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Notes: Summary The present WHO classification of meningiomas has served us well. In keeping with the adage, “if it ain't broke, don't fix it,” alterations should be made with due caution. These proposed modifications of the WHO classification are prompted by advances in our understanding of the pathobiology of meningeal neoplasms, as well as a need for an orderly scheme based upon factors of clinical importance. The author is well aware, that given the vastly differing technologies available to those utilizing the “blue book,” its application must have a basis in routine histology rather than in “high-tech” procedures. No classification is ideal, but the modifications suggested represent a compromise between the pathologist's need for a complete morphologic exposition and the clinician's desire for a concise classification of therapeutic and prognostic significance.

Notes: Summary Primary intracranial osteosarcoma not originating in the skull is a distinctly rare tumour, as is post-irradiation sarcoma of short latency. The authors report the case of a 56 year old caucasian male who underwent resection of a glioblastoma of the left temporal region and was subsequently administered partial field external beam radiation therapy (XRT) to a total dose of 5940 cGy. Seven months following the completion of XRT, an enhancing region adjacent to the surgical site was noted on followup magnetic resonance images (MRI), one which increased in size on serial studies. Initial biopsy of the dural lesion adjacent to the temporal resection site revealed a sarcoma with a suggestion of osseous differentiation. Subsequent reoperation with resection of the lesion showed it to be a primary meningeal tumour, and histological evaluation of the lesion demonstrated an osteosarcoma. Immunohistochemical staining for p53 protein performed on both the original glioblastoma and the subsequently resected osteosarcoma showed widespread nuclear positivity. The clinical, radiographic and pathologic features of this unusual case are discussed. Meningeal osteosarcoma should be included among the rare secondary sarcomas of the meninges which may be associated with malignant glioma.

Notes: Summary Cavernous haemangiomas rarely occur in the pineal region, only eight histologically verified cases have been reported to date. Clincally and radiographically, they are often confused with other tumours of the pineal region, particularly germ cell tumours. When radiotherapy is performed without the benefit of biopsy, cavernous haemangiomas as well as other radioresistant neoplasms may be unnecessarily treated. We report two surgically treated cases of cavernous haemangioma of the pineal region, and comment upon one treated by shunt placement alone. Two cases were associated with an adjacent venous malformation. In all instances, magnetic resonance imaging (MRI) permitted a correct pre-operative diagnosis. We conclude that surgical exploration and total resection is the treatment of choice when the diagnosis of cavernous haemangioma is suspected on the basis of neuro-imaging. A conservative attitude is justifiable in the case of elderly patients with a higher surgical risk.

Notes: Leiomyosarcoma (LMS) of dermal and subcutaneous tissues is an uncommon neoplasm. In order to analyze the specialized pathologic features of this tumor, we undertook a histological, ultrastructural, and immunohistochemical study of 9 superficial LMS, including 7 dermal lesions and 2 subcutaneous neoplasms. These were compared with 12 examples of “deep” extracutane-ous LMS. Metastases to the skin from two of the latter neoplasms were also examined. Immunohistochemistry was found to be a useful diagnostic adjunct to light microscopic and ultrastructural studies in that all LMS coexpressed vimentin and des-min, regardless of site, and 90% also expressed muscle-specific actin. Variable expression of cathepsin B and niyelin basic protein was noted in 8 and 10 tumors, respectively, whereas none contained cytokeratin. Weak cytoplasmic positivity for epithelial membrane antigen was seen in 1 dermal and 3 extracutaneous LMS. Of 7 dermal LMS, 4 contained S-100 protein, whereas this determinant was found in only 1 of 12 extracutaneous tumors. Conversely, Leu 7 reactivity was present in 7 of 12 extracutaneous LMS, but only 2 of 9 superficial lesions. Review of clinical features confirmed that subcutaneous LMS is capable of aggressive behaviour, whereas dermal LMS was more likely to behave in an indolent fashion. However, one example of dermal LMS exhibited aggressive local recurrences and distant metastasis, ultimately leading to the death of the patient. Therefore, careful clinical followup is indicated in all cases.

Notes: Abstract The cellular nature of the giant eosinophilic cells of tuber and of the cells comprising subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis (TS) remains unclear. To assess the characteristics of these lesions, 13 tubers and 6 SEGA were immunohistochemically studied with glial and neuron-associated antigens. In addition to conventional ultrastructure, 6 tubers and 8 SEGA were fibrillary acidic protein (GFAP) and somatostatin. Eosinophilic giant cells of tubers were positive for vimentin (100%), GFAP (77%) and S-100 protein (92%); such cells were also found to a various extent to be reactive for neuron-associated antigens, including neurofilament (NF) proteins (38%) or class III β-tubulin (77%). SEGA also showed variable immunoreactivity for GFAP (50%) or for S-100 protein (100%); NF epitopes, class III β-tubulin, and calbindin 28-kD were expressed in 2 (33%), 5 (83%) and 4 (67%) cases, respectively. Cytoplasmic staining for somatostatin (50%), met-enkephalin (50%), 6-hydroxytryptamine (33%), β-endorphin (33%) and neuropeptide Y (17%) was noted in SEGA, but not in tubers. Ultrastructurally, the giant cells of tubers and the cells of SEGA contained numerous intermediate filaments, frequent lysosomes and occasional rectangular or rhomboid membrane-bound crystalloids exhibiting lamellar periodicity and structural transition to lysosomes. Some SEGA cells showed features suggestive of neuronal differentiation, including stacks of rough endoplasmic reticulum, occasional microtubules and a few dense-core granules. Furthermore, in one case of tuber, a process of a single large cell was seen to be engaged in synapse formation. Intermediate filaments within a few cells of both lesions were decorated by gold particle-labeled GFAP antiserum. Within the tumor cells of SEGA, irregular, non-membrane-bound, electron-lucent areas often contained somatostatin-immunoreactive particles, whereas the latter could not be detected in tuber. The present study provides further evidence of divergent glioneuronal differentiation, both in the giant cells of tubers and the cells of SEGA. The findings of similar cells at different sites, including the subependymal zone, white matter (“heterotopias”), and cortex indirectly supports the idea that these lesions of TS result from a migration abnormality.

Notes: Abstract The cellular nature of the giant eosinophilic cells of tuber and of the cells comprising subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis (TS) remains unclear. To assess the characteristics of these lesions, 13 tubers and 6 SEGA were immunohistochemically studied with glial and neuron-associated antigens. In addition to conventional ultrastructure, 6 tubers and 8 SEGA were subjected to immunoelectron microscopic study for glial fibrillary acidic protein (GFAP) and somatostatin. Eosinophilic giant cells of tubers were positive for vimentin (100%), GFAP (77%) and S-100 protein (92%); such cells were also found to a various extent to be reactive for neuron-associated antigens, including neurofilament (NF) proteins (38%) or class III β-tubulin (77%). SEGA also showed variable immunoreactivity for GFAP (50%) or for S-100 protein (100%); NF epitopes, class III b-tubulin, and calbindin 28-kD were expressed in 2 (33%), 5 (83%) and 4 (67%) cases, respectively. Cytoplasmic staining for somatostatin (50%), met-enkephalin (50%), 5-hydroxytryptamine (33%), β-endorphin (33%) and neuropeptide Y (17%) was noted in SEGA, but not in tubers. Ultrastructurally, the giant cells of tubers and the cells of SEGA contained numerous intermediate filaments, frequent lysosomes and occasional rectangular or rhomboid membrane-bound crystalloids exhibiting lamellar periodicity and structural transition to lysosomes. Some SEGA cells showed features suggestive of neuronal differentiation, including stacks of rough endoplasmic reticulum, occasional microtubules and a few dense-core granules. Furthermore, in one case of tuber, a process of a single large cell was seen to be engaged in synapse formation. Intermediate filaments within a few cells of both lesions were decorated by gold particle-labeled GFAP antiserum. Within the tumor cells of SEGA, irregular, non-membrane-bound, electron-lucent areas often contained somatostatin-immunoreactive particles, whereas the latter could not be detected in tuber. The present study provides further evidence of divergent glioneuronal differentiation, both in the giant cells of tubers and the cells of SEGA. The findings of similar cells at different sites, including the subependymal zone, white matter ("heterotopias"), and cortex indirectly supports the idea that these lesions of TS result from a migration abnormality.

Notes: Abstract Subependymal giant cell astrocytoma (SEGA) is the most common neoplastic process involving the brain in patients with tuberous sclerosis complex (TSC). Morphologically, these tumors exhibit a wide range of cytoarchitecture with spindle and epithelioid cells resembling astrocytes, and also large, occasionally giant cells, some of which have a distinctly ganglion-like appearance. Unresolved questions regarding SEGAs center on: (a) their cytogenesis, i.e., whether they are derived from single or multiple precursors; and (b) their differentiating capacity along glial or neuronal lines. We sought to determine whether SEGAs represent truly mixed tumors or whether they consist of a single population of cells with a capacity for divergent differentiation. Twenty SEGAs were assessed for immunophenotypic features of either neuronal or glial differentiation or both. Only tumors from patients with a clinically confirmed diagnosis of TSC were included. Immunoreactivity for glial fibrillary acidic protein (GFAP) and/or S-100 protein was considered indicative of a glial phenotype, whereas the presence of neuronal differentiation was assessed by staining for cytoskeletal proteins [neurofilament epitopes, class III β-tubulin, microtubule-associated protein 2 (MAP2), synaptophysin], neurosecretory substances [serotonin, cholecystokinin, β-endorphin, substance P, somatostatin, met-enkephalin, neuropeptide Y, vasoactive intestinal polypeptide (VIP)], and for the 28-kDa neuron-associated calcium binding protein calbindin. Of the tumors examined, 18 exhibited both glial and neuronal epitopes, the staining pattern being variable. In 19 tumors, the constituent spindle, polygonal and giant or ganglion-like cells showed variable immunoreactivity for GFAP and S-100 protein, both within the cell body and processes. Neuron-associated cytoskeletal proteins were present in 18 cases. Class III β-tubulin immunoreactivity was demonstrated in 17 tumors, both within the bodies of all three cell types and to varying degrees within their processes. Neurofilament protein and calbindin staining was present in 8 tumors, with reactivity for the former being distributed in a phosphorylation-dependent manner. MAP2 was detected in a few cells of two tumors. Immunoreactivity for neuropeptides was observed in 17 lesions. Somatostatin and met-enkephalin staining was noted in 10 tumors (50%), being present particularly within polygonal cells. Neuropeptide Y, serotonin and β-endorphin reactivity was found in 6 (30%), 5 (25%), and 4 tumors (20%), respectively; β-endorphin was lacking in giant cells, whereas neuropeptide Y and serotonin were seen within their cell bodies. Substance P and VIP were evident in only occasional polygonal cells of 2 (10%) and 1 tumor (5%), respectively. Stains for cholecystokinin were negative. The observation of immunoreactivity for both glial- and neuron-associated epitopes within tumor cells of the same morphology suggests that SEGAs represent proliferations of cell lineages with the capacity to undergo divergent glioneuronal as well as neuroendocrine differentiation to a greater extent than do other mixed glial-neuronal neoplasms.

Notes: Summary MR images in 54 patients with biopsy-proven diffuse or “fibrillary” astrocytomas were analyzed and compared with the histopathologic features in order to determine which histopathologic characteristics underlie the radiographic findings in these gliomas and whether radiographic findings are more closely correlated with individual histopathologic characteristics than with histologically determined tumor grade. The MRI features studied included tumor heterogeneity, edema, mass effect, border sharpness, “anatomic invasion”, contrast enhancement, hemorrhage, and the presence of flow voids, calcium and cyst formation. The histopathologic characteristics studied included cellular atypia, mitoses, cellularity, endothelial proliferation, necrosis and tumor grade. Edema (P〈0.01), flow voids (P=0.02) and contrast enhancement (P〈0.01) demonstrated a direct correlation with tumor grade, but edema (P〈0.01) and contrast enhancement (P〈0.01) also demonstrated a significant correlation to tumor cellularity. Tumor heterogeneity was associated with the presence of necrosis (P=0.01). Hemorrhage occurred only in high grade tumors, where it correlated with endothelial proliferation (P=0.04).

Notes: Abstract 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 patient 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.