Single versus multiple reoperations for recurrent intracranial meningiomas.

PURPOSE: To identify the risk factors and management of the multiple recurrences and reoperations for intracranial meningiomas. METHODS: Data of a neurosurgical series of 35 patients reoperated on for recurrent intracranial meningiomas were reviewed. Analyzed factors include patient age and sex, tumor location, extent of resection, WHO grade, Ki67-MIB1 and PR expression at initial diagnosis, time to recurrence; pattern of regrowth, extent of resection, WHO grade and Ki67-MIB1 at first recurrence were also analyzed. All these factors were stratified into two groups based on single (Group A) and multiple reoperations (Group B). RESULTS: Twenty-four patients (69%) belonged to group A and 11 (31%) to group B. The age < 65 years, male sex, incomplete resection at both initial surgery and first reoperation, and multicentric-diffuse pattern of regrowth at first recurrence are risk factors for multiple recurrences and reoperations. In group B, the WHO grade and Ki67-MIB1 increased in further recurrences in 54% and 64%, respectively. The time to recurrence was short in 7 cases (64%), whereas 4 patients (36%) further recurred after many years. Eight patients (73%) are still alive after 7 to 22 years and 2 to 4 reoperations. CONCLUSION: The extent of resection and the multicentric-diffuse pattern of regrowth at first recurrence are the main risk factors for multiple recurrences and reoperations. Repeated reoperations might be considered even in patients with extensive recurrent tumors before the anaplastic transformation occurs. In such cases, even partial tumor resections followed by radiation therapy may allow long survival in good clinical conditions.

Time to Recurrence of Intracranial Meningiomas from a Monoinstitutional Surgical Series.

BACKGROUND: Meningiomas show variable tendency to recur. While risk factors of recurrence have been largely investigated in literature, a paucity of data is available on the time to recurrence. Our purpose was to identify main factors affecting the time to recurrence to assist preoperative treatment decision-making strategy and to define a tailored clinical and neuroradiological follow-up. METHODS: Data of 35 patients with intracranial meningioma recurrences have been retrospectively reviewed. Demographic (patient age at initial diagnosis and sex), radiologic (meningioma location, pattern of regrowth and topography of recurrences at first reoperation), pathologic (WHO grade and Ki67-MIB1 at initial surgery and at first reoperation, progesterone receptor [PR] expression), and surgical (extent of resection at initial surgery according to Simpsons grading system, number of reoperations) factors were analyzed. RESULTS: Time to recurrence ranged from 20 to 120 months. Extent of resection at initial surgery was Simpson grade I in 7 patients (20%), grade II in 10 (28.5%), grade III in 14 (40%), and grade IV in 4 (11.5%). Longer median time to recurrence was observed for skull base localization (P < 0.01), Simpson grades I and II versus grades III (P = 0.01) and IV (P = 0.02), values of Ki67-MIB1 ≤ 4% (P = 0.001), and PR > 60% (P = 0.03); conversely, sex, age, number of reoperations, unchanged/progression of Ki67, and/or World Health Organization grade between first surgery and reoperation did not correlate in statistically significant way with time to recurrence. CONCLUSIONS: The extent of resection and the Ki67-MIB1 represent the most important factors predicting shorter recurrence time of intracranial meningiomas. Patients with incomplete (Simpson grades III and IV) resection and high Ki67-MIB1 values, especially at non-skull base localization and with low PR values, require a closer short-term clinical and radiologic follow-up in the first years after surgery.

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.

Update on the Diagnosis and Management of Meningiomas.

This series of five articles (one original article and four reviews) focuses on the most recent and interesting research studies on the biomolecular and radiological diagnosis and the surgical and medical management of meningiomas [...].

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.

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.

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.

Malignant intraventricular meningioma: literature review and case report.

Malignant intraventricular meningiomas (IVMs) are very rare with only a few reported cases. A midline search up to December 2020 selected 40 articles for a total of 65 patients. The inclusion criteria were series and case reports in English language, as well as papers written in other languages, but with abstracts written in English. Malignant IVMs at the first diagnosis (group A, 50 patients) and those with anaplastic transformation from previous WHO grades I and II tumors (group B, 15 patients) were separately analyzed. The unique personal case among 1285 meningiomas (0.078%) is also added. Malignant IVMs mainly occur in women (61%) with a median age of 45 years and are mainly located in the lateral ventricle (93%) and trigonal region (74%), with no cases in the fourth ventricle. Irregular borders (80%), heterogeneous enhancement (83%), and perilesional edema (76%) are the most frequent radiological findings. The histology was mainly pure anaplastic (85%), whereas papillary (7%), rhabdoid (5%), and mixed forms (3%) are very rare. The CSF spread was found in 60% of the cases. The prognosis is very dismal, with an overall median survival of 17.5 months after surgery for the anaplastic forms. Malignant IVMs at initial diagnosis (group A) show better overall survival (25 months) than those occurring from anaplastic transformation of lower grade tumors (group B) (10.1 months).

Qualitative Heterogeneous Signal Drop on Chemical Shift (CS) MR Imaging: Correlative Quantitative Analysis between CS Signal Intensity Index and Contrast Washout Parameters Using T1-Weighted Sequences.

The aim of this study was to calculate MRI quantitative parameters extracted from chemical-shift (CS) and dynamic contrast-enhanced (DCE) T1-weighted (T1-WS) images of adrenal lesions (AL) with qualitative heterogeneous signal drop on CS T1-WS and compare them to those of AL with homogeneous or no signal drop on CS T1-WS. On 3 T MRI, 65 patients with a total of 72 AL were studied. CS images were qualitatively assessed for grouping AL as showing homogeneous (Group 1, n = 19), heterogeneous (Group 2, n = 23), and no (Group 3, n = 30) signal drop. Histopathology or follow-up data served as reference standard to classify AL. ROIs were drawn both on CS and DCE images to obtain adrenal CS signal intensity index (ASII), absolute (AWO), and relative washout (RWO) values. Quantitative parameters (QP) were compared with ANOVA analysis and post hoc Dunn's test. The performance of QP to classify AL was assessed with receiver operating characteristic analysis. CS ASII values were significantly different among the three groups (p < 0.001) with median values of 71%, 53%, and 3%, respectively. AWO/RWO values were similar in Groups 1 (adenomas) and 2 (benign AL) but significantly (p < 0.001) lower in Group 3 (20 benign AL and 10 malignant AL). With cut-offs, respectively, of 60% (Group 1 vs. 2), 20% (Group 2 vs. 3), and 37% (Group 1 vs. 3), CS ASII showed areas under the curve of 0.85, 0.96, and 0.93 for the classification of AL, overall higher than AWO/RWO. In conclusion, AL with qualitative heterogeneous signal drop at CS represent benign AL with QP by DCE sequence similar to those of AL with homogeneous signal drop at CS, but different to those of AL with no signal drop at CS; ASII seems to be the only quantitative parameter able to differentiate AL among the three different groups.

Progesterone Receptor Expression in Meningiomas: Pathological and Prognostic Implications.

BACKGROUND: The progesterone receptor (PR) is variably expressed in most meningiomas and was found to have prognostic significance. However, the correlation with patient age, tumor location, time to recurrence, and pattern of regrowth has scarcely been discussed. METHODS: A surgical series of 300 patients with meningiomas is reviewed. The PR expression was classified as: 0. absent; 1. low (<15%); 2. moderately low (16-50%); 3. moderately high (51-79%); 4. high (≥80%). The PR values were correlated with the patient age and sex, meningioma location, WHO grade, Ki-67 MIB1, recurrence rate, pattern of recurrence (local-peripheral versus multicentric diffuse), and time to recurrence. RESULTS: The PR expression has shown lower rate of high expression in the elderly group (p = 0.032) and no sex difference (including premenopausal versus postmenopausal women), higher expression in medial skull base and spinal versus other locations (p = 0.0036), inverse correlation with WHO grade and Ki67-MIB1 (p < 0.0001). Meningiomas which recurred showed at initial surgery higher rates of low or moderately low PR expression than the non-recurrent ones (p = 0.0004), whereas the pattern of regrowth was not significant. Higher rates of PR values ≥80% were found in cases with time to recurrence >5 years (p = 0.036). CONCLUSION: The higher PR expression in medial skull base meningiomas, the significant correlation with the time to recurrence, the lack of difference of PR expression between premenopausal and postmenopausal women and between local-peripheral versus multicentric-diffuse recurrences are the most relevant unreported findings of this study. The rate of PR expression must be included in the routine pathological diagnosis of meningiomas because of its prognostic significance.

Cavernous Malformations to Be Investigated for Familiarity: The Role of Ki67 MIB1.

BACKGROUND: Familial forms of cavernous malformations (CMs) often occur as multiple lesions. Nevertheless, the presence of a single CM does not exclude the familiarity. The aim of this study is to establish which patients who undergo surgery for a single cerebral cavernous malformation (CCM), with no family history at initial diagnosis, should be investigated for familiarity through genetic testing and counseling. METHODS: Eight families with 2 or more members affected by CCM have been studied. A control group of sporadic cases operated on, with no family history and followed up 10 years or more, was also included. Analyzed factors were patient age and sex, location, number and size of the lesions, associated developmental venous anomaly, presence of epileptic seizures, symptomatic hemorrhage, focal neurological deficits, and documented growth of the malformation and Ki67 MIB1 proliferation index. RESULTS: The familial group of CCMs showed higher incidence of pediatric patients (P = 0.01), more frequent occurrence of multiple lesions (P = 0.0004), higher rate of large CCMs, and symptomatic hemorrhage; besides, all 3 cases with documented growth belonged to the familial group (14%). The expression of Ki67 MIB1 was positive in 79% of the familial cases versus 0% in the sporadic ones (P < 0.00001). CONCLUSIONS: Patients with CCM and no known family history at the time of the initial diagnosis who present specific features should be studied by genetic screening. The Ki67 MIB1 is a useful biomarker in favor of familial occurrence and may be studied in all patients with CMs to define the indication to the genetic tests.

Does endometrial morular metaplasia represent odontogenic differentiation?

The nature of endometrial morular metaplasia (MorM) is still unknown. The nuclear ß-catenin accumulation and the not rare ghost cell keratinization suggest a similarity with hard keratin-producing odontogenic and hair matrix tumors rather than with squamous differentiation. We aimed to compare MorM to hard keratin-producing tumors. Forty-one hard keratin-producing tumors, including 26 hair matrix tumors (20 pilomatrixomas and 6 pilomatrix carcinomas) and 15 odontogenic tumors (adamantinomatous craniopharyngiomas), were compared to 15 endometrioid carcinomas with MorM with or without squamous/keratinizing features. Immunohistochemistry for ß-catenin, CD10, CDX2, ki67, p63, CK5/6, CK7, CK8/18, CK19, and pan-hard keratin was performed; 10 cases of endometrioid carcinomas with conventional squamous differentiation were used as controls. In adamantinomatous craniopharyngiomas, the ß-catenin-accumulating cell clusters (whorl-like structures) were morphologically similar to MorM (round syncytial aggregates of bland cells with round-to-spindled nuclei and profuse cytoplasm), with overlapping squamous/keratinizing features (clear cells with prominent membrane, rounded squamous formations, ghost cells). Both MorM and whorl-like structures consistently showed positivity for CD10 and CDX2, with low ki67; cytokeratins pattern was also overlapping, although more variable. Hard keratin was focally/multifocally positive in 8 MorM cases and focally in one conventional squamous differentiation case. Hair matrix tumors showed no morphological or immunophenotypical overlap with MorM. MorM shows wide morphological and immunophenotypical overlap with the whorl-like structures of adamantinomatous craniopharyngiomas, which are analogous to enamel knots of tooth development. This suggests that MorM might be an aberrant mimic of odontogenic differentiation.

Handcrafted MRI radiomics and machine learning: Classification of indeterminate solid adrenal lesions.

PURPOSE: To assess a radiomic machine learning (ML) model in classifying solid adrenal lesions (ALs) without fat signal drop on chemical shift (CS) as benign or malignant. METHOD: 55 indeterminate ALs (21 lipid poor adenomas, 15 benign pheocromocytomas, 1 oncocytoma, 12 metastases, 6 primary tumors) showing no fat signal drop on CS were retrospectively included. Manual 3D segmentation on T2-weighted and CS images was performed for subsequent radiomic feature extraction. After feature stability testing and an 80-20% train-test split, the train set was balanced via oversampling. Following a multi-step feature selection, an Extra Trees model was tuned with 5-fold stratified cross-validation in the train set and then tested on the hold-out test set. RESULTS: A total of 3396 features were extracted from each AL, of which 133 resulted unstable while none had low variance (< 0.01). Highly correlated (r > 0.8) features were also excluded, leaving 440 parameters. Among these, Support Vector Machine 5-fold stratified cross-validated recursive feature elimination selected a subset of 6 features. ML obtained a cross-validation accuracy of 0.94 on the train and 0.91 on the test sets. Precision, recall and F1 score were respectively 0.92, 0.91 and 0.91. CONCLUSIONS: Our MRI handcrafted radiomics and ML pipeline proved useful to characterize benign and malignant solid indeterminate adrenal lesions.

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.

Meningiomas in Premenopausal Women: Role of the Hormone Related Conditions.

BACKGROUND: Several epidemiological and pathological findings suggest that the female sex hormones may influence the development of meningiomas. However, the role of pregnancy, oral contraceptives, and fertilization therapies is still controversial. METHODS: From the surgical series of 354 patients with meningiomas operated between 2006 and 2019, the group of 72 premenopausal women was separately considered. The tumor location, WHO grade, Ki67-labeling index (LI), progesterone receptor (PR) expression, and histological types were studied in premenopausal women with and without hormone-related conditions were compared. RESULTS: In this premenopausal group, 24 patients had hormone-related conditions, including use of oral contraceptives in 16, intrauterine fertilization in one, pregnancy in three, and tumors of the female reproductive system in four. The group of patients with hormone-related conditions, as compared to that with no hormone related conditions, showed slightly lower median age (38 versus 43 years) and no significant difference of meningioma location WHO grade, Ki 67-Li, PR expression and histological type. The clinical onset during pregnancy in three patients and tumor growth during contraceptive progesterone therapy in two others were evidenced. CONCLUSION: The biological behavior of meningiomas and their pathological findings, including PR expression, are not correlated with the different hormone related conditions in premenopausal female patients. Contraceptives and fertilization therapies, mainly with progesterone, should be avoided in patients with meningiomas.

HIV prevalence in primary central nervous system lymphoma: A systematic review and meta-analysis.

HIV infection is considered a major risk factor for primary central nervous system lymphoma (PCNSL). However, the percentage of PCNSL that occurs in HIV + patients is not well defined. We aimed to assess the prevalence of HIV infection in patients with PCNSL through a systematic review and meta-analysis. Electronic databases were searched for studies assessing the presence of HIV infection in series of patients with PCNSL. Pooled prevalence of HIV infection in PCNSL was calculated, with a subgroup analysis based on the geographic area. Twenty-seven studies with 6422 patients were included. Overall, pooled prevalence of HIV infection among PCNSL patients was 6.1 % with high heterogeneity. In the subgroup analysis, pooled prevalence was 3.6 % in India with low heterogeneity, 30.2 % (overall) and 16.5 % (after 2000) in the USA with high heterogeneity, 5.7 % in Europe with high heterogeneity, 2.2 % in East Asia with null heterogeneity, 7.3 % in South America with moderate heterogeneity. In conclusion, only a minor part of PCNSL occurs in patients with HIV. The results stratified by geographic area reflect the different prevalence of HIV infection in the general population, except for India, probably due to the shorter life expectancy of HIV + patients.

Inflammation in the neoplasms of the adrenal gland: Is there a prognostic role? An immunohistochemical study.

INTRODUCTION: Adrenal gland neoplasms are mostly benign. The differential diagnosis between adrenocortical adenoma and carcinoma relies on nine morphologic parameters (Weiss criteria) that are mostly subjective. Although rare, carcinomas represent an aggressive disease that require short time follow-up. For this reason, the diagnosis should be accurate. Neoplasms of the medulla are mostly represented by phaeochromocytomas, all potentially metastatic. Prognostic score systems (GAPP and PASS) have been implemented but not enough objective and useful in borderline cases. More objective parameters should be introduced. Little is known in literature on the inflammatory response in these tumors. Aim of our study was the definition (type, density and distribution) of inflammation in the adrenal neoplasms. MATERIAL AND METHODS: Immunohistochemistry for CD45 (inflammatory cells), CD20 (B cells) and CD3 (T cells) antibodies was performed in 15 adrenocortical neoplasms and 17 phaeochromocytomas. A manual count of the signal was set for each marker, to establish the cellular type, their density (cells/mm2) and location within the tumor. Fisher's exact test was applied to assess the correlation between the immunoscore and clinico-pathologic parameters. RESULTS: The difference of cellular density between the three markers was statistically significant (p value = 0.0028), with highest values for CD45 and CD3. No differences were detected between the periphery and the center of the lesions. The most relevant finding was the detection of a higher immunoscore in adrenocortical adenomas, compared to carcinomas. Moreover, most of phaeochromocytomas showed high expression of inflammation, except the only metastatic case. CONCLUSIONS: The present study showed that inflammation could represent a valuable diagnostic and potential prognostic parameter, useful for the correct management of these lesions.

Italian consensus and recommendations on diagnosis and treatment of low-grade gliomas. An intersociety (SINch/AINO/SIN) document.

In 2018, the SINch (Italian Society of Neurosurgery) Neuro-Oncology Section, AINO (Italian Association of Neuro-Oncology) and SIN (Italian Association of Neurology) Neuro-Oncology Section formed a collaborative Task Force to look at the diagnosis and treatment of low-grade gliomas (LGGs). The Task Force included neurologists, neurosurgeons, neuro-oncologists, pathologists, radiologists, radiation oncologists, medical oncologists, a neuropsychologist and a methodologist. For operational purposes, the Task Force was divided into five Working Groups: diagnosis, surgical treatment, adjuvant treatments, supportive therapies, and follow-up. The resulting guidance document is based on the available evidence and provides recommendations on diagnosis and treatment of LGG patients, considering all aspects of patient care along their disease trajectory.