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Brain metastases are an uncommon yet life-limiting manifestation of prostate cancer. However, there is limited insight into the natural progression, therapeutics, and patient outcomes for prostate cancer once metastasized to the brain. This is a retrospective study of 461 patients with metastatic prostate cancer to the brain with a primary outcome of median overall survival (OS). The Surveillance, Epidemiology, and End Results (SEER) database was examined using Cox regression univariate and multivariable analyses, and a corresponding nomogram was developed. The median overall survival was 15 months. In the multivariable analysis, Hispanic patients had significantly increased OS (median OS 17 months, p = 0.005). Patients with tumor sizes greater than three centimeters exhibited significantly reduced OS (median OS 19 months, p = 0.014). Patients with additional metastases to the liver exhibited significantly reduced OS (median OS 3.5 months, p < 0.001). Increased survival was demonstrated in patients treated with chemotherapy or systemic treatment (median OS 19 months, p = 0.039), in addition to radiation and chemotherapy (median OS 25 months, p = 0.002). The nomogram had a C-index of 0.641. For patients with prostate metastases to the brain, median OS is influenced by race, tumor size, presence of additional metastases, and treatment. The lack of an association between traditional prostate cancer prognosis metrics, including Gleason and ISUP grading, and mortality highlights the need for individualized, metastasis-specific prognosis metrics. This prognostic nomogram for prostate metastases to the brain can be used to guide the management of affected patients.
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Background: Choroid plexus tumors (CPTs) are rare neoplasms found in the central nervous system, comprising 1% of all brain tumors. These tumors include choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), and choroid plexus carcinoma (CPC). Although gross total resection for choroid plexus papillomas (CPPs) is associated with long-term survival, there is a scarcity of prospective data concerning the role and sequence of neoadjuvant therapy in treating aCPP and CPC. Methods: From the years 2000 to 2019, 679 patients with CPT were identified from the Surveillance, Epidemiology, and End Result (SEER) database. Among these patients, 456 patients had CPP, 75 patients had aCPP, and 142 patients had CPC. Univariate and multivariable Cox proportional hazard models were run to identify variables that had a significant impact on the primary endpoint of overall survival (OS). A predictive nomogram was built for patients with CPC to predict 5-year and 10-year survival probability. Results: Histology was a significant predictor of OS, with 5-year OS rates of 90, 79, and 61% for CPP, aCPP, and CPC, respectively. Older age and African American race were prognostic for worse OS for patients with CPP. Older age was also associated with reduced OS for patients with aCPP. American Indian/Alaskan Native race was linked to poorer OS for patients with CPC. Overall, treatment with gross total resection or subtotal resection had no difference in OS in patients with CPP or aCPP. Meanwhile, in patients with CPC, gross total resection (GTR) was associated with significantly better OS than subtotal resection (STR) only. However, there is no difference in OS between patients that receive GTR and patients that receive STR with adjuvant therapy. The nomogram for CPC considers types of treatments received. It demonstrates acceptable accuracy in estimating survival probability at 5-year and 10-year intervals, with a C-index of 0.608 (95% CI of 0.446 to 0.77). Conclusions: This is the largest study on CPT to date and highlights the optimal treatment strategies for these rare tumors. Overall, there is no difference in OS with GTR vs. STR in CPP or aCPP. Furthermore, OS is equivalent for CPC with GTR and STR plus adjuvant therapy.
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INTRODUCTION: Atypical teratoid rhabdoid tumor (ATRT) is among the most aggressive central nervous system malignancies. Although rare, this tumor typically afflicts young children and results in mortality within months. Here, we aim to determine key clinical features and treatment options that impact the survival of patients with ATRT. METHODS: From the year 2000 to 2019, 363 patients with ATRT were identified from the Surveillance, Epidemiology, and End Results database. Univariate analysis was used to identify variables that had a significant impact on the primary endpoint of overall survival (OS). Multivariable analysis was then used to identify independent predictors of survival. RESULTS: The median OS of the entire cohort was 13 months. Univariate analysis identified ages between 1 and 3 years, ages between 4 and 17 years, years of diagnosis between 2010 and 2019, and the receipt of treatment to have a significant impact on survival. In multivariable analysis, ages between 1 and 3 years and receipt of treatment were the only significant independent predictors of survival. The median OS was significantly greater in patients who received surgical treatment, chemotherapy, or radiation when compared to those who did not receive any treatment. In general, the receipt of any combination of therapies improved the median OS significantly. The receipt of triple therapy had the greatest impact on survival. DISCUSSION: This study highlights the survival benefit of a multimodal approach in the treatment of ATRT. The use of triple therapy, including surgery, radiation, and chemotherapy, was found to have the greatest survival benefit for patients. Overall, these findings may guide future care for patients with ATRT.
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Neoplasias do Sistema Nervoso Central , Tumor Rabdoide , Teratoma , Criança , Humanos , Pré-Escolar , Lactente , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/patologia , Teratoma/terapia , Teratoma/tratamento farmacológico , Tumor Rabdoide/patologia , Tumor Rabdoide/cirurgia , Terapia CombinadaRESUMO
OBJECTIVE: The natural history, treatment options, and clinical outcomes of pancreatic metastases to the brain remain largely unknown. Here, we seek to investigate characteristics that influence OS in pancreatic metastases to the brain. METHODS: This is a population-based retrospective study of OS in 508 patients with pancreatic metastases to the brain using the SEER database. Univariate and multivariate Cox regression analyses were utilized, and a predictive nomogram was developed. RESULTS: There were 508 patients identified for this study, with a median OS of 2 months. In the univariate analysis, patients older than 65 years had significantly reduced OS (P < 0.001). Patients with liver metastases (P < 0.001) and liver and lung metastases (P < 0.001) exhibited significantly reduced OS. Treatment of the primary tumor with chemotherapy only (P < 0.001), radiation only (P = 0.01), radiation and chemotherapy (P < 0.001), and surgery only (P = 0.01) were associated with increased OS. Resection of a distant metastasis site (P = 0.009) and of a brain metastasis (P = 0.03) were associated with increased OS. In the multivariable analysis, factors that remained significant included patient age (P = 0.01), liver metastases (P < 0.001), liver and lung metastases (P < 0.001), treatment with chemotherapy (P < 0.001), treatment with radiation and chemotherapy (P < 0.001), and treatment with surgery and chemotherapy (P < 0.001). The nomogram had a C-index of 0.766, suggesting congruence between the findings on the nomogram and the results in the internal verification. CONCLUSIONS: Median OS is influenced by age, multiorgan metastases, and treatment of the primary tumor. These data highlight the marginal benefit of treatment, yet improved quality of life (QOL) remains to be elucidated.
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Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias Pancreáticas , Humanos , Prognóstico , Estudos Retrospectivos , Qualidade de Vida , Neoplasias Pancreáticas/terapia , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Programa de SEERRESUMO
INTRODUCTION: Grade 3 solitary fibrous tumor, previously known as anaplastic hemangiopericytoma, is a rare and highly malignant intracranial tumor with a limited understanding of its natural history and treatment outcomes. METHODS: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database spanning 2000-2019 to evaluate the clinical characteristics and treatment modalities that influence overall survival in this tumor entity. A cohort of 249 patients with intracranial grade 3 solitary fibrous tumors was identified. Univariate and multivariable Cox proportional hazard models were employed to determine significant prognostic factors for overall survival. Kaplan-Meier models were used to visualize survival curves, and a nomogram was constructed to predict survival probabilities at 6- and 12-month following diagnosis. RESULTS: Our findings indicated that patient age (<65 years), localized or regional disease burden, surgical resection, and radiation therapy were significant predictors of better overall survival. Combination therapies showed improved survival, with surgery and radiation therapy having the most significant impact. However, chemotherapy alone or in combination did not demonstrate a significant survival benefit, likely due to the limited sample size. The nomogram provided personalized prognostic predictions based on significant clinical factors. CONCLUSIONS: These data emphasize the importance of surgical resection and radiation therapy in the management of grade 3 solitary fibrous tumors, supporting the use of combination therapies to improve overall survival in this rare and aggressive intracranial neoplasm.
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Hemangiopericitoma , Programa de SEER , Tumores Fibrosos Solitários , Humanos , Estudos Retrospectivos , Masculino , Feminino , Tumores Fibrosos Solitários/terapia , Tumores Fibrosos Solitários/mortalidade , Tumores Fibrosos Solitários/patologia , Tumores Fibrosos Solitários/epidemiologia , Pessoa de Meia-Idade , Hemangiopericitoma/terapia , Hemangiopericitoma/mortalidade , Hemangiopericitoma/patologia , Hemangiopericitoma/epidemiologia , Idoso , Prognóstico , Adulto , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/epidemiologia , Nomogramas , Gradação de Tumores , Estimativa de Kaplan-Meier , Adulto Jovem , Idoso de 80 Anos ou mais , Terapia CombinadaRESUMO
BACKGROUND: Diffuse midline glioma with histone H3K27M mutation (H3K27M DMG) is a recently recognized World Health Organization grade IV glioma with a dismal prognosis. Despite maximal treatment, this high-grade glioma exhibits an estimated median survival of 9-12 months. However, little is known with regards to prognostic risk factors for overall survival (OS) for patients with this malignant tumor. The aim of the present study is to characterize risk factors influencing survival in H3K27M DMG. METHODS: This is a population-based retrospective study of survival in patients with H3K27M DMG. The Surveillance, Epidemiology, and End Results database was examined from the years 2018 to 2019 and data from 137 patients were collected. Basic demographics, tumor site, and treatments regimens were retrieved. Univariate and multivariable analyses were conducted to assess for factors associated with OS. Nomograms were built based on the results of the multivariable analyses. RESULTS: Median OS of the entire cohort was 13 months. Patients with infratentorial H3K27M DMG exhibited worse OS compared to their supratentorial counterparts. Any form of radiation treatment resulted in a significantly improved OS. Most combination treatments significantly improved OS with the exception of the surgery plus chemotherapy group. The combination of surgery and radiation had the greatest impact on OS. CONCLUSIONS: Overall, the infratentorial location of H3K27M DMG portends a worse prognosis compared to their supratentorial counterparts. The combination of surgery and radiation had the greatest impact on OS. These data highlight the survival benefit in utilizing a multimodal treatment approach for H3K27M DMG.
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Neoplasias Encefálicas , Glioma , Humanos , Prognóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Estudos Retrospectivos , Glioma/genética , Glioma/terapia , Histonas/genética , Mutação/genéticaRESUMO
Encephaloceles rarely develop following traumatic skull fractures. Given their low incidence, the clinical presentations and management strategies of these lesions are confined to case reports and limited case series. A systematic literature review was performed using PubMed, Ovid, and Web of Science databases to identify relevant articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 37 articles met inclusion criteria, including the case presented herein. These articles reported 52 traumatic encephaloceles. Mean patient age was 25.3 years (range 6 mo-66 y) with a male predominance (63%, 33/52). The most common bony defects resulting in encephalocele formation were the orbital roof (52%, 27/52), ethmoid (35%, 18/52), and sphenoid (10%, 5/52). Mean time from traumatic injury to initial presentation was 21.3 months (range 0 d-36 y) with a bimodal distribution split between immediately following the traumatic injury (57%, 26/46) or in a delayed manner (43%, 20/46). Common presentations of orbital roof, frontonasal, and temporal bone encephaloceles were exophthalmos (85%, 23/27), cerebrospinal fluid rhinorrhea (71%, 17/24), and hearing loss (100%, 4/4), respectively. Operative approach, repair technique, and materials used for encephalocele reduction were highly variable. Surgical intervention afforded definitive symptomatic improvement or resolution in the majority of cases (89%, 42/47). Clinical outcomes did not differ between orbital, frontonasal, or temporal bone encephaloceles ( P =0.438). Traumatic encephaloceles are a rare entity with diverse presenting symptomatology dependent upon the location of fracture dehiscence. Surgical intervention affords symptomatic improvement in the majority of cases irrespective of encephalocele location, time to presentation, or operative approach.
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Rinorreia de Líquido Cefalorraquidiano , Perda Auditiva , Humanos , Masculino , Criança , Feminino , Encefalocele/diagnóstico por imagem , Encefalocele/etiologia , Encefalocele/cirurgia , Osso Temporal/patologia , Órbita/patologia , Perda Auditiva/complicaçõesRESUMO
Metastasis of ovarian carcinoma to the central nervous system occurs in <2% of cases and classically localizes within the brain parenchyma. Moreover, leptomeningeal spread of these tumors is an exceedingly rare phenomenon. Here, we conduct a systematic review of the current literature on the natural history, treatment options, and proposed pathogenic mechanisms of leptomeningeal carcinomatosis in ovarian carcinoma. We also report a case of a 67-year-old female with stage IV metastatic ovarian serous carcinoma initially confined to the peritoneal cavity with a stable disease burden over the course of three years. Follow-up imaging demonstrated an intracranial lesion, which was resected via craniotomy, and pathology was consistent with the original diagnosis. Three months after surgery, she developed rapidly progressive dizziness, generalized weakness, fatigue, and ataxia. Repeat MRI demonstrated interval development of extensive and diffusely enhancing dural nodularity, numerous avidly enhancing supratentorial and infratentorial lesions, enhancement of the bilateral trigeminal nerves, internal auditory canals, and exit wound from the surgical site into the posterior aspect of the right-sided neck musculature consistent with diffuse leptomeningeal dissemination. The present case highlights that leptomeningeal dissemination of ovarian carcinoma is a potential yet rare consequence following surgical resection of an ovarian parenchymal metastasis. Progressive clinical symptomatology that develops postoperatively in this patient population should prompt urgent workup to rule out leptomeningeal disease and an expedited radiation oncology consultation if identified.
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The authors sought to evaluate whether immunologic counts on admission were associated with shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage. A retrospective analysis of 143 consecutive patients with aneurysmal subarachnoid hemorrhage over a 9-year period was performed. A stepwise algorithm was followed for external ventricular drain weaning and determining the necessity of shunt placement. Data were compared between patients with and without shunt-dependent hydrocephalus. Overall, 11.19% of the cohort developed shunt-dependent hydrocephalus. On multivariate logistic regression analysis, acute hydrocephalus (OR: 61.027, 95% CI: 3.890-957.327; p = 0.003) and monocyte count on admission (OR: 3.362, 95% CI: 1.024-11.037; p = 0.046) were found to be independent predictors for shunt dependence. Receiver operating characteristic curve analysis for the prediction of shunt-dependent hydrocephalus confirmed that monocyte count exhibited an acceptable area under the curve (AUC = 0.737, 95% CI: 0.601-0.872; p < 0.001). The best predictive cutoff value to discriminate between successful external ventricular drain weaning and shunt-dependent hydrocephalus was identified as a monocyte count ≥0.80 × 103/uL at initial presentation. These preliminary data demonstrate that a monocyte count ≥0.80 × 103/uL at admission predicts shunt-dependent hydrocephalus in patients with aneurysmal subarachnoid hemorrhage; however, further large-scale prospective trials and validation are necessary to confirm these findings.
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Pineal metastasis is an exceedingly rare finding in patients with systemic malignancies. Such lesions are typically the manifestation of a primary lung cancer; nonetheless, a variety of malignancies have been reported to disseminate to the pineal gland including gastrointestinal, endocrine, and skin cancers, among others. However, to our knowledge, pineal gland metastasis without a primary origin has yet to be described. Carcinoma of unknown primary origin is a heterogeneous group of cancers characterized by the presence of metastatic disease without an identifiable primary tumor on metastatic workup. Here, we present a case of a 65-year-old male found to have a heterogeneously enhancing lesion of the pineal gland as well as an enhancing lesion of the left cerebellar hemisphere. Comprehensive metastatic workup demonstrated multifocal metastatic adenopathy without an identifiable primary lesion. Stereotactic biopsy of the pineal lesion revealed poorly differentiated carcinoma with an immunophenotype most consistent with gastrointestinal origin. To our knowledge, this is the first case to describe a pineal gland metastasis without a primary origin. We discuss the relevant literature on pineal gland metastases as well as carcinoma of unknown primary origin.
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Diferenciação Celular , Neoplasias Primárias Desconhecidas/patologia , Pinealoma/secundário , Idoso , Humanos , Masculino , Neoplasias Primárias Desconhecidas/cirurgia , Pinealoma/cirurgia , PrognósticoRESUMO
Treatment of brain metastases often includes surgical resection, chemotherapeutics and radiotherapy. Given the difficulty in obtaining therapeutic levels of medications within the immune-privileged central nervous system, chemotherapy as a stand-alone treatment modality for brain metastases is an uncommon option. However, there is a growing body of evidence to suggest that immunomodulatory agents can induce a robust immune response in the central nervous system. Here, we describe a 68-year old male who presented with radiographic evidence of new and enlarging lung nodules with mediastinal adenopathy. Lung biopsy was consistent with adenocarcinoma. Immunohistochemical staining demonstrated high expression of programmed cell death protein 1 with a tumor proportion score of 100%. Surveillance magnetic resonance imaging of the brain demonstrated a single enhancing 11 × 7 × 12 mm lesion along the mesial surface of the right frontal lobe. The patient deferred surgical resection as well as stereotactic radiosurgery but agreed to treatment with pembrolizumab. Repeat magnetic resonance imaging at 3-months after initiation of treatment demonstrated complete radiographic resolution of the brain lesion. To our knowledge, this is one of only a few reports in the current literature to document complete resolution of non-small cell lung cancer brain metastasis with pembrolizumab alone. We discuss the emerging literature regarding the efficacy of pembrolizumab in the treatment of brain metastases, central nervous system penetration, and emerging new treatment paradigms involving novel immunotherapy agents.
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BACKGROUND: Recent studies have reported a gender and medical degree disparity for those receiving Research Project Grants in surgical specialties. The aim of the present study is to analyze factors among academics neurosurgeons that correlate to higher amounts of R01 grant monies awarded. MATERIALS AND METHODS: The National Institutes of Health Research Portfolio Online Reporting Tools Expenditures and Results database was queried for neurosurgery funding between 2008 and 2018. Grant recipients were categorized among type of degree, secondary degree(s), professorship, gender, and h - index. Statistical analysis was performed. RESULTS: The National Institutes of Health awarded 480 R01 grants totaling $182,482,644 to 81 allopathic neurosurgeons between 2008 and 2018. No osteopathic neurosurgeons were awarded an R01 grant during this timeframe. There was a significant difference for type of professorship on the total awarded amount at the p < 0.05 level for the three types of professorship [F (2,78) = 4.85, p < 0.01)]. There was a significant difference for magnitude of h - index on total R01 monies (p < 0.00001). Males accounted for the majority of R01 monies (93.99%); however, no significant difference between average amount awarded and gender was identified (p = 0.86). A secondary degree was without significant difference for R01 amount awarded (p = 0.75). CONCLUSIONS: The present study establishes a medical degree disparity for academic neurosurgeons who receive an R01 grant. Statistically significant factors found to affect amount of R01 grant monies awarded were limited to type of professorship and magnitude of h - index.
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BACKGROUND: Cerebral vasospasm and delayed ischemic neurologic deficits are well-known clinical aftereffects of subarachnoid hemorrhage due to rupture of an intracranial aneurysm. However, vasospasm with consequential ischemia after clipping of an unruptured aneurysm is an exceedingly rare sequela encountered in the reported neurosurgical literature. CASE DESCRIPTION: A 53-year-old woman had presented for elective craniotomy with microsurgical clipping of an unruptured left middle cerebral artery bifurcation saccular aneurysm, which was successfully treated without complications. Despite an initially benign clinical course, she experienced diffuse vasospasm with profound ischemic neurologic deficits on postoperative day 13 with a left middle cerebral artery distribution ischemic infarct. Moreover, she developed recurrent delayed spasm of the right posterior cerebral artery on postoperative day 26 and, consequentially, a left homonymous hemianopsia despite treatment with intra-arterial verapamil infusion. CONCLUSIONS: To the best of our knowledge, we have reported the first case of recurrent cerebral vasospasm and delayed ischemia neurologic deficits weeks subsequent to clipping of an unruptured aneurysm. The findings from the present case highlight the importance of considering delayed vasospasm as a cause of acute onset neurologic symptoms for patients who have recently undergone elective aneurysm surgery. We also reviewed the current data regarding the epidemiology, surgical factors, and proposed pathophysiologic mechanisms related to vasospasm after elective cases.
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Isquemia Encefálica/etiologia , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Vasoespasmo Intracraniano/etiologia , Craniotomia , Feminino , Humanos , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/instrumentação , Instrumentos CirúrgicosRESUMO
BACKGROUND: Intracranial aneurysm formation after Gamma Knife radiosurgery (GKRS) is a rare complication that has only recently been reported in the literature. We report the case of a fatal distal superior cerebellar artery (SCA) aneurysm rupture in a woman treated twice with GKRS for trigeminal neuralgia along with a review of the literature regarding radiation-induced aneurysms. CASE DESCRIPTION: A 77-year-old white woman with a history of refractory right-sided trigeminal neuralgia treated with GKRS in 2001, and again in 2006 after a relapse, presented to our emergency department with complaints of a sudden-onset severe headache associated with vomiting, right eye vision loss, left-sided facial droop, and left-sided weakness with no history of hypertension or smoking prior to presentation. Initial head computed tomography scan without contrast demonstrated an intraparenchymal hemorrhage centered in the right middle cerebellar peduncle with subarachnoid hemorrhage in the basal cisterns and extension into the fourth ventricle causing early hydrocephalus. Head computed tomography angiography (CTA) demonstrated a distal right SCA aneurysm adjacent to the hemorrhage. The patient's mental status deteriorated into coma after suspected rerupture during the CTA requiring immediate intubation, external ventricular drain placement, and emergent cerebral angiogram with coil embolization. Ultimately, the patient never recovered despite medical and surgical management; therefore, care was withdrawn in accordance with her known wishes. CONCLUSIONS: The pathophysiologic association of aneurysm formation after GKRS remains to be elucidated, but given the potentially fatal consequences of aneurysm rupture, we advocate for further research and propose serial vascular imaging during the postradiosurgery follow-up period for iatrogenic aneurysm formation surveillance.
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Aneurisma Roto/etiologia , Aneurisma Intracraniano/etiologia , Radiocirurgia/efeitos adversos , Neuralgia do Trigêmeo/cirurgia , Idoso , Aneurisma Roto/diagnóstico por imagem , Angiografia Cerebral , Doença Crônica , Angiografia por Tomografia Computadorizada , Evolução Fatal , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Neuralgia do Trigêmeo/diagnóstico por imagemRESUMO
Rapidly fatal encephalitis associated with atypical lymphoid proliferations after intracranial aneurysm rupture has not been reported. Here, we describe a 52-year-old female who presented to the emergency department with a severe headache. Imaging demonstrated aneurysmal subarachnoid hemorrhage due to a ruptured left posterior inferior cerebellar artery aneurysm, which was treated with endovascular embolization and subsequent external ventricular drain. She recovered without neurologic sequelae by day seven; however, five weeks later she represented with a severe headache associated with nausea and fever. Initial repeat imaging was unremarkable. She deteriorated quickly and was empirically treated for meningitis despite negative cerebrospinal fluid studies. Magnetic resonance imaging revealed diffuse cerebral edema within the basal ganglia and thalamus. Biopsy of the caudate nuclei revealed atypical lymphoid proliferations. She was treated accordingly with no significant improvement. This case highlights the necessity for a better understanding of the etiology, chronology, and natural history of atypical lymphoid proliferations.
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Tumor protein 53 (p53) regulates fundamental pathways of cellular growth and differentiation. Aberrant p53 expression in glioblastoma multiforme, a terminal brain cancer, has been associated with worse patient outcomes and decreased chemosensitivity. Therefore, correctly identifying p53 status in glioblastoma is of great clinical significance. p53 immunohistochemistry is used to detect pathological presence of the TP53 gene product. Here, we examined the relationship between p53 immunoreactivity and TP53 mutation status by DNA Sanger sequencing in adult glioblastoma. Of 41 histologically confirmed samples, 27 (66%) were immunopositive for a p53 mutation via immunohistochemistry. Utilizing gene sequencing, we identified only eight samples (20%) with TP53 functional mutations and one sample with a silent mutation. Therefore, a ≥10% p53 immunohistochemistry threshold for predicting TP53 functional mutation status in glioma is insufficient. Implementing this ≥10% threshold, we demonstrated a remarkably low positive-predictive value (30%). Furthermore, the sensitivity and specificity with ≥10% p53 immunohistochemistry to predict TP53 functional mutation status were 100% and 42%, respectively. Our data suggests that unless reliable sequencing methodology is available for confirming TP53 status, raising the immunoreactivity threshold would increase positive and negative predictive values as well as the specificity without changing the sensitivity of the immunohistochemistry assay.
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Intracranial epidermoid cysts are benign lesions that typically remain asymptomatic; however, although histopathologically benign, these cysts can rarely undergo malignant transformation into squamous cell carcinoma. Primary intracranial squamous cell carcinoma carries a poor prognosis as optimal treatment modalities remain unclear due to their low incidence. Here, we present a case of a cerebellopontine angle epidermoid cyst remnant that underwent malignant transformation into squamous cell carcinoma 40 years after partial resection. To our knowledge, this case establishes the longest time interval to date for an intracranial epidermoid cyst to undergo malignant transformation. We also review the relevant literature and discuss recent retrospective clinical studies that have analyzed the effect of multimodal treatment approaches on survival outcomes in patients with these lesions.
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BACKGROUND: Epidermoid cysts in Meckel cave are exceedingly rare. Since 1971, only 17 cases have been reported in the literature, with most patients presenting with trigeminal hypesthesia. However, outgrowth of these lesions from Meckel cave can rarely lead to compression of the proximate cavernous sinus and the neurovascular structures contained within. To date, 2 cases have reported a Meckel cave epidermoid cyst presenting clinically as an intracavernous cranial nerve palsy, presumably a clinical manifestation of cavernous sinus compression from the lesion. CASE DESCRIPTION: We describe a case involving a 51-year-old woman presenting with unilateral refractory trigeminal neuralgia, facial hypesthesia, abducens palsy, plus new-onset partial ptosis. Magnetic resonance imaging revealed a mass in the left Meckel cave that was T1 hypointense, T2 hyperintense, peripherally enhancing, and restricting diffusion. A stereotactic left subtemporal extradural approach was used to resect the lesion, which alleviated most of the patient's symptomatology except for minimal intermittent left-sided facial hypesthesia that remained at her 1-year postoperative visit. CONCLUSIONS: This is a unique report depicting an epidermoid cyst in the Meckel cave causing numerous cranial nerve deficits because of indirect tumoral compression of cranial nerves within the cavernous sinus.
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Transtornos Cerebrovasculares/etiologia , Doenças dos Nervos Cranianos/etiologia , Cisto Epidérmico/complicações , Neoplasias da Base do Crânio/complicações , Seio Cavernoso , Transtornos Cerebrovasculares/cirurgia , Colesteatoma/complicações , Colesteatoma/patologia , Colesteatoma/cirurgia , Doenças dos Nervos Cranianos/cirurgia , Cisto Epidérmico/patologia , Cisto Epidérmico/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Base do Crânio/patologia , Neoplasias da Base do Crânio/cirurgiaRESUMO
Glioblastoma is a highly aggressive neoplasm with an extremely poor prognosis. Despite maximal gross resection and chemoradiotherapy, these grade IV astrocytomas consistently recur. Glioblastoma cells exhibit numerous pathogenic mechanisms to decrease tumor immunogenicity while promoting gliomagenesis, which manifests clinically as a median survival of less than 2 years and few long-term survivors. Recent clinical trials of vaccine-based immunotherapeutics against glioblastoma have demonstrated encouraging results in prolonging progression-free survival and overall survival. Several vaccine-based treatments have been trialed, such as peptide and heat-shock proteins, dendritic cell-based vaccines, and viral-based immunotherapy. In this literature review, we discuss the immunobiology of glioblastoma, significant current and completed vaccine-based immunotherapy clinical trials, and broad clinical challenges and future directions of glioblastoma vaccine-based immunotherapeutics.