Pathology features of recurrent meningioma

P02.011 (2011). 18 Kaley TJ, Wen PY, Schiff D et al. Phase II trial of sunitinib (SU011248) for recurrent meningioma. Neuro Oncol. 12(Suppl. 4),

INTRODUCTION. Meningiomas occur in 18–34 % of cases of all intracranial neoplasms in adults. Intracranial meningiomas recurrence and progression occurs, on average, in 25 % of patients, even after radical tumor removal and radiotherapy, which significantly worsens the prognosis and functional outcome.PURPOSE. To describe the neuroimaging features picture in patients with Intracranial meningiomas recurrence and progression, to show the capabilities of modern diagnostic methods (MRI, MR perfusion, PET-CT) in assessing the progression in meningiomas.MATERIALS AND METHODS. The basis of the study consisted of patients (n=105) with intracranial meningiomas recurrence and progression Grade I–III, treated in the Department of Neurosurgery No. 4 of the Russian Neurosurgical Institute named after. prof. A.L. Polenov in the period from 2014 to 2022. An analysis of intrascopic data in patients with recurrence and progression of meningiomas was carried out. Tumors were characterized by volume, contours, the presence of perifocal edema and the degree of its severity with analysis in DWI mode (ICD) and assessment of MR perfusion parameters (ASL-perfusion), severity and type of contrast, the presence of a border with normal brain and assessment of additional signs (“comet tail”, hyperostosis, erosion of adjacent bone, extracranial spread, sinus invasion). The PET/CT procedure was performed on a combined system for positron emission and X-ray computed tomography. In case of tumor recurrence, its localization and direction of growth were also assessed. During the study, the results obtained were processed by the STATISTICA 10.0 software system.RESULTS. Introscopy data for recurrent intracranial meningiomas were analyzed, the main trends in the oncogenesis were identified, and the most common diagnostic features of tumor progression were identified, which need to be taken into account for planning surgery and treatment tactics.CONCLUSION. In diagnosing recurrence and progression of intracranial meningiomas it is important to examine patients comprehensively, using the modern research methods of neuroimaging.Patients should be followed up, and if signs of tumor progression occur, immediately be referred to the stages of specialized medical care.

The study objective was to determine the recurrence rate of intracranial meningioma and the risk factors that are contributory to an increase in the incidence of recurrence. A prospective design was used in this study on meningioma patients treated at Cipto Mangunkusumo Hospital between 2010 and mid-2015. Data on the subjects were collected from the Departments of Neurology, Neurology, and Pathology, at the Universitas Indonesia/Cipto Mangunkusumo Hospital. The subjects were adults who had been previously diagnosed with meningioma. Follow-up was performed to assess the patients in relation to their initial clinical presentation. Neuroimaging was carried out to determine recurrence. The histopathological findings, extent of tumor resection (using Simpson’s criteria), and Word Health Organization grade, were also determined. Immunohistochemistry was performed to evaluate the expression of progesterone receptor (PR), Ki-67, and vascular endothelial growth factor (VEGF). The recurrence rate was then analyzed to determine any correlation with the aforementioned risk factors. The recurrence rate was found to be 13%. Ki67, VEGF, and PR expression was positive in 9%, 73%, and 50% of the subjects, respectively. A significant correlation was not found between the study variables (tumor location, the scope of resection based on Simpson’s criteria, histopathologic grade, mitotic index, i.e., Ki-67, and PR and VEGF expression in the meningioma tissue) and the recurrence of meningioma.

Background: Intracranial meningiomas are common primary central nervous system tumors, mostly benign, yet recurrence remains a significant clinical challenge influencing patient prognosis. Understanding the characteristics and determinants of recurrence, particularly in specific populations, is crucial. Data on recurrent meningioma from developing countries like Indonesia are limited. This study aimed to describe the clinicopathological features and surgical management experience of recurrent intracranial meningiomas over a 10-year period at a tertiary referral hospital in Bandung, Indonesia. Methods: A retrospective analysis was conducted on all adult patients (≥18 years) surgically treated for recurrent intracranial meningioma at the Department of Neurosurgery, Dr. Hasan Sadikin General Hospital, Bandung, between January 2012 and December 2022. Patients with incomplete records were excluded. Data collected included demographics, clinical presentation, radiological findings (tumor location, bone infiltration, tumor invasion), surgical history (number of resections, time to recurrence), and histopathological results. Descriptive statistics were used for analysis. Results: Twenty-eight patients met the inclusion criteria. The cohort was predominantly female (n=24, 85.7%) with a median age of 46 years (range 26-67). The most common presenting symptoms were protrusion (n=11, 39.3%) and headache (n=7, 25.0%). Tumors were most frequently located in the parietal (n=10, 35.7%) and sphenoorbital (n=9, 32.1%) regions. Significant bone infiltration was observed in 75.0% (n=21) of cases. Tumor invasion into adjacent structures occurred in 21.4% (n=6), most commonly involving the cavernous sinus (n=2, 7.1% of total / 33.3% of invaded). The median time to recurrence detection was 36 months (range 6-144). Most patients (n=22, 78.6%) underwent two tumor removal surgeries during the study period. Based on available histopathology (n=17), meningothelial (n=10, 35.7% of total / 58.8% of available) and transitional (n=3, 10.7% of total / 17.6% of available) subtypes were the most common WHO Grade 1 diagnoses. One case each of atypical (Grade 2) and malignant (Grade 3) meningioma were identified. Conclusion: Recurrent intracranial meningiomas predominantly affected middle-aged females, often presenting with symptoms related to mass effect in parietal and sphenoorbital locations. High rates of bone infiltration and significant tumor invasion, particularly involving the cavernous sinus, were characteristic features. Recurrence was typically diagnosed within 3 years, with meningothelial and transitional subtypes being the most frequent histologies observed in this recurrent group. These findings underscore the complex nature of meningioma recurrence and highlight the need for tailored management strategies and long-term surveillance, particularly in cases with high-risk features like bone and sinus invasion.

INTRODUCTION. High level expression in tumor cells of various cellular growth factors, their receptors and activation of intracellular signaling pathways take an important part in recurrence of intracranial meningiomas (Grade III). There is a group of patients with aggressive meningiomas characterized by frequent recurrences and low survival rate. The following surgery is associated with high risk of appearance or worsening of neurological deficit, radical tumor removal is not always possible. Radiotherapy is also limited in some cases or not effective enough.AIM. To evaluate the degree of development of the theme of chemotherapy use in patients with meningiomas of different anaplasia degree according to the world literature data; to present our own data on chemotherapeutic treatment of a patient with recurrent meningioma.MATERIALS AND METHODS. The search of printed works in Pubmed, EMBASE, Cohrane Library and eLibrary databases was carried out on the issue of chemotherapeutic treatment use in patients with intracranial meningiomas. There is a description of a clinical case of chemotherapy use in complex treatment of a patient with recurrent intracranial anaplastic meningioma in Polenov Neurosurgical Institute — the branch of Almazov National Medical Research Centre.RESULTS. The results of some experimental studies and clinical use of chemotherapeutic drugs of different groups in patients with intracranial meningiomas are presented. Our own data on chemotherapy use in a patient with recurrent meningioma are given.CONCLUSION. Specific antitumor treatment is a part of complex treatment for patients with recurrent meningiomas Grade II–III. The efficiency and safety of this therapy have been proved in some studies and also shown in our clinical example.

The management of certain meningiomas of the skull base and those involving the dural venous sinuses remains a challenge. In recent reports it has been suggested that hydroxyurea chemotherapy can cause regression of unresectable and recurrent meningiomas. The authors report their experience in using hydroxyurea for the treatment of patients with recurrent or unresectable meningiomas. Hydroxyurea was administered at a dosage of approximately 20 mg/kg/day to 11 women and nine men (median age 59 years, range 31-75 years) with recurrent or unresectable intracranial meningiomas (12 basal, two parasagittal, and six multiple). In 16 patients the meningiomas were benign, in three they had atypical features, and in one the meningioma was malignant. All patients had measurable residual disease. Four patients with benign meningiomas had previously received radiotherapy (two were treated with conventional fractionated radiotherapy and two with stereotactic radiosurgery), three with atypical meningiomas received conventional fractionated radiotherapy, and the one with a malignant meningioma received conventional radiotherapy with additional stereotactic radiosurgery. Tumor enlargement was documented in all patients on neuroimages obtained before initiation of hydroxyurea therapy. All patients were evaluable for response to therapy. In 12 patients with benign meningiomas, the disease had stabilized on neuroimages obtained posttreatment (median duration of treatment 122 weeks, range 8-151 weeks), and two of these showed clinical improvement. One patient with a benign meningioma experienced a minor partial response that was noted after 39 weeks of treatment and was confirmed on neuroimaging and clinical evaluations. In three others with benign meningiomas, progression was confirmed on neuroimages obtained after 41, 55, and 66 weeks, respectively: the 1-year freedom from progression rate was 0.93 (standard error 0.07) in patients with benign meningiomas. In three patients with atypical meningiomas, the tumors had progressed on neuroimages obtained after 12, 19, and 45 weeks, respectively. In the patient with a malignant meningioma, progression was confirmed on neuroimages obtained at 24 weeks. Hydroxyurea has been reasonably well tolerated, although one patient discontinued therapy because of moderate myelosuppression. Although tumor regression appears uncommon, these results indicate that hydroxyurea may arrest progression of unresectable or recurrent benign meningiomas.

Introduction. Meningiomas account for 18–34 % of all intracranial tumors in adults and are the second most common among all intracranial neoplasms. Recurrence and progression account for 25 %, on average, even after radical tumor resection and radiotherapy., that worsens the prognosis and functional outcome of the disease significantly. Clinical manifestations often occur with large tumor sizes, initial symptoms are not taken into account by patients and by doctors during follow-up after surgery.Purpose. To assess the clinical features in patients with recurrence and progression of intracranial meningiomas and to identify the features of clinical manifestations in the progression of meningiomas.Materials and methods. The study was based on patients (132 cases) with recurrence and progression of intracranial meningiomas with Grade I–III according to histology, who were treated in the Department of Neurosurgery No. 4 of the Polenov Neurosurgical Institute in the period of time from 2014 to 2024. Assessment of clinical neurological symptoms was performed according to standard methods in clinical practice. The results were evaluated using the software system STATISTICA 10.0.Results. The multifactorial analysis of the clinical manifestations of the disease in recurrent intracranial meningiomas was performed, the main trends in oncogenesis were identified, and the most common clinical symptoms of tumor progression were identified, which must be taken into account by doctors during follow-up after surgery.

Objective To investigate the relationship between the expression of Pin1 and Ki67 and the clinicopathologic features of gastrointestinal stromal tumors (GIST) . Methods 40 paraffin-embeded specimens of surgical resected GIST from Jan. 2013 to May. 2015 in Pathology Department of Yuhuangding Hospital Affiliated to Qingdao University were retrieved and expressions of Pin1 and Ki67 were detected by immunohistochemical methods. Results The positivity rate of Pin1 and Ki67 in GIST was 80% and 32.5% respectively. The expression of Pin1 was associated with malignancy of GIST, tumor location, tumor size and mitotic counts. The expression of Ki67 is associated with malignancy of GIST, tumor location,tumor size, mitotic counts and tumour necrosis. Pin1 expression was positively related with Ki67 expression. Conclusion Pin1 and Ki67 is closely related with malignancy of GIST, which may be potential factors in predicting prognosis of GIST. Key words: Gastrointestinal stromal tumors; NIMA-interacting peptidylprolyl isomerase; ki-67 antigen; Immunohistochemistry

INTRODUCTION. Meningiomas account for 18–34 % of all intracranial tumors in adults and are the second most common among all intracranial neoplasms. Recurrence and progression account for 25 %, on average, even after radical tumor resection and radiotherapy., that worsens the prognosis and functional outcome of the disease significantly. Clinical manifestations often occur with large tumor sizes, initial symptoms are not taken into account by patients and by doctors during follow-up after surgery.PURPOSE. To assess the clinical features in patients with recurrence and progression of intracranial meningiomas and to identify the features of clinical manifestations in the progression of meningiomas.MATERIALS AND METHODS. The study was based on patients (105 cases) with recurrence and progression of intracranial meningiomas with Grade I – III according to histology, who were treated in the Department of Neurosurgery No. 4 of the Russian Neurosurgical Institute named after professor. A. L. Polenov in the period of time from 2014 to 2022. Assessment of clinical neurological symptoms was performed according to standard methods in clinical practice. The results were evaluated using the software system STATISTICA 10.0.RESULTS. The multifactorial analysis of the clinical manifestations of the disease in recurrent intracranial meningiomas was performed, the main trends in oncogenesis were identified, and the most common clinical symptoms of tumor progression were identified, which must be taken into account by doctors during follow-up after surgery.

Background: The role of fundoplication in the prevention of esophageal adenocarcinoma is controversial. Development of cancer is associated with proliferation and anti-apoptosis, for which little data exist regarding their response to fundoplication. Methods: Ki-67 and Bcl-2 expression was assessed in the esophagogastric junction (EGJ) and the distal and proximal esophagus of 20 patients with gastroesophageal reflux disease (GERD) treated by fundoplication and in 7 controls. Endoscopy was performed preoperatively and 6 (20 patients) and 48 months (16 patients) postoperatively. Results: There were positive correlations between Ki-67 and Bcl-2 levels in the EGJ (p > 0.001) and in the distal (p = 0.001) and proximal esophagus (p = 0.013). Compared to the preoperative level, Ki-67 expression was elevated in the distal (p = 0.012) and proximal (p = 0.007) esophagus at 48 months. In addition, compared to control values, Ki-67 expression was lower at the 6-month follow-up in the EGJ (p = 0.037) and the proximal esophagus (p = 0.003), and higher at the 48-month follow-up in the distal esophagus (p = 0.002). Compared to control values, Bcl-2 was lower at 6 months in the EGJ (p = 0.038). Conclusions: Proliferative activity after fundoplication increased in the long term in the distal esophagus despite a normal fundic wrap and healing of GERD.

Tumor cell proliferation (Ki-67) expression and its prognostic significance in histological subtypes of lung adenocarcinoma

Background: Laryngeal cancer is a common localization of squamous cell carcinoma of the head and neck. The main factor influencing the survival of patients is the presence of regional metastases. The malignant degeneration of a cell is always accompanied by disruption of the cell cycle, in particular a sharp increase in proliferative activity. The molecular marker Ki-67 is used to investigate the proliferative activity of tumor cells. Aim of the study: To study the informative content of immunohistochemical investigation and to determine the expression of the molecular marker Ki-67 in patients with laryngeal cancer, prior to the prediction of regional metastasis and relapse. Materials and Methods: 70 patients with cancer, stage III-IV (T3-4N0-3M0) clinical group II were under observation. Of these, 39 patients from the main group were with regional laryngeal cancer metastases, and 31 patients in the comparison group – without revealed regional metastases. Patients' age ranged from 33 to 74 years. The average age was 61.9 years. Male patients made up the absolute majority of 99% No = 69. All patients were histologically diagnosed with squamous cell carcinoma. Monoclonal antibodies to Ki67 (TermoScientific, USA) were used as the primary molecular markers. The proliferation index (PI) was rated as low in the range of 0-30% and as high in more than 30% of positive cells with an intranuclear label. Results: The study of molecular markers Ki-67 showed its expression at 69 [60.2; 77.5]% (Me [25%; 75%]) for the squamous cell laryngeal cancer group, without metastases – 60 [29; 70.5]%, for the group with metastases – 72 [67; 80]% (P <0.001). In statistical data processing, the AUC value (0.777) was set for Ki-67 for metastasis and showed an increased degree of expression for laryngeal cancer metastasis. Ki-67 has a good diagnostic value and can be used as an additional method for predicting regional laryngeal cancer metastases. However the practical use of this marker as a prognostic one for determining the volume of surgery on the lymphatic structures of the neck requires further investigation. It should be noted that this study did not reveal the link of Ki-67 AUC (0.588) with the degree of differentiation of laryngeal cancer and its recurrence, but more in-depth study of molecular markers in the future may reveal other patterns of tumor growth and be used in the prognosis and personalization of treatment. Conclusion: Expression of Ki-67 allowed to accurately predict tumor metastasis. A 1% increase in Ki-67 expression resulted in an 8.3% increase in the chance of tumor metastasis (95% CI - 1.043-1.142), and the age dependence on metastasis is not reliable. Determination of expression of Ki-67 does not accurately predict the possibility of recurrence of laryngeal cancer (p=0.27; AUC (95% CI) – 0.588 (0.414-0.763)) herewith age dependence of chance of a recurrence was not revealed.

To evaluate hepatic expression of the nuclear proliferative marker Ki-67 and the p53 oncoprotein in hepatitis B virus (HBV)/HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma (HCC). We studied needle liver biopsies from 107 patients with cirrhosis and no HCC (52 HBV, 55 HCV) who had been assessed for protocol studies, and 57 cirrhotic patients with HCC (40 HBV, 17 HCV). We evaluated small and large cell dysplastic changes along with the expression of Ki-67 and p53 by immunohistochemistry. The labelling index (LI) was defined as the proportion (%) of positive-stained nuclei of the 500 measured. Large and small cell dysplastic changes were observed in 12 and 9% of specimens respectively. Only small cell changes were associated with Ki-67 expression. Ki-67 LI was 5.50 +/- 5.7 in cirrhosis (13.90 +/- 3.84 in those with small cell dysplastic changes vs 4.64 +/- 4.98 in those without, P < 0.01), 10.2 +/- 5.95 in cirrhosis with HCC (P < 0.05) and 18.56 +/- 10 in HCC (P < 0.01). Neither the presence of small cell dysplastic changes nor the expression of Ki-67 was related to severity or aetiology of cirrhosis. Expression of p53 was observed in 30% of the non-tumorous and in 53% of the neoplastic tissue obtained from patients with HCC, with no differences between HCV and HBV. Ki-67 and p53 expression was associated with the tumour grade (P < 0.001). Our observations clearly demonstrate the association between the proliferation activity and the morphological changes in the cirrhotic liver from the non-dysplastic to dysplastic lesion to HCC. They also support the hypothesis that p53 alterations are a rather late event in carcinogenesis and related to HCC grade. And finally, they suggest that the final steps of hepatocarcinogenesis are common and independent of the aetiology of the chronic viral infection.

Preoperative identification of high-recurrent pediatric meningiomas with MRI features would help clinicians to make optimal treatment strategies; however, the relationships between radiological features and recurrence of meningiomas in pediatric population have not been clearly demonstrated yet. The aim of this study is to identify preoperative MRI features which are significant risk factors for recurrence of pediatric meningiomas. From January 2005 to December 2012, we retrospectively reviewed 52 pediatric meningiomas in terms of preoperative MRI features and their clinical data and followed them up from 22 to 128months (mean 63months) after the initial surgery. The relationships between these radiological findings and relapse-free survival (RFS) time were assessed initially with univariate Cox analysis and then corrected by multivariate Cox analysis. According to univariate analysis, irregular shape, narrow-based attachment, and skull base location were significantly correlated with shorter time to recurrences of meningiomas in pediatric patients. When corrected by multivariate analysis, irregular shape (P = 0.05; OR 3.442, 95% CI 1.001-11.831) and narrow-based attachment (P = 0.004; OR 7.164, 95% CI 1.894-27.09) were strong independent predictive factors for worse RFS of pediatric meningiomas. In pediatric population, narrow-based attachment and irregular shape were significantly correlated with recurrences of meningiomas. Our results could help clinicians to make optimal therapeutic strategies for pediatric patients with intracranial meningiomas before surgery.

To evaluate the expression of nuclear factor-kappaB (NF-kappaB), Ki-67 and matrix metalloproteinase-9 (MMP-9) in calcifying odontogenic cyst (COC), in order to investigate the proliferation and invasion of COC. Twenty-six cases of COC were classified into calcifying cystic odontogenic tumor (CCOT), dentinogenic ghost cell tumor (DGCT) and ghost cell odontogenic carcinoma (GCOC) based on the WHO classification of odontogenic tumors in 2005. The specimens of COC and 10 classic ameloblastoma (AB) were examined immunohistochemically to determine the expression of NF-kappaB p65, Ki-67 and MMP-9. NF-kappaB was mainly detected in the cytoplasm of most tumor cells, but was only detected in the nucleus of few tumor cells (rate of nuclear staining < 1%). The expression of Ki-67 was significantly higher in GCOC than in CCOT (P < 0.001), DGCT (P < 0.05) and AB (P < 0.005). MMP-9 was detected both in tumor cells and stromal cells. GCOC showed significantly higher percentage of MMP-9 positive cases in stromal cells than CCOT, DGCT and AB (P < 0.05). NF-kappaB may minimally affect the progression and invasion of COC. GCOC shows significantly higher proliferative activity and aggressiveness than CCOT and DGCT. MMP-9 in stroma may play a key role in the invasion of GCOC.