Atypical Teratoid/Rhabdoid Tumor of the Nervous System in Adults: Location-Related Features and Outcome.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) of the nervous system is a rare and highly malignant neoplasm, mainly affecting children, first recognized as a pathologic entity in 1996 and added to the World Health Organization Classification of the Tumors of the Central Nervous System in 2000. AT/RT is even rarer among adults and is associated with a worse prognosis. The aim of the present study was to analyze the different tumor features according to the location in adults. METHODS: A comprehensive and detailed literature review of AT/RTs in adults was made. The demographic, management, and outcome data associated with tumor location were analyzed and compared; histopathologic and molecular features were also discussed. Furthermore, we added our personal case with brain hemispheric localization and reported a progression-free survival of 103 months after gross total resection and adjuvant radiotherapy showing a peculiar histopathologic pattern. RESULTS: Female sex is mainly affected by AT/RT on median localizations, both intracranial and spinal, and by all sellar region cases. Gross total resection is mainly achieved among lateral compared with median localizations. Combined radiotherapy and chemotherapy is the most adopted adjuvant treatment in all tumor localizations and is related to better outcome. Postoperative death is reported only among sellar region localizations, whereas brain hemispheric cases show the best overall survival. CONCLUSIONS: AT/RTs show different and peculiar features according to their location, which significantly affects the outcome; precise knowledge of them helps the neurosurgeon in planning the best strategy for treatment.

Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth.

Despite intense research efforts, glioblastoma remains an incurable brain tumor with a dismal median survival time of 15 months. Thus, identifying new therapeutic targets is an urgent need. Here, we show that the lysine methyltransferase SETD8 is overexpressed in 50% of high-grade gliomas. The small molecule SETD8 inhibitor UNC0379, as well as siRNA-mediated inhibition of SETD8, blocked glioblastoma cell proliferation, by inducing DNA damage and activating cell cycle checkpoints. Specifically, in p53-proficient glioblastoma cells, SETD8 inhibition and DNA damage induced p21 accumulation and G1/S arrest whereas, in p53-deficient glioblastoma cells, DNA damage induced by SETD8 inhibition resulted in G2/M arrest mediated by Chk1 activation. Checkpoint abrogation, by the Wee1 kinase inhibitor adavosertib, induced glioblastoma cell lines and primary cells, DNA-damaged by UNC0379, to progress to mitosis where they died by mitotic catastrophe. Finally, UNC0379 and adavosertib synergized in restraining glioblastoma growth in a murine xenograft model, providing a strong rationale to further explore this novel pharmacological approach for adjuvant glioblastoma treatment.

A "masked" pleomorphic xanthoastrocytoma.

The latest WHO Classification of tumours of the Central Nervous System (CNS) emphasizes the necessity of an integrated diagnostic approach during the workup of a CNS neoplasm. In addition to the mutational status, assessment of methylation profile of a tumour emerged as a helpful (often necessary) tool to make a correct and unequivocal diagnosis. Here we present a case of a Pleomorphic Xanthoastrocytoma with clinical, radiological and histopathological findings remarkably overlapping with a recently described paediatric-type glioma namly Polymorphic Low-grade Neuroepithelial Tumour of the Young (PLNTY). The differential diagnosis here discussed represents a methodological paradigm in the modern neuropathology. In fact, the presentation of this case is a demonstration that in day-to-day practice, clinical, radiological, and histopathological data can all be misleading, and the correct diagnosis can only be reached by integration with molecular analysis. In the modern neuro-oncology, it is by far mandatory for all the specialists dealing with cerebral tumours to "contaminate" their own cultural heritage with other ones, to optimally manage a patient with CNS tumour.

The "chameleon" sellar lesions: a case report of unexpected sellar lesions.

Introduction: The sellar region and its boundaries represent a challenging area, harboring a variety of tissues of different linings. Therefore, a variety of diseases can arise or involve in this area (i.e., neoplastic or not). A total of three challenging cases of "chameleon" sellar lesions treated via EEA were described, and the lesions mimicked radiological features of common sellar masses such as craniopharyngiomas and/or pituitary adenomas, and we also report a literature review of similar cases. Methods: A retrospective analysis of three primary cases was conducted at the Università degli Studi di Napoli Federico II, Naples, Italy. Clinical information, radiological examinations, and pathology reports were illustrated. Results: A total of three cases of so-called "chameleon" sellar lesions comprising two men and one woman were reported. Based on the intraoperative finding and pathological examination, we noticed that case 1 had suprasellar glioblastoma, case 2 had a primary neuroendocrine tumor, and case 3 had cavernous malformation. Conclusion: Neurosurgeons should consider "unexpected" lesions of the sellar/suprasellar region in the preoperative differential diagnosis. A multidisciplinary approach with the collaboration of neurosurgeons, neuroradiologists, and pathologists plays a fundamental role. The recognition of unusual sellar lesions can help surgeons with better preoperative planning; so an endoscopic endonasal approach may represent a valid surgical technique to obtain decompression of the optic apparatus and vascular structures and finally a pathological diagnosis.

WHO grade and pathological markers of meningiomas: Clinical and prognostic role.

In recent years, WHO grading criteria have emerged as an inaccurate tool to correctly predict the risk of progression/recurrence for meningioma patients. Therefore, great efforts were made to find further prognostic factors that could predict the clinical course of meningiomas. Why morphological criteria are not able alone to correctly predict outcome in all patients? What are the biological parameters underlying a more aggressive behavior? Are there any molecular markers can be integrated in the risk assessment? Could new technologies, such as methylome profiling, contribute to provide additional tools in patients prognostic evaluation? We performed a literature review to find answers to these questions. Meningiomas have been demonstrated to be extremely heterogeneous neoplasms, also from the genetic and epigenetic standpoints. However, WHO Classification of Tumours of the central Nervous System 5th edition introduced only CDKN2A/B deletion and TERT promoter mutations as poor prognostic, grade 3 defining parameters. The different proposals of integrated grading, taking into account cytogenetic alterations and study of methylation profile, have not yet been incorporated in WHO grading criteria. Work in progress: this is the summary of current knowledge. Further studies are needed to expand the diagnostic and prognostic equipment to be integrated into clinical practice.

A Rare Adult Primary Intracranial Sarcoma, DICER1-Mutant Identified by Epigenomic Profiling: A Case Report.

Diagnoses of primary malignant mesenchymal brain tumors are a challenge for pathologists. Here, we report the case of a 52-year-old man with a primary brain tumor, histologically diagnosed as a high-grade glioma, not otherwise specified (NOS). The patient underwent two neurosurgeries in several months, followed by radiotherapy and chemotherapy. We re-examined the tumor samples by methylome profiling. Methylome analysis revealed an epi-signature typical of a primary intracranial sarcoma, DICER1-mutant, an extremely rare tumor. The diagnosis was confirmed by DNA sequencing that revealed a mutation in DICER1 exon 25. DICER1 mutations were not found in the patient's blood cells, thus excluding an inherited DICER1 syndrome. The methylome profile of the DICER1 mutant sarcoma was then compared with that of a high-grade glioma, a morphologically similar tumor type. We found that several relevant regions were differentially methylated. Taken together, we report the morphological, epigenetic, and genetic characterization of the sixth described case of an adult primary intracranial sarcoma, DICER1-mutant to-date. Furthermore, this case report underscores the importance of methylome analysis to refine primary brain tumor diagnosis and to avoid misdiagnosis among morphologically similar subtypes.

Neoplasms and tumor-like lesions of the sellar region: imaging findings with correlation to pathology and 2021 WHO classification.

The sellar region represents a complex anatomical area, composed of multiple structures of different embryological derivation, including the skull base and the pituitary gland, along with vascular, nervous, and meningeal structures. Masses arising in this region include benign and malignant lesions arising from the pituitary gland itself, but also from vestigial embryological residues or surrounding tissues, that may require different therapeutic approaches. While assessing sellar region masses, the combination of clinical presentation and imaging features is fundamental to define hypotheses about their nature. MR represents the imaging modality of choice, providing information about the site of the lesion, its imaging features, and relation with adjacent structures, while CT is useful to confirm the presence of lesion calcifications or to reveal tumor invasion of bony structures. The aim of this pictorial review is to provide an overview of the common neoplasms and tumor-like conditions of the sellar region, according to the 2021 WHO Classification of Tumors of the Central Nervous System (fifth edition), with an emphasis on the radiologic-pathologic correlation. After a brief introduction on the anatomy of this region and the imaging and pathological techniques currently used, the most relevant MRI characteristics, clinical findings, and pathological data, including histologic and molecular features, will be shown and discussed, with the aim of facilitating an appropriate differential diagnosis among these entities.

Intracranial Meningiomas in Patients Aged ≥80 Years: Pathological Features and Surgical Problems.

BACKGROUND: Patients aged >80 years frequently have intracranial meningiomas. In the present study, we have discussed the pathological features, comorbidities, and surgical complications for this age group from a surgical series and literature review. METHODS: In the present study, we reviewed a surgical series of 354 intracranial meningiomas and compared the oldest age group (age, ≥80 years) of 17 patients with 73 patients aged 70-79 years and 264 patients aged <70 years. From a literature review, we selected 10 studies of meningiomas in patients aged ≥80 years. The analyzed factors included sex, meningioma location, World Health Organization grade, Ki-67 MIB1, progesterone receptor expression, comorbidities, American Society of Anesthesiologists class, Karnofsky performance scale score, postoperative complications, and death. RESULTS: Patients aged ≥80 years had had higher rates of World Health Organization grade II meningioma, higher rates of Ki-67 expression of >4% and <20%, and progesterone receptor expression <15%. Of the postoperative complications, only neurological deficits and acute bronchopneumonia were significantly more frequent in patients aged ≥80 years. The incidence of intracerebral hematoma, lung embolism, acute heart ischemia, and death were not significantly different between the patients aged ≥80 years and those aged 70-79 years and <70 years. CONCLUSIONS: Patients aged ≥80 years must be considered a true elderly group with higher rates of comorbidities. The very old age is not a limitation to surgery; however, careful patient selection is necessary. In addition, for the oldest age group, the surgical decision should not be delayed because of advancing age.

Granuloma annulare after SARS-CoV-2 vaccination: A case report and a literature review.

INTRODUCTION: During the Cov-19 pandemic, many studies reported a broad spectrum of cutaneous reactions presenting as erythematous rashes or pernio-like, urticaria-like or vesicular/bullous patterns associated with Cov-19-infection and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. METHODS: The authors documented the clinical and histopathological features of an unexpected case of granuloma annulare (GA) arising a few days after the SARS-CoV-2 vaccination and reviewed all GAs reported in the literature following the SARS-CoV-2 vaccination and Cov-19-infection. CASE REPORT: A 69-year-old woman developed a single reddish lesion on the left deltoid region, where the SARS-CoV-2 vaccine seven days earlier was injected. The clinicians performed a punch skin biopsy, and histology revealed an interstitial GA. CONCLUSIONS: Clinicians should be aware of the potential, though rare, GA occurrence as a possible adverse event after the SARS-CoV-2 vaccination. This additional case, like what happens after the administration of other vaccines, supports the idea that GA may result from the immune system activation following the vaccination. However, notwithstanding, they should encourage their patients to obtain immunization to assist the public health systems in overcoming the COVID-19 pandemic.

Extra-Neural Metastases of Late Recurrent Myxopapillary Ependymoma to Left Lumbar Paravertebral Muscles: Case Report and Review of the Literature.

Ependymomas are commonly classified as low-grade tumors, although they may harbor a malignant behavior characterized by distant neural dissemination and spinal drop metastasis. Extra-CNS ependymoma metastases are extremely rare and only few cases have been reported in the lung, lymph nodes, pleura, mediastinum, liver, bone, and diaphragmatic, abdominal, and pelvic muscles. A review of the literature yielded 14 other case reports metastasizing outside the central nervous system, but to our knowledge, no studies describe metastasis in the paravertebral muscles. Herein, we report the case of a 39-year-old patient with a paraspinal muscles metastasis from a myxopapillary ependymoma. The neoplasm was surgically excised and histologically and molecularly analyzed. Both the analyses were consistent with the diagnosis of muscle metastases of myxopapillary ependymoma. The here-presented case report is first case in the literature of a paraspinal muscles metastasis of myxopapillary ependymoma.

Evolution in endoscopic endonasal approach for the management of hypothalamic-pituitary region metastasis: A single-institution experience.

Introduction: Endonasal endoscopic surgery has changed the treatment perspectives for different lesions of the hypothalamic-pituitary region. The metastases of the hypothalamic-pituitary region represent 0.4% of all intracranial metastatic tumors and account for only 1.8% of surgically managed pituitary lesions. The aim of tshis study is to describe a single-center institutional experience with 13 cases of hypothalamic-pituitary metastasis focused on presurgical workup, the evolution of the surgical technique, and postsurgical management according to our protocols, showing effects on progression-free and overall survival rates for this relatively uncommon location. Material and Methods: We retrospectively reviewed the whole series of patients that received the endoscopic endonasal approach at the Division of Neurosurgery at the University of Naples "Federico II" undergoing surgery from January 1997 to December 2021. We identified 13 cases whose pathology reports revealed a metastatic lesion. Statistical analysis was performed to determine the Kaplan-Meier survival function and assess for log-rank differences in survival based on gender, surgical treatment, and postoperative therapy (p-value < 0.02*). Results: The pathology report disclosed lung adenocarcinoma (six cases, 46%), breast adenocarcinoma (two cases, 15.4%), clear cell renal carcinoma (one case, 7%), melanoma (one case, 7%), colorectal adenocarcinoma (one case, 7%), uterine cervix carcinoma (one case, 7%), and follicular thyroid carcinoma (one case, 7%). A standard endoscopic endonasal approach was performed in 10 patients (76.9%), while an extended endonasal procedure was performed in only three cases (23%). Biopsy was the surgical choice in five patients with infiltrative and invasive lesions and a poor performance status (38%), while in the cases where neurovascular decompression was necessary, a subtotal resection was achieved in five patients (38%) and partial resection in three patients (23%). Recovery of visual field defect was observed in six of seven patients with visual loss (85.7%), improvement of oculomotor nerve palsy occurred in four of seven patients with this defect (57.1%), while the impairment of oculomotor palsy was observed in three patients (42.9%). Visual function was stable in the other patients. The median progression-free survival and overall survival were 14 and 18 months, respectively. There were statistically significant differences in PFS and OS in patients who underwent adjuvant radiotherapy (p=0.019 is referred to OS and p=0.017 to PFS, respectively; p-value = 0.02). Conclusions: The endoscopic endonasal approach is a viable approach for the management of hypothalamic-pituitary metastases as this surgery provides an adequate opportunity to obtain tissue sample and neurovascular decompression, both being crucial for continuing the integrated adjuvant therapy protocols.

MGMT and Whole-Genome DNA Methylation Impacts on Diagnosis, Prognosis and Therapy of Glioblastoma Multiforme.

Epigenetic changes in DNA methylation contribute to the development of many diseases, including cancer. In glioblastoma multiforme, the most prevalent primary brain cancer and an incurable tumor with a median survival time of 15 months, a single epigenetic modification, the methylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) gene, is a valid biomarker for predicting response to therapy with alkylating agents and also, independently, prognosis. More recently, the progress from single gene to whole-genome analysis of DNA methylation has allowed a better subclassification of glioblastomas. Here, we review the clinically relevant information that can be obtained by studying MGMT gene and whole-genome DNA methylation changes in glioblastomas, also highlighting benefits, including those of liquid biopsy, and pitfalls of the different detection methods. Finally, we discuss how changes in DNA methylation, especially in glioblastomas bearing mutations in the Isocitrate Dehydrogenase (IDH) 1 and 2 genes, can be exploited as targets for tailoring therapy.

Brain Gliomas and Ollier Disease: Molecular Findings as Predictive Risk Factors?

Background: Ollier disease (OD) is a rare nonhereditary type of dyschondroplasia characterized by multiple enchondromas, with typical onset in the first decade of life. Surgery is the only curative treatment for primary disease and its complications. Patients with OD are at risk of malignant transformation of enchondromas and of occurrence of other neoplasms. Methods: A wide literature review disclosed thirty cases of glioma associated with OD, most of them belonging to the pre-molecular era. Our own case was also included. Demographic, clinical, pathologic, molecular, management, and outcome data were analyzed and compared to those of sporadic gliomas. Results: Gliomas associated with OD more frequently occur at younger age, present higher rates of multicentric lesions (49%), brainstem localizations (29%), and significantly lower rates of glioblastomas (7%) histotype. The IDH1 R132H mutation was detected in 80% of gliomas of OD patients and simultaneously in enchondromas and gliomas in 100% of cases. Conclusions: The molecular data suggest a higher risk of occurrence of glioma in patients with enchondromas harboring the IDH1 R132H mutation than those with the IDH1 R132C mutation. Thus, we suggest considering the IDH1 R132H mutation in enchondromas of patients with OD as a predictive risk factor of occurrence of glioma.

Spinal cervical extradural hemangioblastoma.

Spinal cervical extradural and intra-extradural hemangioblastomas are exceptional, with only nine reported cases. This study reviews the diagnostic and surgical problems of this rare entity. Two female patients, aged 80 years and 25 years, respectively, one with Von Hippel-Lindau disease (VHLD), experienced brachial pain and weakness. On magnetic resonance imaging, a dumbbell intra-extraspinal hemangioblastoma was evidenced. The surgical resection through posterior laminectomy resulted in clinical remission of brachial pain and weakness. The magnetic resonance aspect of a dumbbell lesion suggests a neurogenic tumor; the correct preoperative diagnosis is possible in individuals with VHLD. The surgical problems include high tumor vascularity, vertebral artery control, and nerve root preservation. However, the surgical excision results in clinical remission.

Promoting Laparoscopic Anterior Approach for a Very Low Presacral Primary Neuroendocrine Tumor Arising in a Tailgut Cyst.

BACKGROUND: Tailgut cysts are rare congenital lesions that develop in the presacral space. As they can potentially conceal primary neuroendocrine tumors, surgical excision is suggested as the treatment of choice. However, specific management guidelines have yet to be developed. A posterior approach is usually preferred for cysts extending to the third sacral vertebral body. Conversely, a transabdominal approach is preferred for lesions extending upward to achieve an optimal view of the surgical field and avoid injuries. CASE REPORT: Here, we report a case of a 48-year-old man suffering from perianal pain and constipation. Digital rectal examination and magnetic resonance imaging revealed a presacral mass below the third sacral vertebral body. A laparoscopic transabdominal presacral tumor excision was performed. The final histological diagnosis was a rare primary neuroendocrine tumor arising from a tailgut cyst. The postoperative course was uneventful, and no signs of recurrence were observed at the six-month follow-up. CONCLUSIONS: This study may help establish more well-grounded recommendations for the surgical management of rectal tumors, demonstrating that the laparoscopic transabdominal technique is safe and feasible, even for lesions below the third sacral vertebral body. This approach provided an adequate view of the presacral space, facilitating the preservation of cyst integrity, which is essential in cases of malignant pathologies.

Atypical Teratoid Rhabdoid Tumor: A Possible Oriented Female Pathology?

Atypical teratoid rhabdoid tumor is a rare lesion that occurs mainly in children can be supratentorial or infratentorial and it accounts for 1-2% of pediatric brain tumors and over 10% of central nervous system (CNS) tumors in infants, with a male preponderance up to 3 years of age, more than 50% of these occur in the cerebellum. In this report we describe four new cases of sellar AT/RTs underwent endoscopic endonasal approach and different adjuvant therapies. Our aim is to report the clinical, radiological and pathological features of these rare lesions, focusing on the possibility to perform an early diagnosis and appropriate therapeutic strategy.

Isolated neurofibromas of the great auricular nerve: A rare localization in a pediatric patient with neurofibromatosis type-1.

Peripheral nerve sheath tumors encompass a spectrum of well-defined clinicopathologic entities, ranging from benign tumors, such as neurofibromas, to high grade malignant neoplasms termed malignant peripheral nerve sheath tumors. Morphologic variability of these tumors is wide, and they engender some of the most controversial, difficult differential diagnoses. Localized neurofibromas often involve a major nerve and result typically in fusiform expansion of the nerve trunk (intraneural subtype). We report a case of circumscribed solitary neurofibromas in a 14-year-old boy with NF1 who presented to our department with a left neck swelling. The neurofibromas lesion involved the anterior branch of the great auricular nerve. The sensory symptoms initially reported by the patient (paresthesia and hyperesthesia) in the lower preauricular region. Surgical treatment represents the therapeutic method of choice in the approach to neurofibromas, considering functional disorders and possible aesthetic deformities. The case described presented difficulties in surgical excision, based on risk of functional and aesthetic results.

Primary ectopic orbital craniopharyngioma.

Craniopharyngiomas (CP) ectopic localizations off the midline outside the sellar-suprasellar region are very rare and most often associated to secondary tumor dissemination, being primary ectopic CPs extremely unusual. We herein report the first case of a primary ectopic craniopharyngioma within the orbit. A 15-year-old patient presented with progressive right ptosis, proptosis, and retro ocular pain. Magnetic resonance imaging (MRI) showed a predominantly cystic lesion, occupying the superolateral right corner of the orbit, outside the intraconal space with no evidence of intracranial involvement. An endoscopic transorbital eyelid approach was adopted. Pathology report disclosed a primary ectopic craniopharyngioma.

Neuroinvasive potential of SARS-CoV2 with neuroradiological and neuropathological findings: is the brain a target or a victim?

Coronaviridae family includes pathogen viruses for humans, that lead to clinical conditions with main respiratory involvement; many of these viruses have notoriously a neuroinvasive potential, as demonstrated by published data on SARS-CoV and MERS-CoV epidemics, as well by results obtained in experimental models. During pandemic of coronavirus disease 2019 (COVID-19), it is noticed that the central nervous system involvement represented a truly significant moment in the history of some COVID-19 patients; indeed, clinical and radiological features published in literature regarding COVID-19 disease are consistent with a neurological involvement. It is also known that histopathological data related to SARS-CoV2 infection have been published with considerable delay, which was even greater for neuropathological information. Moreover, many published data are incomplete, and often the lesions described are not directly related to the action of the virus. In this review, we collected the available radiological and neuropathological information, in order to delineate a more complete picture of the relationship between SARS-Cov2 and brain, focusing our attention on the two most important neuroinvasion routes for the virus. We also highlighted what we consider methodological mistakes both in the autopsy procedures and brain study in COVID-19 deaths. We emphasize the need for a complete study of all the organs in case of autopsy. It is important that through this experience, we no longer do the mistake of neglecting the brain.