The study provides novel insights into structural brain alterations of TN patients, which might contribute to disease development and pain maintenance.

Comparison between extended transsphenoidal and transcranial surgery for craniopharyngioma: focus on hypothalamic function and obesity.

PURPOSE: Patients suffering from craniopharyngiomas currently have good survival rates, but long-term sequelae, such as development of obesity, worsen their quality of life. Optimal treatment is still controversial and changed during the decades, becoming less aggressive. Transcranial (TC) surgery was the first approach to be used, followed by extended transsphenoidal (eTNS) access. This study aims to compare the two approaches in terms of risk of hypothalamic damage leading to obesity. METHODS: This is a monocentric retrospective analysis of post-puberal patients treated for primary craniopharyngioma. Postoperative obesity and percentual postsurgical BMI variation were considered proxy for hypothalamic function and used to fit regression models with basal BMI, type of surgery, tumor volume and hypothalamic involvement (anterior vs. anteroposterior). RESULTS: No difference in radicality was observed between the two approaches; eTNS was more effective in ameliorating visual function but was significantly associated with CSF leaks. The TC approach was associated with a higher incidence of diabetes insipidus. Regression analysis showed only tumor volume and basal BMI resulted as independent predictors for both postoperative obesity (respectively, OR 1.15, P = 0.041, and OR 1.57, P < 0.001) and percentual BMI variation (respectively, + 0.92%, P = 0.005, and - 1.49%, P = 0.001). CONCLUSIONS: Larger lesions portend a higher risk to develop postoperative obesity, independently of hypothalamic involvement. Interestingly, basal BMI is independent of lesional volume and is associated with postoperative obesity, but lesser postoperative BMI variation. The surgical approach does not influence the obesity risk. However, eTNS proves valid in managing large tumors with important hypothalamic invasion.