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16 pages, 1162 KiB

Open AccessArticle

Predictors of Progression in a Series of 81 Adult Patients Surgically Managed for an Intracranial Hemangioblastoma: Implications for the Postoperative Follow-Up

by Elisabeth Garrido, Huy Le Ngoc, Jacques Guyotat, Isabelle Pelissou-Guyotat, Timothée Jacquesson, Violaine Delabar, Romain Manet, Clémentine Gallet, Tanguy Fenouil, Nathalie Streichenberger, Alexandre Vasiljevic, David Meyronet, Emmanuel Jouanneau, François Ducray, Chloe Dumot and Thiebaud Picart

Cancers 2024, 16(7), 1261; https://doi.org/10.3390/cancers16071261 - 23 Mar 2024

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Abstract

The aim was to identify predictors of progression in a series of patients managed for an intracranial hemangioblastoma, in order to guide the postoperative follow-up modalities. The characteristics of 81 patients managed for an intracranial hemangioblastoma between January 2000 and October 2022 were [...] Read more.

The aim was to identify predictors of progression in a series of patients managed for an intracranial hemangioblastoma, in order to guide the postoperative follow-up modalities. The characteristics of 81 patients managed for an intracranial hemangioblastoma between January 2000 and October 2022 were retrospectively analyzed. The mean age at diagnosis was of 48 ± 16 years. Eleven (14%) patients had von Hippel–Lindau disease. The most frequent tumor location was the cerebellar hemispheres (n = 51, 65%) and 11 (14%) patients had multicentric hemangioblastomas. A gross total resection was achieved in 75 (93%) patients. Eighteen (22%) patients had a local progression, with a median progression-free survival of 56 months 95% CI [1;240]. Eleven (14%) patients had a distant progression (new hemangioblastoma and/or growth of an already known hemangioblastoma). Local progression was more frequent in younger patients (39 ± 14 years vs. 51 ± 16 years; p = 0.005), and those with von Hippel–Lindau disease (n = 8, 44% vs. n = 3, 5%, p < 0.0001), multiple cerebral locations (n = 3, 17% vs. n = 2, 3%, p = 0.02), and partial tumoral resection (n = 4, 18% vs. n = 1, 2%, p = 0.0006). Therefore, it is advisable to propose a postoperative follow-up for at least 10 years, and longer if at least one predictor of progression is present. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and the Management of Intracranial Tumors)

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11 pages, 1725 KiB

Open AccessArticle

Histopathological Diagnosis of Primary Central Nervous System Lymphoma after Therapy with Corticosteroids or Anticoagulants

by Julia Feldheim, Marvin Darkwah Oppong, Jonas Alexander Feldheim, Ramazan Jabbarli, Philipp Dammann, Anne-Kathrin Uerschels, Oliver Gembruch, Yahya Ahmadipour, Cornelius Deuschl, Andreas Junker, Ulrich Sure and Karsten Henning Wrede

Cancers 2024, 16(6), 1157; https://doi.org/10.3390/cancers16061157 - 14 Mar 2024

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Abstract

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessments is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients [...] Read more.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessments is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p = 0.049), it was only necessary in less than 10% of the cases with preoperative (but discontinued) corticosteroid treatment. Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p = 0.015). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p = 0.02). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for early surgical intervention. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after the discontinuation of CS remains a case-by-case decision. The effect of anticoagulation and dual antiplatelet therapy on diagnostic accuracy might have been underestimated and should be examined closely in future investigations. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and the Management of Intracranial Tumors)

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15 pages, 27139 KiB

Open AccessArticle

RACK1 Promotes Meningioma Progression by Activation of NF-κB Pathway via Preventing CSNK2B from Ubiquitination Degradation

by Ali Abdi Maalim, Zihan Wang, Yimin Huang and Ting Lei

Cancers 2024, 16(4), 767; https://doi.org/10.3390/cancers16040767 - 13 Feb 2024

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Abstract

Higher-grade meningiomas (WHO grade II and III) are characterized by aggressive invasiveness and high postoperative recurrence rates. The prognosis remains inadequate even with adjuvant radiotherapy and currently there is no definitive pharmacological treatment strategy and target for malignant meningiomas. This study aims to [...] Read more.

Higher-grade meningiomas (WHO grade II and III) are characterized by aggressive invasiveness and high postoperative recurrence rates. The prognosis remains inadequate even with adjuvant radiotherapy and currently there is no definitive pharmacological treatment strategy and target for malignant meningiomas. This study aims to unveil the mechanisms driving the malignant progression of meningiomas and to identify potential inhibitory targets, with significant clinical implications. Implementing techniques such as protein immunoprecipitation, mass spectrometry, RNA interference, and transcriptome sequencing, we investigated the malignancy mechanisms in meningioma cell lines IOMM-LEE and CH157-MN. Additionally, in vivo experiments were carried out on nude mice. We discovered a positive correlation between meningioma malignancy and the levels of the receptor for activated C kinase 1 (RACK1), which interacts with CSNK2B, the β subunit of casein kinase 2 (CK2), inhibiting its ubiquitination and subsequent degradation. This inhibition allows CK2 to activate the NF-κb pathway, which increases the transcription of CDK4 and cyclin D3, resulting in the transition of the cell cycle into the G2/M phase. The RACK1 inhibitor, harringtonolide (HA), significantly suppressed the malignant tendencies of meningioma cells. Our study suggests that RACK1 may play a role in the malignant progression of meningiomas, and therefore, targeting RACK1 could emerge as an effective strategy for reducing the malignancy of these tumors. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and the Management of Intracranial Tumors)

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12 pages, 1878 KiB

Open AccessArticle

PD-L1 Expression in Pituitary Neuroendocrine Tumors/Pituitary Adenomas

by Giulia Cossu, Stefano La Rosa, Jean Philippe Brouland, Nelly Pitteloud, Ethan Harel, Federico Santoni, Maxime Brunner, Roy Thomas Daniel and Mahmoud Messerer

Cancers 2023, 15(18), 4471; https://doi.org/10.3390/cancers15184471 - 08 Sep 2023

Cited by 2 | Viewed by 904

Abstract

Background and aim: About a third of Pituitary Neuroendocrine Tumors (PitNETs) may show aggressive behavior. Many efforts have been performed for identifying possible predictive factors to early determine the future behavior of PitNETs. Programmed cell death ligand 1 (PD-L1) expression was associated with [...] Read more.

Background and aim: About a third of Pituitary Neuroendocrine Tumors (PitNETs) may show aggressive behavior. Many efforts have been performed for identifying possible predictive factors to early determine the future behavior of PitNETs. Programmed cell death ligand 1 (PD-L1) expression was associated with a more aggressive biology in different solid tumors, but its role in PitNET is not well-established yet. Our study aims to analyze PD-L1 expression in a surgical cohort of PitNETs to determine its association with radiological invasion and pathology findings, as well as with long-term recurrence rates. Methods: We performed a retrospective analysis in a series of 86 PitNETs. Clinical presentation and radiological features of the preoperative period were collected, as well as pathological data and follow-up data. The rate of PD-L1 expression was immunohistochemically evaluated and expressed as a tumor proportion score (TPS). We assessed its relationship with cavernous sinus invasion and Trouillas’ classification as primary outcomes. Secondary outcomes included the TPS’ relationship with histopathological markers of proliferation, hormonal expression, tumor size and long-term recurrence rates. We calculated the optimal cut-point for the primary outcomes while maximizing the product of the sensitivity and specificity and then we evaluated the significance of secondary outcomes with logistic regression analysis. Results: Eighty-six patients were included in the analysis; 50 cases were non-functional PitNETs. The TPS for PD-L1 showed a highly right-skewed distribution in our sample, as 30.2% of patients scored 0. Using Trouillas’ classification, we found that “proliferative” cases have a significantly higher probability to express PD-L1 in more than 30% of tumor cells (OR: 5.78; CI 95%: 1.80–18.4). This same cut-point was also associated with p53 expression. A positive association was found between PD-L1 expression and GH expression (p = 0.001; OR: 5.44; CI 95%: 1.98–14.98), while an inverse relationship was found with FSH/LH expression (p = 0.014; OR = 0.27, CI 95%: 0.10–0.76). No association was found with CS invasion, tumor size, bone erosion or dura invasion. We could not find any association between PD-L1 expression and recurrence. Conclusions: PD-L1 expression was associated with proliferative grades of Trouillas’ classification and p53 expression. We also confirmed a higher expression of PD-L1 in somatotroph tumors. Larger studies are necessary to investigate the relationship between PD-L1 expression and aggressive behaviors. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and the Management of Intracranial Tumors)

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9 pages, 937 KiB

Open AccessArticle

Radiomics-Based Prediction of TERT Promotor Mutations in Intracranial High-Grade Meningiomas

by Burak Han Akkurt, Dorothee Cäcilia Spille, Susanne Peetz-Dienhart, Nora Maren Kiolbassa, Christian Mawrin, Manfred Musigmann, Walter Leonhard Heindel, Werner Paulus, Walter Stummer, Manoj Mannil and Benjamin Brokinkel

Cancers 2023, 15(17), 4415; https://doi.org/10.3390/cancers15174415 - 04 Sep 2023

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Abstract

Purpose: In meningiomas, TERT promotor mutations are rare but qualify the diagnosis of anaplasia, directly impacting adjuvant therapy. Effective screening for patients at risk for promotor mutations could enable more targeted molecular analyses and improve diagnosis and treatment. Methods: Semiautomatic segmentation of intracranial [...] Read more.

Purpose: In meningiomas, TERT promotor mutations are rare but qualify the diagnosis of anaplasia, directly impacting adjuvant therapy. Effective screening for patients at risk for promotor mutations could enable more targeted molecular analyses and improve diagnosis and treatment. Methods: Semiautomatic segmentation of intracranial grade 2/3 meningiomas was performed on preoperative magnetic resonance imaging. Discriminatory power to predict TERT promoter mutations was analyzed using a random forest algorithm with an increasing number of radiomic features. Two final models with five and eight features with both fixed and differing radiomics features were developed and adjusted to eliminate random effects and to avoid overfitting. Results: A total of 117 image sets including training (N = 94) and test data (N = 23) were analyzed. To eliminate random effects and demonstrate the robustness of our approach, data partitioning and subsequent model development and testing were repeated a total of 100 times (each time with repartitioned training and independent test data). The established five- and eight-feature models with both fixed and different radiomics features enabled the prediction of TERT with similar but excellent performance. The five-feature (different/fixed) model predicted TERT promotor mutation status with a mean AUC of 91.8%/94.3%, mean accuracy of 85.5%/88.9%, mean sensitivity of 88.6%/91.4%, mean specificity of 83.2%/87.0%, and a mean Cohen’s Kappa of 71.0%/77.7%. The eight-feature (different/fixed) model predicted TERT promotor mutation status with a mean AUC of 92.7%/94.6%, mean accuracy of 87.3%/88.9%, mean sensitivity of 89.6%/90.6%, mean specificity of 85.5%/87.5%, and a mean Cohen’s Kappa of 74.4%/77.6%. Of note, the addition of further features of up to N = 8 only slightly increased the performance. Conclusions: Radiomics-based machine learning enables prediction of TERT promotor mutation status in meningiomas with excellent discriminatory performance. Future analyses in larger cohorts should include grade 1 lesions as well as additional molecular alterations. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and the Management of Intracranial Tumors)

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12 pages, 1407 KiB

Open AccessArticle

Pituitary Stalk Morphology as a Predictor of New-Onset Adrenocortical Insufficiency and Arginine Vasopressin Deficiency after Transsphenoidal Resections of Pituitary Macroadenomas: A Retrospective Single-Center Study with a Focus on iMRI

by Ralf Becker, Michal Hlavac, Gwendolin Etzrodt-Walter, Fabian Sommer, Christian Rainer Wirtz, Bernd Schmitz and Andrej Pala

Cancers 2023, 15(15), 3929; https://doi.org/10.3390/cancers15153929 - 02 Aug 2023

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Abstract

Background: A new-onset adrenocortical insufficiency (NAI) is the most critical postoperative endocrinological complication after transsphenoidal surgery for macroadenomas. Because of increased mortality risk, arginine vasopressin deficiency (AVP-D) is also a relevant postoperative complication. This study aimed to identify easy-to-acquire magnet resonance imaging (MRI) [...] Read more.

Background: A new-onset adrenocortical insufficiency (NAI) is the most critical postoperative endocrinological complication after transsphenoidal surgery for macroadenomas. Because of increased mortality risk, arginine vasopressin deficiency (AVP-D) is also a relevant postoperative complication. This study aimed to identify easy-to-acquire magnet resonance imaging (MRI) aspects of the pituitary stalk to predict these insufficiencies after transsphenoidal surgery. Methods: Pituitary stalk morphology was reviewed intraoperatively and three months postoperatively in the MRIs of 48 transsphenoidal surgeries for macroadenomas. NAI was validated in endocrinological follow-up controls 10–14 months post-surgery. Results: Intraoperative pituitary stalk diameters were 0.5 mm larger in patients who developed NAI and AVP-D. The odds ratio was 29 for NAI and 6 for AVP-D in binary regression analysis. A value of 2.9 mm was identified as the optimal cut-off for the minimal pituitary stalk diameter regarding NAI, with a high specificity of 89%. There was no difference in pituitary stalk diameter regarding these insufficiencies three months post-surgery. Conclusions: We identified an increased pituitary stalk diameter in intraoperative MRIs as a predictive factor of NAI and AVP-D after transsphenoidal surgery. These findings might improve the early detection of NAI and, thus, optimal management. However, validating these retrospective findings in prospective studies is obligatory. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and the Management of Intracranial Tumors)

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20 pages, 24290 KiB

Open AccessArticle

Identification, and Experimental and Bioinformatics Validation of an Immune-Related Prognosis Gene Signature for Low-Grade Glioma Based on mRNAsi

by Yuan Wang, Shengda Ye, Du Wu, Ziyue Xu, Wei Wei, Faliang Duan and Ming Luo

Cancers 2023, 15(12), 3238; https://doi.org/10.3390/cancers15123238 - 19 Jun 2023

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Abstract

Background: Low-grade gliomas (LGGs), which are the second most common intracranial tumor, are diagnosed in seven out of one million people, tending to develop in younger people. Tumor stem cells and immune cells are important in the development of tumorigenesis. However, research on [...] Read more.

Background: Low-grade gliomas (LGGs), which are the second most common intracranial tumor, are diagnosed in seven out of one million people, tending to develop in younger people. Tumor stem cells and immune cells are important in the development of tumorigenesis. However, research on prognostic factors linked to the immune microenvironment and stem cells in LGG patients is limited. We critically need accurate related tools for assessing the risk of LGG patients. Methods: In this study, we aimed to identify immune-related genes (IRGs) in LGG based on the mRNAsi score. We employed differentially expressed gene (DEG) methods and weighted correlation network analysis (WGCNA). The risk signature was then further established using a lasso Cox regression analysis and a multivariate Cox analysis. Next, we used immunohistochemical sections (HPA) and a survival analysis to identify the hub genes. A nomogram was built to assess the prognosis of patients based on their clinical information and risk scores and was validated using a DCA curve, among other methods. Results: Four hub genes were obtained: C3AR1 (HR = 0.98, p < 0.001), MSR1 (HR = 1.02, p < 0.001), SLC11A1 (HR = 1.01, p < 0.01), and IL-10 (HR = 1.01, p < 0.001). For LGG patients, we created an immune-related prognostic signature (IPS) based on mRNAsi for estimating risk scores; different risk groups showed significantly different survival rates (p = 3.3 × 10⁻¹⁶). Then, via an evaluation of the IRG-related signature, we created a nomogram for predicting LGG survival probability. Conclusion: The outcome suggests that, when predicting the prognosis of LGG patients, our nomogram was more effective than the IPS. In this study, four immune-related predictive biomarkers for LGG were identified and proven to be IRGs. Therefore, the development of efficient immunotherapy techniques can be facilitated by the creation of the IPS. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and the Management of Intracranial Tumors)

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17 pages, 3051 KiB

Open AccessArticle

Risk Factor and Replacement Therapy Analysis of Pre- and Postoperative Endocrine Deficiencies for Craniopharyngioma

by Lidong Cheng, Hongtao Zhu, Jing Wang, Sisi Wu, Suojun Zhang, Junwen Wang and Kai Shu

Cancers 2023, 15(2), 340; https://doi.org/10.3390/cancers15020340 - 04 Jan 2023

Viewed by 1286

Abstract

Background: Pituitary hormone deficiency (PHD) is one of the most common symptoms and postoperative complications of craniopharyngiomas (CPs). However, the risk factors for PHD in CPs are little known. The purpose of this study was to analyze the risk factors of pre- and [...] Read more.

Background: Pituitary hormone deficiency (PHD) is one of the most common symptoms and postoperative complications of craniopharyngiomas (CPs). However, the risk factors for PHD in CPs are little known. The purpose of this study was to analyze the risk factors of pre- and postoperative PHD and to investigate replacement therapy for CP patients. Methods: A retrospective study of 126 patients diagnosed with CP was performed. Univariate analysis was performed using Pearson’s chi-squared test or Fisher’s exact test, and a multiple logistic binary regression model was used to identify the influencing factors of pre- and postoperative PHD in craniopharyngioma. Results: Children and patients with hypothalamic involvement were more likely to have preoperative PHD. Patients with suprasellar lesions had a high risk of postoperative PHD, and preoperative PHD was a risk factor for postoperative PHD. Conclusion: Children have a high incidence of preoperative PHD. Preoperative PHD can serve as an independent risk factor for postoperative PHD. Preoperative panhypopituitarism can serve as an indication of pituitary stalk sacrifice during surgery. The management of replacement therapy for long-term postoperative endocrine hormone deficiency in patients with craniopharyngioma should be enhanced. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and the Management of Intracranial Tumors)

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16 pages, 1778 KiB

Open AccessSystematic Review

Micro RNAs as a Diagnostic Marker between Glioma and Primary CNS Lymphoma: A Systematic Review

by Mohammad Amin Dabbagh Ohadi, Mir Sajjad Aleyasin, Reza Samiee, Sanaz Bordbar, Seyed Farzad Maroufi, Nikoo Bayan, Sara Hanaei and Timothy R. Smith

Cancers 2023, 15(14), 3628; https://doi.org/10.3390/cancers15143628 - 14 Jul 2023

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Abstract

Differentiating glioma from primary central nervous system lymphoma (PCNSL) can be challenging, and current diagnostic measures such as MRI and biopsy are of limited efficacy. Liquid biopsies, which detect circulating biomarkers such as microRNAs (miRs), may provide valuable insights into diagnostic biomarkers for [...] Read more.

Differentiating glioma from primary central nervous system lymphoma (PCNSL) can be challenging, and current diagnostic measures such as MRI and biopsy are of limited efficacy. Liquid biopsies, which detect circulating biomarkers such as microRNAs (miRs), may provide valuable insights into diagnostic biomarkers for improved discrimination. This review aimed to investigate the role of specific miRs in diagnosing and differentiating glioma from PCNSL. A systematic search was conducted of PubMed, Scopus, Web of Science, and Embase for articles on liquid biopsies as a diagnostic method for glioma and PCNSL. Sixteen dysregulated miRs were identified with significantly different levels in glioma and PCNSL, including miR-21, which was the most prominent miR with higher levels in PCNSL, followed by glioma, including glioblastoma (GBM), and control groups. The lowest levels of miR-16 and miR-205 were observed in glioma, followed by PCNSL and control groups, whereas miR-15b and miR-301 were higher in both tumor groups, with the highest levels observed in glioma patients. The levels of miR-711 were higher in glioma (including GBM) and downregulated in PCNSL compared to the control group. This review suggests that using these six circulating microRNAs as liquid biomarkers with unique changing patterns could aid in better discrimination between glioma, especially GBM, and PCNSL. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and the Management of Intracranial Tumors)

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