Single-Fraction Helical Tomotherapy for Ameloblastic Carcinoma.

Ameloblastic carcinoma (AC) is a rare malignant odontogenic tumor. Surgical resection of the tumor is the mainstay of its treatment. To date, radiotherapy for this tumor remains controversial. This report describes a case of AC with intracranial extension and provides the first report of the efficacy of single-fraction helical tomotherapy for the treatment of residual AC after surgical resection.

Adult classical glioblastoma with a BRAF V600E mutation.

The B-Raf proto-oncogene serine/threonine kinase (B-Raf) is a member of the Raf kinase family. The BRAF V600E mutation occurs frequently in certain brain tumors such as pleomorphic xanthoastrocytoma, ganglioglioma, and pilocytic astrocytoma, and less frequently in epithelioid and giant cell glioblastoma. BRAF V600E mutation in these cases has been canonically detected using Sanger sequencing or immunohistochemistry but not with next-generation sequencing (NGS). Moreover, to our knowledge, there is no detailed report of the BRAF V600E mutation in an adult glioblastoma with classical histologic features (c-GBM). Therefore, we performed NGS analysis to determine the mutational status of BRAF of 13 glioblastomas (GBMs) (11 primary and 2 secondary cases) and detected one tumor harboring the BRAF V600E mutation. We report here the detection of the BRAF V600E mutation in a patient with c-GBM and describe the patient's clinical course as well as the results of histopathological analysis.

BRAF V600E mutation co-existing with oncogenic mutations is associated with aggressive clinicopathologic features and poor prognosis in papillary thyroid carcinoma.

BACKGROUND: The aim of this study was to evaluate the correlation among mutations in cancer-related genes, clinicopathologic features, and clinical outcome in classical papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: A total of 130 patients with classical PTC who underwent curative surgery between April 2012 and June 2023 at Hokuto Hospital were included. Mutations in targeted regions of 160 cancer-related genes were detected by next-generation sequencing (NGS)-based cancer panel testing. RESULTS: The BRAF V600E mutation was detected in 108 (83.1%) of 130 PTC patients. Among the 108 patients with the BRAF V600E mutation, other co-existing oncogenic mutations were found in 12 (9.2%) patients. When we divided into 3 groups of no mutations, BRAF V600E mutation alone, and BRAF V600E and other oncogenic mutations, significant differences were observed in terms of tracheal invasion (P = 0.0024), and bilateral neck lymph node metastasis (P = 0.0047). Kaplan-Meier analysis of overall survival (OS) revealed patients with BRAF V600E and other oncogenic mutations had significantly poorer survival than those with BRAF V600E mutation alone (P = 0.0026). Multivariate cox proportional hazard analysis revealed BRAF V600E and other oncogenic mutations was an independent prognostic factor for OS (HR: 10.559; 95%CI: 1.007-110.656, P = 0.0493). CONCLUSIONS: The BRAF V600E mutation co-existing with other oncogenic mutations but not the BRAF V600E mutation alone was associated with aggressive clinicopathologic features, resulting in poor prognosis in patients with classical PTC. Detection of oncogenic mutations using NGS-based cancer panel testing could enhance understanding of the clinical features of classical PTC.

Prognostic value of isocitrate dehydrogenase 1, O6-methylguanine-DNA methyltransferase promoter methylation, and 1p19q co-deletion in Japanese malignant glioma patients.

BACKGROUND: To determine the prognostic value of isocitrate dehydrogenase 1 (IDH1) mutation, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and 1p/19q co-deletion in Japanese patients with malignant gliomas. METHODS: We studied 267 malignant gliomas, which included 171 glioblastomas (GBMs), 40 anaplastic astrocytomas (AAs), 30 anaplastic oligodendrogliomas (AOs), and 26 anaplastic oligoastrocytomas (AOAs). These malignant gliomas were divided into 2 groups (Group 1: GBM + AA, Group 2: AO + AOA) according to the presence of the oligodendroglioma component. We examined IDH1 mutation and MGMT promoter methylation in each group by direct sequencing and methylation-specific PCR, respectively. We further examined 1p/19q co-deletion in Group 2 by fluorescence in situ hybridization. Survival between groups was compared by Kaplan-Meier analysis. RESULTS: In Group 1, patients with IDH1 mutations exhibited a significantly longer survival time than patients with wild-type IDH1. However, no significant difference was observed in Group 2, although patients with IDH1 mutations tended to show prolonged survival. For both Group 1 and Group 2, patients with MGMT methylation survived longer than those without this methylation. Further, patients with 1p/19q co-deletion showed significantly better outcome in Group 2. CONCLUSIONS: Our study confirms the utility of IDH1 mutations and MGMT methylation in predicting the prognosis of Group 1 patients (GBM + AA) and demonstrated that IDH1 mutations may serve as a more reliable prognostic factor for such patients. We also showed that MGMT methylation and 1p/19q co-deletion rather than IDH1 mutations were prognostic factors for Group 2 patients (AOA + AO). Our study suggests that patients survive longer if they have IDH1 mutations and undergo total resection. Further, irrespective of MGMT promoter methylation status, the prognosis of glioma patients can be improved if total resection is performed. Moreover, our study includes the largest number of Japanese patients with malignant gliomas that has been analyzed for these three markers. We believe that our findings will increase the awareness of oncologists in Japan of the value of these markers for predicting prognosis and designing appropriate therapeutic strategies for treating this highly fatal disease.

Cancer gene analysis of liquid-based cytology specimens using next-generation sequencing: A technical report of bimodal DNA- and RNA-based panel application.

BACKGROUND: As liquid-based cytology (LBC) specimens harbor high-quality DNA, genomic analysis using LBC specimens is beneficial for integrative diagnosis. This study aimed to clarify the feasibility of LBC specimens for a bimodal application of DNA- and RNA-based next-generation sequencing (NGS) panels. METHODS: LBC specimens were prepared from cultured human cancer HEC59 cells using commercially available fixatives (Cellprep, CytoRich Red, and SurePath solutions), and were subjected to NGS for a feasibility study. Clinical LBC specimens of thyroid and salivary gland tumors were prepared using CytoRich Red solution. After DNA and RNA extraction, NGS analyses were performed in a single run using combined DNA- and RNA-based custom-made cancer panels for the detection of gene mutations and fusions. RESULTS: High-quality DNA and RNA were obtained, and the expected gene mutations and fusions were detected in HEC59 cells using all types of LBC fixatives. Most available clinical cases (18 out of 20) exhibited pathogenic gene mutations (15 cases) and fusion genes (3 cases) using the bimodal DNA- and RNA-based panels. Overall, 18 cases (90%) showed oncogenic mutations or fusion genes of diagnostic values. CONCLUSION: Simultaneous application of bimodal DNA- and RNA-based gene panels was useful in NGS analysis using residual LBC specimens for integrative diagnosis. Residual LBC specimens for genomic analysis, including fusion gene analysis, are particularly useful for obtaining genomic information before surgical resection.

A case of clear cell variant of solid-pseudopapillary tumor of the pancreas in an adult male patient.

A clear cell variant of solid-pseudopapillary tumor (SPT) of the pancreas was initially reported in 2006 as a tumor that arose in the pancreatic body and tail in young adults; to date, only 4 cases of this entity have been reported. Here, we present the case of a 58-year-old man with clear cell variant of SPT with distinctive clinicopathologic features. The tumor was well demarcated, was 2.6 cm in size and mostly composed of multivacuolated clear cells with solid growth, and exhibited the characteristic immunohistochemical positivity of ß-catenin in the cytoplasm and nuclei of the neoplastic cells. In contrast to classical SPT with nuclear positivity, this case was negative for E-cadherin. Direct DNA sequencing of exon 3 of ß-catenin gene demonstrated a single amino acid substitution (serine to phenylalanine) in codon 37, which is the phosphorylation site by GSKß and frequently found in classical SPT. Electron microscopy demonstrated enlarged mitochondria and endoplasmic reticulum. Despite the fact that previous cases of clear cell variant of SPT arose mainly in the pancreatic body and tail in female young adults (age, 26-32 years), this case suggested that it is possible for a clear cell variant of SPT to arise in the pancreatic head in a middle-aged man. Because the recognition of the clear cell variant of SPT is important for the appropriate diagnosis of primary pancreatic tumor, the present case with its distinctive characteristics may provide new information for a more profound understanding of the pancreatic SPT.

Outcome of Superficial Temporal Artery-to-Middle Cerebral Artery Bypass in Appropriately Selected Patients with Acute Ischemic Stroke.

Background: Endovascular treatment is the preferred treatment for acute ischemic stroke (AIS) due to main artery steno-occlusive disease, but it has temporal and technical limitations. Moreover, there is no established treatment for progressive stroke. Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass is sometimes considered as a treatment option. Objective: The objective of this paper is to review the treatment outcomes of patients with AIS undergoing urgent STA-MCA bypass. Methods and Material: This was a retrospective study including 32 patients diagnosed with AIS treated with urgent STA-MCA bypass at our facility. The patients had small infarct volumes and a large diffusion-perfusion mismatch. Results: New ischemic lesions in postoperative diffusion-weighted images were detected in 15 patients (46.9%), but only four (12.5%) developed paralysis. Hyperperfusion occurred in nine patients (28.1%), and five (15.6%) had bypass occlusion at 1 week. Delayed wound healing were found in four patients (12.5%). Neurological outcome was measured 3 months after onset: Manual Muscle Testing (MMT), 3-5 in 27 patients (84.4%); modified Rankin scale (mRS), 0-2 in 17 patients (53.1%); and 0-3 in 26 patients (81.3%). Prognosis was better in patients who underwent surgery after 24 h of stroke onset (mRS, 0-2 in 56.0% cases and 0-3 in 88.0% at 3 months). Statistical analyses revealed that MMT before surgery had a significant association with favorable outcomes (P = 0.041). Conclusions: Urgent STA-MCA bypass for progressive stroke may result in a good prognosis if the right patients are selected and may play an important role in cases treated 24 h after onset in whom endovascular treatment is ineffective.

Focused Ultrasound Thalamotomy for Refractory Essential Tremor: A Japanese Multicenter Single-Arm Study.

BACKGROUND: Several feasibility studies and a randomized, controlled, multicenter trial have demonstrated the safety and efficacy of unilateral transcranial magnetic resonance-guided focused ultrasound (FUS) lesioning of the ventral intermediate thalamic nucleus in treating essential tremor. OBJECTIVE: To evaluate the safety and efficacy of FUS thalamotomy in a Japanese patient cohort through a prospective, multicenter, single-arm confirmatory trial. METHODS: A total of 35 patients with disabling refractory essential tremor underwent unilateral FUS thalamotomy and were followed up for 12 post-treatment months. Safety was measured as the incidence and severity of treatment-related adverse events. Efficacy was measured as the tremor severity and quality of life improvements using the Clinical Rating Scale for Tremor and Questionnaire for Essential Tremor. RESULTS: The mean skull density ratio (SDR) was 0.47. There was a significant decrease in the mean postural tremor score of the treated hand from baseline to 12 mo by 56.4% (95% CI: 46.7%-66.1%; P < .001), which was maintained at last follow-up. Quality of life improved by 46.3% (mean overall Questionnaire for Essential Tremor score of 17.4 [95% CI: 12.1-22.7]) and there were no severe adverse events. The most frequent adverse event was gait disturbance and all events resolved. CONCLUSION: Unilateral FUS thalamotomy allowed significant and sustained tremor relief and improved the quality of life with an outstanding safety profile. The observed safety and efficacy of FUS thalamotomy were comparable to those reported in a previous multicenter study with a low SDR, and inclusion of the low SDR group did not affect effectiveness.

Quantitative imaging of spontaneous neuromagnetic activity for assessing cerebral ischemia using sLORETA-qm.

To image cerebral neural activity in ischemic areas, we proposed a novel technique to analyze spontaneous neuromagnetic fields based on standardized low-resolution brain electromagnetic tomography modified for a quantifiable method (sLORETA-qm). Using a 160-channel whole-head-type magnetoencephalographic system, cerebral magnetic fields were obtained pre- and postoperatively from 5 patients with unilateral internal carotid artery occlusive disease and 16 age-matched healthy volunteers. For quantitative imaging, voxel-based time-averaged intensities of slow waves in 4 frequency bands (0.3-2 Hz, 2-4 Hz, 4-6 Hz and 6-8 Hz) were obtained by the proposed technique based on sLORETA-qm. Positron emission tomography with (15)O gas inhalation ((15)O-PET) was also performed in these patients to evaluate cerebral blood flow and metabolism. In all 5 patients, slow waves in every frequency band were distributed in the area of cerebrovascular insufficiency, as confirmed by (15)O-PET preoperatively. In 4 patients, slow-wave intensities in theta bands (4-6 Hz, 6-8 Hz) decreased postoperatively along with improvements in cerebral blood flow and metabolism, whereas delta bands (0.3-2 Hz, 2-4 Hz) showed no significant differences between pre- and postoperatively. One patient with deterioration of cerebral infarction after surgery showed marked increases in slow-wave intensities in delta bands (0.3-2 Hz, 2-4 Hz) postoperatively, with distribution close to the infarct region. The proposed quantitative imaging of spontaneous neuromagnetic fields enabled clear visualization and alternations of cerebral neural conditions in the ischemic area. This technique may offer a novel, non-invasive method for identifying cerebral ischemia, although further studies in a larger number of patients are warranted.

Non-pharmacological treatment changes brain activity in patients with dementia.

Non-pharmacological treatment (NPT) improves cognitive functions and behavioural disturbances in patients with dementia, but the underlying neural mechanisms are unclear. In this observational study, 21 patients with dementia received NPTs for several months. Patients were scanned using magnetoencephalography twice during the NPT period to evaluate NPT effects on resting-state brain activity. Additionally, cognitive functions and behavioural disturbances were measured using the Mini-Mental State Examination (MMSE-J) and a short version of the Dementia Behaviour Disturbance Scale (DBD-13) at the beginning and the end of the NPT period. In contrast to the average DBD-13 score, the average MMSE-J score improved after the NPT period. Magnetoencephalography data revealed a reduced alpha activity in the right temporal lobe and fusiform gyrus, as well as an increased low-gamma activity in the right angular gyrus. DBD-13 score changes were correlated with beta activity in the sensorimotor area. These findings corroborate previous studies confirming NPT effects on brain activity in healthy participants and people at risk of dementia. Our results provide additional evidence that brains of patients with dementia have the capacity for plasticity, which may be responsible for the observed NPT effects. In dementia, NPT might lead to improvements in the quality of life.

A case of central nervous system lymphomatoid granulomatosis; characteristics of PET imaging and pathological findings.

Lymphomatoid granulomatosis (LYG) in the central nervous system (CNS) is an uncommon lymphoproliferative disorder with low grade malignant potential. Here we report a case of CNS-LYG, in particular, its characteristics of radioisotope imaging and pathological findings. A 65-year-old man complained of visual disturbance and homonymous hemianopsia was designated. CT and MRI revealed an edematous, enhanced irregular and nodular lesion in the right occipital and parietal lobes. Although 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan showed low uptake in the lesion, Methionine (MET)-PET scan indicated high uptake. Proton magnetic resonance spectroscopy ((1)H-MRS) at 3T revealed a decrease of the peak of the N-acetylaspartate (NAA), suggesting a possible neoplastic lesion. The patient was diagnosed with CNS-LYG based on the surgically removed material showing perivascular infiltration of CD3-positive small T-lymphocytes with granulomatous lesions. The post-operative steroid therapy was effective and the recurrence or exacerbation has not been observed by radiological imaging until now.

Prediction of seizure outcome following epilepsy surgery: asymmetry of thalamic glucose metabolism and cerebral neural activity in temporal lobe epilepsy.

OBJECTIVE: The objective of this retrospective study is to analyze whether preoperative functional imaging studies using FDG-PET and MEG enable prediction of postoperative seizure outcomes. METHODS: Thirty-six patients with intractable temporal lobe epilepsy were studied. Asymmetry index of tCMRgluc (PET-AI) and the equivalent current dipole intensity of first response of SEF (SEF-AI) were determined preoperatively using (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and magnetoencephalography (MEG), respectively. Seizure outcomes were evaluated according to the classification proposed by the International League Against Epilepsy (ILAE) at least 24 months after resection of epileptic focuses. Twelve healthy volunteers were included in this study to determine the normal value. RESULTS: Quantitative analysis revealed mean PET-AI in the patients was 5.4+/-5.2% (significantly different from normal controls); mean SEF-AI was 25.2+/-20.6% (not significantly different). PET-AI was positive (indicative of epileptic focus) in 29 of 36 patients (80.6%), while SEF-AI was positive in 17 of 36 patients (47.2%). Although no significant correlation between PET-AI and SEF-AI was noted (r=0.43), concordant asymmetry in both PET-AI and SEF-AI was significantly associated with better seizure outcome than discordant or paradoxical asymmetry of both factors (p<0.01). CONCLUSIONS: The results suggest that quantitative analysis of tCMRgluc with SEF may be helpful in characterizing the preoperative epileptogenic condition and predicting postoperative seizure outcome in patients with temporal lobe epilepsy, although a constellation of developmental brain abnormalities and environmental factors that together produce epilepsy need to be further explored.

Vasospasm as a major complication after acute mechanical thrombectomy with stent retrievers.

OBJECTIVE: Mechanical thrombectomy using a stent retriever for acute large vessel occlusion is indispensable in stroke treatment, however, vasospasm may occur. The objective of this retrospective study was to investigate which cases are more likely to experience vasospasm after thrombectomy with stent retrievers. METHODS: We included 29 patients diagnosed with acute cardiogenic cerebral embolism who were treated with stent retrievers at our facility from December 2014 to December 2017. Atherothrombotic brain infarction cases were excluded because it was difficult to evaluate for vasospasms. Vasospasm was defined as reversible arterial narrowing of <80% of the normal vessel diameter after usage of the stent retriever. The age, sex, type of stent retriever, occlusion site, number of procedures, thrombolysis in cerebral infarction (TICI) grade, degree of vasospasm, intracranial hemorrhage by the procedure, and neurological outcomes were analyzed. RESULTS: Among the 29 cases, 12 (41.4%) resulted in vasospasm; nine cases were mild (20-50% stenosis) and 3 cases were severe (≥50% stenosis). Vasospasm frequently occurred in the distal part of the anterior circulation when compared to the proximal part. In addition, the frequency of vasospasm increased as the number of procedures increased. Pooled analysis showed significant difference in the intravenous tissue-type plasminogen activator group (P = 0.029). There was no significant difference in the other groups. CONCLUSION: Stent retrievers appear to cause vasospasm more than expected when including mild cases. Vasospasm tends to occur especially in cases with IV-tPA; prognosis is generally good, and it rarely requires any treatment.

Sonodynamic Therapy for Malignant Glioma Using 220-kHz Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound and 5-Aminolevulinic acid.

Sonodynamic therapy (SDT) is used to treat various malignancies and can be applied to brain tumors using a transcranial magnetic resonance imaging-guided focused ultrasound (TcMRgFUS) device. This study investigated the efficacy of 220-kHz TcMRgFUS combined with 5-aminolevulinic acid (5-ALA) on malignant glioma in vitro and in vivo. F98 cells were irradiated with focused ultrasound (FUS) (4000 J, 20 W, 240 s, 100% duty cycle, target medium temperature <40°C) after treatment with 200 µg/mL 5-ALA, and cell viability and apoptosis were evaluated with the water-soluble tetrazolium-1 assay, triple fluorescent staining and Western blot analysis 20 h later. The anti-tumor effects of 5-ALA combined with FUS (500 J, 18 W, 30 s, 100% duty cycle, 10 repeats, target tissue temperature ≤42°C) were assessed on the basis of changes in tumor volume determined by MRI and histopathological analysis before and after treatment. The FUS/5-ALA combination reduced cell viability by inducing apoptosis and suppressed tumor proliferation and invasion as well as angiogenesis in vivo, while causing minimal damage to normal brain tissue. SDT with 220-kHz TcMRgFUS and 5-ALA can be safely used for the treatment of malignant glioma.

Recovery of spontaneous neuromagnetic activity after extracranial-intracranial bypass in a patient with middle cerebral artery occlusion.

PATIENT AND METHODS: Cerebral blood flow and neuromagnetic activity were measured using (123)I-iodoamphetamine-single photon emission computed tomography (IMP-SPECT) and magnetoencephalography (MEG), before and after extracranial-intracranial (EC-IC) bypass surgery in a 55-year-old woman with unilateral middle cerebral artery occlusion that occurred with intraventricular haemorrhage. Frequency analysis of slow waves measured on MEG was performed using an adaptive beam-former method. RESULTS AND DISCUSSION: Distribution of delta waves was observed pre-operatively corresponding to areas of cerebral hypo-perfusion as confirmed by IMP-SPECT but disappeared post-operatively with improvements in cerebral blood flow. Imaging of slow-wave distributions with MEG may represent a new technique for identifying cerebral ischaemia.

Usefulness of 18F-fluorodeoxyglucose-Positron Emission Tomography in Comparison with Methionine-Positron Emission Tomography in Differentiating Solid Hemangioblastoma from Adult Cerebellar Tumors.

BACKGROUND AND PURPOSE: Among adults with posterior fossa tumors, an intraaxial location of the tumor is less common than an extraaxial location. Moreover, the differential diagnosis of a single cerebellar tumor in adults is sometimes difficult by conventional magnetic resonance imaging. We aimed to report the findings of positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) and methionine in adult patients with intraaxial and solitary metastatic brain tumors. MATERIALS AND METHODS: FDG-PET was performed on 12 patients with posterior fossa tumors: 4 had solid hemangioblastoma (HB), 3 had primary central nervous system lymphomas, 1 had a glioblastoma, and 4 had single metastatic brain tumors (METs). Methionine-PET was performed on 9 patients except for 1 patient with a MET. The maximum standardized uptake value (SUVmax) of the tumor was measured and compared with pathologic findings. RESULTS: The SUVmax of FDG in HB was lower compared with that of other tumors (P = 0.001). On the other hand, the SUVmax of methionine in the HB cases was almost the same as that in other tumors (P = 0.07). CONCLUSION: FDG-PET was helpful in differentiating HBs from adult cerebellar tumors.

Targeted next-generation sequencing of cancer-related genes in thyroid carcinoma: A single institution's experience.

Thyroid carcinoma (TC) has characteristic genetic alterations, including point mutations in proto-oncogenes and chromosomal rearrangements that vary by histologic subtype. Recent developments in next-generation sequencing (NGS) technology enable simultaneous analysis of cancer-associated genes of interest, thus improving diagnostic accuracy and allowing precise personalized treatment for human cancer. A total of 50 patients who underwent thyroidectomy between 2014 and 2016 at Hokuto Hospital were enrolled. Total DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and quantified. Targeted regions of 24 cancer-associated genes were amplified by PCR, barcoded and sequenced using an Illumina MiSeq platform. Subjects included 30 patients with papillary carcinoma (PC), two with PC tall cell variant (TVPC), two with PC follicular variant (FVPC), eight with follicular carcinoma, seven with poorly differentiated carcinoma (PDC), and one with anaplastic carcinoma (AC). The BRAF V600E mutation was present in 25 of 30 (83%) patients with PC, 2 of 2 (100%) patients with TVPC, 6 of 7 (86%) patients of PDC, and one patient with AC. PIK3CA mutations were present in 3 of 30 (delPV104P, A1046T and C420R; 10%) patients with PC and 1 of 7 (H1047R; 14%) patients with PDC. The TP53 mutation was present in 1 of 30 (R306*; 3.3%) patients with PC and 1 of 7 (Q152*; 14%) patients with PDC. The NRAS mutation was present in 1 of 2 (Q61K, 50%) patients with FVPC. Statistical analysis showed that patients without the BRAF V600E mutation had advanced pathologic T and N stages compared with those with the mutation (P=0.047 and P=0.019, respectively). The BRAF V600E mutation was not correlated with overall and disease-free survival in patients with PC. A patient with PC with a mutation in EGFR (K852Q) and the PIK3CA mutation had an aggressive course with multiple bone and lung metastases. Detection of mutations in cancer-associated genes using NGS could enhance the understanding of the clinical behavior of TC.

ANCA-Negative Granulomatosis with Polyangiitis Presenting with Hypertrophic Cranial Pachymeningitis, Abducens Nerve Palsy, and Stenosis of the Internal Carotid Artery.

We report a rare case of granulomatosis with polyangiitis (GPA) presenting with hypertrophic cranial pachymeningitis (HCP), abducens nerve palsy, and stenosis of the internal carotid artery (ICA). A 59-year-old Japanese man presented with a year history of nasal obstruction and a 2-month history of slight headache. Histopathological examination of the granulomatous mucosa in the ethmoid sinuses resected by endoscopic sinus surgery revealed necrotizing vasculitis with multinucleated giant cells. The patient was diagnosed with the limited form of GPA as a result of the systemic examination. He declined immunosuppressive treatment. Eighteen months after the diagnosis of GPA, he presented with diplopia and severe headache. Though nasal findings indicating GPA were not observed in the nasal cavity, CT scan revealed a lesion of the right sphenoid sinus eroding the bone of the clivus. Gadolinium-enhanced MRI of the brain showed thickening of the dura mater around the right cavernous sinus and clivus. Magnetic resonance angiography and cerebral angiography revealed narrowing at the C5 portion of the ICA. Intravenous methylprednisolone pulse therapy followed by oral prednisolone and cyclophosphamide resolved headache and dramatically improved HCP and stenosis of the ICA.

Monocyte chemoattractant protein 1 expression and proliferation in primary central nervous system lymphoma.

Whether the poor prognosis of primary central nervous system lymphoma (PCNSL) compared with systemic diffuse large B cell lymphoma (DLBCL) is attributable to the immune privilege of the intracerebral location or to intrinsic differences in the biological characteristics of two types of lymphoma remains unclear. Monocyte chemoattractant protein 1 (MCP-1) is essential to support tumor cell survival and growth, and the present study aimed to compare MCP-1 expression in PCNSL and peripheral DLBCL. The present study included 19 patients with PCNSL and 16 patients with DLBCL, all of whom had tissue diagnosis and lymphoma tissue samples available for analysis. Histology included immunohistochemistry using antibodies against a panel of lymphoma markers, antibodies specific to MCP-1, and antibodies specific to tumor-associated macrophages. MCP-1 expression was quantified using immunostaining scoring. RNA extraction and reverse transcription-quantitative polymerase chain reaction were used to determine MCP-1 mRNA expression. In addition, a human brain-derived lymphoma cell line, HKBML, was stimulated with MCP-1 and cell proliferation was measured by 5-bromo-2'-deoxyuridine incorporation. The expression levels of MCP-1 mRNA and MCP-1 protein were significantly increased in PCNSL compared with peripheral DLBCL. MCP-1 induced tyrosine phosphorylation of mitogen-activated protein kinase in HKBML cells, as analyzed by western blotting. The results of the present study indicated that MCP-1 expression in PCNSL promoted cell proliferation in an autocrine manner.