Epileptogenic glioma in a 4-year-old child: a case report

We report a rare case of epileptogenic glioma composed of glial progenitor cells that differentiated into an astrocytic and oligodendrocytic tumor. This 4-year-old girl presented with a 1-year history of complex partial seizure. MR scan showed a mass in the left temporal lobe with a cyst and a contrast-enhanced component. Subtotal resection of the tumor was achieved. Histological examination revealed that the tumor exhibited low cellularity composed of astrocytic and oligodendrocytic components, as well as low mitotic activity (MIB-1 = 1%). Immunohistochemical examination revealed GFAP positivity within the astrocytic cells, olig2 positivity within the oligodendrocytic cells, and S100 positivity in both cell types. MAP2 and CD34 were negative, and neurofilament was only positive in preexisting neurons. The pathological diagnosis was epileptogenic glioma (grade I) composed of glial progenitor cells. The postoperative course has been uneventful with good seizure control for 3 years.     

Analyses of proliferative potential in schwannomas

We report studies of schwannomas with a high percentage of MIB-1 positive cells. Thirty-eight specimens from 36 cases of schwannoma in the intracranial and spinal regions comprise the substance of this study. The MIB-1 positive cells were measured using immunohistochemical staining. In nine cases with a positivity index (PI) of 5% or more, immunohistochemical staining using DNA topoisomerase IIα (topo-II) and CD68 was performed. In some cases, we also searched for apoptosis with the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. Three of nine cases with 5% or more positive MIB-1 cells had a very high cellularity with mitotic figures and were considered cellular Schwannomas. Their MIB-1 PI values were 8.21%, 10.00%, and 21.37%. However, the remaining six cases showed little evidence of malignancy. Their PIs were comparatively low, ranging from 5.19% to 8.41%, and the positive findings were localized in many cases. In these cases, we examined the sites where MIB-1 was measured and found that they corresponded to the borderline site between Antoni type A and B patterns and tended to be associated with an infiltration of CD68-positive macrophage. Furthermore, apoptotic cells appeared in the sites. With topo-II staining, the PIs in the same sites of these six cases were low, ranging from 0.78% to 1.93%. This implies that the high MIB-1 PI that was seen in these six cases was caused by reaction of MIB-1 to tumor cells that brought about an abnormality in the cell cycle by degeneration, such as apoptosis. In the site of formation of Antoni type B, MIB-1 may be a false positive in tumors with degenerative findings such as schwannomas. Topo-II was useful in these cases.     

Pineal parenchymal tumor of intermediate differentiation with marked elevation of MIB-1 labeling index

We report a case of pineal parenchymal tumor (PPT) in an 11-year-old girl. Brain magnetic resonance imaging (MRI) revealed a large tumor (48?mm) located in the pineal region with heterogeneous enhancement after gadolinium administration. The patient underwent tumor removal with craniotomy; only partial tumor resection could be performed because of massive intratumoral bleeding. Histopathological examination of the tumor showed lobular proliferation of round cells with moderate atypia. Cellularity varied by area, and focal Homer Wright rosettes were identified. Examination of tumor cells revealed a few mitoses (two mitotic figures per 10 high-powered fields), and immunohistochemical staining revealed positivity for synaptophysin, slight positivity for neurofilament protein (NFP) with antibody clone 2F11, and strong positivity for NFP with clone NF-M+H. The pathological diagnosis was pineal parenchymal tumor of intermediate differentiation grade II according to World Health Organization criteria despite a high (22%) MIB-1 labeling index (LI). The patient had a favorable clinical course after an intensified chemotherapy regimen designed for pineoblastoma and radiotherapy administered to the entire neuraxis, followed by stereotactic radiotherapy. In conclusion, MIB-1 LI could be a useful tool for deciding therapeutic strategies for PPT treatment when there is a discrepancy between clinical findings and pathological grading.     

Partial resection of the second portion of the duodenum for gastrointestinal stromal tumor after effective transarterial embolization

We report herein the case of 64-year-old man with gastrointestinal stromal tumor (GIST), who was treated by partial resection of the duodenum after preoperative transarterial embolization. He presented to our hospital with a history of tarry stools, dizziness, and severe anemia (hemoglobin, 7.5 g/dl). Gastroduodenal endoscopy revealed the presence of a submucosal tumor in the second portion of the duodenum. The presence of the tumor was subsequently confirmed by double-contrast gastrointestinal radiography and abdominal computed tomography. Super-selective angiography showed tumor staining fed from the anterior and posterior superior pancreaticoduodenal arteries, and the inferior pancreaticoduodenal artery. Two weeks after transarterial embolization through these vessels, the tumor size was found to have shrunk to 40% of its original size. Partial resection of the duodenum was performed and absence of tumor cells at the surgical margin was confirmed by intraoperative frozen-section examination. Histopathological examination revealed that the duodenal submucosal tumor consisted of spindle cells, and immunohistochemical analysis revealed positive tumor staining for c-kit protein, CD34 and α-smooth muscle actin (SMA), and negative staining for desmin and S-100; the positivity rate for MIB-1 staining was 2.2%. Based on these findings, the tumor was diagnosed as a GIST of low-grade malignancy, classified as the muscular type. It is considered that preoperative treatment of duodenal GISTs, such as transarterial embolization, may be useful for reducing the extent of resection, from pancreaticoduodenenctomy to a partial resection.     

Increased hyaluronan content and stromal cell CD44 associate with HER2 positivity and poor prognosis in human breast cancer

Previous in vitro studies have suggested interactions between hyaluronan (HA), CD44 and HER2. We have studied the expression of HA and CD44 in a material of 278 breast cancer cases, half of which were HER2‐positive. Intense stromal HA staining was associated with HER2 positivity, large tumor size, lymph node positivity, hormone receptor negativity, poor differentiation, a high body mass index, increased relapse rate and shortened overall survival. Among the 139 HER2‐positive cases, the relapse rate was associated with the intensity of stromal HA staining as most of the relapses occurred in the cases with intense stromal HA staining. The presence of HA in the carcinoma cells was related to the frequency of relapses as none of the patients without HA in carcinoma cells experienced a relapse, whereas 33.3% of those with a high percentage of HA‐positive carcinoma cells suffered a relapse. CD44 positivity in carcinoma cells was related to poor differentiation, postmenopausal status and triple negative breast carcinoma. CD44 positivity in stromal cells was associated with HER2 positivity, large tumor size, hormone receptor negativity, poor differentiation, increased relapse rate and shortened overall survival. The association between HER2 positivity and intense stromal HA staining indicates that HA could be one of the factors involved in the unfavorable outcome of HER2‐positive patients. This study also suggests that HA in breast carcinoma cells and CD44 in stromal cells may have clinical significance.     

A rare case of malignant glioma suspected to have arisen from a cavernous sinus

A 55-year-old woman presented with a right trigeminal dysfunction (dysesthesia) initially, followed by right oculomotor and abducens paresis lasting 1 month. Neuroimaging studies showed an enhanced mass in the right cavernous sinus extending to the trigeminal ganglion. The extraparenchymal tumor located around the right trigeminal ganglion was totally removed, except for an intracavernous lesion, by the orbitozygomatic approach. The solid tumor was completely separated from the brainstem and seemed to be a trigeminal schwannoma arising from the trigeminal ganglion or cavernous sinus at surgery. A histological examination, however, found a typical malignant glioma that consisted primarily of astrocytic tumor cells. Immunohistochemical staining showed the tumor cells stained intensely for GFAP, S-100 protein, and vimentin, but not for NFP, Schwann/2E, CD34, and CD68. The mean MIB-1 index was 12.4%. The tumor recurred after a short time, and then it rapidly disseminated into the subarachnoid space and left the cerebral hemisphere. The patient died 1 year after the initial symptoms in spite of aggressive surgery, radiation, and chemotherapy with temozolomide. There are no previous reports of a malignant glioma arising from either the cavernous sinus or the trigeminal ganglion. From the pathogenetic point of view, this malignant glioma is an extremely rare case that developed clinically and neuroradiologically from the cavernous sinus and was suspected be being derived from ectopic glial tissue.     

A case of a heavily pigmented orbital melanocytoma

We present an extremely rare case of an orbital melanocytoma that occurred in a 51-year-old man. The patient suffered from diplopia and mild exophthalmos of the right eye for 2 months. Brain magnetic resonance imaging showed a well-demarcated round mass 3.5 cm in diameter in the right orbit. We performed total resection of this tumor. Histological findings revealed a proliferation of large polygonal cells with fine pigment granules in the cytoplasm and prominent nucleoli. Although these tumor cells revealed immunohistochemical reactivity in HMB-1, there was no S-100 or Melan A antibody reactivity. Also, there were no malignant findings of nuclear polymorphism, mitoses, or necrosis. The brown pigments were confirmed to be melanin by bleaching and the Fontana-Masson silver stain method. The MIB-1 labeling index was less than 1%. This tumor also consisted of 50% melanophages, which revealed immunohistochemical reactivity in CD68, CD163, and in (1-AT antibodies. These histological findings led us to diagnose an orbital melanocytoma with partial tumor regression.     

Anomalous p27kip1 expression in a subset of malignant gliomas

p27^Kip1 (p27) expression was immunohistochemically investigated in 28 astrocytic tumors, and compared with the cell proliferation index (MIB-1 staining index). Normal rat brains and surgical specimens from human nonneoplastic brain lesions were used as controls. In the rat brains, the astrocytes were exclusively p27-positive. The reactive astrocytes in various disease processes sometimes lacked p27 expression. The distribution of p27-positive cells was uniform in low-grade astrocytomas and heterogeneous in high-grade tumors. Double staining of p27 and MIB-1 showed a reciprocal pattern in most cases. The frequency of p27 expression was inversely correlated with MIB-1 staining index and tumor grade. However, several malignant gliomas showed high p27 expression in spite of high MIB-1 staining indices. In such cases, MIB-1-positive cells were occasionally p27-positive. In this paper we discuss the etiology of the anomalous p27 expression in a subset of malignant gliomas.     

Prognostic factors for node-negative breast cancers: Results of a study program by the Japanese breast cancer society

Background  Prognostic factors for predicting the recurrence of node-negative breast cancers have been controversial. The present study was performed to elucidate practically useful prognostic factors using formalin-fixed paraffin sections. Methods  This was a case-controlled multi-institutional study that composed 40 patients with recurrent node-negative breast cancer and 80 patients with node-negative breast cancer but without recurrence after radical surgery. Tumors were smaller than 3 cm in diameter and were treated surgically between January 1, 1985 and December 31, 1990. The recurrent and non-recurrent cases were matched with regard to their age, adjuvant chemotherapy and the year in which surgery was performed. Fourteen immunohistochemical factors and 8 histological factors of the primary tumor were studied on formalin-fixed, paraffin-embedded sections by immunohistochemical and histochemical analyses. Results  According to univariate analysis, factors such as progesterone receptor (PgR), MIB-1, CD44_v6, CD44_v9 and platelet-derived endothelial cell growth factor (PDECGF) were significantly different between the recurrent and non-recurrent groups (p>0.1; Wilcoxon-Mann-Whitney analysis). Chisquared test showed significant differences in MIB-1, cdc2 and stromal plasminogen activator receptor (suPAR). Histologically, mitotic count was also significantly different between the two groups (p>0.005). Multivariate analysis revealed that positivity for cdc2 (p=0.01), high mitotic count (p=0.04) and negativity for CD44_v9 (p=0.02) were independent prognostic factors among variables selected by univariate analysis, and that positivity for MIB-1 (p=0.03) and cdc2 (p=0.01), and negativity for CD44_v9 (p=0.03) were independent prognostic factors among the immunohistochemical markers examined. Conclusion  Our results indicated that positivity for MIB-1 and cdc2, high mitotic count and negativity for CD44_v9 could serve as independent factors for predicting the recurrence of node-negative breast cancer.     

No evidence of significant activity of the multidrug resistance gene product in primary human breast cancer

Background: The discovery of the multidrug resistance (MDR1) gene product P-glycoprotein (P-gp) has been widely seen as an important milestone in our understanding of the mechanisms underlying the clinical phenomenon of the emergence of resistant cells. MDR1 expression has been shown for numerous solid tumors and for virtually all hematologic malignancies. Nevertheless, results regarding MDR1/P-gp expression in human breast cancer have been controversial and the results of clinical trials on modulation of P-gp activity have not been encouraging.Patients and methods: MDR1/P-gp expression and the function of the P-gp pump were investigated in 61 tumor samples from patients with primary breast cancers by multiparameter analysis using MDR1-RT-PCR, immunohistochemistry with two MAbs (UIC2 and MRK 16) and the rhodamine 123 (Rh123) efflux assay. The cellular composition of the tumor cell suspension was analyzed by using specific MAbs against the P-gp expressing lymphocyte subsets CD4, CD8 and CD56, as well as against the HER-2/neu gene product, which was used to identify breast carcinoma cells.Results: UIC2 and MRK16 revealed a staining positivity in 72% and 75% of samples, respectively. A positive MDR1-RT-PCR signal was detected in 62% of the samples. Nevertheless, no correlation between immunohistochemistry and RT-PCR could be established. Furthermore, there was no correlation between HER-2/neu expression and MDR1-RT-PCR or P-gp immunohistochemical assays. A contamination by CD8+ and CD4+ lymphocytes was established in 100% and 84% of tumor cell suspensions, respectively. As assessed by the Rh123 efflux assay CD8+ and the CD4+ lymphocytes exhibited marked P-glycoprotein activity, whereas such activity was not detectable in a single instance for the breast carcinoma cells. In MDR1-RT-PCR positive samples, contamination by CD8 lymphocytes averaged 4.3%, while the contamination of CD8 cells in the MDR1 mRNA-negative samples was only 2.4% (P = 0.007). This signal vanished after elimination of the lymphocyte subpopulations by T-cell rosetting.Conclusions: In primary breast cancer detection of MDR1 gene expression by means of RT-PCR or immunohistochemical assays is not indicative for the MDR phenotype, since there is no evidence of significant activity of the P-gp pump.     

An immunohistochemical and electron microscopic study of atypical teratoid/rhabdoid tumor

We report two infant cases with atypical teratoid/rhabdoid tumor (AT/RT) located in the cerebellar vermis and spinal cord. MRI showed the tumors were isointense on T₁-weighted images and mixed intensity of isointense and slight high intensity on T₂-weighted images. Postcontrast MRI demonstrated clear margin of tumor and heterogeneous strong enhancement. It was difficult to differentiate the tumor from medulloblastoma by hematoxylin and eosin staining. However, immunohistochemical staining showed that these tumor cells react positively for cytokeratin, smooth muscle actin (SMA), and epithelial membrane antigen (EMA) and helped us with the differentiation. Electron microscopic study has confirmed the presence of mesenchymal components, such as filaments and desmosome junctions in the rhabdoid cells, but no neuronal components. The tumors rapidly increased in size, showing high MIB-1 index, and the prognosis was gave.     

Intratumoral CD8+ T lymphocytes as a prognostic factor of survival in endometrial carcinoma.

PURPOSE: CTLs are a prominent immune component infiltrating many solid tumors. These cells are considered to be a manifestation of host-immune response to the tumor; however, their prognostic significance remains a subject of considerable debate. The objective of this study was to evaluate the distribution pattern and prognostic value of CD8(+) T cells in endometrial carcinoma. EXPERIMENTAL DESIGN: We studied 90 cases of endometrial carcinoma, including 75 endometrioid and 15 papillary serous carcinomas. Immunohistochemical staining for CD8 and granzyme B was performed on paraffin-embedded sections. The number of immunohistochemically staining CD8(+) T cells was enumerated in the following four regions: lymphocytes infiltrating the tumor epithelium at the invasive border, within the underlying tumor stroma, within the superficial tumor epithelium, and in the perivascular areas of the myometrium. RESULTS: Patients with >10 CD8(+) T lymphocytes/high-power field within the tumor epithelium at the invasive border displayed improved overall survival compared with patients with fewer intraepithelial CD8(+) T lymphocytes (87 and 50%, respectively; P = 0.027). Multivariate analysis revealed that stage, vascular invasion, grade, and the number of intraepithelial CD8(+) T lymphocytes at the invasive border were the only independent predictors of survival (P < 0.0001, P = 0.001, P = 0.011, and P = 0.025, respectively). Granzyme B(+) cytoplasmatic granules were detected in a high proportion of CTLs, confirming their activated cytotoxic phenotype. CONCLUSIONS: Our study demonstrates for the first time that increased numbers of CTLs at the invasive border may be a reliable independent prognostic factor of survival in patients with endometrial carcinoma.     

A case of anaplastic clear-cell ependymoma presenting with high erythropoietin concentration and 1p/19q deletions

We describe a 19-year-old woman with onset of epileptic seizure, and a small mural nodule and multicystic lesions with severe brain edema located in the right frontal lobe. At surgery, the tumor and a clear margin was removed, and symptoms improved postoperatively. Extended local radiotherapy (60 Gy) was performed. Histopathological examination revealed oligodendroglioma-like tumor cells with a perinuclear halo. The tumor cells extended processes toward CD34-positive proliferating vessels, which resemble a basement membrane. These proliferating vessels formed a tumor membrane so that there was a clear margin between the tumor and brain tissue. Tumor cells were positive for epithelial membrane antigen in a dot-like pattern. MIB-1 staining index was 50.6%. Electron microscopy showed cilia and zipper-like junctions, and anaplastic clear-cell ependymoma grade III was diagnosed. A characteristic of the case was formation of a tumor membrane by proliferating tumor blood vessels. Fluorescence in situ hybridization showed 1p/19q deletions, and the concentration of erythropoietin in the cyst fluid was abnormally high, at 1,859.4 mIU/ml. Erythropoietin and erythropoietin receptors were verified with immunohistochemical staining.     

Biologic behavior of and p53 overexpression in multifocal renal cell carcinoma of clear cell type: an immunohistochemical study correlating grading, staging, and proliferation markers

BACKGROUND: In the treatment of small renal cell carcinoma (RCC), there is controversy between radical and nephron-sparing surgical treatment because of the risk of tumor multifocality. The biologic behavior of multifocal RCC compared with that of unifocal RCC is not well investigated, and the relevance of p53 and the proliferation markers MIB-1 and proliferating cell nuclear antigen (PCNA) to multifocal RCC is not yet established. METHODS: In this study, p53 protein overexpression was investigated immunohistochemically in 27 multifocal and 65 unifocal clear cell RCCs using a monoclonal antibody (DO-1). The nuclear expression of p53 was compared with the expression of PCNA and MIB-1 (Ki-67 antigen) and other prognostic factors, including grade and stage. RESULTS: Thirty-three RCCs (35.9%) had p53 positive nuclear staining. MIB-1 positivity was significantly higher in p53 positive tumors than in p53 negative tumors. PCNA positivity was not different in p53 positive tumors compared with p53 negative tumors. Proliferation marker expression was not associated with tumor focality. p53 overexpression was more often found in unifocal tumors than in multifocal tumors. Intracellular accumulation of the p53 protein was related to tumor grade but not to the T classification of tumor stage. In addition, lymph node involvement was significantly associated with p53 overexpression in tumors of the kidney. Focality did not influence progression free survival. CONCLUSIONS: This study demonstrated that there is no difference in the proliferative activity or biologic behavior of multifocal and unifocal tumors.     

The proliferative potential of the pilocytic astrocytoma: The relation between MIB-1 labeling and clinical and neuro-radiological follow-up

The proliferative potential of 39 pilocytic and 5 low grade astrocytomas was studied in relation to the Ki-67 activity as measured by the MIB-1 Labelings Index. The results were correlated to the biological behaviour of the tumor as measured by clinical and neuro-radiological (CT- or MRI-scans) follow-up of the patient. This study was undertaken to answer the question whether MIB-1 expression reflects differences in biological behaviour of these tumors, such as rapid progression of residual tumor or stable remaining tumor. MIB-1 LI values ranged from 0 to 19% in the group of pilocytic astrocytomas (mean 4,2%) and from 0 to 15% in the 5 low grade astrocytomas (mean 4,2%). All patients were operated and 23 of them had incomplete tumor resection as proven on postoperative neuro-imaging studies. Those 23 patients could be subdivided into two groups; one without progression of residual tumor during follow-up (n=12) and the other with tumor progression (n=11). mean MIB-1 LI in the group with quiescent tumor tended to be lower than in the group with progressive tumor: 3,3% vs. 6,6%. Residual tumors which were negative for MIB-1 staining showed fewer progressions of residual tumor compared to those being positive for MIB-1 staining, however this difference was not significant (p=0, 15, Fisher exact test). Tumor samples of a second operation of the same patient had lower MIB-1 LI values than those of the samples taken at first operation. The proliferating potential seemed to be decreased after part of the tumor was resected. Pilocytic astrocytomas with a negative MIB-1 LI are unlikely to show progression of residual tumor after partial resection. MIB-1 staining might be an additional tool in determining the frequency and duration of follow-up and in making decisions regarding further treatment of a patient operated for a pilocytic astrocytoma with residual tumor.     

Expression of vascular endothelial growth factor and p53 protein in association with neovascularization in human malignant gliomas

We examined the expression of vascular endothelial growth factor (VEGF) protein, p53 protein, and the MIB-1 index in 43 patients with malignant gliomas in relation to tumor vascularization by an immunohistochemical method. Factor VIII-related antibody was employed for the evaluation of the vascularity and endothelial proliferation. Of the 42 cases of malignant gliomas, 36 (86%) demonstrated immunoreactivity for VEGF in their tumor cells, whereas 22 (52%) had VEGF in their endothelial cells. There was a tendency for the vascularity to be correlated with the immunoreactivity for VEGF (coefficient, 0.340). In addition, a marked increase in endothelial proliferation was evident in cases showing moderate to strong positivity for VEGF as compared with the others. Immunoreactivity for VEGF was found mostly in the malignant gliomas without p53 overexpression and/or with p53 overexpression. However, statistical analysis revealed a correlation between the grade of p53 overexpression and the grade of VEGF expression (coefficient, 0.507), but not between the VEGF and MIB-1 index in our series. There was a tendency for the MIB-1 indices to increase in correlation with increasing vascularity.     

CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer

Introduction

Tumor infiltrating lymphocytes may indicate an immune response to cancer development, but their significance remains controversial in breast cancer. We conducted this study to assess CD8+ (cytotoxic T) lymphocyte infiltration in a large cohort of invasive early stage breast cancers, and to evaluate its prognostic effect in different breast cancer intrinsic subtypes.

Methods

Immunohistochemistry for CD8 staining was performed on tissue microarrays from 3992 breast cancer patients. CD8+ tumor infiltrating lymphocytes were counted as intratumoral when in direct contact with tumor cells, and as stromal in adjacent locations. Kaplan-Meier functions and Cox proportional hazards regression models were applied to examine the associations between tumor infiltrating lymphocytes and breast cancer specific survival.

Results

Among 3403 cases for which immunohistochemical results were obtained, CD8+ tumor infiltrating lymphocytes were identified in an intratumoral pattern in 32% and stromal pattern in 61% of the cases. In the whole cohort, the presence of intratumoral tumor-infiltrating lymphocytes was significantly correlated with young age, high grade, estrogen receptor negativity, human epidermal growth factor receptor-2 positivity and core basal intrinsic subtype, and was associated with superior breast cancer specific survival. Multivariate analysis indicated that the favorable prognostic effect of CD8+ tumor infiltrating lymphocytes was significant only in the core basal intrinsic subgroup (Hazard ratio, HR = 0.35, 95% CI = 0.23-0.54). No association with improved survival was present in those triple negative breast cancers that lack expression of basal markers (HR = 0.99, 95% CI = 0.48-2.04) nor in the other intrinsic subtypes.

Conclusions

CD8+ tumor infiltrating lymphocytes are an independent prognostic factor associated with better patient survival in basal-like breast cancer, but not in non-basal triple negative breast cancers nor in other intrinsic molecular subtypes.     

Leptomeningeal Melanomatosis With Multiple Cutaneous Pigmented Nevi: Tumor Cell Proliferation and Malignant Transformation in an Autopsy Case

We experienced a rare case of leptomeningeal melanomatosis. The proliferative activity and nuclear accumulation of p53 in this tumor were examined, since the relationship between this tumor type and growth has not yet been elucidated. A 33-year-old Japanese man was shown to have leptomeningeal melanomatosis with multiple cutaneous pigmented nevi. The autopsy findings showed the presence not only of benign diffuse melanosis of the leptomeninges but also of leptomeningeal melanomatosis in the subarachnoid space and brain parenchyma. In the brain parenchyma, the direct invasion of tumor cells from the subarachnoid space and Virchow–Robin spaces filled with melanoma cells were observed. Multiple hemorrhagic areas invaded by melanoma cells were also present. Immunohistochemical staining with a monoclonal antibody to melanoma cells showed positivity in the tumor cells. Proliferation analysis using the MIB-1 antibody demonstrated that the labeling index of tumor cells invading brain parenchyma (2.54%) was higher than that in other lesions of the inner (0.89%) and outer layer (0.76%) of the subarachnoid space. Nuclear accumulation of p53 protein was rarely seen in the tumor cells.We reported a case of leptomeningeal melanomatosis. Higher proliferative activity was found in invading cells of the brain parenchyma. Malignant transformation of the tumor did not appear to be associated with p53 gene mutation.     

Apoptosis control and proliferation marker in human normal and neoplastic adrenocortical tissues

We evaluated by immunohistochemistry the expression of the Bcl-2 and p53 proteins, as markers of apoptosis control, and of MIB-1, as a marker of cell proliferation, in a series of normal and neoplastic adrenocortical tissues. The specimens were 13 normal adrenals, 13 aldosterone-producing adenomas, 13 non-functioning adenomas and 16 carcinomas. Results were calculated as percentage of immunostained cells by using specific antibodies. No p53 protein was detected in any of the adrenocortical adenomas (functioning and non functioning) or normal adrenals, while p53 was overexpressed in 15 out of 16 carcinomas. In particular, 10 adrenal cancer specimens (62.5%) showed strong staining in a high percentage (range 10-50%) of the malignant cells. The percentage of Bcl-2 positive cells was higher (P<0.05 or less) in non-functioning adenomas (8.1+/-1.9%) and in carcinomas (14.9+/-5.6%) than in normals (2.9+/-0.9%) and aldosterone-producing adenomas (5.3+/-1.3%) since four specimens of the non-functioning adenomas-group (30.7%) and six of the carcinomas-group (37.5%) showed over 10% positivity (cut-off for normal values, set at 90th percentile of our controls). MIB-1 positivity was 0.50+/-0.36% in normals, 0.54+/-0.08% in non-functioning adenomas and 0.54+/-0.08% in aldosterone-producing adenomas. MIB-1 was expressed in all carcinomas with values (13.7+/-3.1%) significantly (P<0.0006) higher than in the other groups. In conclusion, the present data indicate that the apoptosis control and proliferation activity evaluated by the p53 and MIB-1 proteins are impaired in adrenal carcinomas but preserved in adenomas, independently of their functional status. Therefore, these immunohistochemical markers, overexpressed in carcinomas only, may be useful in the diagnosis of malignancy in adrenocortical tumours. Whether Bcl-2 positivity found in some carcinomas and non-functioning adenomas may constitute, in the latter, a negative prognostic marker is still unknown.     

Parasagittal solitary fibrous tumor resembling hemangiopericytoma

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor in the central nervous system, and the clinical behavior of this tumor is similar to that of meningioma. We report the case of a Japanese woman with parasagittal SFT that resembled hemangiopericytoma (HPC). Histological examination revealed that the tumor was highly cellular, with cells containing oval- or spindle-shaped nuclei arranged in sheets or a pattern-less growth mode. Focal vascular proliferation was also observed. Some areas showed intercellular stroma containing remarkable eosinophilic collagens. Tumor cells showed a strong immunoreactivity for CD34 but were negative for S-100 protein and epithelial membrane antigen. MIB-1 labeling index of the tumor was 6.6%. Owing to the high cellularity, high MIB-1 labeling index, and focal vascular proliferation, it was difficult to distinguish this lesion from HPC. However, the tumor was finally diagnosed as SFT on the basis of the strong immunostaining for CD34 and absence of pericellular reticulin. HPC. The clinical and pathological features of SFT and HPC and their differential diagnoses are discussed.