Pleomorphic xanthoastrocytoma

Pleomorphic xantho-astrocytoma (PXA) is a relatively rare brain tumor of adolescents and young adults characterized by its superficial location with frequent involvement of the meninges, and its slow growth despite features of histological atypia. The authors present a retrospective immunohistochemical analysis of 8 surgically treated cases in order to determine the expression of glial and neuronal markers, and to assess the proliferating cell fraction. The study population comprised 1 female and 7 male patients with a mean age of 26.7 years, most tumors being located in one of the temporal lobes. Epilepsy predominated as a presenting symptom. Five cases were assigned WHO graded II, while the diagnosis of anaplasia (WHO grade III) was established in three, based either on elevated mitotic counts or the presence of necrosis. Immunostaining with the proliferation marker MIB-1 was present in 2.05% of cells in the former groups, while 4.66% showed labeling in the latter. Postoperative follow-up averaged 6.7 years, with only one recurrence of an anaplastic tumor. All tumors expressed some amount of glial fibrillary acidic protein and were shown to elaborate a characteristic pericellular reticulin network. There was focal reactivity for alpha-1-antitrypsin, but neither the monocyte-macrophage associated antigen CD68 nor lysozym could be detected in neoplastic cells. In 7 cases, scattered individual tumor cells exhibited synaptophysin positivity. The authors review problems and prognostic issues of the histologic diagnosis of anaplasia occurring in some 20% of the cases. A possible dysontogenic origin of PXA and its nosologic relationship to the so-called desmoplastic neuroepithelial tumors of infancy are discussed. This is the first study of pleomorphic xanthoastrocytoma in the Hungarian literature.     

Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome

Between July, 1984, and October, 1988, 263 patients (163 male, 100 female), aged from 4 to 83 years (mean 52 years), with malignant brain gliomas underwent surgical procedures: stereotactic biopsy in 160 and resection in 103 patients. There were 170 grade IV astrocytomas, 17 grade IV mixed oligoastrocytomas, 44 grade III astrocytomas, 22 grade III mixed oligoastrocytomas, and 10 malignant oligodendrogliomas. Overall median survival time was 30.1 weeks for grade IV gliomas, 87.7 weeks for grade III gliomas, and 171.3 weeks for malignant oligodendrogliomas. Multivariate analysis in 218 newly diagnosed cases revealed that the variables most strongly correlated with survival time were: tumor grade, patient age, seizures as a first symptom, a Karnofsky Performance Scale score of less than 70%, tumor resection, and a radiation therapy dose greater than 50 Gy. The proportions of patients receiving tumor resection versus biopsy in each of these prognosis factor groups were similar. Since most of the 22 patients with midline and brain-stem tumors were treated with biopsy alone, these were excluded. Considering 196 newly diagnosed patients with cortical and subcortical tumors, grade IV glioma patients undergoing resection of the contrast-enhancing mass (as evidenced on computerized tomography and magnetic resonance imaging) and postoperative external beam radiation therapy lived longer than those undergoing biopsy only and radiation therapy (median survival time 50.6 weeks and 33.0 weeks, respectively; Smirnov test, p = 0.0380). However, survival in patients with resected grade III gliomas was no better than in those with biopsied grade III lesions (p = 0.746). The authors conclude that, in selected grade IV gliomas, resection of the contrast-enhancing mass followed by radiation therapy is associated with longer survival times than radiation therapy after biopsy alone.     

Use of a neural network and a multiple regression model to predict histologic grade of astrocytoma from MRI appearances

Several MRI features of supratentorial astrocytomas are associated with high histologic grade by statistically significant p values. We sought to apply this information prospectively to a group of astrocytomas in the prediction of tumor grade. We used 10 MRI features of fibrillary astrocytomas from 52 patient studies to develop neural network and multiple linear regression models for practical use in predicting tumor grade. The models were tested prospectively on MR images from 29 patients studies. The performance of the models was compared against that of a radiologist. Neural network accuracy was 61% in distinguishing between low and high grade tumors. Multiple linear regression achieved an accuracy of 59%. Assessment of the images by a radiologist yielded 57% accuracy. We conclude that while certain MRI parameters may be statistically related to astrocytoma histologic grade, neural network and linear regression models cannot reliably use them to predict tumor grade.     

Atypical melanosis of the foot

We present a case of a seemingly malignant pigmented lesion on the foot, arising in a Japanese female. Clinically, the lesion was characterized by irregular borders and variegated pigmentation closely mimicking those of acral lentiginous melanoma in situ. However, the histologic findings revealed only focal, slight, melanocytic hyperplasia with minimal cytologic atypia along the basal layer. Despite the malignant clinical features, thorough histologic examination failed to disclose any area with significant melanocytic atypia or evidence of malignancy. To the best of our knowledge, no similar lesions with the clinical appearance of melanoma in situ and completely lacking histologic evidence of malignancy have been reported. We, therefore, prefer to designate this lesion as atypical melanosis of the foot, to highlight the clinically atypical findings and to distinguish this from malignant melanoma in situ of the foot (1).     

Breathing during sleep in patients with nocturnal desaturation

BACKGROUND: The global DNA methylation of 136 breast lesions (117 primary invasive carcinomas, 5 benign phyllodes tumors, 11 fibroadenomas, and 3 sclerosing adenosis) and their respective adjacent parenchyma was analyzed using an in vitro enzyme assay. METHODS: In the group of patients with breast carcinoma, DNA hypomethylation was correlated with clinical and pathologic parameters known to affect disease prognosis. Histopathologic type, disease stage, and tumor grade were evaluated according to the World Health Organization classification, the TNM system, and the criteria of Elston and Ellis' criteria, respectively. DNA flow cytometry was performed in fresh/frozen samples stained with propidium iodide. Hormone receptor (estrogen and progesterone receptor) status was determined by immunocytochemistry. RESULTS: The comparative study of DNA methylation showed that the DNA of breast carcinomas was statistically significantly less methylated than the DNA of the respective adjacent parenchyma (P=0.0001), the DNA of breast benign lesions (P=0.0002), and the DNA of normal parenchyma (P < 0.0001). A statistically significant correlation was found between the global DNA hypomethylation and the disease stage (P=0.0009), tumor size (P=0.0026), and histologic grade (P=0.0097) of malignant neoplasms. A trend for DNA from breast carcinomas with positive axillary lymph nodes (N1) to be more hypomethylated than those without nodal involvement (NO) (P=0.055) was verified. In contrast, no significant association was found between DNA methylation and histologic type of tumors, hormone receptors, DNA ploidy, and S-phase fraction. CONCLUSIONS: The current shows that DNA hypomethylation is increased in breast carcinomas, playing a potentially important role in tumor development. These findings also suggest that DNA methylation status may be a biologic marker with prognostic significance in this group of neoplasms.     

Clonal analysis of gliomas

In malignant gliomas, the characteristically heterogeneous features and frequent diffuse spread within the brain have raised the question of whether malignant gliomas arise monoclonally from a single precursor cell or polyclonally from multiple transformed cells forming confluent clones. Although monoclonality has been shown in surgically resected tissues, these may not include the full spectrum of patterns seen on autopsy material. Little is known about the clonality of low-grade gliomas from which malignant gliomas may sometimes arise. We sought to investigate the clonality of low-grade and malignant gliomas by using and comparing surgical and autopsy material with a Polymerase chain reaction (PCR)-based assay for nonrandom X chromosome inactivation. For that, purpose, archival surgical and autopsy material from 15 female patients (group A) (age 4 to 73 years; median, 45) with malignant gliomas (12 glioblastomas, one gliosarcoma, one anaplastic oligoastrocytoma, one gliomatosis cerebri), surgical material only from 21 female patients (group S) (age 6 to 78 years; median, 60) with low-grade and malignant gliomas (four low-grade astrocytomas, three oligoastrocytomas, two anaplastic astrocytomas, one gemistocytic astrocytoma, four oligodendrogliomas, seven glioblastomas) were analyzed. In group A, representative areas (mean = 5/patient; median = 7) were microdissected from tissue sections and assayed by PCR amplification of a highly polymorphic microsatellite marker locus of the human androgen receptor gene (HUMARA) in the presence of alpha32P with and without predigestion with a methylation-sensitive restriction enzyme (HhaI). Products were resolved by denaturing gel electrophoresis and autoradiographed. In group S, selected tumor areas were used for the assay. Each patient's normal brain tissue was used for control. The band intensity of alleles were measured by densitometric scanning. In group A, 13 of 15 cases were informative (heterozygous). The same pattern of nonrandom X chromosome inactivation was present in all areas of solid dense and moderate tumor infiltration in eight including all components of the gliosarcoma. Two of eight also showed focal loss of heterozygosity (LOH). One of 13 presented global LOH. Two of 13 showed microsatellite instability, one of which in a patient with Turcot syndrome, the other in gliomatosis cerebri. Opposite skewing patterns were seen in distant areas of gliomatosis cerebri consistent with oligoclonal derivation. Clonality remained indeterminate in one glioblastoma and in the anaplastic oligoastrocytoma because of skewed lyonization in the normal control. In group S, 19 of 21 cases were informative. Fifteen of 19 were monoclonal (four low-grade astrocytomas, one anaplastic astrocytoma, one gemistocytic astrocytoma, two oligodendrogliomas, one oligoastrocytoma, six glioblastomas). Four of 19 were indeterminate. We conclude that (1) Low-grade and malignant gliomas are usually monoclonal tumors, and extensively infiltrating tumors must result from migration of tumor cells (2) Gliomatosis cerebri may initiate as an oligoclonal process or result from collision gliomas (3) Biphasic gliomas likely arise from a single precursor cell. (4) LOH at the HUMARA locus is probably related to partial or complete deletion of an X-chromosome, which occurs in malignant gliomas during clonal evolution.     

A molecular genetic model of astrocytoma histopathology

As the molecular events responsible for astrocytoma formation and progression are being clarified, it is becoming possible to correlate these alterations with the specific histopathological and biological features of astrocytoma, anaplastic astrocytoma and glioblastoma multiforme. In WHO grade II astrocytomas, autocrine stimulation by the plateletderived growth factor system coupled with inactivation of the p53 gene may lead to a growth stimulus in the face of decreased cell death with slow net growth ensuing. Such cells would also have defective responses to DNA damage and impaired DNA repair, setting the stage for future malignant change. Such biological scenarios recapitulate many of the clinicopathological features of WHO grade II astrocytomas. Anaplastic astrocytomas further display release of a critical cell cycle brake that involves the CDKN2/p16, RB and CDK4 genes. This results in mitoses seen histologically; clinically, there is more conspicuous, rapid growth. Finally, glioblastomas may emerge from the microenvironmental outgrowth of more malignant clones in a complex vicious cycle that involves necrosis, hypoxia, growth factor release, angiogenesis and clonal selection; growth signals mediated by activation of epidermal growth factor receptors may precipitate glioblastomas. It is clear as well that glioblastoma multiforme can arise via a number of independent genetic pathways, although the clinical significance of these distinctions remains unclear.     

Gliofibromas (including malignant forms), and gliosarcomas: a comparative study and review of the literature

The presence of connective tissue elements in gliomas necessitates in every case a thorough analysis of the character and derivation of such elements to allow the formulation of an appropriate diagnosis. Four cases are presented in this paper. In cases 1 and 2 (anaplastic astrocytomas in two children, 9 and 4 years old, respectively) all the neoplastic elements were astrocytes and their ability to produce or indirectly promote the production of reticulin and collagen fibers accounted for the presence of such elements in close association with the tumor cells. The term "gliofibroma" has been coined for such tumors, but "desmoplastic astrocytoma", (low grade or anaplastic) or in highly malignant cases "desmoplastic glioblastoma", as the case may be, also seem to be appropriate terms for such neoplasms. In contrast, cases 3 and 4 represented composite tumors in adults (66 and 58 years old, respectively) and the neoplasms of these patients consisted of glioblastoma and sarcoma, the latter component demonstrably being of vascular origin. This is the type of tumor usually referred to as gliosarcoma or "Feigin tumor". Although some apparent similarities between the two groups may exist at times, the histogenesis of the latter group's sarcomatous or sarcoma-like portions is different from that of the first group and, therefore, warrants separate diagnostic terms and placement in brain tumor classification.     

Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation

PURPOSE: To determine whether the expression of epidermal growth factor receptor (EGFR) protein was predictive of patient survival independently of other prognostic factors in astrocytic tumors. METHODS AND MATERIALS: Epidermal growth factor receptor protein expression was investigated immunohistochemically in formalin-fixed, paraffin-embedded surgical specimens of 55 glioblastoma multiforme, 14 anaplastic astrocytoma, and 2 astrocytomas given definitive irradiation. We evaluated the relationship of EGFR protein expression and tumor grade, histologic features, age at diagnosis, sex, patient survival, and recurrence-free survival. RESULTS: The percentage of tumor cells which were EGFR positive related to reduced survival by Cox regression analysis in both univariate (p = 0.0424) and multivariate analysis (p = 0.0016). Epidermal growth factor receptor positivity was the only 1 of 11 clinical and histological variables associated with decreased recurrence-free survival by either univariate (p = 0.0353) or multivariate (p=0.0182) analysis. Epidermal growth factor receptor protein expression was not related to patient age, sex, or histologic features. CONCLUSION: Epidermal growth factor receptor positivity was a significant and independent prognostic indicator for overall survival and recurrence-free survival for irradiated patients with astrocytic gliomas.     

Intraoperative electron beam radiotherapy for previously irradiated advanced head and neck malignancies

In patients with malignant astrocytomas or metastatic brain disease treated with high-dose radiotherapy, conventional imaging methods may not adequately distinguish recurrent tumor from radiation change. We used a fast spoiled gradient refocusing technique in the open-configuration intraoperative MR system to assess the rate of regional enhancement of the treated tumor bed and to localize specific sites for pathologic sampling to determine whether gadolinium uptake correlated with histologic data. Twenty-four patients were studied. Fourteen of 15 patients with areas of early enhancement had recurrent tumor present in histologic samples, and 8 of the remaining 9 patients had only reactive changes. Dynamic MRI was predictive of recurrent tumor (P < .0005, Fisher exact test and P < .002, Student t test). We conclude that dynamic MRI in the open-bore magnet is a promising method for localizing potential sites of active tumor growth in patients treated for malignant astrocytomas and metastatic brain lesions.     

Ductal carcinoma in situ of the breast: correlation of pathologic and mammographic features with extent of disease

Optimal treatment of ductal carcinoma in situ (DCIS) of the breast requires an improved understanding of its pathologic extent and propensity for local recurrence. This study was performed to analyze mammographic and pathologic features of DCIS that might predict the extent of disease within the breast and facilitate treatment selection between lumpectomy alone, lumpectomy and radiotherapy, and mastectomy. At our institution, 60 cases of DCIS were diagnosed in 59 patients from June 1985 to February 1995 and form the basis of this retrospective study. Demographic and treatment-related information was obtained from hospital and tumor registry records. Mammograms were reviewed and size estimates of the abnormalities were determined. Pathologic slides from all cases were reviewed and classified according to size group, focality, nuclear grade, necrosis, and histologic subtype. DNA ploidy status and proliferation indices were available for 28 patients. Pathologically, 43 (72%) cases were < 15 mm, 14 (23%) were 16 to 40 mm, and 3 (5%) were > 40 mm. Five (8%) of the lesions were multicentric, 28 (47%) focal, and 27 (45%) multifocal. Thirty-three (55%) patients were treated by mastectomy, 16 (27%) by lumpectomy alone, and 11 (18%) by lumpectomy and radiation therapy. Mammographic size, histologic grade, presence or absence of necrosis, histologic subtype, DNA ploidy, and proliferative index were compared with pathologic size and focality by chi 2 analysis. Mammographic size correlated significantly with pathologic size (chi 2 = 11.3; P = 0.02) but underestimated the extent of disease in 9 cases. Although focality correlated significantly with pathologic size (chi 2 = 15.8; P = 0.003), the remaining histopathologic features did not significantly correlate with pathologic size or focality. Histopathologic features, including DNA studies, do not reliably predict the pathologic extent of DCIS, but mammographic size and focality do significantly correlate with pathologic size. Nevertheless, most cases of DCIS are small focal or multifocal lesions that are amenable to breast conservation approaches; further studies are needed to determine the appropriate use of lumpectomy, radiation therapy, and mastectomy in the treatment of DCIS.     

Experimental headache models in animals and humans

Using multiple regression analysis, six MR parameters were correlated with three histological grades among 43 proven adult supratentorial astrocytic gliomas to ascertain important MR parameters and their optimal contributions. Analysis revealed that two parameters, border definition and tumor hemorrhage, were unreliable. Using the remaining four parameters an equation was derived: Tumor grade = 0.32 (ring enhancement) +0.29 (degree of contrast enhancement) +0.13 (heterogeneity) +0.12 (edema) +0.41. Ring enhancement was the most reliable predictor of tumor grade, followed by degree of contrast enhancement. The maximum accuracies of the "semi-automatic" approach using this equation for predicting low-grade astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme were 91%, 83%, and 88%, respectively. Although "semi-automatic" grading provided relatively high accuracy, possible sampling errors and some atypical cases reduced such accuracy.     

Expression of oligodendrocytic mRNAs in glial tumors: changes associated with tumor grade and extent of neoplastic infiltration

We examined the expression of glial- and neuronal-specific mRNAs within human gliomas using in situ hybridization. We found that low-grade astrocytomas contained a high number of proteolipid protein (PLP) mRNA-positive cells and that the number of PLP-stained cells decreased markedly with increasing tumor grade. Interestingly, the ratio of PLP mRNA-stained cells:myelin basic protein (MBP) mRNA-stained cells in normal white matter and low-grade astrocytoma was about 2:1 but approached 1:1 with increasing tumor grade. This parameter appeared to be a good indicator of tumor infiltration in astrocytomas, so we tested this in the analysis of other gliomas. Unlike astrocytomas, oligodendrogliomas were found consistently to contain few PLP mRNA- or MBP mRNA-expressing cells. In contrast, gemistocytic astrocytomas, typically highly invasive tumors, contained high numbers of PLP-positive cells and a ratio of PLP mRNA:MBP mRNA-stained cells of about 1.5:1, similar to low-grade astrocytomas. Nonradioactive in situ hybridization also enabled the morphological identification of specific cells. For example, gemistocytic astrocytes, which were found to be strongly vimentin mRNA positive, contained little glial fibrillary acidic protein mRNA and did not stain for PLP or MBP mRNAs. Neuronal mRNAs, such as neurofilament 68, were observed in small numbers of entrapped neurons within gliomas but were uninformative with respect to predicting tumor grade. Our results suggest that oligodendrocytes survive low-grade tumor infiltration and that glial tumor cells, unlike cell lines derived from them, do not express oligodendrocyte or neuronal mRNAs. In addition, the expression of mRNAs for the two major myelin protein genes, PLP and MBP, could be used to predict the grade and extent of tumor infiltration in astrocytomas.     

Anaplastic pleomorphic xanthoastrocytoma

Well-documented cases of malignant degeneration in pleomorphic xanthoastrocytoma and of anaplastic pleomorphic xanthoastrocytoma are rare in the literature. We report 2 cases of pleomorphic xanthoastrocytoma, 1 of which demonstrated clear evidence of malignant degeneration in the absence of prior radiation therapy over an 18-year period. Both anaplastic tumors were characterized by foci of necrosis and increased mitotic activity (3 and 2 mitotic figures/10 high-power fields). Both tumors demonstrated focal positive staining for glial fibrillary acidic protein and showed marked reticulin deposition. An MIB-1 labeling index (marker of cell proliferation) in the initial low-grade-appearing tumor in case 1 was 0.1%. The recurrent tumor in case 1 had an MIB-1 labeling index of 4.9%, and the anaplastic tumor in case 2 had an MIB-1 labeling index of 5.4%. Significant cyclin D1 immunoreactivity was not observed in either anaplastic tumor. Two percent to 3% of tumor cells stained positive with p53 protein antibody in the recurrent anaplastic tumor in case 1. Although histology may not reliably predict aggressive behavior in pleomorphic xanthoastrocytomas, the presence of increased mitosis, necrosis, and increased cell proliferation labeling indices may be indicative of a higher grade tumor.     

Fine needle aspiration of basal cell adenocarcinoma of the parotid gland. Report of a case with assessment of DNA ploidy in aspirates and tissue sections by image analysis

BACKGROUND: Basal cell adenocarcinoma of the parotid gland is a low grade malignant neoplasm. It has cytologic features of basal cell adenoma and a histologically infiltrative growth pattern of malignant tumors with perineural and vascular invasion. CASE: Fine needle aspiration biopsy findings of basal cell adenocarcinoma of the parotid gland in a 77-year-old male were supplemented by DNA ploidy analysis. CONCLUSION: No single cytologic feature was found to unequivocally distinguish this lesion from basal cell adenoma and/or solid variant of adenoid cystic carcinoma. Therefore, for diagnostic purposes, we grouped all three lesions under the term basal cell tumor. Evaluation of DNA content of tumor cells revealed diploid histograms in both cytologic material and paraffin-embedded tissue. Infiltrative tumor nests, the histologic basis for differentiating basal cell adenocarcinoma from adenoma, showed the same diploid pattern. Though DNA quantitation may not discriminate basal cell adenoma from basal cell adenocarcinoma, it may prove useful in separating them from adenoid cystic carcinoma, which is considered to be a tumor with high malignant potential.     

Classification and grading of low-grade astrocytic tumors in children

This article reviews current perspectives in the classification and grading of astrocytomas in children and calls attention to several histologically distinct groups of low-grade tumors that characteristically arise during childhood. Recognition of these tumors and the range of histological features that they may exhibit is essential for making rational assessments regarding their expected behavior and, more importantly, for guiding therapeutic intervention. For example, pleomorphic xanthoastrocytoma, which may exhibit "anaplastic" features, generally carries a relatively favorable prognosis and should not be classified with other high-grade gliomas, such as anaplastic astrocytoma and glioblastoma multiforme. Similarly, the finding of anaplastic features, such as vascular proliferation or necrosis, in pilocytic astrocytomas does not automatically portend the unfavorable prognosis that such features would imply for "diffuse" astrocytomas. Increased appreciation of the morphological diversity of astrocytomas in children should help to improve the management of children with low-grade astrocytic tumors by avoiding potentially dangerous overtreatment of otherwise indolent lesions.     

Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine

This study evaluates the usefulness of PET for the preoperative evaluation of brain gliomas and methods of quantification of PET results. METHODS: Fifty-four patients with brain gliomas were studied by PET with 18F-fluorodeoxyglucose (FDG) (n = 45) and/or 11C-methionine (MET) (n = 41) before any treatment. Results of visual analysis, calculation of glucose consumption and five tumor-to-normal brain ratios for both tracers were correlated with two histologic grading systems and with follow-up. RESULTS: Visual analysis (for FDG) and tumor-to-mean cortical uptake (T/MCU) ratio proved to be the best tools for the evaluation of PET results. Methionine was proven to be better than FDG at delineating low-grade gliomas. Tumor-to-mean cortical uptake ratios for FDG and MET were clearly correlated (r = 0.78), leading to the equation T/MCU(FDG) = 0.4 x T/MCU(MET). We showed a good correlation between FDG PET and histologic grading. MET uptake could not differentiate between low-grade and anaplastic astrocytomas but was significantly increased in glioblastomas. Low-grade oligodendrogliomas exhibited high uptake of FDG and MET, probably depending more on oligodendroglial cellular differentiation than on proliferative potential. Uptake was decreased in anaplastic oligodendrogliomas, probably due to dedifferentiation. Care must be taken with peculiar histologic subgroups, i.e., juvenile pilocytic astrocytomas and oligodendrogliomas, because of a discrepancy between high PET metabolism and low proliferative potential (good prognosis). Both tracers proved useful for the prediction of survival prognosis. Methionine proved slightly superior to FDG for predicting the histologic grade and prognosis of gliomas, despite the impossibility of differentiation between Grades II and III astrocytomas with MET. This superiority of MET could be explained by patient sampling (low number of Grade III gliomas submitted to examination with both tracers). The combination of both tracers improved the overall results compared to each tracer alone. CONCLUSION: Both tracers are useful for the prediction of the histologic grade and prognosis. The apparent superiority of MET over FDG could be due to the small number of Grade III gliomas studied with both tracers.     

Contrast-enhanced MR "magnetization transfer technique". Improved tumor contrast, delineation and visibility of intracranial malignant gliomas and metastases in radiosurgical treatment planning

AIMS: To improve tumor conspicuity and delineation on contrast-enhanced T1-weighted MR images with and without magnetization transfer (MT) contrast as a strategy to improve the macroscopic boost volume definition in the planning process of radiosurgery in patients with high grade gliomas or metastatic brain lesions. PATIENTS AND METHODS: Thirty-two patients (mean age 47 years) with histologically proven or suspected high grade glioma (n = 12) or metastatic brain lesions (n = 20) were prospectively examined by MR imaging. After the administration of gadolinium dimeglumine (0.1 mmol/kg body weight) the lesions were imaged with a T1-weighted MT-fast low angle shot (FLASH) pulse sequence and with a conventional T1-weighted SE sequence without MT saturation. RESULTS: The mean CNR of enhancing lesions on T1-weighted MT-FLASH was 15 +/- 5 compared to 11 +/- 4 on SE images, representing a significant (p < .01) improvement. The mean tumor diameter of malignant gliomas was significantly (p < .01) larger measured on T1-weighted MT-FLASH images compared to those obtained from T1-weighted SE images and were comparable for metastatic lesions. Lesion conspicuity and delineation were improved in 50% of patients with high grade gliomas and in 35% of patients with brain metastases. Lesion conspicuity was markedly improved in the posterior fossa. Additional contrast enhancing lesions were detected in 10% of patients with metastases on MT-FLASH images. CONCLUSIONS: It is concluded that contrast-enhanced MT-FLASH images may improve lesion detection and delineation in the planning process of radiosurgery in patients with intracranial high grade gliomas or metastases or even alter the treatment approach.     

Immunohistochemical analysis of progesterone receptor and Ki-67 labeling index in astrocytic tumors

BACKGROUND: Intracranial tumors such as meningiomas express steroid hormone receptors but little is known regarding progesterone receptor (PR) in astrocytic tumors. The authors evaluated expression of PR in 86 astrocytic tumors in relation to tumor proliferative potential. METHODS: Paraffin embedded tumor sections were stained with polyclonal antiprogesterone antibody by the peroxidase-antiperoxidase method and with monoclonal MIB-1-Ki-67 antibody by avidin-biotin complex immunohistochemistry. RESULTS: Sixty-three of the 86 astrocytic tumors (73%) showed positive PR immunoreactivity. PR expression was observed in 4 of 9 pilocytic astrocytomas, 13 of 24 Grade 2 astrocytomas, 15 of 20 anaplastic astrocytomas, and 31 of 33 glioblastomas. In addition to the tumor cells, cells of microvascular endothelial proliferation and the smooth muscle of tumor vessel walls were frequently PR positive. Glioblastomas had a significantly higher percentage of PR positive cells compared with anaplastic (P < 0.0008) and low grade (P < 0.0001) astrocytomas. Patients with PR positive astrocytomas were of an older age than patients with PR negative astrocytomas (48.71 +/- 21.95 years vs. 37.09 +/- 24.69 years; P < 0.04). The mean Ki-67 labeling index (LI) was significantly higher in the high grade (3-4) astrocytomas compared with low grade (1-2) astrocytomas (P < 0.0001). PR positive astrocytic tumors had higher Ki-67 LI than PR negative tumors. PR expression was not correlated with tumor recurrence and patient survival. CONCLUSIONS: The current study suggests that PR in the astrocytic tumors correlates with histologic grade and PR may participate in the growth of these tumors and tumor angiogenesis. The measurement of PR in these tumors may indirectly represent tumor growth potential.