Familial idiopathic basal ganglia calcification: Histopathologic features of an autopsied patient with an SLC20A2 mutation.

Idiopathic basal ganglia calcification (IBGC), or Fahr's disease, is a neurological disorder characterized by widespread calcification in the brain. Recently, several causative genes have been identified, but the histopathologic features of the brain lesions and expression of the gene products remain unclear. Here, we report the clinical and autopsy features of a 62-year-old Japanese man with familial IBGC, in whom an SLC20A2 mutation was identified. The patient developed mild cognitive impairment and parkinsonism. A brain CT scan demonstrated abnormal calcification in the bilateral basal ganglia, thalami and cerebellum. An MRI study at this point revealed glioblastoma, and the patient died 6 months later. At autopsy, symmetric calcification in the basal ganglia, thalami, cerebellar white matter and deeper layers of the cerebral cortex was evident. The calcification was observed in the tunica media of small arteries, arterioles and capillaries, but not in veins. Immunohistochemistry using an antibody against type III sodium-dependent phosphate transporter 2 (PiT-2), the SLC20A2 product, demonstrated that astrocytic processes were labeled in several regions in control brains, whereas in the patient, reactivity in astrocytes was apparently weak. Immunoblotting demonstrated a marked decrease of PiT-2 in the patient. There are few autopsy reports of IBGC patients with confirmation of the genetic background. The autopsy features seem informative for better understanding the histogenesis of IBGC lesions.

M2 macrophage/microglial cells induce activation of Stat3 in primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is one of the most aggressive malignant lymphomas with a median survival of less than 20~40 months. Interest in signal transducer and activator of transcription 3 (Stat3) has increased during the past decade because Stat3 activation was found to contribute to tumor progression by inducing angiogenesis, immunosuppression, and metastasis. We previously demonstrated a significant correlation between Stat3 activation in tumor cells and infiltrating anti-inflammatory (M2) macrophages. Here, we focused on the phenotypes of infiltrating macrophages/microglial cells and Stat3 activation in PCNSL cells. The correlation of Stat3 activation or density of M2 macrophage infiltration with patient prognosis was also evaluated. We performed immunostaining for CD68, CD163, CD204, and pStat3 using paraffin-embedded PCNSL specimens obtained from 43 patients. CD163 and CD204 served as markers of the M2 phenotype. Dense infiltration of CD68(+) macrophages was found in all samples. High numbers of CD163(+) and CD204(+) M2 macrophages/microglial cells were observed in 29 and 25 cases, respectively. Stat3 activation in lymphoma cells was enhanced in the patients who showed denser infiltration of CD163(+) macrophages/microglial cells in tumor tissues. In vitro co-culture experiment to investigate cell-cell interactions between macrophages and lymphoma cells found that Stat3 in lymphoma cells was strongly activated by co-culture with macrophages. Numbers of CD68(+), CD163(+), and CD204(+) tumor-associated macrophages/microglial cells (TAMs) and Stat3 activation in lymphoma cells were not correlated with prognosis. However, because Stat3 involvement in tumor development was demonstrated in several malignant tumors, our present finding that cell-cell interactions of M2 macrophage/microglial cells with lymphoma cells induced Stat3 activation may provide novel insights into PCNSL pathogenesis.

Chordoid glioma of the third ventricle: a report of two cases, one with ultrastructural findings.

Chordoid glioma, which generally occurs in adults, is a rare CNS tumor arising in the anterior part of the third ventricle. We report two cases of chordoid glioma of the third ventricle in a 42-year-old woman and a 51-year-old man, respectively. Both tumors showed essentially the same histological and immunohistochemical features; the tumors were composed of cords and nests of epithelioid, GFAP-immunoreactive cells in a mucinous stroma with lymphoplasmacytic infiltrates at the tumor periphery. Ultrastructural examination in one case revealed that the tumor cells were characterized by the presence of hemidesmosomes and associated focal basal lamina formation, intermediate junctions, microvilli and cilia, and intercellular microrosettes with microvilli. Of interest was that small blood vessels with fenestrated endothelial cells were present in the stroma. In the brain, the presence of fenestrated endothelial cells is a feature of the circumventricular organs (except the subcommissural organ), among which the organum vasculosum of the lamina terminalis is located in the anterior part of the third ventricular floor that is lined by specialized ependymal cells known as tanycytes. These findings further strengthen the hypothesis that chordoid glioma may represent a peculiar clinicopathological subtype of ependymoma (chordoid ependymoma) originating from the lamina terminalis area.

Severe tension pneumocephalus caused by opening of the frontal sinus by head injury 7 years after initial craniotomy--case report.

A 46-year-old man presented with severe tension pneumocephalus triggered by mild head injury 7 years after craniotomy. He had a history of subarachnoid hemorrhage due to ruptured anterior communicating artery aneurysm, coating of the aneurysm performed via a craniotomy, and a ventriculoperitoneal (VP) shunt inserted. He fell from bed in a rehabilitation hospital. Eight hours after the injury, he became comatose and suffered general convulsion. He was then transferred to our hospital. Radiography and computed tomography (CT) revealed a large amount of intracranial air and a widely opened frontal sinus. On the day of admission, the shunt tube was ligated. Surgery was performed to repair the dura mater and close the frontal sinus. Postoperative CT revealed reduction in the amount of air and frontal sinus obstruction. The patient had a good postoperative course without meningitis. Tension pneumocephalus may occur as a complication several years after a craniotomy because of the chronic lowering of intracranial pressure induced by a VP shunt. Complete frontal sinus repair is important during the initial craniotomy.

[A case of orbital osteoma--summary of the case reports in Japan, and the usefulness of the microsurgical drilling procedure in surgical treatment of orbital osteoma].

A 57-year-old woman was admitted with a 3-month history of diplopia and exophthalmos in the right eye. Plain skull X-P and axial CT demonstrated two bony tumors. One involved her right orbit, frontal sinus and ethmoidal sinus, and the other was located in the left occipital bone. The right intraorbital tumor was removed almost totally via the superomedial orbital approach by means of microsurgical drilling. Histopathological examination revealed mature osteoma. The microsurgical drilling procedure was helpful in obtaining an optimal result from surgical treatment of the orbital osteoma.