Pleomorphic xanthoastrocytoma: a comparative pathological study between conventional and anaplastic types.

AIMS: To facilitate the understanding and correct diagnosis of the anaplastic variant of pleomorphic xanthoastrocytoma (PXA). METHODS AND RESULTS: Twelve cases of PXA were divided into six conventional and six anaplastic types. Three anaplastic PXAs developed in recurrent tumours and three occurred as the primary tumour. Anaplastic PXAs were microscopically characterized by monotonous proliferation of atypical cells, increased mitotic activity, necrosis and microvascular proliferation. Characteristic features of conventional PXA are also variously included in all anaplastic PXAs. No remarkable differences were detected in the immunohistochemical profiles including the neuronal phenotype between the conventional and anaplastic types. Ki67 labelling indices of the anaplastic type were significantly higher than those of the conventional type, whereas p53 showed no difference. Immunohistochemical and fluorescence in situ hybridization analyses on epidermal growth factor receptor did not demonstrate overexpression or gene amplification. CONCLUSIONS: The anaplastic PXA, which occurs de novo or through recurrence, should be distinguished from glioblastoma by identifying the salient microscopic features of conventional PXA even in the anaplastic areas; and by demonstrating the expression of neuronal markers, in that the former is expected to have longer survival.

Double pituitary adenomas: six surgical cases.

While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation.

Gliosarcoma: an immunohistochemical, ultrastructural and fluorescence in situ hybridization study.

Three cases of primary gliosarcoma (GS) were studied by immunohistochemical, ultrastructural and fluorescence in situ hybridization (FISH) methods. All tumors occurred in the supratentorial regions of the body. No patient had a prior history of irradiation to the brain. All patients died of tumor within 1 year, and autopsies were performed in two cases. Microscopically, each of the three tumors showed a mixture of glioblastoma (GBM) and a sarcomatous component (SC), which resembled fibrosarcoma with various histological features. Numerous collagen and reticulin fibers were seen in the SC of all tumors. Glial fibrillary acidic protein (GFAP) was immunoreactive only in the gliomatous component (GC). Factor VIII-related antigen was negative except for endothelial cells. One tumor exhibited alpha-smooth muscle actin positivity in the SC. Expression of MIB-1 and p53 protein was demonstrated in both components for all tumors. Labeling indices (LI) for MIB-1 ranged from 7.7 to 36.1%, and LI for p53 protein ranged from 2.9 to 57.0%. Ultrastructurally, astrocytic cells were characterized by a polygonal configuration with many cytoplasmic projections and occasional filaments. Spindle-shaped fibroblasts in the SC contained well-developed rough endoplasmic reticulum. Fluorescence in situ hybridization (FISH) performed on fresh materials or paraffin-embedded tissue demonstrated single signals for chromosome 10 in 40.6-58.3% of cells and for chromosome 17 in 37.9-48.6% of cells. Two tumors were regarded as containing losses of both chromosomes 10 and 17, while the third showed a substantial loss only of chromosome 10. As similar aberrations have been reported in GBM, these chromosomal abnormalities suggest a common pathogenesis in GS and GBM.

Gliomatosis cerebri with secondary glioblastoma formation: report of two cases.

The clinicopathological features of two cases of gliomatosis cerebri associated with secondary glioblastoma formation are reported. In both cases, glial cells were diffusely distributed in the supra- and infratentorial regions and underlying brain structures were preserved from the onset. In spite of such diffuse distribution of neoplastic glial cells, similar to that observed in low-grade astrocytoma, in both cases the tumor underwent complete remission after radiotherapy. However, the tumor recurred as a localized glioblastoma in both cases, 37 months (case 1) and 7 months (case 2) after the radiotherapy. In both cases, recurrence was accompanied by prominent dissemination of CSF. The recurrent tumors were radiation resistant, and the patients' conditions deteriorated rapidly after recurrence. The present two cases demonstrated that gliomatosis cerebri, classified among brain tumors of unknown origin by the World Health Organization, may transform into highly proliferative circumscribed tumors, in spite of their good response to radiotherapy. Examination of pathological features and their correlation with MRI findings may allow us to better understand the response to radiotherapy and the process of recurrence.

Gliomatosis cerebri with good prognosis.

A 52-year-old man was admitted to our clinic with severe headache and bilateral papilledema. Magnetic resonance (MR) images on admission demonstrated diffuse swelling of the cerebral cortex without formation of a tumor mass. Biopsy revealed diffuse infiltration with neoplastic glial cells. After radiation and chemotherapy, the MR images returned to normal. The morphological and neurological features of the present case met the criteria for gliomatosis cerebri. However, this patient showed an unusually good response to radiation and chemotherapy.

Immunohistochemical localization of lysosomal cathepsin D in schwannomas.

The immunohistochemical localization of cathepsin D (CD) was demonstrated for the first time in 54 schwannomas (32 intra- and 22 extracranial; 47 benign and 7 malignant) and 5 normal nerve fibers. Granular or vesicular CD-reactive structures were observed in all normal Schwann cells. All tumors contained CD-reactive tumor cells, although the population of CD-reactive tumor cells, the density, intracellular localization, and morphology of CD-reactive structures, and the intensity of CD immunoreactivity varied from case to case, portion to portion, and cell to cell, differing variously from those in normal Schwann cells. The variations were greater in malignant than in benign schwannomas. In mildly degenerate tumor cells, CD immunoreactivity was increased, possibly in response to the increased intracellular degenerate proteins, suggesting that the mechanism of induction of lysosomal proteases preserved in normal cells is not affected by the process of neoplastic transformation. In lesions of severe degeneration or necrosis, CD immunoreactivity was lost in most tumor cells but was strong in macrophages invading the lesions and perivascular regions. CD immunoreactivity was observed at various intensities in tumor cells in the Antoni type A area but not in most tumor cells in the Antoni type B area, suggesting that Antoni type B lesions show degenerative changes. The presence of CD-reactive tumor cells in all tumors examined and strong CD immunoreactivity observed at the invasion front of tumors in some cases of benign or malignant schwannoma suggests the possible role of CD in tumor invasion in some cases.

Double pituitary adenoma--two case reports.

A 43-year-old male and a 39-year-old male presented with multiple pituitary adenomas with two distinct histological types. The first patient who had multiple endocrine neoplasia type 1 had developed acromegaly due to a growth hormone-releasing hormone (GHRH)-producing pancreatic tumor. Both plasma GHRH and growth hormone (GH) levels decreased to normal after resection of the pancreatic tumor. However, the plasma GH level gradually increased again and magnetic resonance imaging revealed pituitary adenoma formation. Histological examination revealed two different histological types of pituitary adenoma: GH cell adenoma and null cell adenoma. The second patient, with no such genetic condition, had a non-functioning pituitary adenoma. Histological examination revealed two different histological types of silent GH cell adenoma and silent gonadotroph adenoma. Careful histological examination is required to exclude the possibility of multiple pituitary adenomas.

[A case report of dysembryoplastic neuroepithelial tumor associated with neurofibromatosis type 1].

Dysembryoplastic neuroepithelial tumor (DNT) in a newly proposed mixed neuroglial tumor in the cerebral cortex. However, DNT associated with phacomatosis has mostly been considered exceptional. In this paper, a case of DNT associated with neurofibromatosis type 1 is reported. A 23-year-old male was admitted to our hospital complaining of intractable complex-partial seizure. He had a history of neurofibromatosis type 1 (NF - 1) and pituitary dwarfism. On general physiological examination, many cafe au lait spots and freckling could be noted, showing that the case was neurofibromatosis type 1. In addition, neurological examination showed no abnormal findings. MR images revealed a small area of abnormal intensity on the right temporal. This region showed high intensity on T2 weighted image and low intensity without enhancement on T1 weighted image. On electroencephalography (EEG), an epileptic spike focus was demonstrated in the right temporal lobe. So, lobectomy was performed for control of epilepsy. Postoperative course was uneventful and without seizure. On histological examination, the tumor was composed of three different components : specific glioneural element, foci of oligodendrocyte-like cell, and cortical dysplasia. All of these findings were consistent with the definition of DNT by Daumas-Duport et al, except for the association with NF - 1. Although reported cases of DNT associated with FN - 1 are exceptionally rare, both DNT and NF - 1 originate from maldevelopment of the fetal central nervous system. It is very interesting that our case indicated the possibility of co-existence of both diseases.

[Hemangioblastoma and von Hippel-Lindau disease].

Intracranial hemangioblastoma (Lindau's disease) is vascular-rich benign neoplasm, arise from vascular endothelium. They account for about 2-3% of all intracranial tumors. Its most common location is adult posterior fossa. Except for the cerebellum, they were sometimes found in the brainstem or spinal region. Common macroscopical findings is mural nodule with cyst in the cerebellum. Contrary, solid form is common in spinal and brainstem region. The lesions are readily identified by image diagnostic procedures. Intracranial hemangioblastoma associated with retinal hemangioblastoma is called "von Hippel-Lindau's disease", hereditary disease of autosomal dominant form with chromosome abnormalities of 3p25-26. In other particular type of "von Hippel-Lindau's disease", intracranial hemangioblastomas are associated with renal cell carcinoma, pancreatic cyst or pheochromocytoma sometimes without retinal hemangioblastoma. Surgical extripation is the best choice of treatment for this disease. However, brainstem or spinal hemangioblastomas are sometimes difficult to remove totally.

Effects of trapidil and suramin on growth factor-induced calcium response and tyrosine phosphorylation in human glioma cells.

Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) induce the proliferation of glioma cells in vitro. Trapidil and suramin inhibit this growth factor-stimulated glioma cell growth, but the mechanisms are not fully understood. The effects of trapidil and suramin on PDGF- and EGF-induced early biochemical events in T98G cells were studied. PDGF induced a rapid increase of intracellular free calcium concentration ([Ca2+]i) in fura-2/acetoxymethyl ester-loaded single glioma (T98G) cells. This increase was completely inhibited by removal of extracellular Ca2+ with ethylene glycol bis(beta-aminoethyl ether)-N,N,N,N-tetraacetic acid but not by an L-type calcium channel blocker (nicardipine), suggesting that PDGF may cause calcium influx through voltage-independent calcium channels in T98G cells. Trapidil and suramin blocked the PDGF-induced calcium response and inhibited the PDGF-initiated tyrosine phosphorylation of the PDGF receptor as detected by Western blot analysis using an antibody specific for phosphotyrosine. Trapidil and suramin also inhibited EGF-initiated calcium response in T98G cells, but only partially inhibited EGF-initiated tyrosine phosphorylation at the same concentrations. Our results suggest that trapidil and suramin inhibit PDGF- and EGF-initiated early biochemical events, and thus suppress growth factor-induced cell proliferation.

[Two cases with metastatic intracerebral alveolar soft part sarcoma].

The alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor which usually occurs in the lower extremity of young girls. The incidence of metastasis is said to be highest in the lung (38%), and second highest in the bone and brain (33%). This report describes two cases of metastatic intracerebral alveolar soft part sarcoma, originating in the lower extremity. A female patient noticed a painless swelling in her right leg at the age of 11, and 10 years later she underwent total removal of the tumor. The diagnosis was alveolar soft part sarcoma. At 37 she was admitted to our service with a diagnosis of cerebral metastasis in the left frontal lobe. Since then she has undergone surgical removal 4 times for recurrent cerebral metastasis and twice for lung metastasis. Now she is 55 years old and doing well except for mild left hemiparesis. She survives without cerebral or general metastasis 44 years following the onset of the sarcoma in her right leg and 18 years following the onset of the metastatic brain tumor. A 30-year-old man, who noticed a painless swelling in his left thigh in January 1991, underwent total removal of the tumor and the diagnosis was alveolar soft part sarcoma. He was admitted to our service with no neurological deficits in October 1992, but a CT scan showed a metastatic brain tumor in the left parieto-occipital region. Total removal of this metastatic brain tumor was successfully performed in November 1992. However, he died because of multiple brain and lung metastasis in February, 1994.(ABSTRACT TRUNCATED AT 250 WORDS)

Two different pituitary adenomas in a patient with multiple endocrine neoplasia type 1 associated with growth hormone-releasing hormone-producing pancreatic tumor: clinical and genetic features.

The clinical and genetic features of a 43-year-old male patient with multiple endocrine neoplasia type 1 were reported. He developed hyperparathyroidism, a GHRH-producing pancreatic tumor, and acromegaly between 1980 and 1983. Because his pituitary gland increased in size even after resecting the GHRH-producing pancreatic tumor, transsphenoidal hypophysectomy was performed six years later. The pituitary contained two histologically-different adenomas composed of somatotroph cells and null cells. Genetic analyses revealed loss of heterozygosity on chromosome 11 in common in the pituitary adenomas, the pancreatic endocrine tumors, and a parathyroid hyperplasia. On the other hand, mutations of ras, p53, Gs alpha, and Gi2 alpha genes were not found in these tumors. The loss of the tumor suppressor gene on chromosome 11q12-13 was involved in the formation of two pituitary adenomas, two pancreatic endocrine functioning tumors, and a parathyroid hyperplasia in this patient, but the tumorigenic factors in the specific endocrine organs remain to be studied.

[Intensive and high-dose chemotherapy with peripheral blood stem cell transfusion for pediatric malignant brain tumor].

In this study, the newly developed marrow-rescue therapy during myelosuppression is utilized. In this therapy, peripheral blood stem cell transfusion (PBSCT) is administered following high-dose chemotherapy. Harvest of peripheral blood stem cells (PBSC) during myelosuppression following marrow-ablative chemotherapy is a safe, reliable procedure in children with leukemia. And administration of these cryopreserved PBSC is useful in reducing myelosuppression following intensive/ultra high-dose chemotherapy. In this study, several courses of intensive chemotherapy (1 course: VP-16 300mg/m2 x 5 days + carboplatin 400-500mg/m2 x 3 days) and one course of ultra-high dose chemotherapy (1 course: VP-16 400mg/m2 x 8 days + carboplatin 800mg/m2 x 5 days + MCNU 250, 200mg/m2 x each day) with PBSC transfusion were applied in four cases of pediatric malignant brain tumors (2 cases of medulloblastoma, one case of pineoblastoma and anaplastic ependymoma) after surgical reduction. With PBSC transfusion, myelosuppression following high-dose chemotherapy could be overcome without serious complication in all cases. Three cases showed complete remission and one showed partial remission after the operation and intensive chemotherapy. However, CSF dissemination appeared in two cases and they died 20 and 28 months after the onset respectively. Intensive/ultra high-dose chemotherapy with PBSC transfusion is a safe procedure in children with malignant brain tumors. This procedure may enable the postponement of radiation for pediatric malignant brain tumor cases under three years of age.

Non-invasive characterization of brain tumor by in-vivo proton magnetic resonance spectroscopy.

We studied the feasibility of characterizing brain tumor tissue by localized proton magnetic resonance spectroscopy (1H-MRS). Twenty-six newly diagnosed tumors were examined by in-vivo 1H-MRS. The NAA (N-acetylaspartate)/Cho (choline) ratio of Grade 2 astrocytoma was higher than that of Grade 4. The Cho/Cr (creatine and phosphocreatine) ratio of meningioma was considerably higher than that of glioma of all grades. We have experienced only two cases of ependymoma and the Cho/Cr ratios of both were lower than that of glioma. It seems likely that 1H-MRS can be used to differentiate Grade 2 from Grade 4 in most cases of astrocytoma based on the NAA/Cho ratio, though a few cases will overlap. Meningioma can be distinguished easily from glioma, and the results of our study suggest that ependymoma shows a characteristic pattern on 1H-MRS, different from those of other brain tumors.

Neuropathological changes following occlusion of the superior sagittal sinus and cerebral veins in the cat.

Superior sagittal sinuses (SSS) of 36 mongrel cats were occluded by polymer injection. Immediately prior to the occlusion, Evans-blue (EB) was administered intravenously. The cats were killed 1,3,6,12,24,72 and 120 h after sinus occlusion. Two sham-operated cats were killed 6 h and two 120 h after the operation. In 16 cats in which the occlusion was limited to the SSS, as well as in the sham-operated cats, no EB extravasation was present. However, ultrastructurally in two animals, the extracellular spaces were moderately enlarged, corresponding to increased permeability for water without opening of the BBB for proteins. In 20 cats in which cortical veins were occluded, in addition to the SSS, EB was extravasated. In nine of these cats, which had moderate oedema, EB-staining was present only in the cortex. In 11 cats with severe oedema, massive EB was extravasated. In nine of these cats, which had moderate oedema, EB-staining was present only in the cortex. In 11 cats with severe oedema, massive EB extravasation was observed also in the white matter. The U-fibre layer was free of EB, suggesting that the extension of oedema was blocked by this zone. Cats with severe oedema showed extensive haemorrhagic cerebral infarction widely, but not completely, overlapping with ischaemic necrosis, and corresponding to the differences in the territories of arterial supply and of venous drainage. Seven animals displayed haematomas in the parasagittal white matter. Electron microscopy (EM) showed damage to the endothelium of capillaries and venules with extravasation of platelets. In cats which survived longer than 24 h, the extracellular spaces were filled with proteinaceous transudate.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain abscess observed by localized proton magnetic resonance spectroscopy.

We encountered a case of brain abscess that was difficult to differentiate from glioblastoma. Localized 1H-MRS was found to be useful for obtaining information on the biochemical status of brain abscess. The peak of lipid and high residual peak of NAA (N-acetyl-aspartate) were observed in the cystic lesion of the brain abscess by 1H-MRS. The NAA/Cho (Choline-containing compounds) ratio in brain parenchyma showing an edematous lesion before therapy gradually increased with the relief of inflammation.

Subcortical U-fibers layer preservation in brain edema.

The mechanism involved in the relative preservation of the subcortical U-fibers in the arcuate zone was studied in a post infarct edema after sagittal superior sinus occlusion. Superior sagittal sinus (SSS) of 36 mongrel cats were occluded by polymer injection. Immediately before the occlusion Evans-blue (EB) was administered intravenously. The cats were killed 1, 2, 3, 6, 12, 24, 72 and 120 hours after sinus occlusion. In 20 cats in which cortical veins were occluded, in addition to the SSS, EB was extravasated. In 9 of these cats, which had moderate edema, EB-staining was present only in the cortex. In 11 cats with severe edema, massive EB extravasation was observed also in the white matter. The U-fiber layer was free of EB, suggesting that the extension of edema was blocked by this zone. Our findings demonstrated that the U-fibers act not only as a resistance against extension of edema from white to gray matter, but also in a reverse direction. The characteristics of the spread of brain edema is not yet completely understood; both anatomical and biochemical peculiarities from its basis. Different morphological patterns in the astrocytic reaction as well as the U-fibers sector vascularization are important. To evaluate the role of each one of these factors in the preservation of subcortical U-fiber layer in brain edema further investigations should be done.

[Clinicopathological study on choroid plexus tumors: immunohistochemical features and argyrophilic nucleolar organizer regions values].

Immunohistochemical features and numbers of argyrophilic nucleolar organizer regions (Ag-NORs) were investigated on 6 cases with choroid plexus tumors: 3 adult and one pediatric cases with choroid plexus papilloma (CPP) and 2 pediatric cases with choroid plexus carcinoma (CPC) clinicopathologically. One of the 2 children with CPC developed a recurrence with dissemination to the CSF and died 2 years postoperatively (case 6), while the other survived following surgery (case 5). This outcome suggested the existence of biological differences in these tumors. We conducted an immunohistochemical examination of prealbumin, S-100 protein, glial fibrillary acidic protein (GFAP), cytokeratin (CKER), and epithelial membrane antigen (EMA) using avidin-biotin complex (ABC) methods and the silver colloid staining technique for Ag-NORs. All 4 CPP were positive for prealbumin and S-100 protein, with 3 of them being strongly positive; 3 of 4 were positive for GFAP and 2 were positive for CKER and EMA. Two cases of CPC were weakly positive for prealbumin. However the part of reserved papillary structure of case 5 was strongly positive for it. The tumor of the survived child was positive for S-100, GFAP, CKER, while negative for EMA. A positivity for S-100 protein and prealbumin was associated with a good outcome, whereas that for GFAP, CKER, and EMA was not. The mean number of Ag-NORs in the 2 cases with CPC exceeded that in cases with CPP. Of the 2 cases with CPC, fetal one (case 6) showed a higher number of Ag-NORs than the survived patient.(ABSTRACT TRUNCATED AT 250 WORDS)

[MRI findings and endocrinological dysfunction in hemorrhagic pituitary adenoma].

Magnetic resonance image (MRI) findings, intraoperative macroscopic findings and endocrinological functions were reported in 13 cases of hemorrhagic pituitary adenoma (HPA) according to clinical severity. The cases were divided into 3 groups: (1) classical pituitary apoplexy (PA) (n = 2), (2) subacute PA (n = 4), (3) asymptomatic HPA (n = 7). Based on MRI intensity and intraoperative findings, there were 7 cases with hemorrhagic PA and 5 with necrotic cyst formation. MRI intensities predicted the cyst contents, either hemorrhagic or xanthochromic, more accurately than CT findings. In addition, two classical cases of the PA group disclosed niveau formation on MRI, but MRI intensity in the first case differed from that in the second case. Classical PA of the first case occurred during the pregnancy. MRI intensity in the case 7 months after the onset disclosed high intensity of the upper part and normointensity of the lower part. T1 weighted image and proton image showed homogeneous intensity. On the contrast, PA of the second case showed water-like intensity on the upper part and methemoglobin-like intensity on the lower part. These different MRI intensities suggest different etiologies of niveau formation. MRI findings in the first case may indicate the chronic stage of massive intratumoral hemorrhage but the mechanism may be the same in both cases. From MRI intensity and clinical course, the cause of niveau formation in the second case is similar to that found in the literature. That is, hemorrhage was thought to have occurred in the pre-existing cyst cavity.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaplastic ganglioglioma of the brain stem demonstrating active neurosecretory features of neoplastic neuronal cells.

An autopsy case of anaplastic ganglioglioma in the brain stem of a 12-year-old girl is reported. The ill-defined tumor involved the right cerebellar peduncle, medulla oblongata and upper cervical spinal cord, and showed mixed proliferation of many ganglioid cells and atypical pilocytic astrocytes with necrotic areas. Immunohistochemical studies revealed the presence of chromogranin A in most ganglioid cells and of metenkephalin in some large ganglioid cells. Glial cells were positive for glial fibrillary acidic protein and vimentin. Ultrastructurally, numerous dense-core granules of 90-220 nm in diameter were demonstrated in ganglioid cells and abundant glial filaments in glial cells. High neurosecretory activity in neuronal cells, suggested by chromogranin-immunoreactivity and dense-core granules, seems to be the most characteristic property of ganglion cell tumors.