A nationwide survey of hypertrophic pachymeningitis in Japan.

OBJECTIVES: To clarify the prevalence, frequent causes and distinct features of hypertrophic pachymeningitis (HP) according to background conditions in a nationwide survey in Japan. METHODS: The study began with a preliminary survey to determine the approximate number of HP patients diagnosed from 1 January 2005 to 31 December 2009, and was followed by a questionnaire survey for clinical and laboratory findings. HP was defined as a condition with thickening of the cranial or spinal dura mater with inflammation, evidenced by MRI or histology. RESULTS: Crude HP prevalence was 0.949/100 000 population. The mean age at onset was 58.3±15.8 years. Among 159 cases for whom detailed data were collated, antineutrophil cytoplasmic antibody (ANCA)-related HP was found in 54 cases (34.0%) and IgG4/multifocal fibrosclerosis (MFS)-related HP in 14 cases (8.8%). Seventy cases (44.0%) were classified as 'idiopathic' and 21 (13.2%) as 'others'. ANCA-related HP cases showed a female preponderance, a higher age of onset, and higher frequencies of otological symptoms and elevated systemic inflammatory biomarkers, but lower frequencies of diplopia compared with idiopathic HP. IgG4/MFS-related HP cases showed a marked male predominance; all had cranial HP while none had isolated spinal HP or decreased sensation. CONCLUSIONS: HP is not extremely rare. ANCA-related HP is the most frequent form, followed by IgG4/MFS-related HP. Both forms have unique features, which may help to differentiate background causes.

Granulofilamentous meningioma.

A 55-year old female was referred to the Department of Neurosurgery, Kitasato Hospital, because of a hearing impairment. Neuroimaging revealed a typical meningioma attached to the falx in the right frontal region. During surgery, an encapsulated, circumscribed, reddish-gray, slightly hard tumor attached to the falx was completely removed by an interhemispheric approach. On light microscopy, many of the tumor cells contained eosinophilic inclusions with single or multiple vacuoles that displaced the cytoplasm. The nuclei of the tumor cells were eccentric. There were no signs of malignancy in the specimen. Electron microscopy revealed that most of the eosinophilic inclusions were composed of filaments measuring 12 nm in diameter. There have been several reports of benign meningiomas with eosinophilic inclusions composed of intermediate filaments. The microscopic differences between these types of tumor and rhabdoid meningiomas are very subtle, and it is important the two types of tumors are not confused. Benign meningiomas with eosinophilic inclusions comprising intermediate filaments, for example the tumor described in this report, have been diagnosed as granulofilamentous meningiomas, which is a subtype of benign meningioma.

Clinicopathological features of human brainstem gliomas.

We describe the clinicopathological features of 25 brainstem gliomas (BSGs). Twenty BSGs located in the pons and were all in children. Four BSGs located in the medulla oblongata were in 2 children and 2 adults. One (in a child) was located in the midbrain. Radiological findings on MR images were low-intensity on T1 weighted images and high-intensity on T2 weighted images. Mean survival when pontine glioma was treated by radiotherapy and/or use of temozolomide was 14 months, although 4 patients (3 cervicomedullary types and one focal type arising from midbrain) are alive. Follow up was from 5 months to 6 years. Histopathological features of 10 cases of the diffuse type were: 4 grade II astrocytomas, 4 grade III astrocytomas, and 2 glioblastomas. MIB-1 index was from 0.8 to 38 %. P53 was positive for 80 % of 15 tumors and there were no negative results. MGMT was positive in 60 % of 15 tumors and negative in 12.4 %. IDH1 was negative in 61.6 %. There was no positive result for IDH1 in this study. Thus, our histopathological results were indicative of high p53 immunoreactivity and no IDH1 immunoreactivity related to secondary malignant change.

Investigation of IgG4-positive cell infiltration in biopsy specimens from cases of hypertrophic pachymeningitis.

This study was an immunohistological study of IgG4-positive cell infiltration in 6 cases of hypertrophic pachymeningitis excluding secondary hypertrophic pachymeningitis caused by infectious diseases such as aspergillosis. The cases included 5 males and 1 female, ranging in age from 36 to 82 years (mean, 55 years). A biopsy was performed in all of the cases for diagnostic purposes, revealing fibrous dural hyperplasia with nonspecific inflammatory cell infiltration histologically. Two of the 6 patients had been treated with steroids before the biopsy, which was taken for poor response to steroid treatment. In these two cases, some IgG-positive cell infiltration of the thickened dura was observed; however, most of the cells were IgG4-negative. In the remaining four cases, many IgG- and IgG4-positive cells infiltrated the thickened dura and the IgG4-positive/IgG-positive cell ratio exceeded 40%. One of these patients was finally diagnosed with IgG4-related sclerosing disease, since he was diagnosed subsequently with retroperitoneal fibrosis. There was no evidence of any other lesions associated with IgG4-related sclerosing disease, other than in the dura. It is not rare for IgG4-positive cells to appear in the dura in cases of hypertrophic pachymeningitis; however, no IgG4-related systemic disease is present in these cases. Hypertrophic pachymeningitis with IgG4-positive cells may have some kind of relation to other systemic autoimmune diseases.

An operation in the park bench position complicated by massive tongue swelling.

This paper presents a case of massive tongue swelling as a complication after an operation in the park bench position. A 43-year-old male who had undergone a resection of a mass in the petrous bone of the clivus showed massive tongue swelling after the surgery in the left park bench position. A direct compression of the bite block caused the swelling of tongue. Tongue swelling may become fatal if it progresses to an airway obstruction; therefore the intraoperative and postoperative management is important.

Modified wound dissection preserving the greater occipital nerve in foramen magnum decompression: a technique to reduce postoperative pain.

Patients undergoing foramen magnum decompression for Chiari malformation may experience severe postoperative pain in the area innervated by the greater occipital nerve (GON). We developed a modified dissection to lessen this pain. A midline skin incision was extended 2 cm in a cephalad direction to the inion and the skin was minimally retracted. After exposing the occipital bone, the semispinalis capitis and the trapezius muscles were detached subperiosteally in a caudal-to-cephalad direction. Consequently, the muscles and skin containing the GON were retracted in a single layer. We retrospectively compared the intensity of postoperative pain recorded on the visual analogue scale (VAS) by patients who underwent decompression using our (group A, n = 5) and the conventional layer-by-layer dissection technique (group B, n = 5). The VAS scores were not different on the day of surgery, but subsequently they fell faster in group A. Group A patients received a mild analgesic for a short period. Group B patients required a stronger analgesic for prolonged periods. Postoperative GON numbness/tenderness was observed only in group B. With respect to most evaluation criteria, the difference between the two groups was significant. Our anatomically rational dissection that protects the GON results in less postoperative pain.

Adult cerebellar glioblastoma cases have different characteristics from supratentorial glioblastoma.

This study is a histological and clinical investigation of four cases of cerebellar glioblastoma, a rare tumor. The cases included three males and one female, from 33 to 67 years in age (mean 49 years). Tumor resection, postoperative irradiation and chemotherapy were performed in all cases. Two patients died of local tumor recurrence after 14 and 27 months. Another patient relapsed after 10 months; however, after additional tumor resection and second line chemotherapy, she remains disease-free 41 months after the initial treatment. The fourth patient has not relapsed in the 6 months since initial treatment. The histopathology of all cases was glioblastoma with pseudopalisading necrosis. However, low-grade glioma histopathology was found in three patients. All glioblastomas were immunopositive for p53 and immunonegative for epidermal growth factor receptor (EGFR) and isocitrate dehydrogenase 1 (IDH1). These adult cerebellar glioblastoma cases had similar clinical and pathological characteristics, and had different characteristics compared with supratentorial glioblastomas.

Pilocytic astrocytoma with abundant oligodendroglioma-like component.

An 18-year-old girl presented with a history of visual disturbance without headache, nausea, or vomiting in May 2010. In July 2010, the patient visited our hospital because of visual disturbance. Head magnetic resonance images revealed hydrocephalus caused by a ring-enhancing mass lesion located in the vermis. Total tumor removal was performed. Histological findings revealed that honeycomb cells resembling oligodendrocytes accounted for most parts of the tumor. Rosenthal fibers and hyaline droplets were seen in a small portion. The tumor cells were immunoreactive for GFAP and Olig2, but none of the tumor cells were immunoreactive for Symaptophysin, EMA, or IDH 1. according to these findings, the tumor was diagnosed as pilocytic astrocytoma with an abundant oligodendroglioma-like component. Pilocytic astrocytoma is known to be associated with an oligodendroglioma-like component; however, the differential diagnosis for oligodendroglioma may be difficult when an oligodendroglioma-like component occupies most of the tumor.

Rathke's cleft cyst with xanthogranulomatous change--case report.

A 58-year-old man presented with a rare case of Rathke's cleft cyst (RCC) manifesting as headache and visual disturbance. Goldman's perimeter showed he had bitemporal hemianopia. Magnetic resonance imaging revealed a solid intrasellar lesion. He underwent surgery via a right pterional approach. The lesion was red, solid, and fibrous. Histological examination revealed a few columnar epithelial cells with poor cilia in a xanthogranulomatous lesion. Only 13 cases of RCC with granulomatous change have been diagnosed by pathological examination, including 4 xanthogranulomatous cases. Xanthogranuloma of the sellar region is relatively rare. The etiology is still unknown. We speculate that xanthogranulomas of the sellar region may be caused by reaction to the presence of RCC.

Utility of intraoperative fluorescent diagnosis of residual hemangioblastoma using 5-aminolevulinic acid.

Hemangioblastoma is a benign tumor of the cerebellum, and treatment involves surgical excision, both as the initial treatment and also in case of recurrence. Recurrence of hemangioblastoma can be local due to incomplete resection or can be distant and separate from the tumor resection region. Local recurrence can largely be avoided by verifying for any residual tumor intraoperatively before closure. In this study, we used intraoperative fluorescent diagnosis using 5-aminolevulinic acid (5-ALA) to verify the presence of a residual tumor during surgical resection. Nine patients with hemangioblastoma were given 1 g of 5-ALA orally before surgery, and a laser beam of 405 nm was focused on the tumor during resective surgery. Fluorescence of protoporphyrin IX (PPIX) was observed in the core of tumor in all the cases. Fluorescence of PPIX was observed in the peritumoral cyst wall in two patients after tumor resection, and in both of them fluorescent parts of PPIX were resected and histological examination showed tumor cells. Usually, there are no tumor cells in the peritumoral cyst of a hemangioblastoma, yet hemangioblastomas may sometimes recur from an unresected cyst wall. It is thus necessary to excise an infiltrating cyst of tumor cells to prevent recurrence. Intraoperative fluorescent diagnosis using 5-ALA is a useful method to discern whether tumor cells are present in the peritumoral cyst wall of a hemangioblastoma.

Effectiveness of interferon-beta therapy for recurrent glioblastoma: a case report.

AIMS AND BACKGROUND: Glioblastoma has a poor prognosis, with few therapeutic options if it recurs. We report a case in which we were able to inhibit the growth of a recurrent glioblastoma by weekly single-dose administration of interferon-beta. CASE REPORT: A patient with recurrent glioblastoma after radiation and chemotherapy was treated with nimustine and interferon-beta. After 2 cycles of nimustine, the patient's leukocyte, neutrophil, and platelet counts showed grade 4 toxicity according to the National Cancer Institute's Common Toxicity Criteria. The patient was treated with a weekly single dose of interferon-beta at 6 x 10(6) IU. The tumor showed no remarkable changes after 18 months, and the patient's Karnofsky performance status remained at 50%. CONCLUSIONS: The administration of interferon-beta produced long-term control in one case of glioblastoma and may be an effective therapy.

Linear fractures invisible on routine axial computed tomography: a pitfall at radiological screening for minor head injury.

Computed tomography (CT) is now widely used as the only screening method for fractures in patients with head injury. However, clear depiction of a fracture requires a discontinuity in the skull, so linear fractures parallel to the CT slice may not be visualized. We retrospectively evaluated 302 patients with minor head injuries aged from 0 to 91 years, who had undergone routine skull radiography (anteroposterior and lateral views) and head CT to study these types of fracture and discuss the risk of nondetection. Three patients had linear fractures (0.99%) that were invisible on bone window axial CT but detected on skull radiography, which all ran parallel to the scan slice. Two patients developed acute epidural hematoma or traumatic subarachnoid hemorrhage. Evaluation of head injury by only axial CT may miss such fractures and result in sequelae, so diagnosticians should be alert to the possible presence of this type of fracture.

Epstein-Barr virus (EBV)-associated primary central nervous system lymphoma: is incidence of EBV expression associated with median survival time?

The frequency and clinical features of Epstein-Barr virus (EBV)-associated primary central nervous system lymphoma (PCNSL) in elderly patients were investigated in this study. Thirty-three PCNSL cases were enrolled in the retrospective study. Biopsies were performed, and tissue was embedded in paraffin and sectioned. In-situ hybridization of EBV-encoded small RNAs was then conducted. Specimens were scored as having one of three possible results: negative (no EBV-positive cells), slightly positive (<50% EBV-positive cells), and strongly positive (>50% EBV-positive cells). Fifteen cases were negative for EBV expression. Sixteen cases were slightly positive, and two cases (68 and 79 years of age) were strongly positive. The incidence of strongly positive EBV expression in PCNSL was 6.1%. The incidence of strongly positive EBV expression in PCNSL patients ≥65 years of age was 13%. Median survival time differed significantly among PCNSL patients treated with high-dose methotrexate and radiotherapy. Importantly, the strongly EBV-positive PCNSL cases had the worst outcomes, and the EBV-negative PCNSL cases had the best outcomes. These results suggest that EBV infection may affect the treatment outcome of PCNSL. In the future, examination of EBV expression in PCNSL patients who receive individualized treatment may be useful.

Subependymal giant cell astrocytoma with oncocytic change.

A 49-year-old woman presented with a history of periodic episodes of nausea and vomiting starting in 2006. In June 2009, the patient lost consciousness and was transported to our hospital. Head computed tomography (CT) revealed hydrocephalus caused by an enhancing mass lesion with calcification located in the right lateral ventricle around the foramen of Monro. Total tumor removal was performed. Histologic findings revealed fibrillated spindle tumor cells and giant tumor cells with abundant cytoplasm. The spindle tumor cells were immunoreactive for GFAP and S-100 protein, but none of the giant tumor cells were immunoreactive for GFAP or S-100 protein. Electron microscopic examination revealed abundant mitochondria in the tumor cell cytoplasm. According to these findings, this tumor was diagnosed as subependymal giant cell astrocytoma (SEGA) with oncocytic change, which is extremely rare.

Primary central nervous system lymphoma in acquired immune deficiency syndrome mimicking toxoplasmosis.

A 37-year-old man, a hepatitis B virus carrier due to mother-to-child transmission, had a medical examination in September 2008 in nearby hospitals due to anorexia and weight loss. He was transported to our hospital because computed tomography (CT) detected intracranial lesions, and he had a positive human immunodeficiency virus (HIV) antibody test. Head computed tomography (CT) revealed multiple hemorrhagic lesions and enhancement effect, suggesting a thin wall. Also, an enhancement effect was present in the ventricle walls and the subarachnoid space. No accumulation was found in the thallium-201 scintigraphy. The enhancement effect of the ventricle walls and the subarachnoid space disappeared after oral administration of pyrimethamine, sulfadiazine, and calcium folinate, contributing to the diagnosis of an abscess and meningitis due to toxoplasma. However, mass lesions did not reduce. A biopsy was performed on 30 October, and the pathological diagnosis was malignant lymphoma. He died from respiratory function deterioration on 8 November. Lymphoma cells were found in ventricle wall tissue and the subarachnoid space at the autopsy. Toxoplasmosis will typically occur as a brain lesion most commonly in acquired immune deficiency syndrome (AIDS), whereas malignant lymphoma commonly manifests as a brain neoplastic lesion. However, differentiating between images of these lesions is difficult, so diagnosis by early biopsy is recommended.

Linear fractures occult on skull radiographs: a pitfall at radiological screening for mild head injury.

BACKGROUND: Skull radiography is widely used to screen for fractures in patients with mild head injury. However, the clear depiction of a fracture requires a gap in the skull separated by the fracture that is wide enough to allow the passage of x-rays. We studied atypical linear fractures that were not visualized clearly, because a specific anatomical configuration hampered the passage of x-rays. METHODS: We retrospectively evaluated 278 patients with mild head injuries who had undergone routine skull radiography (anteroposterior and lateral views) and head computed tomography (CT). We found that some patients negative for linear fracture on skull radiographs were positive on bone window CT scans. RESULTS: Of the 278 patients aged between 2 months and 66 years, 8 (2.9%) manifested a linear fracture on CT scans that presented as a cross section of the fracture oblique to the direction of the x-rays. Four of the 8 developed acute epidural hematoma; 2 of these patients underwent craniotomy. CONCLUSIONS: Radiographic study returned false-negative results, because x-rays were absorbed by the double-layered skull along fractures whose cross section was oblique to the direction of the x-rays. The evaluation of head injury by radiography only may miss these fractures and their undetected presence may result in sequelae such as intracranial hematoma.

PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas.

Gene rearrangement in the form of an intragenic deletion is the primary mechanism of oncogenic mutation of the epidermal growth factor receptor (EGFR) gene in gliomas. However, the incidence of platelet-derived growth factor receptor-α (PDGFRA) gene rearrangement in these tumors is unknown. We investigated the PDGFRA locus in PDGFRA-amplified gliomas and identified two rearrangements, including the first case of a gene fusion between kinase insert domain receptor (KDR) (VEGFRII) and the PDGFRA gene, and six cases of PDGFRA(Δ8, 9), an intragenic deletion rearrangement. The PDGFRA(Δ8, 9) mutant was common, being present in 40% of the glioblastoma multiformes (GBMs) with PDGFRA amplification. Tumors with these two types of PDGFRA rearrangement displayed histologic features of oligodendroglioma, and the gene products of both rearrangements showed constitutively elevated tyrosine kinase activity and transforming potential that was reversed by PDGFR blockade. These results suggest the possibility that these PDGFRA mutants behave as oncogenes in this subset of gliomas, and that the prevalence of such rearrangements may have been considerably underestimated.

Preventive stitching for migration of a peritoneal catheter into the abdominal wall after ventriculoperitoneal shunting.

Migration of the distal end of a ventriculoperitoneal shunt into the abdominal wall (epi-peritoneal layer) is a complication which is especially likely in obese patients with high intra-abdominal pressure and wide dead space around the catheter remaining after laparotomy. A preventive abdominal stitching method for this complication was developed consisting of sutures beside the catheter penetrating the peritoneum, posterior and anterior sheath of rectus abdominis muscle, and subcutaneous fat. This method was applied to more than 20 patients who underwent ventriculoperitoneal shunting. No patient experienced shunt migration. The technique is easy and safe to perform, avoids leaving a dead space around the peritoneal catheter, and prevents catheter migration.

Primary central nervous system large B-cell lymphoma with prolific, mixed T-cell and macrophage infiltrates, mimicking multiple sclerosis.

Although tissue confirmation is essential for a diagnosis of primary central nervous system large B-cell lymphoma (PCNSBL), accurate assessment may still be difficult, even when tissue is obtained. We report a 59-year-old man, first diagnosed as multiple sclerosis by open biopsy at another institution, who was then correctly diagnosed as PCNSBL after stereotactic biopsy at our hospital. The initial biopsy showed heavy lymphoid and macrophage influx with visible demyelination. On rebiopsy, a diffuse infiltrate of small to medium-sized lymphocytes was prominent and largely stained as T cells (CD3) by immunohistochemistry. There was also an admixture of macrophages, but this time, relatively low numbers of large malignant cells were also identified. The latter stained as B cells (CD20), enabling a diagnosis of B-cell lymphoma, and the condition responded fully to high-dose methotrexate. It is thus possible for PCNSBL to be histologically misinterpreted as a result of ancillary inflammation, characterized here as a profusion of T cells and macrophages.

Prognostic significance of nuclear DJ-1 expression in astrocytoma.

The present study was conducted to determine whether any correlation exists between the expression of DJ-1 and WHO grading of the tumor or patient prognosis, and to analyze the function of this oncogene in astrocytomas. Twenty-nine formalin-fixed and paraffin-embedded glioblastomas (grade IV), 21 anaplastic astorocytomas (grade III), and 14 diffuse astrocytomas (grade II) were immunohistochemically studied to identify the expression of DJ-1 protein. The expression of DJ-1 was detected both in the nucleus and cytoplasm of tumor cells; however, such expression varied from case to case. While there was no difference in the cytoplasmic expression of DJ-1 among astrocytomas, its nuclear expression was inversely correlated with the WHO grading of astrocytomas. Moreover, the overall survival of patients with maintained (group 1) or mixed (groups 2 and 3) was significantly longer than those with decreased (group 3) expression (p=0.0063). The present study demonstrated that the survival of patients with astrocytomas was correlated with the nuclear DJ-1 status of the tumor. We herein demonstrated for the first time that the DJ-1 molecule might therefore play an important role as a tumor suppressor in astrocytomas.