Increased expression of leucine-rich α-2 glycoprotein 1 as a predictive biomarker of favorable progression-free survival in meningioma.

Most meningiomas, which are frequent central nervous system tumors, are classified as World Health Organization (WHO) grade 1 because of their slow-growing nature. However, the recurrence rate varies and is difficult to predict using conventional histopathological diagnoses. Leucine-rich α-2 glycoprotein 1 (LRG1) is involved in cell signal transduction, cell adhesion, and DNA repair and is a predictive biomarker in different malignant tumors; however, such a relationship has not been reported in meningiomas. We examined tissue microarrays of histological samples from 117 patients with grade 1 and 2 meningiomas and assessed their clinical and pathological features, including expression of LRG1 protein. LRG1-high meningiomas showed an increased number of vessels with CD3-positive cell infiltration (P = 0.0328) as well as higher CD105-positive vessels (P = 0.0084), as compared to LRG1-low cases. They also demonstrated better progression-free survival (hazard ratio [HR] 0.11, 95% confidence interval [CI] 0.016-0.841) compared to LRG1-low patients (P = 0.033). Moreover, multivariate analysis indicated that high LRG1 expression was an independent prognostic factor (HR, 0.13; 95% CI, 0.018-0.991; P = 0.049). LRG1 immunohistochemistry may be a convenient tool for estimating the prognosis of meningiomas in routine practice. Further studies are required to elucidate the key role of LRG1 in meningioma progression.

Visual-evoked potential predicts the efficacy of the optical canal decompression for traumatic optic nerve neuropathy showing blindness: A case report.

Background: The indication for surgical optic canal decompression (OCD) for traumatic optic neuropathy (TON) remains controversial because there is no reliable predictor of a good outcome. We report the case of a blind patient with TON whose remaining visual-evoked potential (VEP) suggested recovery potential of the injured optic nerve after OCD. Case Description: A 48-year-old man had fallen from a height of 7 m, striking his head. He immediately complained of right-eye blindness. He had no light perception and the direct light reflex disappeared from the right pupil, although there was no fracture or traumatic lesion on computed tomography and magnetic resonance imaging. Because the amplitude of the VEP with the right eye stimulation remained unchanged, we performed the right OCD. During surgical OCD, the amplitude and latency of VEP began to improve. Finally, the visual field improved in almost all directions, and eyesight improved to 0.2. Conclusion: The retained VEP activity in TON may suggest the recovery potential of the injured optic nerve, even in cases of blindness. It is possible that VEP is an indicator of aggressive treatment for TON such as OCD.

Visual Outcomes and Surgical Approach Selection Focusing on Active Optic Canal Decompression and Maximum Safe Resection for Suprasellar Meningiomas.

The goal of treating patients with suprasellar meningioma is improving or preserving visual function while achieving long-term tumor control. We retrospectively examined patient and tumor characteristics and surgical and visual outcomes in 30 patients with a suprasellar meningioma who underwent resection via an endoscopic endonasal (15 patients), sub-frontal (8 patients), or anterior interhemispheric (7 patients) approach. Approach selection was based on the presence of optic canal invasion, vascular encasement, and tumor extension. Optic canal decompression and exploration were performed as key surgical procedures. Simpson grade 1 to 3 resection was achieved in 80% of cases. Among the 26 patients with pre-existing visual dysfunction, vision at discharge improved in 18 patients (69.2%), remained unchanged in six (23.1%), and deteriorated in two (7.7%). Further gradual visual recovery and/or maintenance of useful vision were also observed during follow-up. We propose an algorithm for selecting the appropriate surgical approach to a suprasellar meningioma based on preoperative radiologic tumor characteristics. The algorithm focuses on effective optic canal decompression and maximum safe resection, possibly contributing to favorable visual outcomes.

Systemic inflammation caused by an intracranial mesenchymal tumor with a EWSR1::CREM fusion presenting associated with IL-6/STAT3 signaling.

Pediatric neoplastic diseases account for about 10% of cases of fever of unknown origin (FUO), and most neoplastic disease cases are leukemia, lymphoma, and neuroblastoma. Brain tumors are rarely reported as the cause of FUO, although craniopharyngioma, metastatic brain tumor, and Castleman's disease have been reported. We report a case of intracranial mesenchymal tumor (IMT) with a FET:CREB fusion gene, which had inflammatory phenotype without neurological signs. A 10-year-old girl was admitted with a 2-month history of intermittent fever and headache, whereas her past history as well as her family history lacked special events. Sepsis work-up showed no pathological organism, and empirical antibiotic therapy was not effective. Bone marrow examination showed a negative result. Cerebrospinal fluid examination showed elevated protein as well as cell counts, and head magnaetic resonance imaging showed a hypervascular mass lesion with contrast enhancement in the left cerebellar hemisphere. The patient underwent tumor excision, which made the intermittent fever disappear. Pathological examinations resembled those of classic angiomatoid fibrous histiocytoma (AFH), but the morphological features were distinct from the AFH myxoid variant; then we performed break-apart fluorescence in situ hybridization and confirmed the tumor harbored the rare EWSR1::CREM fusion gene (Ewing sarcoma breakpoint region 1 gene (EWSR1) and cAMP response element binding (CREB) family gene). Consequently, we diagnosed the condition as IMT with EWSR1::CREM fusion. Elevated serum concentration of interleukin 6 (IL-6) was normalized after tumor resection, which suggested the fever could be caused by tumor-derived IL-6. This is the first case of IMT with EWSR1::CREM fusion that showed paraneoplastic symptoms associated with the IL-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Although brain tumors are rarely diagnosed as a responsible disease for FUO, they should be considered as a cause of unknown fever even in the absence of abnormal neurological findings.

Endoscopic aqueductal membrane fenestration was effective for intractable hydrocephalus after removal of a nongerminomatous germ cell tumor exhibiting growing teratoma syndrome: a case report.

BACKGROUND: Primary central nervous system (CNS) germ cell tumors (GCTs) are rare neoplasms predominantly observed in the pediatric and young adult populations. A mixed GCT including immature teratoma exhibiting growing teratoma syndrome is presented. The pathogenesis of growing teratoma syndrome remains unclear, and its treatment strategy has not been established. GCTs are often located within the ventricles, causing hydrocephalus, which sometimes improves after removal of the tumor due to restoration of cerebrospinal fluid (CSF) flow. On the other hand, even if the flow route of CSF from the third ventricle to arachnoid granulations on the brain surface quadrigeminal cistern is restored after removal of the tumor, hydrocephalus may not improve. CASE PRESENTATION: A case whose intractable hydrocephalus improved after penetrating the aqueductal membrane via endoscopy is described. An 11-year-old boy was treated for pineal intracranial growing teratoma syndrome (IGTS). The tumor grew rapidly in a short period, and hydrocephalus progressed despite endoscopic third ventriculostomy (ETV). Although the obstruction was removed by radiation, chemotherapy, and total tumor resection, the hydrocephalus did not improve. Endoscopic membrane perforation was performed because a membrane-like structure was seen at the entrance of the cerebral aqueduct on magnetic resonance imaging. The hydrocephalus improved immediately after the operation, and the patient's consciousness disturbance also improved significantly. CONCLUSION: The purpose of this report is to update the current knowledge and standards of management for patients with growing teratoma syndrome, as well as to drive future translational and clinical studies by recognizing the unmet needs concerning hydrocephalus.

"Motion-specific Headache": A Predictor for Diagnosis and Favorable Prognosis after Surgery in Young Patients with Chiari Malformation Type 1.

As headache is known as one of the most common symptoms in the patients with Chiari malformation type 1 (CM1), it is difficult to find out CM1-related headache among the symptoms because headache itself is commonly seen. Herein, we retrospectively review the cases of six CM1 patients complaining only of headache by which they complained of deterioration in daily life activities. The symptom of headache worsened during anteflexion (n = 2; 33%), retroflexion (n = 1; 17%), jumping (n = 3; 50%), going up the stairs (n = 1; 17%), and running (n = 1; 17%). Mean age at the onset was 15.7 years old (ranging 11-18) and four out of six were female. These inductive factors were clearly different from "Valsalva-like maneuvers," although the mechanism might originate from dynamic tonsil changes. We named these headaches as "motion-specific." These headaches radiated to the posterior side. MRI revealed that the extent of tonsillar ectopia was 11.3 mm, while syringomyelia was observed in three out of six patients (50%). All patients underwent surgical treatment, with the "motion-specific headache" completely disappearing 12.5 days thereafter. Although headaches are common, "motion-specific headache" may be a good candidate symptom to distinguish CM1 patients, especially among teenagers with headaches, and a good predictor for favorable outcomes after surgical treatment.

A case of lymphomatoid granulomatosis with central nervous system involvement successfully treated with IFNα.

Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus (EBV)-driven B-cell lymphoproliferative disease affecting mainly extranodal sites such as the lung, central nervous system (CNS), skin, kidney, and liver. We report a case of low-grade LYG involving the CNS that was successfully treated with interferon alpha (IFNα). A 69-year-old woman developed necrotic erythema of the skin and was initially diagnosed with pyoderma gangrenosum based on skin biopsy. She showed a limited response to prednisolone. Approximately 6 months after the initial onset, low-grade LYG was diagnosed after detection of CNS lesions on brain biopsy. The whole blood EBV-DNA load determined by real-time polymerase chain reaction was slightly elevated. Two months into IFNα therapy, skin and CNS lesions had responded favorably and the EBV-DNA load decreased. IFNα plays an important role in treatment of LYG through its antiproliferative, immunomodulatory, and anti-EBV effects. To our knowledge, this is the first case report of successful treatment with IFNα in Japan. Further investigation is necessary to determine optimal use of IFNα for LYG.

Intracranial solitary fibrous tumor/hemangiopericytoma mimicking cystic meningioma: A case report and literature review.

Intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a relatively rare type of tumor that originates from meningeal mesenchyme. A 30-year-old man presented leaning his body to the left and with weakness of his left lower limb. Computed tomography revealed a heterogeneous mass with multiple cystic components and hyperostosis of the right cranial convexity. Magnetic resonance imaging showed the mass was broadly attached to the dura matter with dural tail sign. In addition, the lesion had extensive cystic degeneration and a solid compartment showing low apparent diffusion coefficient values. The patient underwent gross total resection of the intracranial lesion and presented no recurrence within a 12-month follow-up period. Histopathology confirmed SFT/HPC (World Health Organization grade Ⅱ). Although there have been several useful techniques reported to differentiate SFT/HPC from meningioma, in this case the atypical findings for SFT/HPC made it difficult. We report the imaging findings of this case and some literature reviews.

Primary Pituitary Adenoid Cystic Carcinoma: A Rare Salivary Gland-Like Tumor in the Sella.

Adenoid cystic carcinoma (ACC) is a tumor of the exocrine glands that originates primarily from the minor and major salivary glands, nasopharynx, and lacrimal glands. ACC grows slowly but is locally aggressive and prone to recurrence. It is uncommon for ACCs to develop in the pituitary gland as a primary tumor. We present a case of primary pituitary ACC extending to the sphenoid sinus resembling an invasive adenoma in a 71-year-old woman with a history of nasal epistaxis. We reviewed other reported cases of pituitary ACCs with retrospective validation of whether the tumor was primary or not. The intrasellar tumor exhibited MYB rearrangement with enlargement and destruction of the sella turcica and dural tears toward the sphenoid sinus, which would be consistent for a tumor originating from the pituitary gland. Including our case, only four intrasellar and one suprasellar ACC have been confirmed as primary tumors. All intrasellar ACCs had the characteristic of some form of invasion of neighboring structures with evidence of hyperprolactinemia. ACC could develop in the pituitary gland as a form of salivary gland-like tumor derived from the ectopic salivary gland rests. ACCs rarely arise from the pituitary gland; however, the accurate determination of primary occurrence is difficult because of the invasive nature of these tumors, and the anatomical relationship with the sphenoid sinus and the cavernous sinus. Excessive bleeding from the tumor or unexpected internal carotid artery injury should be avoided during surgery for primary and secondary pituitary ACC.

The Multipotential of Leucine-Rich α-2 Glycoprotein 1 as a Clinicopathological Biomarker of Glioblastoma.

Leucine-rich α-2 glycoprotein 1 (LRG1) is a diagnostic marker candidate for glioblastoma. Although LRG1 has been associated with angiogenesis, it has been suggested that its biomarker role differs depending on the type of tumor. In this study, a clinicopathological examination of LRG1's role as a biomarker for glioblastoma was performed. We used tumor tissues of 155 cases with diffuse gliomas (27 astrocytomas, 14 oligodendrogliomas, 114 glioblastomas). The immunohistochemical LRG1 intensity scoring was classified into 2 groups: low expression and high expression. Mutations of IDH1, IDH2, and TERT promoter were analyzed through the Sanger method. We examined the relationship between LRG1 expression level in glioblastoma and clinical parameters, such as age, preoperative Karnofsky performance status, tumor location, extent of resection, O6-methylguanine DNA methyltransferase promoter, and prognosis. LRG1 high expression rate was 41.2% in glioblastoma, 3.7% in astrocytoma, and 21.4% in oligodendroglioma. Glioblastoma showed a significantly higher LRG1 expression than lower-grade glioma (p = 0.0003). High expression of LRG1 was an independent favorable prognostic factor (p = 0.019) in IDH-wildtype glioblastoma and correlated with gross total resection (p = 0.002) and the tumor location on nonsubventricular zone (p = 0.00007). LRG1 demonstrated multiple potential as a diagnostic, prognostic, and regional biomarker for glioblastoma.

Pituitary Gangliocytoma Producing TSH and TRH: A Review of "Gangliocytomas of the Sellar Region".

PURPOSE: Pituitary gangliocytomas (GCs) are rare neuronal tumors that present with endocrinological disorders, such as acromegaly, amenorrhea-galactorrhea syndrome, and Cushing's disease. Most pituitary GCs coexist with pituitary adenomas pathologically and are diagnosed as mixed gangliocytoma-adenomas. Herein, we report a case of 45-year-old man who presented with the syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH) and discuss the pathogenesis of pituitary GCs. METHODS: Pituitary magnetic resonance imaging showed an 8-mm homogeneous and poorly enhanced mass inside the pituitary gland. Endoscopic transsphenoidal surgery was performed under a preoperative diagnosis of thyrotroph adenoma. However, the tumor was finally diagnosed as gangliocytoma without an adenomatous component. The tumor was further analyzed via immunohistochemistry and electron microscopy. Additionally, we searched MEDLINE and PubMed for previously published cases of isolated pituitary GCs and analyzed the reported clinicopathological findings. RESULTS: The patient showed complete clinical and endocrinological recovery after an operation. The tumor was positive for thyrotropin (TSH), TSH-releasing hormone (TRH), Pit-1, GATA-2, and most neuronal markers. Electron microscopy demonstrated the presence of intracytoplasmic secretory granules and neuronal processes. Co-secreting hypothalamic and pituitary hormone inside the tumor indicated autocrine/paracrine endocrinological stimulation. CONCLUSION: Herein, we report a case of SITSH caused by an isolated pituitary gangliocytoma, expressing both TSH and TRH, which, to our best knowledge, is the first reported case of such a condition. The multidirectional differentiation and multihormonal endocrine characteristics of these tumors indicate that they are a member of neuroendocrine neoplasms, further supporting that they are derived from neural crest cells.

Central nervous system neuroblastic tumor with FOXR2 activation presenting both neuronal and glial differentiation: a case report.

A subset of central nervous system neuroblastomas (CNS NB), rare primary embryonal CNS tumors, has been encompassed in CNS NB with FOXR2 activation (CNS NB-FOXR2) and usually shows the primitive neuronal architecture and occasional neurocytic differentiation. Here, we report a rare case of 3-year-old female with uncommon morphology of CNS embryonal tumor with FOXR2 activation presenting bidirectional differentiation to neurocytic small primitive cells and astrocytic spindle cells both of which are positive for synaptophysin and GFAP. Ultrastructural study also showed that there were presynaptic structure and intermediate filament in the tumor cells, suggesting glioneuronal differentiation. This case indicates the possibility of CNS neuroblastic tumor to differentiate neuronal and glial lineages.

Expression of GLUT1 in Pseudopalisaded and Perivascular Tumor Cells Is an Independent Prognostic Factor for Patients With Glioblastomas.

Glioblastomas are highly aggressive brain tumors with a particularly poor prognosis. Glucose transporter-1 (GLUT1/SLC2A1), a uniporter that is expressed by various carcinomas and may be involved in malignant neoplasm glycometabolism, may also be related to prognosis in glioblastomas. GLUT1 is essential to central nervous system glycometabolism. To clarify the exact role of GLUT1 in glioblastoma, we assessed the expression and localization of GLUT1 in patient samples by immunohistochemistry and in situ RNA hybridization. This revealed that GLUT1 was mainly expressed on perivascular and pseudopalisaded tumor cell membranes. All samples expressed GLUT1 to some degree, with 30.8% showing stronger staining. On the basis of these data, samples were divided into high and low expression groups, although SLC2A1 mRNA expression was also higher in the high GLUT1 expression group. Kaplan-Meier survival curves revealed that high GLUT1 expression associated with lower overall survival (log-rank test, p = 0.001) and worse patient prognoses (p = 0.001). Finally, MIB-1 staining was stronger in high GLUT1 expression samples (p = 0.0004), suggesting a link with proliferation. We therefore hypothesize that GLUT1 expression in glioblastomas may enhance glycolysis, affecting patient prognosis. Examination of GLUT1 in patients with glioblastomas may provide a new prognostic tool to improve outcome.

Leptomeningeal Carcinomatosis After Neoplastic Cerebral Aneurysm Rupture.

BACKGROUND: Several possible mechanisms exist for the spread of a primary tumor to the leptomeninges in leptomeningeal carcinomatosis. This report describes a case caused by direct bleeding in the subarachnoid space from a neoplastic cerebral aneurysm rupture. CASE DESCRIPTION: A 48-year-old Japanese woman, who was diagnosed with breast carcinoma (pT3 pN2 M0) at the age of 45 years and underwent mastectomy and chemotherapy, was admitted in a coma following a sudden-onset severe headache. Computed tomography revealed diffuse hemorrhage in the subarachnoid space, and angiography revealed an aneurysm at the distal middle cerebral artery. Superficial temporal artery-middle cerebral artery bypass, aneurysmal trapping, and aneurysm resection were performed within 24 hours of admission. Staining for AE1/AE3 revealed accumulation of atypical cells with a high nuclear-cytoplasmic ratio in the aneurysmal wall. After showing initial improvement, she developed disturbed consciousness due to complicated ventricular enlargement on day 45. Although the cerebrospinal fluid in the acute phase had no atypical cells, subsequent testing revealed atypical cells, which supported a diagnosis of leptomeningeal carcinomatosis due to breast cancer dissemination. The patient died on day 78 after receiving standard endocrine therapy and radiation therapy. CONCLUSIONS: Tumor cells reach the leptomeninges via hematogenous spread or direct extension from preexisting lesions and can undergo neuraxis dissemination via the cerebrospinal fluid. Subarachnoid hemorrhage and leptomeningeal carcinomatosis are both devastating conditions with extremely poor prognoses. This patient experienced delayed disturbed consciousness leptomeningeal carcinomatosis with decreased performance status, which made it difficult to justify aggressive treatment on the basis of her poor prognosis.

Endoscopic Endonasal Removal of Primary/Recurrent Meningiomas in the Medial Optic Canal: Surgical Technique and Long-Term Visual Outcome.

BACKGROUND: Tuberculum sellae meningiomas frequently extend into the optic canals, which leads to a progressive longitudinal visual loss. Therefore, in addition to tumor removal, unroofing and exploration inside the optic canal are important procedures. OBJECTIVE: To perform endoscopic endonasal tumor removal with optic canal decompression for small primary or recurrent meningiomas associated with a progressive visual loss at the inferior-medial optic canal, which corresponded to a blind corner in the ipsilateral pterional/subfrontal approach. METHODS: We retrospectively reviewed 2 cases of primary meningiomas that arose in the inferior-medial optic canal and 4 recurrent cases from the remnant inside the medial optic canal that had previously undergone craniotomy for tuberculum sellae meningiomas, and were treated by the endoscopic endonasal approach. RESULTS: All tumors were detectable and could be removed without manipulation of the affected optic nerve. The average maximum diameter of the tumor was 8.4 mm (range: 5-12 mm). Two patients who had a long history of progressive visual disturbance and papillary atrophy did not recover from severe visual disturbances postoperatively. However, others showed considerable improvement, maintaining postoperative visual function during follow-up. There were no postoperative complications. CONCLUSION: Endoscopic endonasal approach has several advantages for meningiomas in the medial optic canal and associated with progressive visual disturbance. In surgery of tuberculum sellae meningiomas, optic canal decompression and exploration inside the optic canal are important procedures to avoid symptomatic recurrence, which may be facilitated by the endoscopic endonasal approach. Papillary atrophy and duration of visual deterioration are predictive factors for postoperative visual outcomes.

Human leukocyte antigen class II expression is a good prognostic factor in adult T-cell leukemia/lymphoma.

Attenuated human leukocyte antigen (HLA) class I expression is implicated as a major immune escape mechanism in several types of tumor. We previously reported that HLA class I/ß2 microglobulin and programmed death ligand-1 expression are prognostic factors in adult T-cell leukemia/lymphoma. A recent report suggested that HLA class II expression is also an important prognostic factor for the clinical outcome of programmed death-1 blockade therapy in recurrent/refractory Hodgkin lymphoma. This prompted us to evaluate HLA class II expression in adult T-cell leukemia/lymphoma and to compare the findings with the patients' clinicopathological features. Of the 132 biopsy specimens examined from newly diagnosed patients, lymphoma cells were positive for HLA class II expression in 44 patients (33.3%), whereas programmed death ligand-1 expression was observed on neoplastic cells from nine patients (6.9%) and on stromal cells in the tumor microenvironment in 83 cases (62.9%). HLA class II-positive cases showed a significantly better overall survival compared to the HLA class II-negative cases (P<0.0001). Patients positive for HLA class II and programmed death ligand-1 microenvironmental expression had significantly better prognosis than the other groups (P<0.0001). HLA class II-positive and HLA class II-negative groups also showed a significant difference in complete remission rate (P=0.0421), HLA class I/ß2 microglobulin expression (P=0.0165), and the number of programmed death-1-positive tumor infiltrating cells (P=0.0020). HLA class II expression was a prognostic factor for overall survival both in univariate and multivariate analyses (P<0.0001 and P=0.0007, respectively). Our study reveals that HLA class II is a novel prognostic factor in adult T-cell leukemia/lymphoma.

Malignant progression of an extraventricular neurocytoma arising from the VIIIth cranial nerve: A case report and literature review.

A rare case of extraventricular neurocytoma (EVN) arising from the VIIIth cranial nerve in a 34-year-old woman is reported. The patient had a 20-year history of hearing loss and facial palsy. Computed tomography showed a 3-cm enhancing lesion in the left cerebellopontine angle (CPA). At operation, the tumor was seen to originate from the cochlear and vestibular nerves. The tumor was subtotally resected. Histologically, the tumor consisted of uniform cells with oval to round nuclei and scant cytoplasm. Immunohistochemically, the tumor cells were positive for synaptophysin, but negative for glial fibrillary acid protein and S-100 protein. The Ki-67 labeling index was 0%. Twelve years after the operation, magnetic resonance imaging (MRI) showed tumor recurrence at the left CPA. The tumor was subtotally resected, and radiation therapy was given. Histologically, the tumor consisted of round cells with mild atypia and one mitosis/20 high-power fields (HPF). Immunohistochemically, tumor cells showed the same findings as the first operation sample, except for the Ki-67 labeling index (3%). Twelve years after the second operation, MRI showed a second tumor recurrence at the left CPA and surroundings of the brain stem. The tumor was subtotally resected. Histologically, the tumor consisted of anaplastic short spindle cells and five mitoses/10 HPF. The immunohistochemical findings were almost the same as the earlier operation samples. However, the Ki-67 labeling index was 20%. In addition, tumor cells from the third specimen were more strongly and more diffusely positive for GAB1 (growth factor receptor-bound protein 2-associated binding protein 1) compared to those of the earlier specimens. Electron microscopy showed the presence of numerous cell processes with a dense core and clear vesicles and microtubules. GAB1 immunostaining also indicated that malignant progression might be associated with the sonic hedgehog signaling pathways. To the best of our knowledge, this is the first report of an EVN arising from the VIIIth cranial nerve with malignant progression.

[Head Injuries due to Ladder-related Falls].

We examined the clinical characteristics and outcomes of patients who had fallen from ladders and statistically analyzed the prognostic factors, highlighting the impact of the coexistence of head injuries on their prognoses. The clinical records of patients who had experienced ladder-related falls who were admitted to the Advanced Emergency Medical Service Center at Kurume University Hospital between April 2013 and August 2015 were retrospectively reviewed. A total of 86 patients were enrolled. The mean patient age was 69.2 years, and 82 patients were male. The median fall height was 2.55 m. Sixty patients fell during non-professional use of the ladder. Forty-four patients experienced some type of head injury. Although the older patients had more frequent complications with head injuries, the height of the fall was not related statistically. The group of patients with head injuries exhibited trends of older age, lower Glasgow Coma Scale scores, higher Injury Severity Score, and poorer outcomes than those of the group of patients without head injuries. Multivariate analysis showed that head injury and non-professional use were independent risk factors for poor outcomes. Our results revealed that ladder-related falls with head injury can occur when older people are working at home, even if they have fallen from a low height. Especially when older men work with the ladder at home, local community-based education and guidance for the prevention of ladder-related fall injuries are needed.

Clinicopathological and genetic association between epithelioid glioblastoma and pleomorphic xanthoastrocytoma.

Epithelioid glioblastoma (eGBM) is a rare variant of GBM which was adopted in the 2016 WHO classification. eGBM and pleomorphic xanthoastrocytoma (PXA) sometimes show overlapping features histologically and genetically, such as epithelioid pattern and a highly frequent V600E mutation in the gene for vRAF murine sarcoma viral oncogene homolog B1 (BRAF), respectively. Accurate diagnosis of these rare tumors is challenging according to the new criteria in the revised 2016 WHO classification. It is an urgent task to elucidate the biological properties of the tumors and to select appropriate treatment. Twenty consecutive cases diagnosed as PXA or eGBM histologically were investigated. Twelve of the 20 cases were PXAs and eight were eGBMs. Morphologically, mitotic activity, necrosis and degenerative changes such as intracellular lipid accumulation, eosinophilic granular bodies and reticulin fiber deposits were scored. Immunohistochemical and molecular biological assessment for isocitrate dehydrogenases 1 and 2 (IDH1/2), α-thalassemia/mental-retardation-syndrome-X-linked gene (ATRX), p53, BRAF, telomere reverse transcriptase promoter (TERT-p), H3F3A, and integrase interactor 1 (INI1) were performed. eGBM tended to lack the degenerative changes characteristic for PXA. Of the 20 cases tested, Sanger technique showed no mutation in IDH1/2. BRAF mutation at T1799 > A (V600E) was detected in 4/12 (33.3%) PXA and 4/8 (50.0%) eGBM, while TERT-p mutation was detected at C228 > T in 2/12 (16.7%) PXA and at C250 > T in 1/8 (12.5%) eGBM. Retained nuclear ATRX was observed in 12/12 (100%) PXA and 6/7 (85.7%) eGBM while p53 mutation was observed in 2/10 (20%) PXA and 7/7 (100%) eGBM. All tumors retained INI1 expression in their nuclei. None of the tumors harbored H3F3A mutation. One PXA without BRAF mutation acquired TERT-p mutation at recurrence and one eGBM harbored both BRAF and TERT-p mutation. Molecular biological similarity between eGBM and PXA was suggested in our series, while degenerative changes reflected the features of PXA. It was speculated that the common genetic alterations for development and progression of eGBM and PXA might include BRAF and TERT-p mutations.