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Neurologia Sep 2020No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of... (Review)
Review
INTRODUCTION
No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures.
METHODS
We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis.
RESULTS
AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect.
CONCLUSIONS
Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.
PubMed: 32896461
DOI: 10.1016/j.nrl.2020.06.014 -
Cancer Jun 2007Histopathologic evaluation of the degree and extent of anaplasia is a useful prognostic parameter in pediatric medulloblastomas. Whether the same applies to adult...
BACKGROUND
Histopathologic evaluation of the degree and extent of anaplasia is a useful prognostic parameter in pediatric medulloblastomas. Whether the same applies to adult medulloblastomas is not known.
METHODS
The study included 74 adult patients with histologically confirmed medulloblastomas and retrospectively reassessed 67 cases with available slides for the presence of nodularity, collagen deposition (desmoplasia without nodules), and degree and extent of anaplasia.
RESULTS
Patients included 43 men and 31 women with the following age distribution: 18-40 years (84%); 41-50 years (9%); and 51-70 years (7%). At last follow-up, 56 patients were alive with a mean follow-up of 6.3 years (range, 0.1-20.8 years). A variety of treatments were employed during the study period, including postoperative radiation (85%) and chemotherapy (27%). Precise treatment modalities were unknown in 12% of patients. Anaplasia was absent (34%), mild (34%), moderate (27%), or severe (5%). Severe anaplasia was diffuse in 2 cases and focal in 1, although in the latter cases severe anaplasia was diffusely present at the time of disease recurrence. Male sex was associated with decreased 10-year recurrence-free survival (40% vs 66%; P = .021) and overall survival (38% vs 68%; P = .005). Severe anaplasia at first resection was found to be an independent predictor of decreased recurrence-free survival (P = .005) and overall survival (P = .015).
CONCLUSIONS
The incidence of severe anaplasia in adult medulloblastomas is lower than in the pediatric population. Male sex and the presence of severe anaplasia at the time of first resection are predictors of decreased recurrence-free and overall survival. However, the significance of severe anaplasia should be regarded with caution based on the small number of tumors with this feature in the current study.
Topics: Adolescent; Adult; Age Distribution; Aged; Cerebellar Neoplasms; Female; Humans; Immunoenzyme Techniques; Incidence; Male; Medulloblastoma; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Sex Distribution; Survival Rate
PubMed: 17487854
DOI: 10.1002/cncr.22717 -
PeerJ 2019Cyclin A overexpression is found in a variety of human tumors and correlates with unfavorable outcome. We analyzed immunohistochemical expression of cyclin A in Wilms...
BACKGROUND
Cyclin A overexpression is found in a variety of human tumors and correlates with unfavorable outcome. We analyzed immunohistochemical expression of cyclin A in Wilms tumor (WT) in relation to clinicopathological characteristics, preoperative chemotherapy (PrOpChTh), and overall survival (OS).
METHODS
This retrospective study involved 43 patients who underwent nephrectomy from January 1996 to October 2010. Tumor stage and histological subtype were determined by revised Societé International d'Oncologie Pediatrique protocol, based on histological components/alterations caused by PrOpChTh, within the prognostic group of low, intermediate and high risk, and with criteria for anaplasia. The regressive/necrotic changes in total tumor mass of primary tumor and the proportion of epithelial, blastemal, and stromal components in the remaining viable tumor tissue were also determined. Cyclin A expression was evaluated by immunohistochemistry using a polyclonal rabbit, antihuman antibody (H-432).
RESULTS
Cyclin A overexpression was found in 34.3% of WTs, with higher frequency in tumors with epithelial (31.3%) and blastemal (37.1%) components than those with stromal component (17.7%). Regarding histological type, cyclin A overexpression was found most often in focal anaplasia (100%), stromal (60%), and diffuse anaplastic (66.7) WTs. The overexpression was also more frequent in stages 3 and 4 (77.8% and 66.7%, respectively) compared to tumors in stages 1 and 2 (13.3% and 12.5%, respectively; = 0.004) in all components, as well as in blastemal component in stages 3 and 4 (77.8% and 66.7%, respectively) vs. stages 1 and 2 (13.3% and 25%, respectively, = 0.009). Cyclin A overexpression in all components was 66.7% in WTs with metastasis and 31.3% in WTs without metastasis ( = 0.265, Fisher test). Log-rank testing revealed differences of OS regarding stage ( = 0.000), prognostic groups ( = 0.001), and cyclin A expression in blastemal component ( = 0.025). After univariate analysis, tumor stage ( = 0.001), prognostic group ( = 0.004), and cyclin A expression in blastemal component ( = 0.042) were significant prognostic factors for OS; however, after multivariate analysis, none of these factors were confirmed as independent predictors of survival.
DISCUSSION
This study showed that cyclin A overexpression might be associated with the development and progression of WT with anaplasia. Also, cyclin A overexpression was more often observed in advanced stages (3 and 4) of WT, in the group of high-risk WTs, and in focal and diffuse anaplasia WTs. There was no relation of cyclin A overexpression and metastatic ability of WT. Although this study has not confirmed the prognostic value of cyclin A overexpression, its association with unfavorable prognosis should be further evaluated.
PubMed: 30648000
DOI: 10.7717/peerj.6212 -
Cancer Feb 2021WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare contiguous gene deletion syndrome with a 45% to 60% risk of...
BACKGROUND
WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare contiguous gene deletion syndrome with a 45% to 60% risk of developing Wilms tumor (WT). Currently, surveillance and treatment recommendations are based on limited evidence.
METHODS
Clinical characteristics, treatments, and outcomes were analyzed for patients with WAGR and WT/nephroblastomatosis who were identified through International Society of Pediatric Oncology Renal Tumor Study Group (SIOP-RTSG) registries and the SIOP-RTSG network (1989-2019). Events were defined as relapse, metachronous tumors, or death.
RESULTS
Forty-three patients were identified. The median age at WT/nephroblastomatosis diagnosis was 22 months (range, 6-44 months). The overall stage was available for 40 patients, including 15 (37.5%) with bilateral disease and none with metastatic disease. Histology was available for 42 patients; 6 nephroblastomatosis without further WT and 36 WT, including 19 stromal WT (52.8%), 12 mixed WT (33.3%), 1 regressive WT (2.8%) and 2 other/indeterminable WT (5.6%). Blastemal type WT occurred in 2 patients (5.6%) after prolonged treatment for nephroblastomatosis; anaplasia was not reported. Nephrogenic rests were present in 78.9%. Among patients with WT, the 5-year event-free survival rate was 84.3% (95% confidence interval, 72.4%-98.1%), and the overall survival rate was 91.2% (95% confidence interval, 82.1%-100%). Events (n = 6) did not include relapse, but contralateral tumor development (n = 3) occurred up to 7 years after the initial diagnosis, and 3 deaths were related to hepatotoxicity (n = 2) and obstructive ileus (n = 1).
CONCLUSIONS
Patients with WAGR have a high rate of bilateral disease and no metastatic or anaplastic tumors. Although they can be treated according to existing WT protocols, intensive monitoring of toxicity and surveillance of the remaining kidney(s) are advised.
LAY SUMMARY
WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare genetic condition with an increased risk of developing Wilms tumor. In this study, 43 patients with WAGR and Wilms tumor (or Wilms tumor precursor lesions/nephroblastomatosis) were identified through the international registry of the International Society of Pediatric Oncology Renal Tumor Study Group (SIOP-RTSG) and the SIOP-RTSG network. In many patients (37.5%), both kidneys were affected. Disease spread to other organs (metastases) did not occur. Overall, this study demonstrates that patients with WAGR syndrome and Wilms tumor can be treated according to existing protocols. However, intensive monitoring of treatment complications and surveillance of the remaining kidney(s) are advised.
Topics: Anaplasia; Antineoplastic Protocols; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; Gene Deletion; Humans; Infant; Kidney; Liver; Male; Progression-Free Survival; Risk Factors; WAGR Syndrome; Wilms Tumor
PubMed: 33146894
DOI: 10.1002/cncr.33304 -
Folia Neuropathologica 2016Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a... (Review)
Review
Pilocytic astrocytomas (PAs) are the most frequent primary astroglial tumours affecting children and adolescents. They occur sporadically or in association with a genetically determined syndrome - neurofibromatosis type 1. Classic PA usually manifests as a well-circumscribed, often cystic, slowly growing tumour, which corresponds to WHO grade I. The majority of pilocytic tumours arise along the neuraxis, predominantly in the cerebellum. They are associated with favourable long-term outcome or spontaneous regression, even after incomplete resection. However, the behaviour and prognosis might also be related to tumour histology and location. Pilomyxoid astrocytoma (PMA) represents a variant of classical PA with more invasive growth and increased risk of recurrences and dissemination. Typically, PAs exhibit distinct histology with biphasic architecture of loose, microcystic and compact, fibrillary areas. However, some tumours arise in an uncommon location and display heterogeneous histopathological appearance. The morphological pattern of PA can mimic some other glial neoplasms, including oligodendroglioma, pleomorphic xanthoastrocytoma, ependymoma or diffuse astrocytoma. Not infrequently, the advanced degenerative changes, including vascular fibrosis, and recent and old haemorrhages, may mimic vascular pathology. Sometimes, the neoplastic piloid tissue can resemble reactive gliosis, related to long-standing non neoplastic lesions. Not infrequently, PA exhibits histological features typical for anaplasia, including necrosis, mitoses and glomeruloid vascular proliferation that can suggest a diffuse high-grade glioma. However, even those PAs that lack distinct histological features of anaplasia can behave unpredictably, in a more aggressive manner, with leptomeningeal spreading. Genetic alterations resulting in aberrant signalling of the mitogen-activated protein kinase (MAPK) pathway have been considered to underlie the development of PAs. The most commonly identified KIAA1549-BRAF fusion is important for appropriate tumour molecular diagnosis. In this paper we summarize the clinicopathological presentation of PAs, with emphasis on their heterogeneous morphology, based on our own experience in the field of surgical neuropathology and the literature data. Diagnosis of pilocytic tumours requires careful analysis of clinical, histopathological and molecular features to avoid misinterpretation of these benign neoplastic lesions.
Topics: Animals; Astrocytes; Astrocytoma; Brain Neoplasms; Glioma; Humans; Mitogen-Activated Protein Kinases; Neoplasm Recurrence, Local
PubMed: 27764513
DOI: 10.5114/fn.2016.62530 -
Anticancer Research Nov 2018Cystathione β-synthase (CBS) catalyzes the conversion of homocysteine and cysteine to hydrogen sulfide (HS) and cystathione, via the trans-sulfuration pathway. CBS...
BACKGROUND
Cystathione β-synthase (CBS) catalyzes the conversion of homocysteine and cysteine to hydrogen sulfide (HS) and cystathione, via the trans-sulfuration pathway. CBS protein expression levels are increased in several different human malignancies, with increased protein expression correlating with parameters such as tumor stage, anaplasia, metastases, and chemotherapy resistance.
MATERIALS AND METHODS
This study employed tissue microarrays to examine CBS expression in benign thyroid tissue, thyroid oncocytomas, thyroid follicular adenomas, and in follicular, papillary, anaplastic, and medullary thyroid carcinomas.
RESULTS
CBS expression was increased in all thyroid carcinomas types compared to benign thyroid tissue, but not in thyroid follicular adenomas or oncocytomas. A similar pattern was observed for nicotinamide phosphoribosyltransferase (NAMPT) tissue microarray analysis comparing thyroid adenomas and follicular carcinomas.
CONCLUSION
For the first time, we showed that an HS-syntheszing enzyme plays a role in thyroid malignancies. Additionally, our data suggest that CBS and NAMPT immunohistochemistry may be useful in differentiating follicular adenomas from follicular carcinomas.
Topics: Adenocarcinoma, Follicular; Adenoma, Oxyphilic; Carcinoma, Neuroendocrine; Cystathionine beta-Synthase; Cytokines; Humans; Hydrogen Sulfide; Immunohistochemistry; Nicotinamide Phosphoribosyltransferase; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Tissue Array Analysis
PubMed: 30396922
DOI: 10.21873/anticanres.12958 -
Oncology (Williston Park, N.Y.) May 1996Usually considered benign tumors, meningiomas can display aggressive behavior characterized by multiple recurrences and invasion of the brain, dura, and adjacent bone.... (Review)
Review
Usually considered benign tumors, meningiomas can display aggressive behavior characterized by multiple recurrences and invasion of the brain, dura, and adjacent bone. The aggressive or malignant phenotype is difficult to characterize due to the broad spectrum of behaviors exhibited by meningiomas. Recent classification schemes based on features of anaplasia rather than histopathology have been used successfully to identify meningiomas that exhibit features of the aggressive phenotype. Some such tumors can be identified preoperatively by radiographic characteristics. Surgery is the cornerstone of treatment for all types of meningiomas. Conventional radiation therapy is beneficial for patients with recurrent (or incompletely resected) benign meningiomas and is recommended for those with aggressive and malignant meningiomas. Stereotactic radiation and interstitial brachytherapy are useful in some refractory or recurrent meningiomas. Traditional chemotherapeutic agents are not very effective against meningiomas, but hormonal manipulation is under study for patients with inoperable tumors or those who are medically unsuitable for surgery.
Topics: DNA, Neoplasm; Female; Gonadal Steroid Hormones; Humans; Male; Meningeal Neoplasms; Meningioma; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Pregnancy
PubMed: 8738830
DOI: No ID Found -
Journal of Neurosurgery. Case Lessons Mar 2022Primary intramedullary spinal cord (IMSC) pilocytic astrocytoma (PA) with anaplasia is extremely rare.
BACKGROUND
Primary intramedullary spinal cord (IMSC) pilocytic astrocytoma (PA) with anaplasia is extremely rare.
OBSERVATIONS
A 50-year-old man presented to our hospital with numbness of the left posterior rib region, back, and bilateral lower limbs. Contrast-enhanced T1-weighted magnetic resonance imaging (MRI) revealed an intramedullary lesion at T2-T3 with no contrast enhancement. The patient opted for conservative treatment. Eighteen months after the first consultation, the patient presented with slowly progressive numbness of the bilateral upper limbs, paraparesis, and dysuria, with rapid deterioration over the following 3 months. T1- and T2-weighted MRI revealed expansion of the intramedullary lesion, which extended from C7 to T5, and syringomyelia at C5-C6. Contrast-enhanced T1-weighted MRI revealed an enhancing intramedullary lesion at C7-T5. Open biopsy and C5-T5 laminectomy were performed for diagnosis and decompression. PA with anaplasia was diagnosed based on pathological and immunohistochemical findings. The patient received postoperative radiotherapy and chemotherapy.
LESSONS
Rapidly progressive IMSC PA with a change in contrast enhancement is extremely rare in adults. PA may undergo a spontaneous malignant transformation during its natural clinical course. In this case, the change in contrast enhancement may have been associated with the malignant transformation of the PA.
PubMed: 36273864
DOI: 10.3171/CASE21702 -
Brain Pathology (Zurich, Switzerland) Jan 2019Myxopapillary ependymomas (MPE) are considered benign (World Health Organization (WHO) grade I) neoplasms with favorable prognosis. However, malignant behavior occurs in...
Myxopapillary ependymomas (MPE) are considered benign (World Health Organization (WHO) grade I) neoplasms with favorable prognosis. However, malignant behavior occurs in a small subset. To our knowledge, only five anaplastic MPEs have been reported without consensus on diagnostic criteria. We retrieved 14 anaplastic MPEs from the pathology archives of six institutions. Each tumor included at least two of the following features: ≥5 mitoses per 10 high power fields, Ki-67 labeling index (LI) ≥10%, microvascular proliferation (MVP) and spontaneous necrosis. These features were typically encountered in the foci of hypercellularity and reduced mucin. There were eight male and six female patients (age range 6-57 years, median = 16.5). Ten tumors displayed anaplasia at initial resection, and 4 were anaplastic at a second surgery for recurrence (ranging from 9 months to 14 years following initial resection). The Ki-67 LI ranged between 8% and 40% in the anaplastic foci and <3% in the foci of classic MPE. There was documented cerebrospinal fluid (CSF) dissemination in seven cases, recurrence following an anaplastic diagnosis in three cases and bone or soft tissue invasion in two cases. One patient suffered lung metastases. Two cases evaluated by targeted next-generation sequencing and one evaluated by fluorescence in situ hybridization (FISH) showed nonspecific chromosomal gains. We conclude that although rare, anaplastic MPE occurs in both pediatric and adult patients, similar to other ependymomas. At a minimum, closer follow-up is recommended, given the concern for aggressive biologic potential. Further study is needed to determine WHO grading criteria and genetic indicators of tumor progression.
Topics: Adolescent; Adult; Antigens, Nuclear; Child; Ependymoma; Female; Humans; In Situ Hybridization, Fluorescence; Ki-67 Antigen; Male; Middle Aged; Neoplasm Recurrence, Local; Spinal Cord Neoplasms
PubMed: 30417460
DOI: 10.1111/bpa.12673 -
Modern Pathology : An Official Journal... Jan 2020DICER1 syndrome is a hereditary cancer predisposition syndrome caused by deleterious germline DICER1 mutations. Characteristic "hotspot" somatic mutations of DICER1 have...
DICER1 syndrome is a hereditary cancer predisposition syndrome caused by deleterious germline DICER1 mutations. Characteristic "hotspot" somatic mutations of DICER1 have been identified in DICER1-associated tumors. With the exception of genitourinary embryonal rhabdomyosarcoma and anaplastic sarcoma of the kidney, sarcomas are rarely reported in DICER1 syndrome. Herein, we report the clinical, histopathologic, and molecular findings of a germline DICER1-associated ovarian sarcoma in a 5-year-old female, a somatic DICER1-associated metastatic peritoneal sarcoma in a 16-year-old female, and a somatic DICER1-associated primary intracranial sarcoma in a 4-year-old male. A comprehensive review of the literature, including 83 DICER1-associated sarcomas, illustrates an unequivocal histologic pattern mimicking pleuropulmonary blastoma, regardless of the site of origin. The features include undifferentiated small round blue cells, poorly differentiated spindle cells, and large bizarre pleomorphic cells (anaplasia), often with rhabdomyoblastic and/or chondroid differentiation, and rare bone/osteoid formation. This unique heterogeneous histologic pattern should raise suspicion for pathogenic DICER1 mutation(s) warranting a detailed review of the family history and DICER1 mutation analysis. In addition to expanding the phenotypic spectrum of DICER1-associated conditions, identification of pathogenic DICER1 variants facilitates optimized genetic counseling, caregiver education and judicious imaging-based surveillance.
Topics: Adolescent; Brain Neoplasms; Child, Preschool; DEAD-box RNA Helicases; Female; Genetic Predisposition to Disease; Humans; Male; Mutation; Ovarian Neoplasms; Peritoneal Neoplasms; Ribonuclease III; Sarcoma
PubMed: 31537896
DOI: 10.1038/s41379-019-0366-x