Primary Intracranial Ewing Sarcoma With an Unusual Presentation: A Case Report.

Primary extraosseous intracranial Ewing sarcoma (ES) is an extremely rare disease, limited to the pediatric population, that primarily originates in the skull. Here, we present an unusual case of adult Ewing's sarcoma originating from the brain parenchyma. The 50-year-old male patient visited our hospital with severe headache lasting 3 weeks. MRI presented 6.1×6.2×5.2 cm sized heterogeneously enhanced mass containing peritumoral edema in the right frontal lobe. The patient underwent right frontal craniotomy, at which time the gray and red masses adhered to the surrounding brain parenchyma. The mass was completely resected using neuronavigation and electrophysiological monitoring. Histopathological examination revealed ES-compatible findings of small round cell tumor and CD-99 positive membranous immunostaining. Next generation sequencing revealed translocation and fusion of EWSR1 and FLI1, consistent with a confirmed diagnosis of ES. Consequently, the patient underwent postoperative radiotherapy. The present case revealed adult primary intracranial ES arising from the frontal lobe. Although its etiology remains poorly understood, intraparenchymal ES should be included in the differential diagnosis of parenchymal brain tumors.

A prospective multicenter assessor blinded pilot study using confocal laser endomicroscopy for intraoperative brain tumor diagnosis.

In this multi-center, assessor-blinded pilot study, the diagnostic efficacy of cCeLL-Ex vivo, a second-generation confocal laser endomicroscopy (CLE), was compared against the gold standard frozen section analysis for intraoperative brain tumor diagnosis. The study was conducted across three tertiary medical institutions in the Republic of Korea. Biopsy samples from newly diagnosed brain tumor patients were categorized based on location and divided for permanent section analysis, frozen section analysis, and cCeLL-Ex vivo imaging. Of the 74 samples from 55 patients, the majority were from the tumor core (74.3%). cCeLL-Ex vivo exhibited a relatively higher diagnostic accuracy (89.2%) than frozen section analysis (86.5%), with both methods showing a sensitivity of 92.2%. cCeLL-Ex vivo also demonstrated higher specificity (70% vs. 50%), positive predictive value (PPV) (95.2% vs. 92.2%), and negative predictive value (NPV) (58.3% vs. 50%). Furthermore, the time from sample preparation to diagnosis was notably shorter with cCeLL-Ex vivo (13 min 17 s) compared to frozen section analysis (28 min 28 s) (p-value < 0.005). These findings underscore cCeLL-Ex vivo's potential as a supplementary tool for intraoperative brain tumor diagnosis, with future studies anticipated to further validate its clinical utility.

Corrigendum: Clinical feasibility of miniaturized Lissajous scanning confocal laser endomicroscopy for indocyanine green-enhanced brain tumor diagnosis.

[This corrects the article DOI: 10.3389/fonc.2022.994054.].

Recurrence of Rathke's Cleft Cyst Following Surgery and Histopathological Considerations for Recurrence: A Case Presentation.

Recurrence of Rathke's cleft cysts (RCC) following surgery is not uncommon. We present a 33-year-old male patient with chronic headache and visual disturbances whose MRI showed mostly cystic, suprasellar mass with peripheral enhancement. Endoscopic extended transsphenoidal approach and tumor resection was performed and RCC was pathologically confirmed postoperatively. Early recurrence was first suspected at 3 months following surgery, and his serial MRIs showed a recurred mass without associated clinical symptoms. Upon further histopathological study, extensive squamous metaplasia and high Ki-67 were seen. Also, in this study, we discuss important factors associated with cyst recurrence following surgery.

The significance of decompressive craniectomy for older patients with traumatic brain injury: a propensity score matching analysis from large multi-center data.

The efficacy of decompressive craniectomy (DC) for traumatic brain injury (TBI) have been investigated in two recent randomized clinical trials (RCTs) and DC is recommended as an optional treatment for improving overall survival compared to medical treatment. However, the two RCTs enrolled extremely young adults, and the efficacy of DC in older adults remains questionable. Therefore, to identify the efficacy of DC in older adults, we compared patients who received medical care with those who underwent DC after propensity score matching (PSM). From the Korea Multi-center Traumatic Brain Injury Database, 443 patients identified as having intracranial hypertension and a necessity of DC were retrospectively enrolled. The patients were classified into the DC (n = 375) and non-DC (n = 68) groups according to operation records. The PSM was conducted to match the patients in the DC group with those receiving medical care (non-DC). After PSM, the newly matched group (DC, n = 126) was compared with patients without DC (non-DC, n = 63). The mean difference in the logit of the propensity scores (LPS) was 0.00391 and the mean age of enrolled patients were 65 years. The results of the comparative analyses after PSM showed that the 6-month mortality rate of the non-DC group was higher than that of the DC group (61.9% vs. 51.6%, p = 0.179). In terms of favorable outcomes (modified Rankin Scale [mRS] score < 4), the DC group showed a lower rate of favorable mRS scores (11.9% vs. 17.5%, p = 0.296) than the non-DC group.

Calcipotriol, a synthetic Vitamin D analog, promotes antitumor immunity via CD4+T-dependent CTL/NK cell activation.

To overcome the hurdles of immunotherapy, we investigated whether calcipotriol, a synthetic vitamin D analog, could overcome the immune evasion of glioblastoma multiforme (GBM) by modulating immune responses and the immunosuppressive tumor microenvironment. Administration of calcipotriol considerably reduced tumor growth. Both in vivo and in vitro studies revealed that CD8+T and natural killer (NK) cell gene signatures were enriched and activated, producing high levels of IFN-γ and granzyme B. In contrast, regulatory T cells (Treg) were significantly reduced in the calcipotriol-treated group. The expression of CD127, the receptor for thymic stromal lymphopoietin (TSLP), is elevated in CD4+T cells and potentially supports T-cell priming. Depleting CD4+T cells, but not NK or CD8+T cells, completely abrogated the antitumor efficacy of calcipotriol. These data highlight that the calcipotriol/TSLP/CD4+T axis can activate CD8+T and NK cells with a concomitant reduction in the number of Tregs in GBM. Therefore, calcipotriol can be a novel therapeutic modality to overcome the immune resistance of GBM by converting immunologically "cold" tumors into "hot" tumors. DATA AVAILABILITY: Data are available upon reasonable request. The RNA-seq dataset comparing the transcriptomes of control and calcipotriol-treated GL261 tumors is available from the corresponding author upon request.

Clinical feasibility of miniaturized Lissajous scanning confocal laser endomicroscopy for indocyanine green-enhanced brain tumor diagnosis.

Background: Intraoperative real-time confocal laser endomicroscopy (CLE) is an alternative modality for frozen tissue histology that enables visualization of the cytoarchitecture of living tissues with spatial resolution at the cellular level. We developed a new CLE with a "Lissajous scanning pattern" and conducted a study to identify its feasibility for fluorescence-guided brain tumor diagnosis. Materials and methods: Conventional hematoxylin and eosin (H&E) histological images were compared with indocyanine green (ICG)-enhanced CLE images in two settings (1): experimental study with in vitro tumor cells and ex vivo glial tumors of mice, and (2) clinical evaluation with surgically resected human brain tumors. First, CLE images were obtained from cultured U87 and GL261 glioma cells. Then, U87 and GL261 tumor cells were implanted into the mouse brain, and H&E staining was compared with CLE images of normal and tumor tissues ex vivo. To determine the invasion of the normal brain, two types of patient-derived glioma cells (CSC2 and X01) were used for orthotopic intracranial tumor formation and compared using two methods (CLE vs. H&E staining). Second, in human brain tumors, tissue specimens from 69 patients were prospectively obtained after elective surgical resection and were also compared using two methods, namely, CLE and H&E staining. The comparison was performed by an experienced neuropathologist. Results: When ICG was incubated in vitro, U87 and GL261 cell morphologies were well-defined in the CLE images and depended on dimethyl sulfoxide. Ex vivo examination of xenograft glioma tissues revealed dense and heterogeneous glioma cell cores and peritumoral necrosis using both methods. CLE images also detected invasive tumor cell clusters in the normal brain of the patient-derived glioma xenograft model, which corresponded to H&E staining. In human tissue specimens, CLE images effectively visualized the cytoarchitecture of the normal brain and tumors. In addition, pathognomonic microstructures according to tumor subtype were also clearly observed. Interestingly, in gliomas, the cellularity of the tumor and the density of streak-like patterns were significantly associated with tumor grade in the CLE images. Finally, panoramic view reconstruction was successfully conducted for visualizing a gross tissue morphology. Conclusion: In conclusion, the newly developed CLE with Lissajous laser scanning can be a helpful intraoperative device for the diagnosis, detection of tumor-free margins, and maximal safe resection of brain tumors.

Gender differences in adult traumatic brain injury according to the Glasgow coma scale: A multicenter descriptive study.

PURPOSE: Patients' gender, which can be one of the most important determinants of traumatic brain injury (TBI) outcomes, is also likely to interact with many other outcome variables of TBI. This multicenter descriptive study investigated gender differences in epidemiological, clinical, treatment, mortality, and variable characteristics in adult TBI patients. METHODS: The selection criteria were defined as patients who had been diagnosed with TBI and were admitted to the hospital between January 1, 2016 and December 31, 2018. A total of 4468 adult TBI patients were enrolled at eight University Hospitals. Based on the list of enrolled patients, the medical records of the patients were reviewed and they were registered online at each hospital. The registered patients were classified into three groups according to the Glasgow coma scale (GCS) score: mild (13-15), moderate (9-12), and severe (3-8), and the differences between men and women in each group were investigated. The risk factors of moderated and severe TBI compared to mild TBI were also investigated. RESULTS: The study included 3075 men and 1393 women and the proportion of total males was 68.8%. Among all the TBI patients, there were significant differences between men and women in age, past history, and GCS score. While the mild and severe TBI groups showed significant differences in age, past history, and clinical symptoms, the moderate TBI group showed significant differences in age, past history, cause of justice, and diagnosis. CONCLUSION: To the best of our knowledge, this multicenter study is the first to focus on gender differences of adult patients with TBI in Korea. This study shows significant differences between men and women in many aspects of adult TBI. Therefore, gender differences should be strongly considered in TBI studies.

Repurposing Penfluridol in Combination with Temozolomide for the Treatment of Glioblastoma.

Despite the presence of aggressive treatment strategies, glioblastoma remains intractable, warranting a novel therapeutic modality. An oral antipsychotic agent, penflurido (PFD), used for schizophrenia treatment, has shown an antitumor effect on various types of cancer cells. As glioma sphere-forming cells (GSCs) are known to mediate drug resistance in glioblastoma, and considering that antipsychotics can easily penetrate the blood-brain barrier, we investigated the antitumor effect of PFD on patient-derived GSCs. Using five GSCs, we found that PFD exerts an antiproliferative effect in a time- and dose-dependent manner. At IC50, spheroid size and second-generation spheroid formation were significantly suppressed. Stemness factors, SOX2 and OCT4, were decreased. PFD treatment reduced cancer cell migration and invasion by reducing the Integrin α6 and uPAR levels and suppression of the expression of epithelial-to-mesenchymal transition (EMT) factors, vimentin and Zeb1. GLI1 was found to be involved in PFD-induced EMT inhibition. Furthermore, combinatorial treatment of PFD with temozolomide (TMZ) significantly suppressed tumor growth and prolonged survival in vivo. Immunostaining revealed decreased expression of GLI1, SOX2, and vimentin in the PFD treatment group but not in the TMZ-only treatment group. Therefore, PFD can be effectively repurposed for the treatment of glioblastoma by combining it with TMZ.

Tumor Control and Cranial Nerve Outcomes After Adjuvant Radiosurgery for Low-Grade Skull Base Meningiomas.

OBJECTIVE: We evaluated the tumor control and cranial nerve (CN) outcomes after adjuvant stereotactic radiosurgery (SRS) for petroclival, cavernous sinus, and cerebellopontine angle meningiomas. METHODS: From our prospectively maintained database of 2022 patients with meningioma who had undergone Leksell SRS during a 30-year interval, we found 43 patients with petroclival, 94 with cavernous sinus, and 13 patients with cerebellopontine angle meningiomas who had undergone adjuvant SRS after surgical resection of the meningioma. The patients included in the present report had had ≥1 CN deficit at the initial presentation and a minimum follow-up period of 12 months. The median age at SRS was 54 years (range, 22-81). SRS was performed for residual tumor in 104 patients (69%) and recurrent tumor in 46 patients (31%). The median tumor volume treated with SRS was 8.1 cm3 (range, 0.3-42), and the median margin dose was 13 Gy (range, 10-20). RESULTS: Tumor control was achieved in 135 patients (90%) at a median follow-up point of 75 months. The progression-free survival rate after SRS was 99.5% at 1 year, 98% at 3 years, 95% at 5 years, and 90% at 10 years. Overall, 29 of the 150 patients (19%) reported improvement in CN function. Deterioration in CN function after SRS developed in 15 patients (10%). The rate of deterioration was 3.5% at 1 year, 5.5% at 3 years, and 7% at 5 years. CONCLUSIONS: Adjuvant SRS provides effective tumor control and a low rate of new or worsening CN deficits.

Gamma Knife stereotactic radiosurgery for cavernous sinus meningioma: long-term follow-up in 200 patients.

OBJECTIVEThe authors of this study evaluate the long-term outcomes of stereotactic radiosurgery (SRS) for cavernous sinus meningioma (CSM).METHODSThe authors retrospectively assessed treatment outcomes 5-18 years after SRS in 200 patients with CSM. The median patient age was 57 years (range 22-83 years). In total, 120 (60%) patients underwent Gamma Knife SRS as primary management, 46 (23%) for residual tumors, and 34 (17%) for recurrent tumors after one or more surgical procedures. The median tumor target volume was 7.5 cm3 (range 0.1-37.3 cm3), and the median margin dose was 13.0 Gy (range 10-20 Gy).RESULTSTumor volume regressed in 121 (61%) patients, was unchanged in 49 (25%), and increased over time in 30 (15%) during a median imaging follow-up of 101 months. Actuarial tumor control rates at the 5-, 10-, and 15-year follow-ups were 92%, 84%, and 75%, respectively. Of the 120 patients who had undergone SRS as a primary treatment (primary SRS), tumor progression was observed in 14 (11.7%) patients at a median of 48.9 months (range 4.8-120.0 months) after SRS, and actuarial tumor control rates were 98%, 93%, 85%, and 85% at the 1-, 5-, 10-, and 15-year follow-ups post-SRS. A history of tumor progression after microsurgery was an independent predictor of an unfavorable response to radiosurgery (p = 0.009, HR = 4.161, 95% CI 1.438-12.045). Forty-four (26%) of 170 patients who had presented with at least one cranial nerve (CN) deficit improved after SRS. Development of new CN deficits after initial microsurgical resection was an unfavorable factor for improvement after SRS (p = 0.014, HR = 0.169, 95% CI 0.041-0.702). Fifteen (7.5%) patients experienced permanent CN deficits without evidence of tumor progression at a median onset of 9 months (range 2.3-85 months) after SRS. Patients with larger tumor volumes (≥ 10 cm3) were more likely to develop permanent CN complications (p = 0.046, HR = 3.629, 95% CI 1.026-12.838). Three patients (1.5%) developed delayed pituitary dysfunction after SRS.CONCLUSIONSThis long-term study showed that Gamma Knife radiosurgery provided long-term tumor control for most patients with CSM. Patients who underwent SRS for progressive tumors after prior microsurgery had a greater chance of tumor growth than the patients without prior surgery or those with residual tumor treated after microsurgery.

How to improve obliteration rates during volume-staged stereotactic radiosurgery for large arteriovenous malformations.

OBJECTIVEThe management of large-volume arteriovenous malformations (AVMs) with stereotactic radiosurgery (SRS) remains challenging. The authors retrospectively tested the hypothesis that AVM obliteration rates can be improved by increasing the percentage volume of an AVM that receives a minimal threshold dose of radiation.METHODSIn 1992, the authors prospectively began to stage anatomical components in order to deliver higher single doses to AVMs > 15 cm3 in volume. Since that time 60 patients with large AVMs have undergone volume-staged SRS (VS-SRS). The median interval between the first stage and the second stage was 4.5 months (2.8-13.8 months). The median target volume was 11.6 cm3 (range 4.3-26 cm3) in the first-stage SRS and 10.6 cm3 (range 2.8-33.7 cm3) in the second-stage SRS. The median margin dose was 16 Gy (range 13-18 Gy) for both SRS stages.RESULTSAVM obliteration after the initial two staged volumetric SRS treatments was confirmed by MRI alone in 4 patients and by angiography in 11 patients at a median follow-up of 82 months (range 0.4-206 months) after VS-SRS. The post-VS-SRS obliteration rates on angiography were 4% at 3 years, 13% at 4 years, 23% at 5 years, and 27% at 10 years. In multivariate analysis, only ≥ 20-Gy volume coverage was significantly associated with higher total obliteration rates confirmed by angiography. When the margin dose is ≥ 17 Gy and the 20-Gy SRS volume included ≥ 63% of the total target volume, the angiographically confirmed obliteration rates increased to 61% at 5 years and 70% at 10 years.CONCLUSIONSThe outcomes of prospective VS-SRS for large AVMs can be improved by prescribing an AVM margin dose of ≥ 17 Gy and adding additional isocenters so that ≥ 63% of the internal AVM dose receives more than 20 Gy.

Extraocular Pressure Measurements to Avoid Orbital Compartment Syndrome in Aneurysm Surgery.

BACKGROUND: Orbital compartment syndrome (OCS) is a rare but devastating complication following pterional craniotomy. Although the causes of OCS are unclear, external compression of the orbit by a myocutaneous flap is commonly mentioned as a major factor. We evaluated the ocular influence of external compression using an extraocular pressure monitor. METHODS: We measured extraocular pressure in 86 patients who underwent surgery for cerebral aneurysm via a pterional approach. Clinical information and radiologic parameters, including the area of the medial rectus muscle (MRM) and the craniotomy height from the bottom of the anterior skull base, were collected. As a control group, 117 patients who underwent surgery without pressure monitoring were also evaluated. RESULTS: Extraocular pressure reached a maximum during craniotomy (mean, 22.0 mm Hg; range, 18.4-51.0 mm Hg) and decreased after myocutaneous flap adjustment (mean, 7.9 mm Hg; range, 5.4-17.5 mm Hg). Pressure before myocutaneous flap manipulation differed between patients with anterior communicating artery (Acomm) aneurysms and other patients (mean, 16.5 mm Hg vs. 9.4 mm Hg; P = 0.003). Among Acomm aneurysm cases, the monitored group showed a significantly lower MRM swelling ratio (postoperative MRM area/preoperative MRM area) compared with the control group (1.03 ± 0.10 vs. 1.17 ± 0.15; P = 0.036). CONCLUSIONS: Myocutaneous flaps can produce unnoticed overpressure on the orbit, resulting in OCS-related blindness during aneurysm clipping surgery, especially in cases involving mandatory lower craniotomy. The continuous extraocular compressive pressure monitoring technique is a simple and effective approach to prevent such a serious complication.

Cranial nerve outcomes after primary stereotactic radiosurgery for symptomatic skull base meningiomas.

OBJECTIVE: To evaluate cranial nerve (CN) outcomes after primary stereotactic radiosurgery (SRS) for petroclival, cavernous sinus, and cerebellopontine angle meningiomas. METHODS: From our prospectively maintained database of 2022 meningioma patients who underwent Leksell stereotactic radiosurgery (SRS) during a 30-year interval, we found 98 patients with petroclival, 242 with cavernous sinus, and 55 patients with cerebellopontine angle meningiomas. Primary radiosurgery was performed in 245 patients. Patients included in this report had at least one CN deficit at the time of initial presentation and a minimum of 12 month follow up. Median age at the time of SRS was 58 years. Median follow up was 58 months (range 12-300 months), Median tumor volume treated with SRS was 5.9 cm3 (range 0.5-37.5 cm3), and median margin dose was 13 Gy (range 9-20Gy). RESULTS: Tumor control was achieved in 229 patients (93.5%) at a median follow up of 58 months. Progression free survival rate (PFS) after SRS was 98.7% at 1 year, 96.4% at 3 years, 93.7% at 5 years, and 86.4% at 10 years Overall, 114 of the 245 patients (46.5%) reported improvement of CN function. Patients with CP angle meningiomas demonstrated lower rates of CN improvement compared to petroclival and cavernous sinus meningioma patients. Deterioration of CN function after SRS developed in 24 patients (10%). The rate of deterioration was 2.8% at 1 year, 5.2% at 3 years, and 8% at 10 years. CONCLUSION: Primary SRS provides effective tumor control and favorable rate of improvement of preexisting CN deficit.

Metastatic Intracerebral Plasmacytoma Treated with Radiation and Thalidomide, Dexamethasone with Cyclophosphamide Chemotherapy.

Intracerebral plasmacytoma is an extremely rare disease for which no treatment protocol has been established. The authors present a case of metastatic intracerebral plasmacytoma that was partially resected and treated with radiation therapy. For tumor recurrence, a combination chemotherapy regimen was initiated. A 48-year-old male patient presented with dizziness and memory loss. Conventional magnetic resonance imaging (MRI) of the brain revealed a multilobulated mass with enhancing cystic and solid components measuring 7 × 7 × 6 cm in the left frontal lobe. The patient had undergone subtotal gastrectomy and transverse colectomy 8 years before admission and had been diagnosed with extraosseous plasmacytoma. At the time of the current presentation, the patient underwent craniotomy for the parenchymal lesion. Partial tumor resection was performed. Histologic and immunohistochemical examinations confirmed the diagnosis of plasmacytoma. Fractionated radiotherapy was administered, and no enhancing mass was observed on follow-up MRI. One year after radiotherapy, tumor recurrence was observed in a different area of the cerebral parenchyma. Combination thalidomide, dexamethasone, and cyclophosphamide chemotherapy was administered. After three cycles of chemotherapy, the tumor was well controlled on MRI. Hereafter, two more times of tumor recurrence occurred in the other sites of the cerebral parenchyma, but with chemoradiation therapy, the tumor was well suppressed. The findings of this case suggest that the cerebral parenchyma can be one of the metastatic sites for extraosseous plasmacytoma. In addition, combination chemotherapy with thalidomide, dexamethasone, and cyclophosphamide may be a useful treatment option for intracerebral plasmacytoma.

Factors Associated with Clinical Outcomes in Patients with Primary Intraventricular Hemorrhage.

BACKGROUND Primary intraventricular hemorrhage (PIVH) is an uncommon type of intracerebral hemorrhage. Owing to its rarity, the clinical and radiological factors affecting outcomes in patients with PIVH have not been widely studied. MATERIAL AND METHODS We retrospectively reviewed 112 patients (mean age 53 years) treated for PIVH at our institution from January 2004 to December 2014. Clinical and radiological parameters were analyzed 3 months after initial presentation to identify factors associated with clinical outcomes, as assessed by the Glasgow Outcome Scale (favorable ≥4, unfavorable <4). RESULTS Of the 99 patients who underwent angiography, causative vascular abnormalities were found in 46%, and included Moyamoya disease, arteriovenous malformation, and cerebral aneurysm. At 3 months after initial presentation, 64% and 36% of patients were in the favorable and unfavorable outcome groups, respectively. The mortality rate was 19%. However, most survivors had no or mild deficits. Age, initial Glasgow Coma Scale (GCS) score, simplified acute physiology score (SAPS II), modified Graeb score, and various radiological parameters reflecting ventricular dilatation were significantly different between the groups. Specifically, a GCS score of less than 13 (p=0.015), a SAPS II score of less than 33 (p=0.039), and a dilated fourth ventricle (p=0.043) were demonstrated to be independent predictors of an unfavorable clinical outcome. CONCLUSIONS In this study we reveal independent predictors of poor outcome in primary intraventricular hemorrhage patients, and show that nearly half of the patients in our study had predisposing vascular abnormalities. Routine angiography is recommended in the evaluation of PIVH to identify potentially treatable etiologies, which may enhance long-term prognosis.

Glioma-derived cancer stem cells are hypersensitive to proteasomal inhibition.

Although proteasome inhibitors (PIs) are used as anticancer drugs to treat various cancers, their relative therapeutic efficacy on stem cells vs. bulk cancers remains unknown. Here, we show that stem cells derived from gliomas, GSCs, are up to 1,000-fold more sensitive to PIs (IC50, 27-70 nM) compared with their differentiated controls (IC50, 47 to ¼100 µM). The stemness of GSCs correlates to increased ubiquitination, whose misregulation readily triggers apoptosis. PI-induced apoptosis of GSCs is independent of NF-κB but involves the phosphorylation of c-Jun N-terminal kinase as well as the transcriptional activation of endoplasmic reticulum (ER) stress-associated proapoptotic mediators. In contrast to the general notion that ER stress-associated apoptosis is signaled by prolonged unfolded protein response (UPR), GSC-selective apoptosis is instead counteracted by the UPR ATF3 is a key mediator in GSC-selective apoptosis. Pharmaceutical uncoupling of the UPR from its downstream apoptosis sensitizes GSCs to PIs in vitro and during tumorigenesis in mice. Thus, a combinational treatment of a PI with an inhibitor of UPR-coupled apoptosis may enhance targeting of stem cells in gliomas.

World Health Organization Grade II Oligodendroglioma Occurring after Successful Treatment for Childhood Acute Lymphoblastic Leukemia.

When treating childhood acute lymphoblastic leukemia (ALL), secondary neoplasms are a significant long term problem. Radiation is generally accepted to be a major cause of the development of secondary neoplasms. Following treatment for ALL, a variety of secondary tumors, including brain tumors, hematologic malignancies, sarcomas, thyroid cancers, and skin cancers have been reported. However, oligodendroglioma as a secondary neoplasm is extremely rare. Herein we present a case of secondary oligodendroglioma occurring 13 years after the end of ALL treatment.